CPG Hypertension.pdf

"#$%&!'()%!Philippine Obstetrical and Gynecological Society (POGS), Foundation, Inc. ! CLINICAL PRACTICE GUIDELINES on HYPERTENSIVE COMPLICATIONS OF PREGNANCY ! April 2010 Task Force on Clinical Practice Guideline In the Diagnosis and Management of Hypertensive Complications of Pregnancy Philippine Obstetrical and Gynecological Society (POGS), Foundation, Inc. ! CLINICAL PRACTICE GUIDELINES on HYPERTENSIVE COMPLICATIONS OF PREGNANCY April 2010 Task Force on Clinical Practice Guidelines In the Diagnosis and Management of Hypertensive Complications of Pregnancy . MD . 2010 The 2nd Edition of the Clinical Practice Guideline (CPG) on Hypertensive Complications of Pregnancy is a timely addition to our growing number of “must have” reference books. (POGS). MD President Philippine Obstetrical and Gynecological Society (Foundation). scientifically validated data in the detection and management of one of the leading challenges of obstetric practice. Your unselfish contribution to this body of work is a testimony of your unwavering commitment and support to a major mission of POGS. the Millennium Development (MDG) Countdown Program. PICHAY. was in response to our resolve in reducing the unacceptably high rate of attendant maternal and fetal morbidity and mortality. It is envisioned that with this book more of our colleagues and partners will help the country reach its MDG 4 and 5 before 2015. The urgency and dispatch with which this edition came to be. I commend the teamwork of the 2010 Committee on CPG and the Taskforce on CPG . In line with the thrust of this year’s centerpiece project. Inc. FOREWORD! ! REGTA L.Hypertensive Complications of Pregnancy. this CPG is a significant tool in providing health workers & stakeholders with fresh. REGTA L. PITHAY. . MD. The CME Committee members. MD. EFREN J. The Task Force on the Diagnosis and Management of Hypertensive Complications of Pregnancy and the Committee on Continuing Medical Education. PhD Chair. (POGS). Inc. AdHoc Committee on the Clinical Practice Guidelines. (Foundation). and making it responsive to the most current and acceptable standard in this procedure. the Chairs and Training Officers of the Residency-Training Accredited Institutions. DOMINGO. 2010. The Philippine Obstetrical and Gynecological Society. This is also envisioned to provide the academic institutions in the country and in Southeast Asia updated information on Hypertensive Complications of Pregnancy treatments being practiced in the Philippines. The Board of Trustees. 2010 The Clinical Practice Guidelines on Hypertensive Complications of Pregnancy is the Second Edition of this Publication. The Task Force Reviewers/Contributors. This Clinical Practice Guideline on Hypertensive Complications of Pregnancy is envisioned to become the handy companion of the Obstetrician-Gynecologist in his/her day-to-day rendition of quality care and decision making in managing the Obstetric patient. PhD . DOMINGO. through the Committee on Clinical Practice Guidelines initiated and led to completion the publication of this manual in plenary consultation with the Residency Accredited Training Hospitals’ Chairs and Training Officers. and the 2010 POGS Board of Trustees. specifically on Hypertensive Complications of Pregnancy. This publication represents the collective effort of the POGS in updating the clinical practice of Obstetrics and Gynecology. The Regional Board of Directors. the Regional Directors. Profound gratitude is extended to all the members of the POGS. A greater part of the inputs incorporated in this edition are the contributions originating from the day-to-day academic interactions from the faculty of the different Residency-Accredited Hospitals in Obstetrics and Gynecology in the country. INTRODUCTION! EFREN J. BOARD OF TRUSTEES 2010 OFFICERS Regta L. MD . Luna. MD. delos Reyes. Decena. PhD Virgilio B. MD Blanca C. Cynthia Fernandez-Tan. MD Treasurer Gil S. Quillamor. Pichay. MD Public Relations Officer BOARD OF TRUSTEES Efren J. MD Vice President Ditas Cristina D. MD Ma. MD Raul M. Domingo. MD President Sylvia delas Alas Carnero. de Guia. Gonzales. MD Secretary Jericho Thaddeus P. MD Rey H. Castro. MD Annelee B. MD Rommel Z. Trinidad. COMMITTEE ON CLINICAL PRACTICE GUIDELINES ON HYPERTENSIVE COMPLICATIONS OF PREGNANCY Efren J. Enriquez Ms. MD Genara Manuel-Limson. MD (Region 10) Ameila A. Duenas. MD (Region 2) Concepcion P. MD Milagros T. MD Lisa T. de Leon. Co. MD Sharon A. MD Grace delos Angeles. MD Diosdado M. MD. Castillo. MD Sol M. Capule. Vega. Capito. MD Rainerio S. Pangan. MD Ma. Santos. Mariano. Emiliana C. Jhasmin G. Tusalem. Dionio. MD Gilbert Reyes. MD TECHNICAL STAFF ASSISTANTS Ms. Lojo. MD MANAGING EDITOR Ana Victoria V. MD Chair Members Walfrido W. Mariano. De Guzman TASK FORCE ON DIAGNOSIS AND MANAGEMENT OF HYPERTENSIVE COMPLICATIONS OF PREGNANCY Ernesto S. Quevedo. MD Ronaldo R. MD Eugenia Mendoza. MD Aida San Jose. MD Jennifer T. Prodigalidad-Jabson. MD Rodante P. MD Mila Zaragoza-Ibay. delos Reyes. MD (Region 7) Fe G. MD (Region 4) Diosdado V. MD Ma. Uichanco. MD Christine D. MD (Region 4A NCR) Cecilia Valdes-Neptuno. MD TASK FORCE REVIEWERS AND PLENARY REVIEWERS Regta L. MD Lourdes B. MD (Region 3) Ernesto S. PhD Chair MEMBERS Ann Marie C. Jocson. Abad. MD (Region 1) Noel C. Habana. Dizon. MD Zaida N. Acu. MD Mario A. MD Paz Leticia Anacta. Prodigalidad-Jabson. MDCarmencita B. MD Pilar Lagman-Dy. MD Analyn Matignas. MD Regional Directors Betha Fe M. MD Florentina A. Naval. Gamilla. Villanueva. Torres. MD Teresita Cardenas. MD Joseph U. Argonza. MD Ma. Parado. MD Ramon M. MD (Region 6) Belinda N. Domingo. MD Ma. Trinidad. Duenas. Tiongco. Olivar. MD Julieta Cadano. MD Belen P. MD Lisa T. MD Rey H. MD Ann Marie C. MD Marilyn D. MD (Region 9) Jana Joy R. Castro. Mendiola. MD Raul M Quillamor. MD Sherri Ann L. Galiza. MD Ma. Merin. Luisa S. MD Nelinda Pangilinan. Victoria V. MD Rogelio P. MD (Region 11) . Pañares. Pichay. Carmen H. MD Carmelita Pasay-Recto. MD Ma. Cristina P. de Guia. MD Virgilio B. MD Blanca C. MD (Region 5) Evelyn R. MD Amaryllis Digna Yazon. Ruaro. Suplido. MD Janette Tuquero. Lacson. Gonzales. MD Rommel Z. MD (Region 8) Cynthia A. Lorelli P. Crisologo. Dy Echo. Antonia E. Rajagulgul. Bernardino. Sumpaico. 2009. • In behalf of the POGS. its officers and general membership. April 2010. • This is the ownership of the POGS. ! ! ! ! ! ! . to clarify. its officers. the general practitioner. DISCLAIMER. and its entire membership. to a valauable pathway that leads to the discovery of clinical tests leading to clinical treatments and eventually recovery. or part. • The reader is encouraged to deal with each clinical case as a distinct and unique clinical condition which will never fit into an exact location if reference is made into any or all part/s of this CPG. RELEASE AND WAIVER OF RESPONSIBILITY • This is the Clinical Practice Guidelines (CPG) on Hypertensive Complications of Pregnancy. conference audits/controversies. the student. • This is the publication of the Philippine Obstetrical and Gynecological Society. or the entirety of any topic. (Foundation). quote. the patient. not this CPG. disagreements. refer to. any capacity of the person or individual who may read. • The intention and objective of this CPG is to serve as a guide. or for that matter. or acknowledge. the allied medical practitioner. subject matter. the Committee on The Clinical Practice Guidelines. It is always encouraged to refer to the individual clinical case as the one and only answer to the case in question. as well as the Commiittee on the Clinical Practice Guidelines and its Editorial Staff in any or all clinical or other disputes. • It is hoped that with the CPG at hand. this CPG is meant to make each one of us a perfect image of Christ. Inc. solution and treatment for clinical conditions and situations. (POGS). the clinician will find a handy guide that leads to a clue. diagnostic condition or idea/s willfully release and waive all the liabilities and responsibilities of the POGS. • The obstetrician-gynecologist. its Board of Trustees. case discussions/critiquing. any. It is not the intention or objective of this CPG to serve as the exact and precise answer. the Healer. to make clear the distinction. cite. Second Edition. Epidemiology of Hypertensive Complications of Pregnancy …………………………. M. Raul M. Uichanco. Cristina P. and Diosdado V.D. Antonia E. and Sherri Ann L. Gestational Hypertension and Mild Pre-eclampsia ……………………………………. Luisa S. Santos. 5. M. Predictive Tests for Hypertensive Complications of Pregnancy ………………………. M. Sumpaico.! CPG ON HYPERTENSIVE COMPLICATIONS OF PREGNANCY TABLE OF CONTENTS / AUTHORS! ! 1.D.D.D. 2.. and Sol M.D.1 Ramon M.D. M. M. Castro. Bernardino. M. Crisologo. and Ronaldo R. 8.. Acu. .D. M. Trinidad. M. and Milagros T. Tongco. M.D. 7. Ma. Chronic Hypertension …………………………………………………………………… Virgilio B. 6. Complications of Pregnancy Induced Hypertension (HELLP. M. Jocson. M. 9.D.D ! ! ! ! ! ! ! . and Ann Marie C. 3.D. and Carmencita B. 4. Severe Pre-eclampsia …………………………………………………………………… Mario A. Prevention of Pre-eclampsia ……………………………………………………………. and Joseph Olivar. Quillamor. M. Walfrido W. The Classification of Hypertensive Complications of Pregnancy ……………………… Ernesto S. M.D.. Gonzalez.D. Eclampsia ……………………………………………………………………………….D. Ma. M. Pilar Lagman-Dy.. M. Pangan. Habana. M. M. M.D.D and Ma. Abruptio Placenta) ……. Mariano.D.D. Suplido. This may arise in situations in which effective immunization by a previous pregnancy is lacking. The etiology therefore. as in first pregnancies. it is now thought that this tolerance rather involves cytokines through the tolerance network called T helper 2 (Th2) reaction. especially preeclampsia have been documented to occur primarily in first pregnancies. It decreased to 1.1 Previous Pregnancy Complicated by Preeclampsia / Eclampsia / HELLP Women who had previous pregnancies complicated by preeclampsia have an increased risk for recurrence in subsequent pregnancies. Ronaldo Santos MD and. More recently. Pregnancy- induced hypertensive disorders. therefore of primiparity is the epidemiological cornerstone of this disease. is more likely to be multifactorial. ! Primiparity ! The only well accepted risk factor for preeclampsia is primiparity. Preeclampsia caused by the failure of the trophoblast invasion can be considered as a kind of rejection reaction by the mother towards the trophoblast antigens through a failure of the tolerance system allowing the invasion. Normal pregnancy is well known to be an immunological stimulation towards the tolerance pathway and not an immunological depression of the mother. Clues regarding the etiology may be derived from the various risk factors that have been identified. Carelle Roux-Ong MD ! Preeclampsia is a life threatening complication of pregnancy characterized by hypertension and proteinuria that contribute greatly to maternal morbidity and mortality. . It occurs in about 3% of all pregnancies.5 million women). In the past the theory was that this immunological tolerance could be due to blocking antibodies. Gonzalez MD.4 Immunologic Factors There is circumstantial evidence to support the theory that preeclampsia is immune mediated. severe preeclamptic women in an initial pregnancy have a recurrence rate of as high as 50%. This disease has long been recognized but the exact etiology of preeclampsia is still obscure despite many attempts to identify possible causes. the risk of preeclampsia in first pregnancies was 3%. Epidemiology of Hypertension in Pregnancy Ramon M. This is primarily due to an abnormal implantation of trophoblasts in the placenta as well as poor placental perfusion.1 In a population based study in Norway covering all births since 1967 (about 1.7% in the second pregnancy. The concept. hiding the father’s antigens. The immunization concept is supported by observations that preeclampsia develops less often in multiparas who had a prior term pregnancy. Moreover. 2%.9). In a study by Sibai involving 366 eclamptic women.3% and 14. It increases from 4.1-42.8 (95% CI 1. If two sisters have the same father but different mothers the risk of preeclampsia is 1.4 The pathophysiologic role for genetic and behavioural factors that cluster families is consistent with the likelihood of preeclampsia among sisters of women with previous preeclamptic pregnancies.5 Family History of Preeclampsia The predisposition to hereditary hypertension undoubtedly is linked to preeclampsia and the tendency for preeclampsia–eclampsia is inherited.3).8 Underlying Medical Conditions Underlying medical conditions with vascular and connective tissue disorders or renal implications are at risk for developing preeclampsia . the incidence of gestational hypertension and preeclampsia are both significantly increased. the rate of recurrence of eclampsia in subsequent pregnancies was 2% and the risk for developing preeclampsia was 22%.3% for women with a body mass index (BMI) less than 19. . were 1. Women with preeclampsia were 2.01-2.2% respectively compared with women with normal BMI which was 11.5% and 65% when the previous pregnancy was complicated by severe preeclampsia. In a study by Stamilio the odds ratio was 6. about 75%. Sibai and Sullivan in separate studies revealed a recurrence rate of preeclampsia with previous pregnancies with HELLP syndrome to be 19% and 43% respectively. Those with pre-existing chronic hypertension had higher rates of preeclampsia. In a population based cohort study in Missouri between 1989-1997 obese and overweight women had higher risks of recurrent preeclampsia 19.9 (95% CI 1. the frequency of preeclampsia rose with increasing severity of diabetes. Pregnancy Related Conditions Conditions with an increased trophoblast mass like hydrops fetalis and multifetal gestation are at increased risk for preeclampsia. Those with gestational hypertension on the other hand.10 Body Mass Index The relationship between maternal weight and the risk of preeclampsia is progressive.6 times more likely to have a sister with gestational hypertension.In a study by Campbell and coworkers. In women with twin gestations compared with those with singletons.8 kg/m2 to 13.7 More so. Among 462 women with pregestational diabetes.3 times more likely to have a sister who had preeclampsia. Sibai and co-workers demonstrated a 20% occurrence of preeclampsia. Van Rijn and co-workers showed that there was a 25% chance of recurrence in women with a history of early onset preeclampsia resulting in delivery before 34 weeks of gestation. 13% in singletons and 5-6% in twins. the rate of recurrence of preeclampsia was 7.3% in those with a BMI greater than 35 kg/m2. al.8 (95% CI 1. In support of this theory. The role of the father has long been hypothesized to be central in the primipaternity model which can be interpreted by an immunogenetic hypothesis. Maternal Infection Systematic review and meta-analysis of observational studies were done to examine the relationship between maternal infection and preeclampsia.2-2.1% whereas the recurrence rate for twins was only 6.6).Although multiple gestations are considered at risk for preeclampsia.76. if a woman becomes pregnant by a man who has fathered a preeclamptic pregnancy in a different woman.5 Primipaternity Recently. Conclusion was that urinary tract infection and periodontal diseases increased the risk of developing preeclampsia. 95% CI 1. Within the first four months the risk is 40% compared to 3-5% over 12 months. They found out that for women with a previous singleton pregnancy complicated with preeclampsia. This may be interpreted as an immunological habituation to paternal antigens through contact between the sperm and the female genital tract.18). a higher risk for preeclampsia has also been observed in women who had artificial insemination by an unknown donor. Moreover.6 . Having a new sexual partner will expose the mother to new paternal antigens to which she may not be tolerant.1 Regardless of parity. The risk of preeclampsia was increased in patients with urinary tract infection (OR 1. the recurrence rate was 14. Thus. Immunogenetic factors explain the primipaternity phenomenon. Sexual Co-habitation Robillard. changing the father. the length of sexual co-habitation was noted to be inversely related to the incidence of pregnancy induced hypertension. the lower the risk of preeclampsia.218 women between 1967 and 1998.45-1. There is a linear decrease of the risk of preeclamsia with the timing of conception within the first year of sexual co-habitation. One explanation is that the mother adapts to the imprinted antigens from the father. A longer period of sexual co-habitation with the father before conception reduces the risk of preeclampsia. it has been suggested that primipaternity rather than primiparity is the relevant risk factor. 95% CI 1. the risk for recurrence in subsequent pregnancies is not clear. Trogstad and co-workers examined a total of 550. her risk of developing preeclampsia is 1. suggested that preeclampsia is a “disease of new couples” and that the longer the duration of co-habitation (without barrier contraceptives). This disease therefore.43-2.70) and periodontal disease (OR 1.57. et.8%. may be a problem of primipaternity rather than primigravity.4 Paternal genes in the fetus may therefore contribute substantially to a woman’s risk of preeclampsia. for a woman with no history of preeclampsia may increase her risk to the same level that she would have had as a primipara. Gestational Age at Delivery in the First Pregnancy The risk of recurrent preeclampsia is inversely related to the gestational age at the first delivery: 38. A sister’s risk: family history as a predictor of preeclampsia.2005. al. Int J Obstet Gynecol 2001. paternity. 7. ! ! . Rasmussen S. Recurrence of preeclamsia: Effects of gestational age at delivery of the first pregnancy. Tegan C.8 A previous preterm delivery and small for gestational age newborn increases the risk of preeclampsia in subsequent pregnancies. Tungsiripat R. Kallogjeri D. Commentary: revisiting the primipaternity theory of preeclampsia.6% for <28 weeks gestation. Am J Obstet Gynecol 2005:193(3):965-972. 9. Harley K. Am J Obstet Gynecol 2008:198(1):7-22.Williams Obstetrics 22nd ed. 10.9 Socioeconomic Status Women from different socioeconomic status share the similar risk of developing preeclampsia. New York NY:McGraw- Hill. 2.9% for >37 weeks age of gestation. Hauth J. et. 5. Am J Obstet Gynecol 2000:364-369. 3. Mostello D. Cunningham F. Holcomb W. Lindheimer M. ironically. Dildy G.266(2):237-241. References 1. et. Sidney S. Mostello D. Sem Perinat 2007:31(3):135-141. Eskanazi B. Maternal infection and risk of preeclampsia: systematic review and meta-analysis. Dekker G. Risks of preeclampsia and adverse neonatal outcome among women with pregestational diabetes mellitus. body mass index. Agudelo AC. This disease is the only major perinatal risk factor which is not reported to be evidently associated with poor social status. Eskenazi B. Leet T. 6.30:1323-1324. Grant NF. Fenster L. smoking has consistently been associated with a reduced risk of hypertension during pregnancy. Epplein M. Revisiting the epidemiological standard of preeclampsia: primigravidity or primipaternity? Eur J Obstet Gynecol Reprod Bio 1999. and interval between births. al. Caritis S. Johnson C.e7. Brunborg H. Robillard P. Villar J. Lie RT. Roman L.9% for 33-36 weeks and 12. Preeclampsia in the parous woman: who is at risk? Am J Obstet Gynecol 2002. Multivariate analysis of risk factors for preeclampsia.1% between 29-32 weeks. Smulian J. JAMA 1991.316:1343-1347. Sibai B.84(1):37-41.e1-55. 8. al. et. 4. 11. 29. Smoking Although smoking during pregnancy causes a variety of adverse pregnancy outcomes. al. Darcy C. Hulsey T. 21. Fetal and maternal contributuions to risk of preeclampsia: population based study BMJ 1998. Belfort M. Leet T. Preeclampsia recurrence and prevention. Am J Obstet Gynecol 2008: 55.187(2):425-429. et. Recommendations of the Consensus Meeting The committee recommends the following classification of hypertensive complications of pregnancy. Some terms are used interchangeably. Suplido.! ! Classification of Hypertensive Complications of Pregnancy Ernesto S. The committee is presenting this classification system for uniformity and standardization in practice. Severe C. Gestational hypertension / non. MD and Sherri Ann L. Hypertension The National High Blood Pressure Education Program (NHBPEP) Working Group defines hypertension in pregnant women as having a systolic blood pressure (BP) of 140 mmHg or higher or a diastolic blood pressure of 90 mmHg or higher on more than 1 occasion1 (American College of Obstetrics and . Pre-eclampsia 1. Uichanco. based on a review of three commonly-used classification system used presently in the Philippines and several recommendations from different societies and guidelines abroad. Chronic Hypertension E. The various classification systems each have their own defects and deficiencies. Chronic Hypertension with Superimposed Pre-eclampsia Definition of Terms 1. encompassing and meaningful in the clinical situation. The confusions brought about by these numerous classification methods may be one of the reasons why it is difficult to come up with researches on the topic with significant results and conclusions. Local medical centers are using a combination of the various definitions and classification system of hypertensive disorders in pregnancy. Eclampsia D. Mild 2. Classification of Hypertensive Disorders in Pregnancy A. adding to the confusion when trying to give a diagnosis and in labeling a patient.proteinuric hypertension of pregnancy / transient hypertension B. MD Modern day obstetrics is still wanting of a classification of hypertensive disorders of pregnancy that is simple. These criteria are no longer used because evidence reveals that these women are unlikely to suffer adverse perinatal outcomes and because similar increases are seen in uncomplicated pregnancies. The diagnosis of hypertension should be based on office or in-hospital BP measurement and is based on the average of at least two measurements. 3. Edema This is defined as swelling of the hands and the face or leg edema after an overnight rest. Although this is the case.hour or timed collection1 (ACOG. 4. Pregnancy Induced Hypertension This is defined as hypertension that develops as a consequence of pregnancy and regresses post-partum however The term pregnancy-induced hypertension should be abandoned. Level II-2. Level II. regardless if absolute values were below 140/90 mmHg. the Working Group recommends “close observation” of these patients. 5. it has been recommended that an incremental increase of 30 mmHg systolic or 15 mmHg diastolic pressure be used as a diagnostic criteria. which usually correlates with a +1 (30 mg/dl) or greater. as its meaning in clinical practice is unclear 2 (NGC. It may also be defined as greater than 30 mg/mmol urinary creatinine in a spot (random) urine sample2 (NGC. Korotkoff phase V is used to designate diastolic blood pressure2 (NGC. Level I. Pre-eclampsia Preeclampsia is a multiorgan disease process characterized by the presence of hypertension and proteinuria occurring after 20 weeks of gestation in a woman with a previously normal blood pressure.3 grams or 300 mg or more of protein in a 24. Level III). In the past. Level III). Level III. Gestational Hypertension The NHBPEP Working Group has recommended that the term “gestational hypertension” replace the term “pregnancy-induced hypertension” to describe cases in which elevated blood pressure without proteinuria develops in a woman after 20 weeks of gestation and blood pressure levels return to normal 12 weeks postpartum1 (ACOG. Grade B). . Proteinuria Proteinuria is defined as the presence of 0. Grade D). 3. and is no longer a criterion for the diagnosis of pre-eclampsia. Level III). Gynecology (ACOG). but should be confirmed with a random urine dipstick evaluation or and a 24. taken using the same arm2 (National Guideline Clearinghouse (NGC). Grade A-B).hour urine specimen. Grade A). 2. 6. sudden increase in proteinuria if already present in early gestation. Chronic Hypertension Chronic hypertension is characterized by elevation of blood pressure that antecedes pregnancy or persists post-partum. Mild pre-eclampsia Pre-eclampsia is characterized as mild if the patient does not manifest any of the signs and symptoms of severe pre-eclampsia. It is defined by the NHBPEP Working Group on High Blood Pressure in Pregnancy as hypertension present before the 20th week of pregnancy or hypertension present before pregnancy1 (ACOG. Level III). The diagnosis is also made in a woman taking anti- hypertensive medications before conception. 10. Severe pre-eclampsia Pre-eclampsia is characterized as severe if the patient manifests any of the following3 (ACOG. or the development . a sudden increase in hypertension. Chronic Hypertension with Superimposed Pre-eclampsia This is characterized by elevation of blood pressure that antecedes pregnancy or persists post-partum with associated signs and symptoms of pre- eclampsia. 8. Diagnostic criteria include “new-onset proteinura” in a woman with hypertension before 20 weeks gestation. It is classified as mild (BP > 140/90 mm Hg) or severe (BP > 180/110 mmHg. Level III): • BP > or = 160 mm Hg systolic or > or = 110mm Hg diastolic taken at least 6 hours apart on 2 occasions while the patient is on bed rest • Proteinuria > or = 5 g/24 hrs or >/= +3 in 2 random urine samples collected at least 4 hours apart • Elevated serum creatinine • Pulmonary edema • Oliguria < 500 ml/24 hrs • Microangiopathic hemolysis • Thrombocytopenia • Hepatocellular dysfunction (elevated alanine transaminotransferase or aspartase aminotransferase) • Intrauterine growth restriction or oligohydramnios • Symptoms suggesting end-organ involvement: Headache Visual disturbances Epigastric or right upper quadrant abdominal pain 7. and is also present if the hypertension persists longer than 12 weeks post delivery3.3 9. Eclampsia Eclampsia is defined as hypertension in pregnancy with proteinuria along with convulsions or the occurrence of grand mal seizures in a patient with pre- eclampsia. The patient should be seated (or supine) or in the left lateral recumbent position with arms bared.1 Method of Indirect Measurement of Blood Pressure 1. the ACOG. elevated liver enzymes. and should not have smoked or ingested caffeine within 30 minutes before measurement. The bladder should be inflated to 30 mmHg above the point of radial pulse extinction as determined by a preliminary palpatory determination. 2. Table 2.3. Level II-1. the Royal College of Obstetricians and Gynecologists (RCOG) and the NGC. softening of the sounds should be used as diastolic pressure (Korotkoff phase IV). Aneroid. patients may be reclassified to amore definitive category. The measurement of blood pressure will follow the recommendations presented by the Multi-sectoral Task Force on the Detection and Management of Hypertension convened by the Philippine Society of Hypertension.5 times upper arm circumference while the bladder should cover at least 80% of the arm circumference. Should any other classification system is to be used. Grade A)2. and are calibrated and tested on a regular basis. Systolic pressure should be recorded at the appearance of the 1st clear tapping sound (Korokoff phase 1). supported. A mercury manometer is ideal for accurate measurement. Level II-2.) This is now no longer encountered in any of the recent guidelines and literature except for ICD-9 2101 which included Unspecified Hypertension. however. provided that they satisfy technical requirements for accuracy. and low platelet count. with the stethoscope bell placed directly over the brachial artery. as they may give inaccurate blood pressure readings7 (RCOG. 4. 11. with the bladder directly over brachial artery. Automated methods. The manometer cuff should cover at least 2/3 of the length of the patient’s arm. Grade A). or the length 1. unless these are still present near 0 mmHg in which case. They should not have rested for at least 5 to 10 minutes. The acronym HELLP describes a variant of severe preeclampsia characterized by hemolysis. Grade A).1). . it is recommended that the system of classification be mentioned and proper definitions presented for clarification. 1997 (Table 2. Unclassified Hypertension – hypertension when essential clinical information is lacking (This classification is put to insure that “pregnancy induced” and “chronic” are not confused by the inclusion of equivocal cases and to enable all patients to be placed in a definite category. Post-partum. 3. Level II. the NHBPEP Working Group on High Blood Pressure in Pregnancy. It should then be deflated at a rate of 2 mmHg/beat. Grade B). The edge of the cuff should be placed 1 inch above the elbow crease. digital or other automated devices provide reasonable alternatives2 (NGC. and at heart level7 (RCOG. of HELLP syndrome3. need to be used with caution. Diastolic blood pressure should be recorded at the disappearance of these sounds (Korotkoff phase V)2 (NGC. Level I. should be regarded as the patient’s blood pressure. William’s Textbook of Obstetrics.2 and 2. Level III. A review of the classifications and definitions of hypertensive disorders in pregnancy used in local hospitals and medical centers appeared to take their origins from definitions and classifications used in the following sources. taken at least 2 minutes apart. Subsequent determination should then be performed on the arm with a higher pressure reading. XIIth World Congress of Gynecology & Obstetrics in Rio De Janeiro D. International Statistical Classification of Disease and Related Health Problems by the World Health Organization C. a 3rd reading should included in the average. Level III. Grade B) Basis for the Recommendations The above recommendations were based on a discussion on the classifications used in the Philippines. For every visit. evaluation and management of the hypertensive disorders of pregnancy H. 33 on Diagnosis and Management of Pre-eclampsia and Eclampsia and ACOG Practice Bulletin No. the mean of readings. ACOG Practice Bulletin No. Level II.5. 6. Classification of Hypertensive Disorders Complicating Pregnancy from William’s Textbook of Obstetrics .3. Grade B). RCOG Evidence-based Clinical Guideline Number 10 A on The Management of Severe Pre-eclampsia/ Eclampsia F. If blood pressure is being taken for the first time. 8. the procedure should be repeated with the outer arm. National Guideline Clearinghouse Guideline on Diagnosis. Grade B). A. 22nd Edition B. Patients should be instructed on proper BP measurement technique if they are to perform home BP monitoring2 (NGC. the arm with the higher values should be used for all BP measurements2 (NGC. namely: A. 29 on Chronic Hypertension in Pregnancy E. Ambulatory BP monitoring (by 24-hour or home measurement) may be useful to detect isolated office (white coat) hypertension2 (NGC. 9. NHBPEP Report on Hypertension in Pregnancy 2000 G. If the first 2 regarded differ by 5 mmHg or more. International Statistical Classification of Diseases and Related Health Problems (ICD-10) A summary and comparison of the above classifications and definitions are presented in Tables 2. If BP is consistently higher in one arm. 7. 2). also adapts the current scheme of the Working Group of the NHBPEP in 2000. The ICD 10 also included the term “Moderate Pre-eclampsia” (ICD 10 code 014). Diagnosis of Pregnancy – aggravated hypertension or superimposed preeclampsia) is given when a pre-existing chronic hypertension worsen and is usually accompanied by proteinuria or pathologic edema. which is the 22nd edition. The latest edition. to make the diagnosis of gestational hypertension. Hypertension is used to correspond to the term “pre-eclampsia”. . Hypertension (140/90 mm Hg or greater) antecedent to pregnancy 2. where Gestational Hypertension without significant proteinuria. or Gestational Hypertension not otherwise specified are also known as Mild Pre- eclampsia. proteinuria and hypertensive disorders in pregnancy. Persistent hypertension long after delivery Additional factors that support the diagnosis are multiparity. Perhaps this may be indicative on broader outlook at the possible complications of pregnancy with regards to this topic – possibly initially starting as to involve other organ systems even prior to the clinical manifestation of overt elevation in blood pressure. there should be no proteinuria. our country most strongly influenced by teachings from the United States. Edema is not included because it was noted not to have prognostic significance. This classification may be easily compared to the ACOG classification and the NHBPEP Working Group presented above and corresponding classes may be matched. there is a section on “Oedema. Hypertension detected before 20 weeks or 3. childbirth and the puerperium”. B. Without a corresponding category though is the class Gestational edema and proteinuria without hypertension (ICD 10 code 012. hypertension complicating a previous pregnancy and a strong family history of hypertension. International Statistical Classification of Disease and Related Health Problems by the World Health Organization (ICD-10) In this comprehensive classification of diseases. In the past editions of Williams’ Obstetrics. Another difference in the classification is ICD 10 code 013. According to the 22nd edition of Williams Obstetrics and the Working Group. This is perhaps the most popular definition and classification used in the Philippines. This is the classification system used mainly by the group of the Fetal As A Patient but the term EPH Gestosis (Edema. The diagnosis of chronic underlying hypertension is suggested by the following: 1. the term “pregnancy-induced hypertension” was utilized. Proteinuria. C. XIIth World Congress of Gynecology & Obstetrics This is a classification based solely on the physical signs of hypertension and proteinuria – with the intention of defining clinical categories without necessarily implying a particular etiology or pathology. and gestational hypertension.2. In this proposal. intrapartum or postpartum types because of possible differences in clinical. This scheme and the criteria for each category differ from former diagnostic schemes and the current schemes of other groups. proteinuria and proteinuric hypertension are further subdivided into antepartum. pathologic and prognostic significance. This classification however. a serious. The Unclassified hypertension and/or proteinuria in pregnancy is used for cases when essential clinical information is lacking – which happens quite often. 29 on Chronic Hypertension in Pregnancy and National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy The National High Blood Pressure Education Program’s (NHBPEP) Working Group on High Blood Pressure in Pregnancy recently issued a report identifying four hypertensive disorders of pregnancy namely: chronic hypertension that predates pregnancy. 29 and 33. ACOG Practice Bulletin No. preeclampsia-eclampsia. in which the pathophysiologic perturbations of the preeclampsia syndrome do not occur before delivery. Gestational hypertension. In this classification. The American College of Obstetricians and Gyneocologists adapt the present scheme of the NHBPEP Working Group. severe hypertension and severe proteinuria should be defined separately. please see Table 2. For example. or B. For a more detailed breakdown of the three classification systems. is no longer encountered in any of the recent guidelines and latest literature. or nonproteinuric hypertension of pregnancy. systemic syndrome of elevated blood pressure. DBP of 120 mmHg or more on any one occasion. Important features of the preeclampsia elimination of a change in blood pressure as a diagnostic criterion wherein the group recommends using cut-off of 140/90 mm Hg. complications are to be classified separately. Suggested criteria for “severe” hypertension are as follows: A. chronic hypertension with superimposed preeclampsia. The gestational hypertension category is used in women with nonproteinuric hypertension of pregnancy. . DBP of 110 mmHg or more on two or more consecutive occasions 4 or more hours apart D. as reported in the ACOG Practice Bulletin No. elimination of edema as a criterion. because this finding is so common in healthy pregnant women and absolute requirement of proteinuria of more than 300 mg per 24 hours for the diagnosis. Eclampsia and ACOG Practice Bulletin No. 33 on Diagnosis and Management of Pre- eclampsia. proteinuria and other findings. This is important to insure that “chronic or “ gestational categories are not confused by the inclusion of equivocal cases and enable patients to be placed in a definite category. Proteinuria A.Table 2. superimposed on eclampsia eclampsia Chronic Hypertension Unspecified hypertension Unspecified hypertension Used interchangeably with w/o proteinuria gestational hypertension Gestational edema & Gestational proteinuria (w/o proteinuria w/o hypertension) hypertension Chronic renal dis.2: Classification of Hypertensive Disorders in Pregnancy WHO (ICD-10) XIIth World Congress Williams Obstetrics 22nd Ed/NHBPEP Working Group/ACOG Gestational hypertension Gestational hypertension The term “pregnancy- w/o sig. proteinuria (w/o proteinuria) induced hypertension” is now replaced by gestational hypertension Same 5 Types of Hypertensive Gestational hypertension Disease in Pregnancy: with sig. Pre-eclamsia Mild Severe Eclampsia Eclampsia C. Eclampsia Pre-existing hypertension Chronic hypertension w/o D. superimposed pre. Gestational Hypertension/ Transient Hypertension B. Chronic Hypertension proteinuria Pre-existing hypertension Chronic hypertension w/ E. Pre-eclampsia w/ superimposed pre. (w/ or w/o hypertension) Unclassified proteinuria (wo hypertension) . IV) > 300 mg per 24 hours 0.3 g/L in 24 hr collection 300 mg in 24 hours 30 mg/dl (+1) dipstick in random 0.IV) (Korotkoff Ph.1 g/L or 2+ in 2 random 1 g/L or 2+ in 2 random 4 Proteinuria urine samples 6 hours apart hours apart 0.030 & pH < 8) Abandoned as diagnostic criterion Swelling of hands & face Edema Weight gain of 5 lbs (2. !15 mmHg diastolic (4 hours apart) Korotkoff phase V is used to (6 hours apart) define diastolic BP (Korotkoff Ph.3 g/L or 1+ on reagent (SG >1.3: Definitions Williams Obstetrics 22nd WHO (ICD – 10) XIIth World Congress Ed/NHBPEP Working Group/ACOG >/=140/90 mm Hg 140/90 DBP 110 mmHg Incremental increase in BP is no !30mmHg systolic or DBP 90 mmHg Hypertension longer included.27 kg) in a week . Table 2. 99(1):159-167. American College of Obstetricians and Gynecologists. Williams Obstetrics.gov/about/inclusion. Sibai BM. Diagnosis and management of hemolysis. Magann EF. 6. elevated liver enzymes. 22 ed. Diagnosis. Am J Obstet Gynecol 2000. and management of the syndrome of hemolysis. 9. elevated liver enzymes. 5. 3. The Management of Severe Pre-eclampsia/ Eclampsia: Evidence-based Clinical Guideline Number 10 A. ACOG Committee on Practice Bulletins— Obstetrics. ACOG Committee on Practice Bulletins— Obstetrics. Diagnosis. and low platelet count. evaluation and management of the hypertensive disorders of pregnancy. 8.103(5 pt 1):981-991. American College of Obstetricians and Gynecologists.183(1):S1-S22. National Guideline Clearinghouse. Diagnosis and management of preeclampsia and eclampsia. 2. and low platelets syndrome. Barton JR. Obstet Gynecol 2001. Cunningham. ACOG Practice Bulletin No. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. ! ! ! ! . 7. July 2001. Twelve steps to optimal management of HELLP syndrome. Sibai BM. 98: 177-185.2005. Obstet Gynecol 2004. ACOG Practice Bulletin No. Royal College of Obstetricians and Gynaecologists. 2006. Clin Obstet Gynecol 1999.42(3):532-550. controversies.guideline. 29.al.31(4):807-833. Clin Perinatol 2004. 33. http://www. January 2002. et. Obstet Gynecol 2002. Martin JN Jr.References 1. March. Chronic Hypertension in Pregnancy. 4.aspx. or with twins or hydatidiform mole (3) has preexisting vascular disease. Cristina P. such as referral to a tertiary centre.17 Table 3. MD Hypertensive Complications of Pregnancy are more likely to develop in a woman who – (1) is exposed to abnormal chronic villi for the first time (2) is exposed to super abundance of chorionic villi.1. Predictive Tests for Hypertensive Complications of Pregnancy Ma. Cooper and Siston (1971) examined the possibility that susceptibility to pre-eclampsia is dependent upon a single recessive gene. Crisologo. MD and Ma. The availability of such markers could have decisive impact not only on the medical management of pregnant women and their child. but multifactorial inheritance cannot be excluded. but also on the health costs associated with this prevalent medical condition. Risk Factors for Hypertension in Pregnancy Factor! Risk Ratio Diabetes Mellitus 2:1 Hypertension in previous pregnancy 2-3:1 Nulliparity 3:1 Change of partner for second or subsequent 3:1 pregnancy Age > 40 years 3:1 Twin gestation 4:1 Family History of PIH 5:1 Chronic Hypertension 10:1 Chronic renal disease 20. Chesley and Cooper (1986) reanalyzed Chesley’s extensive data and concluded that the single gene hypothesis fits well. Habana.1 Anti-phospholipid syndrome 10:1 Angiotensinogen gene Homozygous 20:1 Heterzygous 4:1 Regardless of the lack of existing prophylactic and therapeutic means to address preeclampsia. Risk factors for hypertensive complications of pregnancy are found in Table 3. There are many proposed strategies on the detection or prediction of hypertensive complication of pregnancy. the search for non-invasive markers that could predict the development or assist in the detection of this life-threatening pregnancy disorder is still of utmost importance. Antonia E. .1. or (4) is genetically predisposed to hypertension developing during pregnancy The tendency to develop pre-eclampsia is said to be heritable. 6). Supine Pressure Test or Roll Over Test Originally described by Gant.39 (95% CI 0. similar to the results of the angiotensin sensitivity test. al.46 (95% CI 0.0-5.8 (95% CI 1.18-0.9 (Level I.20 Recent reports suggest the sensitivity of this test may be much lower (22-35%) any may be of little value in predicting preeclampsia. A positive roll over test is associated with a 3-fold increase of developing pre-eclampsia. Gant. Screening Maneuvers a.21 In a systematic review looking at MAP and BP measurements in predicting preeclampsia. In women deemed to be at high risk.18 The lower critical cut off in the second trimester represents the mid-trimester drop in blood pressure (BP) which strengthens the belief that throphoblastic proliferation at this time has resulted in dilatation of the spiral arterioles. Mean Arterial Pressure The mean arterial pressure (MAP) is defined as diastolic blood pressure (DBP) + 1/3 the pulse pressure [MAP = DBP + 1/3 (systolic blood pressure (SBP)-DBP)]. Grade B) b. The following are suggested predictive tests for pre-eclampsia: 1.8-3. the positive predictive value of this test in predicting preeclampsia is only 33 percent. with 20 mmHg as the positive response.hypertensive states7. (1973) and Oney and Kaulhausen (1982) infused angiotensin II and demonstrated increased pressor response in primigravidas. the absence of a mid-trimester drop in BP despite MAP -2 values < 90 mmHg may predict future pregnancy induced hypertension (PIH) based on the absence of arteriolar vasodilatation and should alert the physician for closer follow-up. An increase of at least 20 mmHg in the diastolic pressure constituted a positive roll over test. Therefore.early and late-onset preeclampsia. A MAP value in the second trimester (MAP -2) > 90 mmHg (sensitivity of 61-71% and specificity of 62-74%) or a MAP value in the third trimester (MAP -3) > 105 mmHg has resulted in an increased incidence of pre-eclampsia. which might suggest a different pathogenesis for these . second trimester MAP of 90 mm Hg or more showed a positive likelihood ratio of 3. Several authors suggest that the MAP -2 value may be more predictive for chronic hypertension or essential or transient hypertension.75). (Level I. et.0) and a negative likelihood ratio of 0. Health service providers are encouraged to measure the blood pressure at each patient visit and consultation (either on outpatient or on emergency basis) even if the patient complains for unrelated symptoms. al. However. coupled with uterine artery Doppler assessment showed that these seem to select two different populations . DBP. et. in 1974. a DBP of 75 mm Hg or more at 13 to 20 weeks' gestation best predicted pre-eclampsia: positive likelihood ratio 2.71). Grade A) 2.19. (Level II. women were seen between 28-32 weeks of pregnancy when their DBP in the superior arm were first stabilized in the left lateral recumbent position. When BP is measured in the first or second trimester of pregnancy. Thus. or an increase of BP.5 (95% CI 2. negative likelihood ratio 0. Grade B) . Reviewing maternal history for potential risk factors. The women were then rolled over to the supine position and BP readings were taken immediately and after 5 minutes. the MAP is a better predictor for pre-eclampsia than SBP.16-0. Case Finding as part of General Physical Examination Opportunities for case finding are common in general practice. 24 Bilateral notching of uterine arteries at 12-14 weeks is a useful tool in predicting the development of hypertensive disorders in high-risk pregnancies. women without a notch constitute a very low risk group with < 1% having delivery before 34 weeks. The negative predictive values ranged from 86 to 97%.4 (Level II-1) Doppler velocimetry of the uterine and uteroplacental arteries at 24 weeks is an effective test to predict PIH. specificity between 41 and 78%. not only sensitivity.24 (Level II-2) 3.4% vs. the test accurately diagnosed 93% of the 60 women who later developed pregnancy induced hypertension or pre-eclampsia. specificity and predictive values should be taken into account. and the specificity and the positive predictive values increased from 41 to 94% and from 7 to 70%. sensitivity between 54 and 77%. 24 hours Ambulatory BP and Heart Rate The sensitivity in predicting pre-eclampsia for MAP of ! 85 mmHg at 20 weeks was 65%. DBP and MAP.2% for pre-eclampsia. patient's acceptability and quality control a. with a positive predictive value for a test combining MAP ! 85 mmHg and a heart rate ! 90 bpm were 53% and 45% respectively. This rose to 99% by the third trimester. the prediction rate increased to 78%. Hyperbaric Index (HBI) – The HBI was calculated as a time-specified BP excess over a pre-set tolerance limit for SBP.23 (Grade C) f. Doppler Velocimetry Diminished blood flow may be reflected as an increased systolic/diastolic ratio (Stuart Index) or the more ominous absence or reversed end diastolic (ARED) blood flow.23 (Grade C) e. This allows diagnosis before blood pressure becomes elevated. 48-hour BP Monitoring In the first trimester. Persistence of the early diastolic notch in both uterine arteries strongly correlates with severe PIH requiring delivery before 34 weeks with a sensitivity of 81% and specificity of 87%. the sensitivity of abnormal uterine artery Doppler results defined by twin nomograms vs.22 (Grade B) d. the MAP -2 test or the roll over test predicted a 60% risk hypertension or pre-eclampsia later in pregnancy but when a MAP -2 value >90 mmHg and a positive roll over test are combined. Laboratory Tests When evaluating new screening strategies. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. It is additionally examines lower blood pressure in women and fluctuations between activity and the rest during different trimesters. The sensitivity of bilateral notching in predicting hypertensive disorders of pregnancy decreased with advancing pregnancy from 91 to 35%. respectively. In contrast. Combination of the MAP-2 and Roll Over Test Performed singly. The test does not require monthly monitoring during pregnancy which was done during the study to validate the test.25 When used to predict hypertension in twin pregnancies. c. the predictive value was low for all three methods. Despite . singleton nomograms was 36. but also costs. 18. In a study comparing its predictive efficacy with standard sphygmomanometry and 48-hour ambulatory BP monitoring. These results suggest that serial plasma fibronectin measurements before 24 weeks' of gestation may be helpful in the early detection of preeclampsia in normotensive gravid women who are destined to become clinically preeclamptic. its severity and increased perinatal mortality. A fall in repeat hematocrit values may denotes clinical improvements.26 c. requiring a full 24-hour urine for accurate results. sensitivity ranged from 85-87%. . For protein/creatinine ratio 130-150 mg/g.12 (Level II-2) c. causing pre-eclampsia and consequent growth restriction in twin gestations. Negative predictive values of uterine Doppler studies in twin gestations are lower compared to those reported in unselected singleton pregnancies. that is unrelated to uteroplacental insufficiency. In a study among 125 pregnant women.26 e. Proteinuria Amounts greater than 300mg/24 hr urine sample or dipsticks values of +1 or more have been said to denote poor prognosis. i. the elevated maternal plasma fibronectin level over 40 mg/dL is capable of predicting preeclampsia in the third trimester with a sensitivity of 73% and a specificity of 92%. and specificity ranged from 96-97%. and specificity ranged from 33-65%. sensitivity ranged from 81- 98% and specificity ranged from 52-99%. elevated SGPT and thrombocytopenia comprise the diagnosis of the HELLP syndrome. Random protein/creatinine ratio determinations are helpful primarily when they are below 130-150 mg/g. uterine artery Doppler studies in twin gestations had an overall low sensitivity in predicting adverse obstetric outcome. for protein/creatinine ratio 300 mg/g.14 d. for protein/creatinine ratio 600-700 mg/g. a systematic review concluded that even increasing levels of protenuria are not predictive of poor maternal nor fetal outcomes. This suggests that there is an additional pathomechanism. maternal and fetal complications occur more frequently despite normal uterine artery waveforms. in that 300 mg or more proteinuria is unlikely below this threshold. Serum uric acid Uric acid values correlate with the development of pre-eclampsia.13 Deemed more important than the proteinuria values is the urinary protein/creatinine ratio in its ability to predict hypertensive complications during pregnancy. Midrange protein/creatinine ratio (300 mg/g) has poor sensitivity and specificity. Fibronectin This glycoprotein are derived principally from the liver and endothelial cells. Hematocrit Pre-eclampsia represents a state of hemoconcentration and increased hematocrit levels. Hemoglobinuria. sensitivity ranged from 90-99%. and its release into plasma is a marker of vascular disruption and endothelial cell activation.e.10 (Level II-2) b. using specially constructed twin nomograms. however. Increased levels have been found to predict pre-eclampsia but not in chronic hypertension. Several promising markers have been described. However. these markers might not be clinically useful to predict preeclampsia in women with previous previous preeclamspia and/or chronic hypertension. after adjustment for these and other potential confounders. Hypocalciuria and the calcium/creatinine ratio are tests to predict pre-eclampsia from chronic hypertension. Grade C) Biochemical Plasma Concentrations Reported Altered levels are Marker 1st 2nd Manifest combinations also correlated trimester trimester preeclampsia for prediction with: sflt-1 -. Glucose Intolerance Insulin resistance is associated with and may be causal in essential hypertension.15 g. as do levels obtained at 24-28 weeks with onset of preeclampsia at less than 37 weeks. but the relation between insulin resistance and hypertension arising de novo in pregnancy is unclear. However. To be effective. In the recent years.17 i. an abnormal glucose loading test remained a significant predictor of development of hypertension and.8 mmol/L) than women who remained normotensive. there is a need for worldwide large scale prospective studies to confirm the sensitivity and specificity of these promising markers and assess their utility in different subtypes of preeclampsia before they could serve in clinically useful screening tests.26. Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. these data came often from small case studies with selected populations. PlGF IUGR Ultrasound HELLP .5 4. nonproteinuric hypertension in pregnancy. other biochemical markers have been proposed as potential predictors for preeclampsia. ! ! sEng.27 h. Maternal serum alpha fetoprotein (MSAFP) levels > 2 multiples of median (MOM) were associated with a higher incidence of pre-eclampsia compared to controls. preterm delivery and intrauterine fetal demise. (Level III. women who developed hypertension in pregnancy had significantly higher glucose levels on 50-g oral glucose loading test and a significantly higher frequency of abnormal glucose loading tests (> or = 7. specifically. PlGF VEGF Ultrasound sEng -. f. This elevation also correlated with a higher likelihood of developing adverse perinatal outcomes such as growth restriction. ! ! sflt-1. alone or in combination. because the corresponding sensitivities and/or positive predictive values were low. a screening test need to be sufficiently sensitive and specific and must provide an adequate positive predictive value. that might fulfill these criteria. In a retrospective case-control study. However. Women who developed hypertension also had greater prepregnancy body mass index and baseline systolic and diastolic blood pressures. Therefore. although all subjects were normotensive at baseline by study design. Inhibin A and circulating angiogenic factors levels obtained at 12 to 19 weeks’ age of gestation have significant associations with onset of preeclampsia at less than 27 weeks.2 The following table summarizes the potential predictive biochemical markers for preeclampsia. PlGF: placental growth factor. 2. " ADAM12 ! -. Ikin K. Trisomy 21 Trisomy 18 SGA PTX3 " " " -. Matthews J. a systematic review of these reviews were conducted. resistance index. Zanetti-Dällenbach R. Holzgreve W. Grill S. Roberts L. IUGR: Intrauterine growth retardation. PAPP-A: pregnancy-associated plasma protein A. SGA: Small for gestational age. -. 2. ADAM12: A disintegrin and metalloprotease 12. low platelets Because of the abundance of tests evaluating the predictive value of different parameters in predicting preeclampsia. Hahn S. fibronectin (cellular and total). Only Doppler (any/unilateral notching. although the ideal would be to avoid both. Tercanli S. and uterine artery Doppler (bilateral notching) measurements reached specificity above 90%.114(8):984-93. PTX3: Pentraxin 3. birthweight Visfatin -. sEng: soluble Endoglin. "! "! -. Type-2 diabetes mellitus Gestational diabetes mellitus Obesity IUGR Adrenomedullin " " " -. only a body mass index of > 34. PP-13: Placental protein 13. Dunsmuir W. Rusterholz C. trimester. sflt-1 SGA PP-13 ! " " Ultrasound IUGR Preterm delivery P-Selectin " " " Activin A sflt-1 Other adhesion molecules Cell-free fetal " " " Inhibin A IUGR DNA Polyhydramnios Trisomy 21 Preterm labor Cell free DNA -. Davis G. Mackenzie C. sflt-1: soluble fms-like tyrosine kinase 1. IUGR PAPP-A ! ! ! -. High sensitivity is a more useful attribute in early detection of pre-eclampsia than specificity because consideration of benefits. SGA PlGF ! ! ! sEng. HELLP: Hemolysis elevated liver enzymes. Lapaire O. and combinations) measurements were over 60% sensitive. -.11 References 1. Vascular disorders Summary of potential biochemical markers for the prediction (1. Further research should focus on tests which offer much higher levels of sensitivity than tests currently available. alpha-fetoprotein. Can we predict recurrence of pre-eclampsia or gestational hypertension? BJOG 2007. trimester) or the detection (Manifest preeclampsia) of preeclampsia in maternal peripheral blood. Brown MA. harms and costs indicates a much greater preference for minimizing false negatives than false positives. -. Mangos G. Potential . Where multiple studies were available. 1062-7.7-10. 16. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. 1995 27.268. 10. Meis P. AJOG 1998. 5. ter Riet G. Miodovnik M. 1976 19. O'Mahony F. Acta Obstet Gynecol Scand 2009. Vatten LJ. Vives A. Odegård RA. 9. Hauth J. Coomarasamy A. Ismail KM.7:70. Nilsen ST. ter Riet G. Mol BW. Chaddha V. Landon M. Mäenpää J. Martins-Costa S. Wolf H.199:3. Juan M.112(1):135-44. Dombrowski M. van Montfrans G. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review. Leeflang MM. ambulatory blood pressure and sphygmomanometry measurements in predicting gestational hypertension and preeclampsia J Hypertens 2010. Kujansuu E. Third trimester maternal plasma total fibronectin levels in pregnancy- induced hypertension: results of a tertiary center. Salvesen KA.336(7653):1117-20. Vainio M. Caritis S. Ramos JG. Guelen I. BJOG 2000 Nov. Krapp M. Khan KS. Rudge MV. BMC Med. Freire S.179:4. Jan 1996 18. Spinnato JA. Cabero L. 1996 . Thangaratinam S. Roberts J. Page and Christianson. 8. Chesley and Sibai. 7. 14. García- Valdecasas B. 2006. Bartz J. Sayin NC. McNellis D. 1997 26. Protein/creatinine ratio in preeclampsia: a systematic review. Aydin T. fetal growth restriction and birth weight discordance.23:717-721 17. 1994. Hyde C. Cecatti JG. Bilateral notching of uterine arteries at 12--14 weeks of gestation for prediction of hypertensive disorders of pregnancy. Koch MA.107(11):1410-6. VanDorsten P. Varol FG. Sibai B. Germer U.12(1):33-9. Meads CA. Doppler assessment of the uterine circulation in the second trimester in twin pregnancies: prediction of pre-eclampsia. 2010 25. 1974 20. Thom E. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis. Papanna R. Epub 2009 May 27. 15. Kingdom J. Obstet Gynecol Int 2009:275613. Carreras E. Cnossen JS. Thurnau G. Vollebregt KC. BMJ 2000. 2009. Klebanoff M. 1987 22. Acta obstetr et gynecol Scan 2005. Vollebregt KC. Pinto e Silva JL. Vollebregt. 13. Are tests for predicting pre-eclampsia good enough to make screening viable? A review of reviews and critical appraisal. Franx A. Berg C. ACOG Technical Bulletin. Gisolf J. Khan KS. Mann LK. Gembruch U. Geipel A. 2008.24. Llurba E. 2008. Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia? AJOG 2008. Obstet Gynecol. markers of preeclampsia – a review. Sibai BM. Koivisto AM. Chesley and Sibai. Maternal history and uterine artery Doppler in the assessment of risk for development of early. 1993 24. 12. Kouides RW. Millán P.84:11. Lindheimer M. Lim and Cardenas. Austgulen R. Boer K. Risk factors and clinical manifestations of pre-eclampsia. Hypertension. Cnossen JS. 4. Graves SW. Limited accuracy of the hyperbaric index. Toal M. Zamora J. Greene MF and Seely EW. Khan KS. 11. de Barros Santos C. Paul R.e1-9. Ultrasound detection of placental insufficiency in women with elevated second trimester serum alpha-fetoprotein or human chorionic gonadotropin. Glucose intolerance as a predictor of hypertension in pregnancy. Sumpaico. Sharp S. Smrcek J. Mol BW. van der Post JA. 1988 21.88(7):758-65. Kyle and Clark. Katalinic A. Reprod Biol Endocrinol 2009.28(1):127-34. Windrim R. Solomon CG. Glantz JC. Chesley and Sibai. Hermosilla E. 6. Sumpaico and Santillan. Predictors of pre-eclampsia in women at high risk. Gratacós E.20(6):541-5. 1982 23. Costa R. Astor J. Ultrasound Obstet Gynecol 2002.and late-onset preeclampsia and intrauterine growth restriction.30(3):198-206. Clin Appl Thromb Hemost. van der Post JA. de Vrieze N. Calero I.946-51. 3. Pangan. J Obstet Gynaecol Can. Sumpaico.5 to 2g per day before 32 weeks age of gestation (AOG) until delivery. (Level I. vitamin E. selenium)3. However.37). (Level I. Grade A) 3. Calcium supplementation to pregnant women (both low risk and those at risk for developing pre-eclampsia).73-1. either ASA or dipyridamole.2 which included 59 RCTs comparing antiplatelet agents with either placebo or no antiplatelet agent. 95% CI 0. There was no overall difference in the risk of placental abruption between the comparison groups (RR 1. marine oil or other prostaglandin precursor9 and garlic10 in the prevention of pre-eclampsia. In fact.64-1. et. Prevention of Pre-eclampsia Milagros J. exercise6. Women included in the studies were either at moderate to high risk in developing pre-eclampsia. appears to decrease the risk of developing hypertension by around a third and pre-eclampsia by half. reduced salt intake8.89-1. This intervention has not been shown to increase the risk of placental abruption. on use of antiplatelet agents for preventing pre-eclampsia and its complications. There was no overall effect on the risk of preterm birth (RR 0. 95% CI 0.1 which included 12 randomized controlled trials (RCTs) of good quality. the only strategies found to significantly reduce the risk of this complication are calcium supplementation and use of antiplatelet agents.77-0.09)1. had significantly reduced incidence of hypertension (RR 0. diuretics7.. (Level I-II. MD and Walfrido W. lycopene. al.5 to 2g per day before 32 weeks AOG until delivery.70. There are insufficient evidence to support the use of anti-oxidants (vitamin C. also showed a significant reduction (by 17%) in the risk of pre- eclampsia among those given antiplatelet agents (RR 0. the latest issue of the Cochrane Database of Systematic Reviews revealed a number of meta-analyses on various interventions aimed at preventing preeclampsia. et.86) and pre-eclampsia (RR 0. (ranging from 60 mg to 150 mg/day) and dipyridamole (200 mg to 400 mg/day in combination with ASA except in one study). showed that pregnant women who were given calcium supplementation at dose of 1. Grade A) 2.57-0. has also been shown to reduce the risk of pre-eclampsia by 17% among moderate to high risk women. Use of antiplatelet agents. rest during pregnancy5. although conclusion of the authors was that doses of ASA up to 75 mg appear to be safer. Grade A-B). 95% CI 0.83. given at a dose of 1.89). red palm oil. al. nitric oxide4. The meta-analysis by Duley.2 Recommendations 1. MD ! Strategies to effectively prevent pre-eclampsia have been the subject of investigations for decades. The meta-analysis by Hofmeyr.81.48. Tia-Jocson.33-0. 95% CI 0.03) nor on stillbirth or neonatal death prior to discharge (RR 0.89. 95% CI 0.10. 95% CI 0. . Interventions varied as to the doses of aspirin (ASA).69) when compared to those taking placebo. Meher S. Exercise or other physical activity for preventing pre-eclampsia and its complications. Issue 3. Issue 3. Cochrane Database Syst Rev 1999. Duley L. Cochrane Database Syst Reviews 2006. Issue 1. 4. Meher S. 9. Duley L. Meher S. 8. Meher S. Cochrane Database Syst Rev 2006. Marine oil. Nitric oxide for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007.References 1. 7. Duley I. Issue 3. Antioxidants for preventing pre-eclampsia. Olsen S. Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. Meher S. Cochrane Database Syst Rev 2007. Issue 2. in pregnancy. Atallah AN. Henderson-Smart D. Reduced salt intake compared to normal dietary salt. and other prostaglandin precursor. supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. Churchill D. Issue 2. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Antiplatelet agents for preventing pre-eclampsia and its complications. Diuretics for preventing pre-eclampsia. ! . Cochrane Database Syst Rev 2008. King JF. Issue 2. Rhodes C. Duley I. Crowther CA. Duley. Issue 1. 6. Cochrane Database Syst Rev 2006. 2. Makrides M. Cochrane Database Syst Rev 2006. 10. Rumbold A. Haslam RR. 5. Duley I. Duley I. Duley L. Hofmeyr GJ. Henderson-Smart DJ. Issue 2. 3. Beevers GCG. Cochrane Database Syst Rev 2006. Garlic for preventing pre-eclampsia and its complications. or high intake. Cochrane Database Syst Rev 2007. Duley L. Meher S. Issue 3. they are allowed a regular diet. Proteinuria < 1. the nature and frequency of which has not been established. Tongco. 2. M.000/mm 6. Mild Preeclampsia Definition: 1. Systolic pressure ! 140 mm Hg 4. Home blood pressure and urine protein monitoring or frequent evaluation visits by a visiting nurse or training midwife are acceptable. in an upright sitting blood pressure after a 10-minute rest. Gestational Hypertension and Mild Pre-eclampsia Pilar Lagman-Dy. These women should receive heightened maternal and fetal surveillance. During such home management. The following should be part of the management of Gestational Hypertension/Mild Preeclampsia: 1. Diastolic pressure ! 100 mm Hg 3. without salt restriction. Platelet count > 120. Ability to comply with recommendation 2.7 (Grade B) Patients having all of the following criteria can be managed at home: (Grade B) 1. M.000 mg 24 hr or < 2+ on dipstick 5. or 90 mmHg diastolic or higher. She should also be instructed about recording fetal kick counts and about immediate reporting of symptoms. and they are allowed to be up and about as desired. Approximately 35% of women with gestational hypertension with onset at < 34 weeks develop preeclampsia.D. Gestational Hypertension Definition: Blood pressure elevation of 140/90 unaccompanied by proteinuria after 20 weeks gestational age and usually resolves by six weeks postpartum.D. and the associated risks of serious maternal (2%) and perinatal complications (16%) are high. These women should be instructed in detail about reporting symptoms. This may continue as long as the disease does not worsen and if fetal growth restriction is not suspected. Sedentary activity throughout the greater part of the day is essential. Home Health Care As long as the criteria for severe pre-eclampsia are excluded. defined as urinary excretion of 300 g protein or higher in a 24-hour urine specimen. Normal fetal growth and testing . and Carmencita B. this may be recommended for women with mild hypertension without heavy proteinuria. Blood pressure of 140 mmHg systolic or higher. that occurs after 20 weeks of gestation in a woman with previously normal blood pressure. Proteinuria. especially with the increasing pressure to curb medical expenses. they reported on 135 patients with gestational hypertension entered on a randomized trial.8 Women who develop gestational hypertension/preeclampsia at an earlier age tend to have an earlier gestational age at delivery. and worse fetal outcome when compared with those who develop the disease at term.14 Ambulatory management was also recommended for a select group of patients in the 1993 issue of Williams’ Obstetrics. 7. No indications for delivery Summary of Evidence The management of gestational hypertension/mild preeclampsia during pregnancy was based largely on clinical experience rather than the result of randomized controlled trials. they reduced hospital admissions by 72% when only patients with proteinuric hypertension were hospitalized. a worsening of the disease status. and gestational age) at time of enrolment. shorter pregnancy prolongation. hospital admission for bed rest could delay or prevent progression of hypertension to severe preeclampsia and might reduce the frequency of eclampsia or abruption placentae.9 Hospitalization was not associated with an overall improvement in fetal growth or reduction in the neonatal morbidity. Patients having any of the following should be hospitalized and considered for delivery: (Grade A) Gestational age ! 40 weeks Gestational age ! 37 weeks if there is: .16 2. several programs were introduced during the past decade to manage such patients at home.4 In an attempt to reduce hospitalization.10 Several other studies supported the idea of out-patient management of gestational hypertension and mild pre- eclampsia.15 The success rate of outpatient management depends mostly on maternal status (presence or absence of proteinuria. In a subsequent study. obstetricians were increasingly using outpatient management of gestational hypertension.8 This practice was challenged in 1971 by a British team who showed a reduction in perinatal mortality in patients with nonproteinuric hypertension despite ambulatory management. improved patient satisfaction and reduce costs. with improvement in fetal survival. amount of proteinuria. Outpatient ambulatory management was endorsed by American College of Obstetricians and Gynecologists (ACOG) provided the patient had a thorough initial evaluation. As a result of this policy. They showed that complete bed rest in hospital appeared to have no advantage over ‘ambulation as desired’ in controlling the severity of maternal disease. Timing of Delivery The delivery of patients with gestational hypertension-mild preeclampsia will depend on fetal gestational age and fetal testing as well as maternal blood pressure. and an increased requirement for antepartum hospitalization as compared with pregnancies with gestational hypertension. In theory. and maternal symptoms. diastolic blood pressure.11-13 Recently. Pregnancies complicated by mild preeclampsia with proteinuria are associated with a lower gestational age at delivery. All such programs involved some form of maternal and fetal evaluation. Non-stress tests at regular intervals (Grade B) d. Platelet count and liver enzymes at regular intervals (Grade B) c.17 Please refer to the recommendations for medications in the section on severe pre-eclampsia. Medications: Magnesium sulfate and other anti-convulsants are not recommended and should be withheld in cases of gestational hypertension/mild preeclampsia. Outpatient management of patients with gestational hypertension/mild preeclampsia has been documented to be more cost. Blood pressure at each visit (Grade A) b. (Grade B) Summary Management of women with gestational hypertension/mild preeclampsia must always consider maternal safety first and then the delivery of a newborn who will not require intensive and prolonged neonatal care. This weekly check-up should include the following: a. Subsequently management should depend on results of maternal and fetal conditions. Therefore. Low dose aspirin and high dose calcium are not recommended for the prevention of the progression to severe preeclampsia. Fetal growth every 2 to 3 weeks (Grade B) In contrast. Bishop score > 5 Fetal weight <10th percentile Non-reactive NST Gestational age 34 weeks and above with the presence of: Labor Rupture of Membranes Vaginal bleeding Abnormal biophysical profile Criteria for severe preeclampsia Expectant management should be considered for women remote from term who have mild preeclampsia. out-patient management must provide evaluation of maternal and fetal status similar to that of in-patient management. (Grade B) Patients with mild preeclampsia and gestational hypertension will be given anti- hypertension medications only if there is an increase in blood pressure readings from baseline. Monitoring of Fetal Well-Being The patient should be evaluated by a physician for maternal and fetal well-being at least once weekly.effective than similar in- patient therapy. patients with gestational age < 37 weeks who do not satisfy the criteria for home management should be immediately hospitalized. (Grade A) 4. . (Grade C) 3. Br J Obstet Gynecol 1989. al. New York. Shuttleworth TP. Cunningham GF. (Eds) Williams Obstetrics. Patel IR.ncbi. Churchill Livingstone. Tuffnell DJ. http://www. Dawson AJ.cochranelibrary.ihs. Cochraine Library Syst Revs. Obstetrics: Normal and Problem Pregnancies.nih. Middlemiss C. Technical Bulletin: Hypertension in pregnancy. al.289:2560-2571. American College of Obstetricians and Gynecologists. et. Lancet 1982. .nlm. 14. (Level III) http://jama.96:1319. Bouwmeester AM. Hamlin RHJ. 13. Coles EC. detection. et. 219.com/publications/educational_bulletins/pb033.htm> 2. Br J Obstet Gynecol 1971. Obstet Gynecol 2002. A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. The prevention of eclampsia-preeclampsia.acog. Lilford RJ. Barton JR. BMJ 1984. 2002. 33.339:224. A randomized study of a domiciliary antenatal care scheme: The effect on hospital admissions. Aki S. Atallah AN. 8. Sibai BM. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. al. Matthews DD. 17.99:13. Feeney JE. Agarwal V. 10. Stanzino GJ.288:1046. Outpatient management of toxemia. (Level III) 4. January 1996. 2001. 4th Ed. Section 7. The seventh report of the joint national committee on prevention. Sibai BM. fcgi?cmd=Retrieve&db=PubMed&list_uids=10920346&dopt=Abstract 3. Ashurst HM.167:879. Gabbe SG.78:610. McGraw-Hill. Crowther CA. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. evaluation. Matthews DD. Duley L. Simpson JL (Eds). Sibai BM. Br J Obstet Gynecol 1980. (Level III) 5. Am J Obstet Gynecol 2000.170:765. 16. Chapter 28. Barton JR. 21st Edition. Hypertension. Am J Obstet Gynecol 1992. Frangieh AY. Hypertensive Disorders in Pregnancy.99:159-167 (Level III) <http://www. Randomized controlled trial of day care for hypertension in pregnancy.87:1095. Monitored outpatient management of mild gestational hypertension remote from term. Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension? Br J Obstet Gynecol 1992. Diagnosis and management of preeclampsia and eclampsia. 24:567-618. ACOG Practice Bulletin No. The effect of rest and ambulation on plasma urea levels in pregnant women with proteinuric hypertension.gov/generalweb/webapps/sitelink/ site. 12. (Level III) http://www. 15.183:S1-S22. Am J Obstet Gynecol 1994.gov/entrez/query. Sengupta SM. JAMA 2003. American College of Obstetricians and Gynecologists. Chobanian AV. Lancet 1992. Hypertension in pregnancy managed by community midwives. 11. and treatment of high blood pressure.asp?link=http://www. 945-1004. Contemporary OB-Gyn 1996:67. Washington DC. Neibyl JR. et. 9.References 1. Buchan PC.com/enter/# 7.1:64.org/cgi/content/full/289/19/2560 !"## Hofmeyr GJ. Outpatient management of gestational hypertension and mild preeclampsia.ama- assn. 5 The development of preeclampsia cannot be accurately predicted nor effectively prevented. 6. 3. Severe Pre-eclampsia Mario A. the timing of delivery is critical to optimize maternal and perinatal outcome. which is primarily due to iatrogenic prematurity.5 and one must not be complacent with mild preeclampsia6 because apparently mild disease may progress rapidly to severe disease. the incidence of severe preeclampsia is 2- 5% and is the 2nd most common cause of maternal death. To prevent convulsions. M. To completely restore the health of the mother. 2. To reduce its severity or prevent progression of the disease process. hypertension is reported to complicate 5 – 6% of all pregnancies worldwide. Delivery of the fetus and placenta remains the only definitive treatment. A diagnosis of severe preeclampsia requires evidence of new-onset proteinuric hypertension occurring at > 20 weeks age of gestation with > 1 of a series of complications (see Table 1). 4.4 It is also associated with a high perinatal mortality and morbidity rate.3 Locally. Background Incidence As the most common medical disorder of pregnancy. To deliver the mother of a fetus at the optimum time and with the least trauma.1. To detect and appropriately treat end-organ damage. 5. and Joseph U.D. Classification of Preeclampsia Preeclampsia is classified as mild and severe.10 % being severe.1 with 5. It is emphasized that only 1 of the listed criteria in Table 1 is required for the diagnosis of severe preeclampsia. The distinction between mild and severe preeclampsia is important because it dictates management. Bernardino. M. Olivar.D. Mild preeclampsia refers to disease that meets the criteria for the diagnosis of preeclampsia but is not severe disease.6 .6! For all these reasons.2 It is the 2nd most common cause of maternal death in the US. The objectives in the management of severe preeclampsia include the following: 1. To control severe hypertension. 6%&%'<=4&3*8'>??@'0' Management The main objective in the management of severe preeclampsia must always be the safety of the mother and the fetus.#')&+*%&'()*+'%&)+0'!+'9':. traditional management has focused on maternal safety with expedited delivery. In the past. Because these pregnancies are associated with high rates of maternal morbidity and mortality and with potential risks for the fetus.%/0'12$&3%#4%'+#4#5&+&4%'*('6&7&)&'$)&&38#+$6. !"#$%&"'()*+'. Once the diagnosis of severe preeclampsia is established.7. confirmation of gestational age and assessment of fetal well-being.9 Complications of prematurity include respiratory distress syndrome. there is general agreement that such patients should be delivered if the disease develops > 34 weeks of gestation.5 The initial management of preeclampsia includes stabilization of the mother’s condition.*)-. necrotizing enterocolitis. it may not be optimal for the premature fetus (< 34 weeks). intraventricular hemorrhage. sepsis and even death.8 Although delivery is always appropriate for the mother. it was believed that infants born prematurely to severely preeclamptic women had lower . rates of neonatal morbidity and mortality than infants of similar gestational age born to non- preeclamptic women. In contrast, several recent case-control studies have demonstrated that premature infants born after severe preeclampsia have neonatal complications and mortality similar to those of other premature infants of similar gestational age and have higher rates of admission to NICU.10 In addition, case-control studies have revealed that fetuses of preeclamptic women do not exhibit accelerated lung or neurological maturation.10 There are 3 circumstances in which expectant management of severe preeclampsia remote from term (< 34 weeks) is clearly acceptable. The first is severe preeclampsia by proteinuria.5 Neither the amount of protein spilled in the urine nor the rate of increase correlates with maternal or perinatal outcome.11,12 As such, proteinuria > 5 grams per 24 hours is not, of itself, an indication for delivery.5 The second is severe preeclampsia on the basis of IUGR alone with good fetal testing. Although not candidates for immediate delivery, such patients should be treated as in-patients5 with at least daily fetal well-being studies. Third, there is precedent in the literature to support the expectant management of women with severe preeclampsia by blood pressure criterion. This approach, although potentially dangerous for the mother, has been substantiated in a number of clinical trials.7,8 There are only 2 published randomized trials on the expectant management of severe preeclampsia. In 1990, Odendaal, et. al. studied 38 patients with severe preeclampsia at 28-34 weeks of gestation. 20 patients underwent aggressive treatment (steroid therapy followed by delivery in 48 hours), and 18 patients were treated expectantly (steroid therapy followed by delivery only for maternal and fetal indications). In the conservative group, the authors reported no increase in maternal complications but with statistically significant prolongation of pregnancy (mean, 7.1 days), a reduction in neonates that required ventilation (11% vs 35%), and a reduction in total neonatal complications (33 vs 75%).7 Sibai, et. al. studied 95 patients with severe preeclampsia at 28-32 weeks of gestation: 46 patients underwent aggressive treatment and 49 were assigned to expectant management. In women who were treated conservatively, there was no increase in maternal complications, but there was a statistically significant prolongation of pregnancy (mean 15.4 vs 2.6 days), less time in neonatal intensive care unit (NICU) (20.2 vs 36.6 days), and a reduce incidence of respiratory distress syndrome (22.4% vs 50.5%).8 These 2 trails7,8, demonstrated improved perinatal benefit with reasonable maternal safety when expectant management was conducted in a select group of patients with severe preeclampsia at 28-34 weeks of gestation.13! Recently, the results of several retrospective and observational studies that described expectant management of severe preeclampsia at 24-34 weeks of gestation have suggested that such management improves perinatal outcome without increasing maternal morbidity.14-23 In 2005, Sibai published an algorithm in the expectant management of preeclampsia < 34 weeks. !"#$%&%'&()*'+&),"&"-($.-+/&01$%-& • Maternal-fetal evaluation for 24 hours • Magnesium sulfate for 24 hours • Antihypertensives if systolic blood pressure >160 mmHg, diastolic blood pressure > 110 mmHg, or mean arterial pressure >125 mmHg !,/&'2&%3-&2'(('4$,5&6+-0-,%7& • Eclampsia • Pulmonary edema Magnesium sulfate • Acute renal failure and delivery • Disseminated intravascular coagulation Yes • Suspected abruptio placenta • Non-reassuring fetal status • Labor or rupture of membranes >34 weeks’ gestation No • HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelets) Steroids • Persistent symptoms Yes No < 23 weeks 23–32 weeks 33 – 34 weeks • Steroids • Steroids Terminate • Antihypertensives if needed • Delivery after 48 pregnancy • Daily evaluation of maternal- hours fetal condition • Delivery if: with indications (see Table 2) • Delivery at 32-34 weeks DD 8$51+-&9:&&;),)5-#-,%&'2&0-.-+-&6+--<()#60$)&=&>?&4--@0:&&A!")6%-"&2+'#&B$*)$:C & Table 2. Indications for Delivery During Expectant 45 !"#$%&"'()*+',-.#-'#/"'0#)%*/1'2334 ' 6*%&7'89$&)%&/:-*/'-:';/<*/%)*==&"'>?&/'%?&'0@')&+#-/:'-/'%?&':&A&)&')#/B&'"&:$-%&'+#C-+;+'"*:&:'*('#/%-?9$&)%&/:-A&'#B&/%:D''!<<*)"-/B'%*' ' +*:%')&$*)%:1'%?&'+#C-+;+'"*:&'*('?9")#=#E-/&'-:'23'+B'FGH'6-(&"-$-/&'I3'+B'@J'#/"'6-<#)"-$-/&'")-$'K3'+BL?*;)D' ' ' Perinatal Complications Though the main aim of expectant management is to improve perinatal outcome by prolonging gestation and reducing neonatal morbidities (acute and long term)13 due to prematurity, expectant treatment has potential complications. During expectant management of patients with severe preeclampsia at 24-34 weeks of gestation, the rate of perinatal death ranged from 0 to 16.6 %.7,8 Abruptio placenta is also a reported complication and it ranged from 4.1% to 22.9%.8,22 In addition, delivery for non- reassuring fetal status ranged from 26-75%.18,20 In all the reported studies, intensive fetal monitoring for early detection of fetal compromise is recommended. The most common indication for delivery was deterioration in fetal status underscoring the need that these In pregnancies before 23 weeks. any protocol for management of severe preeclampsia has potential for maternal complications. pulmonary edema (0-8.14. the perinatal survival rate was 18%.24.23 Aggressive treatment in the form of immediate delivery will usually result in high neonatal mortality rate. provide prompt intervention for symptoms of hepatic dysfunction (HELLP syndrome or subcapsular hematoma of the liver).8.27 Furthermore. maternal complications were common and there were no infant survivors.26 If the fetus survives.27.5 During expectant management. Maternal Complications The main aim of the expectant management of severe preeclampsia remote from term is prolonging gestation without jeopardizing maternal safety.20 Expectant management must provide heightened surveillance to ensure adequate maternal oxygenation. Severe preeclampsia that develops in the mid-trimester of pregnancy is associated with high perinatal mortality and morbidity rates.27 Overall. For women with pregnancies at 24 to 26 weeks.1-27.25. maternal morbidities were very high. and it averaged 90% for those at 26 weeks.1%).23. in these studies. Thus. perinatal survival approached 60%. eclampsia and acute renal failure (<1%). For those at 23 weeks. Progressive deterioration in maternal condition during the clinical course of severe preeclampsia may occur.pregnancies managed expectantly should be observed in centers that are capable of rapid intervention for fetal reasons.5%).16.5 Severe Preeclampsia < 25 weeks Only few literatures are published regarding maternal and perinatal outcomes during expectant treatment of patients with severe preeclampsia at <25 weeks of gestation.4. the authors recommended pregnancy termination for these women. attempts to prolong pregnancy may result in fetal death and may expose the mother to severe morbidity. Thus. maternal complications in reported studies include: HELLP syndrome (4.14. and particularly provide evaluation of the fetal status and maternal presentation given the risks of placental abruption. with few newborn infant surviving without handicap.29 Because this syndrome is associated with increased rates of maternal morbidity and mortality. some authors consider its presence an .28 On the other hand. significant neonatal complications are expected and these will require prolonged hospitalization in the NICU.16. the perinatal death rate ranged from 71% to 100%. but long term perinatal morbidity is yet unknown.24. Preeclampsia with HELLP The clinical course of women with HELLP syndrome is characterized by progressive and sudden deterioration in the maternal condition.25.28 There was one reported maternal death in a patient who had eclampsia and HELLP syndrome who underwent expectant treatment at 23 weeks age of gestation.14.5 Bombrys and colleagues29 found small studies that focused on expectant management of severe preeclampsia before 28 weeks. 14-16. 5 Clinical Considerations and Recommendations A. women should be managed according to a careful clinical assessment rather than relying overly on precise criteria. What is the initial management in a woman with severe preeclampsia? In a woman with severe preeclampsia. the overall perinatal outcome was not improved. (Level III. such approach is currently experimental. (Level I. Grade C) Although the classification of severity of preeclampsia is primarily based on the level of blood pressure and the degree of proteinuria. the woman should be rested sitting at 45-degree angle. Korotkoff phase 5 is the appropriate measurement of diastolic blood pressure. Assessment of the Woman B1. ! 2 systolic blood pressure (SBP) >150 mmHg or diastolic blood pressure (DBP) > 100 mmHg.6 Hospitalization is indicated in cases in which the woman is unreliable. except for the benefit of steroid for fetal lung maturity in gestation at 24-34 weeks. How should the BP be taken? When taking the blood pressure. Grade A) Automated methods should be used with caution.5 There are 3 studies30-32 published regarding expectant management in patients with HELLP syndrome at < 34 weeks of gestation. other organ may be potentially involved and clinicians should be vigilant when assessing the maternal risk.34 It is emphasized that only 1 of the listed clinical features in addition to hypertension (! 140/90 mmHg) and proteinuria (!300 mg/24 hours) is required for the diagnosis of severe disease. Their results suggest that expectant treatment is possible in a select group of women with alleged HELLP syndrome at < 34 weeks of gestation. Grade A) Hospitalization is considered in women with severe preeclampsia. (Level I. The cuff should be of the appropriate size and should be placed at the level of the heart. despite pregnancy prolongation in some of these cases.34 B. heavy proteinuria or persistent maternal symptoms.5 Ultimately as many clinical criteria are subjective. (Level II-2. What are the clinical features of severe preeclampsia? A diagnosis of severe preeclampsia requires evidence of new onset proteinuric hypertension along with ! of a series of complications (summarized in Table 1). Since the sample size in these studies is inadequate. Multiple readings should be used to confirm the diagnosis. immediate admission preferably in a high risk unit is mandatory.35.36 B2.indication for immediate delivery. However. compared with cases of similar gestational age who were delivered within 48 hours after steroid therapy. Grade B) . The blood pressure should be checked every 4 hours except between midnight and morning if a conservative management plan is in place and the woman is stable and asymptomatic.6 In view of this.37 Automated methods can systematically underestimate particularly the systolic blood pressure. blood film to look for fragmented red cells or total bilirubin >1. What other laboratory exams should be requested? The following laboratory exams should be requested in cases of severe preeclampsia: CBC with platelet count. Grade C) A falling platelet count is associated with worsening disease and is itself a risk to the mother. Multiple readings are required to accurately assess the blood pressure because of natural variations.46 Clotting studies are not required if the platelet count is over 100 x 106/L. Korotkoff phase 5 is the appropriate method for diastolic blood pressure. liver enzymes (AST. (Level III. The blood pressure should be checked every 15 minutes until the woman is stabilized and then every 30 minutes in the initial phase of the assessment. either by LDH levels (! 600U/L). peripheral blood smear.13 B3. How should proteinuria be measured? The usual screening test is visual dipstick assessment. Grade C) When taking the blood pressure the woman should be appropriately positioned and the cuff should be of an appropriate size placed at the level of the heart.45 A platelet count persistently less than 100 x 106/L should be a consideration for delivery.40 approximate equivalence is +1 = 0.41 B4.39 However. A diagnosis of HELLP syndrome needs confirmation of hemolysis. uric acid. ALT). and total bilirubin.2 . 38 It has been suggested that mercury sphygmomanometers should be used to establish baseline blood pressure as a reference. laboratory testing usually by a 24 hour urine collection is recommended to confirm significant proteinuria unless the clinical urgency dictates immediate delivery. (Level III.3 g/L. A (+)1 dipstick measurement can be taken as evidence of proteinuria but a negative (-) dipstick may not be accurate. (Level III. even in severe cases. it is not until the count is less than 100 x 106/L that there may be an associated coagulation abnormality. many units no longer have mercury sphygmomanometers and a baseline check with another validated device would be an alternative. +2 = 1g/L and +3 = 3g/L. creatinine. a more accurate test (24 hour urine protein collection) is required to confirm this. Ideally. Grade C) While it has to be acknowledged that there is poor predictive value from urine dipstick testing. On the other hand. False negative as well as false positive results are possible with the use of dipstick assessment 40 because the degree of proteinuria may fluctuate widely over the 24 hour period. Initial assessment of the woman with severe preeclampsia requires more frequent monitoring of the blood pressure until the woman is stabilized. LDH. HELLP syndrome or sepsis. respiratory rate and oxygen saturation is important.48 If creatinine is found to be elevated early in the disease process. underlying renal disease should be suspected.34 MgSO4 can be given in 2 ways: continuous intravenous infusion and intermittent intramuscular injections (see Table 3). In women with mild disease. and circulation. (Level I. there can be a rise in uric acid that correlates with poorer outcome for both mother and the fetus.47 This rise confirms the diagnosis of preeclampsia but the levels should not be used for clinical decision-making. How should seizure be prevented? Magnesium sulfate (MgSO4) is the drug of choice for the prevention of convulsions. A loading dose of 4 grams should be given over 5-10 minutes. The relative risk reduction was similar regardless of the severity of preeclampsia. serum creatinine can be seen to rise and is associated with a worsening outcome 48 but renal failure is not uncommon in preeclampsia and when it does occur. Anti-Seizure Prophylaxis C1. Grade A) The MagPie Trial (Magnesium sulfate for Prevention of Preeclampsia) has demonstrated that administration of MgSO4 to women with preeclampsia reduces the risk of an eclamptic seizure. Grade A) . mg/dL. C2. (Level III. regular assessment of the urine output. In severe disease.34 C. breathing. the decision is less clear and will depend on individual case assessment. it is usually associated with hemorrhage. followed by a further infusion of 1 gram / hour maintained for 24 hours after the last seizure. once a delivery decision is made and in the immediate postpartum period. Renal function is generally maintained in preeclampsia until the late stage unless HELLP syndrome develops. How should seizure be controlled? The principles of management should follow the basic principles of airway. the diagnosis is partial HELLP syndrome. maternal reflexes. When MgSO4 is given. This drug should be considered for women with preeclampsia for whom there is concern about the risk of eclampsia. More women need to be treated when preeclampsia is not severe (109) to prevent one seizure when compared with severe preeclampsia (63).6 In preeclampsia. This is usually in the context of moderate to severe preeclampsia (at least 150-160/100-110 mmHg).42 Women allocated MgSO4 had a 58% lower risk of an eclamptic seizure (95% CI 40-71%). elevated liver enzymes (AST or ALT >70 U/L) and low platelet (< 100 x 106/L). Grade C) MgSO4 is the therapy of choice to control seizures.5 If only 1 or 2 of the 3 criteria are met. (Level I. plasma magnesium concentration is excessive if glomerular filtration is decreased substantively.43 Once stabilized.34 Because magnesium is cleared almost exclusively by renal excretion.6 Magnesium toxicity can also be assessed by clinical assessment of the maternal deep tendon reflexes and respiratory rate. and whenever it is 1. the magnesium infusion should be halted. The initial standard dose of MgSO4 can be safely administered without knowledge of renal function. Urine output should be closely observed and if it becomes reduced below 20 ml/hour.44 The intravenous route is has few side effects. Magnesium toxicity is unlikely with the recommended regimens and the levels do not need to be routinely measured. Place the woman in left lateral recumbent position and administer oxygen. only half of the maintenance MgSO4 dose is given. or an increase in the infusion rate to 1. If there is loss of the deep . Assess the airway and breathing and check the pulse and blood pressure.3 mg/dL or higher. MgSO4 is mostly excreted in the urine. assuming that there is no acute fetal concern such as fetal bradycardia.5 grams or 2 grams/hour. (Level I. plans should be made to deliver the woman but there is no particular hurry and a delay of several hours to make sure the correct care is in hand is acceptable. Renal function is thereafter estimated by measuring plasma creatinine. The use of the pulse oximeter is helpful. Grade A) Do not leave the woman alone but call for help.34 MgSO4 is the therapy of choice and diazepam and phenytoin should no longer be used as first-line drugs.Recurrent seizures should be treated with either a further bolus of 2 grams MgSO4. Ensure that it is safe to approach the woman and do effort to prevent maternal injury during the convulsion. An alternative is to increase the infusion rate to 1. since prolonged use of diazepam is associated with an increase in maternal death. tendon reflexes (DTRs) and the respiratory rate falls below 12 cpm. A catheter is advisable in the acute situation. then alternative agents such as diazepam or thiopentone may be used. Calcium gluconate 1 gram (10 ml) over 10 minutes can be given if there is concern of MgSO4 toxicity. intubation is likely to be necessary to protect the airway and maintain oxygenation. (Level III. fluid balance is more difficult and fluid restriction is inappropriate. (Level III. After this time.44 If convulsions persist.43 There is no evidence that maintenance of a specific urine output is important to prevent renal failure.34 Fluid restriction should be maintained until there is postpartum diuresis. How should fluid balance be managed? Fluid restriction is advisable to reduce the risk of fluid overload in the intrapartum and postpartum periods. which is rare. Grade C) Close fluid balance with charting of input and output is essential.34 Patients with severe preeclampsia who are expectantly managed should receive MgS04 for 24 hours. If there is associated hemorrhage. but only as a single dose. Grade C) Pulmonary edema is a significant cause of maternal death. How should the fetus be assessed? A baseline cardiotocography (CTG) should be undertaken. There is no evidence of the benefit of fluid expansion49 and a fluid restriction regimen is associated with good maternal outcome.34 In the collaborative eclampsia trial.34 E. the risk of convulsion is again present. MgS04 is discontinued. Grade B) . D.5 grams or 2 grams/hour. In usual circumstances. especially in the immediate postpartum period. Grade B) Women in labor with severe preeclampsia should have continuous electronic fetal monitoring (EFM). Transfer to intensive care facilities with intermittent positive pressure ventilation is appropriate in these circumstances. total fluids should be limited to 80 ml/hour or 1 ml/kg/hour. MgS04 should be given once the blood pressure rises again and remains in the severe range. If there are repeated seizures. If blood pressure is controlled adequately and fetal testing is reassuring. MgS04 is cleared by the kidneys 4 hours after the last dose. This gives information about fetal well-being at that time but does not give any predictive information.44 a further bolus of 2 gram MgSO4 was administered for recurrent seizures. as oliguria is common with severe preeclampsia. or when delivery is planned. (Level II-2. (Level II-2. the MgSO4 infusion should be halted. This should be continued up to 24 hours postpartum.38 This has often been associated with inappropriate fluid management. 53 There is also a consensus that. (Level III. Since. defined as ! 160/110 mmHg requires treatment because these women are at increased risk of intracerebral hemorrhage.50 The main pathology affecting the fetus. because the degree to which placental blood flow is autoregulated is not established. then further assessment of the fetus with ultrasound measurements of fetal size every 2 weeks. It gives information concerning fetal well-being at that time but has little predictive value. and aggressive . Reduced amniotic fluid volume is also associated with placental insufficiency and fetal growth restriction. there is no immediate need for antihypertensive therapy. and that treatment decreases the risk of maternal death. then continuous EFM is appropriate. treatment can be considered at lower degrees of hypertension. Serial estimations of amniotic fluid volume can detect fetal compromise. If conservative management is planned. alarming rise in blood pressure may be anticipated. Antihypertensive treatment should be started in woman with BP ! 160/110 mmHg. Ultrasound assessment of fetal size. anti-hypertensive treatment at lower blood pressure levels may be justified. improves neonatal outcome52 and serial investigations of this and other fetal vessels can be used to follow pregnancies under treatment and optimize delivery.51 F. Grade C) In treating severe hypertension. apart from prematurity is placental insufficiency leading to intrauterine growth restriction (IUGR). at the time of the initial presentation with hypertension. If the woman is in labor. (Level I. is a valuable measurement to assess fetal growth. Grade A) CTG is the mainstay of fetal monitoring. if the blood pressure is below 160/110 mmHg.38 F2. Grade C) There is consensus that severe hypertension in pregnancy. biophysical screening (BPS) and amniotic fluid index (AFI) measurement at least twice weekly. How should we control the blood pressure? F1. What blood pressure is the aim of anti-hypertensive therapy? The aim of anti-hypertensive therapy is to keep systolic blood pressure between 140 and 155 mmHg and diastolic blood pressure between 90 and 105 mmHg. Measurement of the abdominal circumference is the best method of assessment since IUGR in this case is usually asymmetrical. in this situation. such as heavy proteinuria or disordered or haematological test results. (Level III. Randomized trials have shown that investigation with umbilical artery Doppler using absent or reversed-end diastolic flow. Serial assessment will allow timing of delivery to be optimized. In woman with other markers of potentially severe disease. An exception may be if there are markers of potentially more severe disease. it is important to avoid hypotension. umbilical artery Doppler once a week and daily nonstress test (NST) should be undertaken. A review has suggested that hydralazine may be less preferable. Labetalol given orally or intravenously. although the evidence is not strong enough to preclude its use. long experience of safety repeat every 3 hours. If no success with 20 mg IV or 30 mg IM. lowering may cause fetal distress. Consideration should be given to initiating agents for treatment of acute severe hypertension at lower doses.5 to and efficacy 10. its use now supplants that of hydralazine. for infusion: 0. once BP controlled NHBEP. Grade A) The preferred therapeutic agents are labetalol. because these patients may be intravascularly volume depleted and may be at increased risk for hypotension. intravenous hydralazine. Labetalol has the advantage that it can be given initially by mouth in severe hypertension and then.1 mg/ mL Start drip at 10 ugtts/min (equivalent to 1 mg/hr) Titrate every hour (increments of 1 mg/hr). maternal hypotension and other for infusion: 1 to 2 mg/min adverse effects. (Level I. Maximum dose 10 mg/hr Note: The IV infusion site must be changed every 12 hours . intravenously.53 F3. nifedipine or hydralazine. Not available locally. if needed. then 5 to 10 mg every A drug of choice according to 20 to 40 minutes. IV or IM. Drugs for Urgent Control of Severe Hypertension in Pregnancy Drug (FDA Risk*) Dose and Route Precaution & Adverse Effect Labetalol ( C ) 10 to 20 mg IV. or oral nifedipine can be used for the acute management of severe hypertension. Hydralazine ( C ) 5 mg.0 mg/hr.54 The National High Blood Pressure Education Program (NHBEP) Working Group Report on High Blood Pressure in Pregnancy published in the journal of American Heart Association the recommended drugs for urgent control of severe hypertension in pregnancy. then 20 to 80 mg every Because of a lower incidence of 20 to 30 minutes. avoid in women with asthma or congestive heart failure. repeat in 45 minutes if needed concomitantly used with MgSO4 IV Nicardipine D5W 90 mL + Nicardipine 10 mg in Should be used with caution if soluset concomitantly used with MgSO4 Concentration = 0. consider another drug Nifedipine ( C ) Tablets recommended only: 10 to 30 mg Should be used with caution if PO. maximum of 300 mg. 57 Although others have concluded that agents other than parenteral hydralazine (eg labetalol or nifedipine) are preferable because of reduced maternal and fetal adverse effects. Doctors should use the drugs with which they are familiar. Nifedipine (10mg or 30 mg XR) should be given orally not sublingually and should be used with caution if concomitantly used with magnesium sulfate.Treatment of moderate hypertension may assist in the prolongation of pregnancy. Maternal adverse effects include tachycardia. Maternal treatment is associated with a reduction of severe hypertensive crises and a reduction in the need for further antihypertensive therapy. If no success with 20 mg IV. headache and facial flushing. hydralazine is the first line drug in the urgent control of severe hypertension in pregnancy. (Level III. With treatment.58 One study has shown efficacy and safety of long-acting oral nifedipine in pregnant patients with .55 Methyldopa and labetalol were the most commonly used therapies. Diuretics are relatively contraindicated for hypertension and should be reserved for pulmonary edema. Note: Since Labetalol is not locally available. Grade C) There is continuing debate concerning women with blood pressure between 150 – 160 systolic and 100 – 110 diastolic. angiotensin receptor blocking drugs (ARB) and diuretics should be avoided during pregnancy. F4. Atenolol. Grade C) Calcium antagonists given sublingually are now not recommended for the treatment of hypertension in nonpregnant patients because of reports of myocardial infarction and death in hypertensive patients with coronary artery disease. and this is usually a calcium channel blocker (oral nifedipine or IV nicardipine). A recent meta- analysis of 24 trials concluded that there is insufficient data to favour one agent over another. Patients with resistant severe hypertension after maximum doses of these drugs should be delivered. peripheral edema.56 The NHBEP Working Group Report on High Blood Pressure in Pregnancy published in the journal of American Heart Association the recommended drugs for the treatment of gestational hypertension and chronic hypertension (Table 4). Grade B) Atenolol is associated with an increase in fetal growth restriction. a prolongation of pregnancy of an average of 15 days is possible as long as there is no other reason to deliver. another drug should be considered. Methyldopa has been proven safe in long term follow-up of the delivered babies. palpitation. (Level II- 2. angiotensin converting-enzyme (ACE) inhibitors.54 F5. The maximum dose of oral nifedipine is 50 mg PO and 10mg/hour for IV nicardipine.34 F6. ACE inhibitors and ARBs would appear contraindicated because of unacceptable fetal adverse effects. (Level III. 61 these medications are commonly use together without increased risk. (Level III.60 In a recent evaluation. or circulatory collapse in some cases. Drugs for Gestational or Chronic Hypertension in Pregnancy severe hypertension in pregnancy. Grade A) . drug interactions between nifedipine and magnesium sulfate were reported to cause neuromuscular blockade. Grade C) Diuretics can be used during the postpartum period.59 A concern with the use of calcium antagonists for BP control in preeclampsia has been the concomitant use of magnesium sulfate to prevent seizures. (Level I.Table 4. Grade C) Agents commonly used in the antepartum period may be used or continued postpartum. myocardial depression. F7. (Level III. How is postpartum hypertension managed? Anti-hypertensive drugs should be given if the BP exceed 150 mmHg systolic or 100 mmHg diastolic during the postpartum. Grade A) In pregnancies less than 34 weeks and the pregnancy can be prolonged in excess of 24 hours.65 and the effects on blood pressure in non-pregnant individuals are well documented. Grade C) Postpartum. Does steroid therapy have a role in the treatment of HELLP syndrome? The use of dexamethasone or other steroids for therapy specific for HELLP syndrome is not recommended and this approach should be considered experimental. there seems to be some benefit to a brief course of furosemide diuresis in the days postpartum. (Level I. (Level III. Grade A) Two trials70-71 compared treatment with dexamethasone vs. steroids help to reduce fetal respiratory mortality.66-67 There is probable benefit from steroid therapy even if delivery is less than 24 hours after administration.63 but in general. Choice of antihypertensive agent in the postpartum period is often influenced by breast feeding.68-69 G2. Home blood pressure monitoring by the patient is helpful in this regard. Is corticosteroid therapy indicated for fetal lung maturity? Between 24-34 weeks. G. these drugs should be used cautiously or should perhaps be avoided. the agents commonly used in the antepartum period may be continued postpartum. Use of Corticosteroids G1.64 A few case reports have suggested that nonsteroidal anti-inflammatories may contribute to blood pressure elevation postpartum. The recommended regimens are the following: Betamethasone 12 mg IM every 24 hours for 2 doses Dexamethasone 6mg IM every 12 hours for 4 doses (Level I. no guidelines currently exist with regard to antihypertensive medications but Tan and de Swiet62 have suggested that antihypertensive drugs should be given if the BP exceeds 150 mmHg systolic or 100 mmHg diastolic in the first 4 days of the puerperium. . Both studies revealed outcomes that were not significantly different between 2 groups. It is prudent to avoid non-steroidal anti-inflammatories in postpartum women who are hypertensive. The medication may be discontinued when the blood pressure normalizes.53 In select cases of women with severe preeclampsia. Thus. corticosteroids should be given to enhance fetal lung maturity. in postpartum patients who are already hypertensive. One study72 suggests that corticosteroids use lead to a more rapid resolution of the biochemical and hematological abnormalities but there is no evidence that they reduce morbidity. placebo in women with HELLP syndrome. the benefits of conservative management should be reassessed. (Level I. After 34 weeks with cephalic presentation. How should the woman be managed following delivery? I1. Grade C) I2. Anti-hypertensive treatment should be continued throughout assessment and labor. (Level III. Grade A) If the gestation is greater than 34 weeks and complicated by severe preeclampsia. (Level III. Grade C) I3. Vaginal prostaglandins will increase the chance of success. Vaginal delivery is generally preferable but.34 As the gestational age approaches 34 weeks.H. Anti-hypertensive medication should be continued after delivery as dictated by the blood pressure.74 have reported a reduction in neonatal complications with an expectant approach to management of severe early-onset preeclampsia with no increase in maternal complications.69 Two small randomized controlled trials73. Women with persisting hypertension and proteinuria at 6 weeks may have renal disease and should be considered for further investigation. and the potential benefits of expectant management becomes less compelling.68. a carefully planned delivery is appropriate. (Grade C) In all situations.68. It may be necessary to maintain treatment for up to 3 months. together with the likelihood of success of induction of labor after assessment of the cervix. When is the woman with severe preeclampsia delivered? Pregnancies ! 34 weeks of gestation complicated by severe preeclampsia is best managed by delivery after maternal stabilization. fetal survival is already similar to that of term gestations. corticosteroids should be given. What is the mode of delivery? The mode of delivery should be determined after considering the presentation of the fetus and the fetal condition. Clinicians should be aware of the risk of late seizures and ensure that women have a careful review before discharge form the hospital.8. short and long term neonatal outcomes are excellent. although after 24 hours. Grade A) If the fetus is less than 34 weeks of gestation and delivery can be deferred. Several case series have also reported similar outcomes in different settings with gestations as early as 24 weeks.7.34 I. vaginal delivery should be considered. Delivery H1. (Level I.69 H2. caesarean section is more likely as the success of induction is reduced. Prolonging the pregnancy at very early gestation may improve the outcome for the premature infant but can only be considered if the mother remains stable. (Level III. delivery after stabilization is recommended. Grade C) .5. if gestation is below 32 weeks.34 The obstetrician should discuss the mode of delivery with the mother. 76 The decision about discharge from hospital needs to consider the risk of late seizures. 5. In: Edmond DIC. Severe preeclampsia can occur postpartum. Expectant management of severe preeclampsia remote from term. to be weaned off therapy as an outpatient. visual disturbances. Expectant management of severe preeclampsia remote from term: Hope for the best. blood pressure should not be allowed to exceed 160/100 mmHg. Sibai BM. Most women with severe preeclampsia or eclampsia will need inpatient care for 4 days or more following delivery. al. treatment and delivery indication. Kao L. Singapore Med J 2008.53 References 1. Cunningham. ed. Robson SC.75 As eclampsia has been reported up to 4 weeks postnatally. . Am J Obstet Gynecol 1994. Cox K.514:E1-9. A protocol for managing severe preeclampsia in the second trimester. New York: Mc-Graw-Hill 2010:706-756. it usually rises again at around 24 hours postpartum. ACOG. 175: 1313-6. Leveno KJ. Am J Obstet Gynecol 1996. 2. Expectant versus aggressive management in severe preeclampsia remote from term. Pregnancy Hypertension. et. Hall DR. 8. blood pressure can take up to 3 months to return to normal. Odendaal HJ. the optimum length of inpatient postnatal stay is unclear but the incidence of eclampsia and severe preeclampsia falls after the 4th postpartum day. After preeclampsia. Sibai BM. Expectant management of severe preeclampsia remote from term: Patient selection. 4. et. 7.77:1-6. Morette M. The importance of urinary protein excretion during conservative management of severe preeclampsia. Am J Obstet Gynecol 1990. Careful assessment of the woman to ensure improving clinical signs is needed before disacharge. Friedman SA. There is no reason why the woman cannot go home on treatment. blood pressure may fall.163:733-8. 6th ed.76:1070-5. In: Williams Obstetrics. Urinary protein excretion and expectant management of early onset severe preeclampsia.34 Antihypertensive therapy should be continued after delivery. Sibai BM. Hypertension and Renal Disease in Pregnancy. Am J Obstet Gynecol 2000. Schiff E. Grive D. 33. Obstet Gynecol 2002. al.1999:166-85. 13. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks gestation: A randomized controlled trial. Although. Am J Obstet Gynecol 2007. Aggressive versus expectant management of severe preclampsia at 28-32 weeks gestation: A Randomized controlled trial. however. Fairlie F. 23rd ed. 11. Schiff E. Sarsam DS. Am J Obstet Gynecol 2008:209-212. it is good practice to avoid the use of methydopa in the postnatal period because of its adverse effect profile. but expect the worst. Int J Gynaecol Obstet 2002. 14. 10. Barton JR. 6.49(9):698. Diagnosis and Management of Preeclampsia and Eclampsia: ACOG Practice Bulletin No. F6. Clin Obstet Gynecol 1999. Obstet Gynecol 1990. During this time.183:S1-22. 3. initially. Akl S. 99: 159-67. Sibai BM. Steyn DW. Friedman SA. Odendaal HJ. 12. Sibai BM. A reduction in anti-hypertensive therapy should be made in a stepwise fashion. Dewhuret’s Texbook of Obs and Gyn for Postgraduates. nausea and vomiting or epigastric pain) should be assessed.171:818-22. Phillipine Obstetrical and Gynecological Society Committee on Nationwide Statistics 2005-2008. Women who develop hypertension or symptoms of preeclampsia postnatally (headaches. Atenolol and metoprolol are also found to be concentrated in the breastmilk. Gant NF. 9. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Lobarsky SL.42:470-8. particularly depression.Oxford: Blackwell Science Ltd.34. Norwitz ER. There is insufficient evidence to recommend any particular drug. for severe preeclampsia.112:84-8. 22.190:1590-5. Eur J Obstet Gynecol 2001. et al. Nguyen TM. Walenburg HCS. Odendaal HJ. Nuwayhid BS. 33. Buksh MJ. Severe preeclampsia at <25 weeks of gestation: maternal and neonatal outcomes. Grove D. and low platelet count. Bots ML. Koopman C. 35. Randomized trial of management of hypertensive pregnancies by korotkoff phase IV or phase V. Bonsel GJ. elevated liver enzymes. Management of severe. 39. Bousel GJ. Pottecler T.63:147-54.. 17. Visser W. January 27 2009. BJOG 2005. 1: 3-22. 19. al. Boxter Jk.46:407-12. Redman WG. 38. 27. 28. Expectant management of severe preeclampsia between 24 and 34 weeks’ gestation. Hall DR. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation. Odendaal HJ. Budden A. Shear RM. A randomized placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term. Rinfret D. Golara M. Morbidity and development in childhood of infants born after temporisisng treatment of early onset preeclampsia. van Runnard Heimel PJ. Inflationary oscillometry provides accurate measurement of blood pressure in preeclampsia BJOG 2002.El. Leduc L. Royal College of Obstetricians & Gynecologists. et. Rep A. al. 18. severe preeclampsia: perinatal outcome. McCowan L. Aust N Z J Obstet Gynaecol 2006. Am J Obstet Gynecol 2004. Westenberg SM.96:168-72. Withagen MIJ. Visser W. 36. Head BB. The management of Severe Preeclapmsia.109:1143-7. Ganzevoort W. BJOG 1995. Visser W. 30. Sibai BM. 24. Hauth JC. Am J Obstet Gynecol 2002. Pregnancy outcome in women presenting with preeclampsia at less than 25 weeks’ gestation. Wallenburg HCS. Withagen M. Maternal . 2008. Bruinse HW.186:790-5. Early onset severe preeclampsia: expectant management at a secondary hospital in close association with a tertiary institution. Eur J Obstet Gynecol Reprod Biol 2006. Sibai BM. Eur J Obstet Gynecol Reprod Biol 1995. Castro LC. Deis S. Smith J.15. Hall DR.192: 1119-25.51:175-80. Wallenburg HCS.Fetal Medicine. Wolf H. Expectant management of severe preeclampsia in the mid-trimester. 26. Huisjes AJM. one with and one without plasma volume expansion. van Pampus MG. London: RCOG Press. 2006. Gee H. 29. Diagnosis.103:981-91. Roux A. et. Steegers EAP. Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe preeclampsia remote from term. 34.107:24-7.128:187-93. A randomized controlled trial comparing two temporizing management strategies. Obstet Gynecol 2004. 20. Li MA. Multidisciplinary Management of Severe Preeclampsia. BJOG 2000. Hop WCJ. Hypertensive Disorders. Olah KS. 32. Eur J Obstet Gynecol Reprod Biol 2003. Oettle C. Steyn DW. Treffers PE. Cabrol D.76:31-6. Grove D. Daniel BJ.352:777-81. BJOG 2005. 21. Temporising management of severe preeclampsia with and without HELLP syndrome. Brown MA. 25.183:853-8. The Sixth Report of the Confidential Inquiries into Maternal Deaths in the United Kingdom. et al. Wilkinson L. Evidence Based Clinical Guideline No 10 (A). . 2004. Eur J Obstet Gynecol Reprod Biol 2001. Evidence Based Guidelines 2007. Why Mothers Die 2000-2002. controversies and management of the syndrome of hemolysis. Vigil-DeGarcia P. Lancet 1998. 37. Hall D. Jenkins SM. 23. al. Kristen GF.107:1258-64. et. Eur J Obstet Gynecol Reprod Biol 1998. Chammas MF. et. Fraux A. early preeclampsia: Is conservative management justified? Eur J Obstet Gynecol Reprod Biol 1993. Lewis G. Expectant management of severe preeclampsia at less than 27 weeks gestation: maternal and perinatal outcome according to gestational age by weeks at onset of expectant management: Am J Obstet Gynecol 199:247. der Post V. Bombrys AE. Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction? Am J Obstet Gynecol 2005. Goffinet F. 16. Haddad B. Expectant management of early onset. London: RCOG Press.112:1358-68.112:910-4. 31. Maternal and perinatal outcome after expectant management of HELLP syndrome compared with preeclampsia without HELLP syndrome. Expectant management of severe preterm preeclampsia: Is intrauterine growth restriction an indication for immediate delivery? Am J Obstet Gynecol 2000. Neonatal outcome of temporizing treatment in early onset preeclampsia.102:111-7. editor. BJOG 2004. al.94:211-5. Montufar-Rueda C. Ruiz J. al. 64.92:1326-1331. Prophylactic corticosteroids for preterm birth.180:1373-84. Am J Obstet Gynecol 1999. 49. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. 62. 53. Lindheimer MD.101:262-263. The combination of magnesium sulfate and nifedipine: a cause of neuromauscular blockade. et. Drugs for treatment of very high blood pressure during pregnancy. Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in pregnancy. BJOG 2005. Am J Obstet Gynecol 1995. benefit from magnesium sulphate? The Magpie Trial: A randomized placebo-controlled trial. 58. et. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium related maternal side effects in women with preeclampsia. 54. Brown MA. 63. Outcome of severe preeclampsia/ eclampsia in Yorkshire 1999/2003. 56. al.21:85-95. al.109:733-736. Evidence Based Clinical Guideline No. al. New York. Preeclampsia. Sharma SK. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. et. 8. Waugh J.327:955-60. London: RCOG Press. 55. et. Which anticonvulsant for women with preeclampsia? Evidence from the Collaborative Eclampsia Trial. and their babies. The Use of Electronic Fetal Monitoring. 52. Cunningham FG (eds): Chesley’s Hypertensive Disorder of Pregnancy 3rd ed.90:385-90. 59. Intrauterine Growth Restriction (IUGR): biometric and doppler assessment.190:577- 578. et. 3:CD001449. al. al. Duley L. Beardmore KS. BMJ 2003. Makris A. al. et. et. al. p.49:125-30. 66. et. et. Early platelet consumption in preeclampsia. al. Circulation 1995. 44. 47. The management of postpartum hypertension. et. Magee LA. Cunningham FG. et. BMJ 1999. Magee LA. BJOG 2002. 61. al.345(8963):1455-63. 2009. Prenat Diagn 2002. Magpie Triad Collaborative Group: Do women with preeclampsia. 46. et. al. al. Hypertens Pregnancy 2002. 65. Br J Obstet Gynaecol 1994. Ben-Ami M.(6111):467-9. Assessment of changes in coagulation in parturient with preeclampsia using thromboelastography. Lancet 1995. Alfirevic Z. 42. 2003. Leveno KJ. Dose-related increase in mortality in patients with coronary heart disease. Cochrane Database Syst Rev 2000(2):CD001805. 50. Postpartum hypertension and non-steriodal analgesia. et. et. Duley L. Optimal bedside urinalysis for the detection of proteinuria in hypertensive proteinuria: a study of diagnostic accuracy? BJOG 2005: 112: 412-17. et. Anesthesiology 1999. Furberg CD. et.172:1379-87. Crowley P. Crithchley H. et. Am J Obstet Gynecol 2000. Martin JN. . 67.180:1407-14. Galan HL. Cochrane Database Syst Rev 2006. al. et. al. 45. al. al. London: RCOG Press.105:29-33. Am J Obstet Gynecol 2005:193:153- 163. methyldopa in the treatment of pregnancy induced hypertension. 43. Am J Obstet Gynecol 1999. Nifedipine. In Press. Magee LA. Labetalol vs. RCOG.40. et. 57. 48.183:S1-S22. elevated liver enzymes and low platelet count) syndrome classification. Ascarelli MH. Fortnightly Review: management of hypertension in pregnancy. Cochrane Database Syst Rev 2000 (2): CD000065. et. Martin JN. 41. Tan LK. Obstet Gynecol 2005. Redman CW. al. Doppler ultrasonography in high risk pregnancies: systematic review with meta-analysis. Postpartum preeclampsia management with Furosemide: A randomized clinical trial. El-Qarmalawi AM.22:331-7. Am J Obstet Gynecol 2004. Roberts JM. al. et. Int J Gynaecol Obstet 1995. 51. Trufnell DJ. al. 60. Early risk assessment of severe preeclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity. al. The spectrum of severe preeclampsia: comparative analysis of HELLP (hemolysis. Excretion of anti-hypertensive medication into human breastmilk: a systematic review. al. Lancet 359:1877-2002.395. 2001.318:1322-6. Am J Obstet Gynecol 2002:187:1046-1050. Plasma volume expansion for treatment of women with preeclampsia. de Swiet M.112:875-80. Br Med J 1978. Maternal and perinatal outcome during expectant management of 239 severe preeclampsia women between 24-33 weeks gestation. placebo- controlled. and delivery Indications. al. A double blind.27:134-41. Clenny TL. et. 78. Postpartum dexamethasone for women with. et. et. Viera AJ. randomized clinical trial. A Double blind placebo-controlled. Magan EF. al. Neonatal outcome in severe preeclampsia at 24-36 weeks gestation: Does the HELLP Syndrome matter? Am J Obstet Gynecol 1999. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome. 2008. Sibai BM. et.83:502-5. al.19:221-31.3:18-36. Deis S. 77.190-1590-7.283. Clinical presentation of women readmitted with postpartum severe preeclampsia or eclampsia. Mortality and morbidity associated with early onset preeclampsia. Cabral D. Bartom JR. Obstet Gynecol1994.270-2. Haddad B.1:206-9. Lubarsky SL. 73. J Soc Gynecol Investig 1994. 70. 72. Am J Obstet Gynecol 193:1591. Atterburry JL. Hypertens Pregnancy 2000. Stirrat GM. . Bramovici D. J Obstet Gynecol Neonatal Nurs 1998. Am J Obstet Gynecol 2007. Katz L. 75. Fonseca JE.2005. OBG Management 2005. et. Goffinet F. Am J Obstet Gynecol 198. Expectant management of preeclampsia.68. 76. Late postpartum eclampsia revisited. Am J Obstet Gynecol 2004. Paniel BJ. 74.180:221-5. Sibai BM.329. Sabai BM. 71. Expectant management of severe preeclampsia remote from term: patient selection treatment. Neonatal salvage by weeks’ gestation in pregnancies complicated by HELLP syndrome. 69. randomized clinical trial. el. Sibai BM. HELLP Syndrome. BMJ 2004.514:E1-E9. al. al. Corticosteroid for HELLP syndrome. Murphy DJ. Loading doses of 4 g IV slowly over 5-10 minutes and 10 g deep IM (5 g to each buttock). MD and Diosdado V. One may reduce the drip to 1 g/hr after 24 hours. Respiratory rate of not less than 12/min. Incorporate 20 g MgSO4 (four 10-ml ampules of 50% MgSO4) to 1000 ml D5W or Normosol-M.2 Patellar reflexes disappear with plasma levels of 8-10 meq/L. (Pritchard 1984). Maintenance of plasma magnesium levels at 4-7 meq/L almost always prevents eclamptic convulsions. Loading dose of 4 g IV followed immediately by IV infusion of 2 g per hour. Presence of patellar reflex 3. Grade A) B. although no significant reduction in maternal and perinatal mortalities was noted among the three groups. (Level I. then 5 g IM every 4 hours until 24 hours after delivery. Serum magnesium levels may be taken at certain intervals to monitor for magnesium toxicity (Level III. Grade C). 2. Hospitalization . Urine output of at least 30 ml for the past hour or 100 ml for the past 4 hours 2. The recommended MgSO4 dosage schedules for severe preeclampsia and eclampsia have been previously mentioned in the chapter on management of severe pre-eclampsia (Section Six) but they are restated here for emphasis: 1. MD The aims in the treatment of eclampsia are: • control of seizure • correction of hypoxia and acidosis • control of blood pressure • delivery after control of seizure The protocol of active management of eclampsia consists of: A. The following precautions must be observed prior to administration of succeeding doses: 1. via infusion pump or soluset (Anderson 1986). Significantly fewer recurrences of seizures were noted among patients given magnesium sulfate than those given diazepam or phenytoin. This sign warns of impending magnesium toxicity since respiratory depression develops at 12 meq/L. and infuse IV at a rate of 100 ml/hour (2 g/hr).required for all patients with eclampsia. IV Calcium gluconate (10 ml of 10% solution) available at bedside for MgSO4 overdose. Eclampsia Raul M. Quillamor. . 4. followed by respiratory and cardiac paralysis and arrest. The Eclampsia Collaborative Trial Group in 1995 has established the superiority of magnesium sulfate over diazepam and phenytoin in the treatment of convulsions. Control of seizures and prevention of recurrence Magnesium sulfate (MgSO4) is currently considered the drug of choice in the prevention of eclamptic seizures as well as the reduction of recurrent seizures. Mariano. 5. other anti-seizure options that may be used are: Diazepam A loading dose of 10 mg IV over 2 minutes. The sublingual route is not recommended for pregnant patients because of the acute fluctuations in blood pressure levels and the absence of good studies on fetal effects of calcium antagonists. followed by an intravenous infusion of 40 mg in 500ml normal saline for 24 hours. Since phenytoin is only recommended for the prevention of seizures. It may be used with Phenytoin in the management of convulsions in the absence of magnesium sulfate. the full loading dose must have been given and the patient should be accompanied by a responsible health personnel. Anti-hypertensive therapy Patients with severe hypertension should be started on IV therapy. then 80 mg every 10 minutes but not to exceed a total of 220 mg per episode treated. The rate of infusion is titrated based on the level of consciousness. (Level II-2. and labetalol7 (Level I. repeated if convulsions recurred. (Level II-2. with the aim of overcoming restlessness and keeping the patient sedated but rousable. although the dose may be varied according to the patient’s weight. (Level II-1. Thereafter. (Level II-2. Grade B) a. The drugs that may be used are hydralazine (drug of choice). 10mg diazepam IV should be given to control the seizures. if they occur. Grade A) Give Hydralazine by IV boluses of 5 or 10 mg at 20 to 30 min intervals until the desired BP is attained. Grade B) Phenytoin There is no consensus about an ideal phenytoin regimen. Nifedipine 5 or 10 mg can be given orally and takes effect within 15-50 minutes. with provisions for control of seizures and other complications. an infusion of 20 mg diazepam in 500 ml normal saline is given and slowly reduced. Administering hydralazine via an IV drip is not recommended because of the instability of the preparation. Grade B).8 This drug should be avoided in women with asthma or congestive heart failure. Grade C) c. . and followed by succeeding doses of 100 mg every 6 hours for the next 24 hours. give 40 mg. Labetalol can be given with an initial dose of 20 mg IV bolus. During the next 24 hours. Clonidine IM 75-150 mcg is the next recommended drug. Grade B) If MgSO4 is not available. an initial phenytoin loading dose of 1 gm slow IV (over 20 min) is given with continuous cardiac monitoring. 6. Grade B) C.7. (Level II-2. b. If the desired BP is not attained within 10 minutes. If a patient is to be transferred to another hospital. clonidine and nifedipine (Level II-2. Magnesium Sulfate versus diazepam for eclampsia. 2. 7. In comatose patients. since temporization to gain fetal maturity in the presence of eclampsia is always risky. Creasy RK. Greer I. Clin Exp Hypertens B8:277. 4. Second line therapy with nifedipine in severe pregnancy induced hypertension. March 2006: The Management of Severe Preeclampsia/Eclampsia. Sibai BM. and Management of Eclampsia. Saunders Elsevier. al. Cochrane Database Syst Rev (4):CD000127. Prevention. Resnik R. Diagnosis. References 1. ACOG 2002. 105:402-10. vaginal delivery does not appear easy and imminent 2. Cunningham FG. 8. al. there is fetal compromise. or 3. The McGraw-Hill Companies. National High Blood Pressure Education Program 2000 ! ! . there is failure of progress after induction. It is recommended to induce labor or to perform a cesarean section as soon as the patient becomes conscious and oriented. 2009. Anticonvulsant therapy should be continued for at least 24 hours after delivery. Sixth Edition.D. Walker J. Grade B) It has been observed that the uterus is sensitive to oxytocin so that labor can be induced even with an “unfavorable” cervix and assisted vaginal delivery can be performed if labor progresses. Creasy & Resnik’s Maternal-Fetal Medicine Principles and Practice.1989. et. Inc. Delivery after control of seizures It is generally accepted that continuation of pregnancy in eclamptic patients constitutes a significant threat to maternal and fetal well being such that pregnancy should be terminated. et. Obstetr Gynecol 2005. a neurologic evaluation with possibly a CT scan should be performed. (Level II-3. 6. Williams Obstetrics 23rd Edition 2010. Henderson-Smart D. Cesarean section is reserved if: 1. Leveno K. RCOG Guideline Number 10. 3. Duley L. 2003. 5. hypertensive disease during a previous pregnancy. and many others are contraindicated. (Level II-2. chronic hypertension) (Grade A) Some women are more resistant than others to the effects of aspirin. Methyldopa 250–500mg PO BID-QID (max 2g/day) b.g. Labetalol 100–400mg PO BID-TID (max 1200 mg/day) . to prolong pregnancy for as long as safely possible. Antihypertensive therapy should be reinstituted if BP exceeds 150-160 systolic or 100-110 diastolic. Angiotensin converting enzyme (ACE inhibitors) and Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy. Low dose Aspirin (65-85 mg PO) at bedtime everyday from 12 weeks until birth should be considered in women with historical risk factors to decrease superimposed preeclampsia (e. Grade A) 3. defined as BP 140/90 mm Hg either predating pregnancy or developing before 20 weeks’ gestation and hypertension that persists 12 weeks postpartum. Trinidad. Recommendations 1. 2. and in women who develop new-onset hypertension in the second half of pregnancy. The challenge is in deciding when to use antihypertensive medications and what level of BP to target. Castro. type 1 or type 2 diabetes. autoimmune disease such as systemic lupus erythematosis or antiphospholipid syndrome. however. Chronic Hypertension Virgilio B. MD Definition Chronic hypertension. (Grade B) 4. because only a small proportion of currently available drugs have been adequately evaluated in pregnant women. Initial antihypertensive therapy include the following: a. Antihypertensive agents are mainly used to prevent and treat severe hypertension. This complication may result in significant maternal. chronic renal disease. The choice of antihypertensive agents is less complex. Prevention of preeclampsia is desirable. The goal of treatment is to maintain BP at a level that minimizes maternal cardiovascular and cerebrovascular risk. The beta blocker atenolol may be associated with growth restriction and is not recommended for use in pregnancy. current evidence has not shown that either specific BP targets in pregnancy or specific antihypertensive agents modify the risk of superimposed preeclampsia in women with pre-existing hypertension. MD and Ann Marie C. fetal and neonatal mortality and morbidity. thereby maximizing the gestational age of the infant and to minimize fetal exposure to medications that may have adverse effects. However. a dose of at least 75 mg/d may be necessary to inhibit both platelet and placental thromboxane. a dose of 100 mg/d may affect fetal prostacyclin synthesis. Hypertensive disorders during pregnancy occur in women with pre-existing primary or secondary chronic hypertension. serum potassium and urinalysis. If with suspicion of preeclampsia. serum creatinine. renal insufficiency and retinopathy. For women with pre-existing hypertension laboratory exams at initial visit include complete blood count (CBC). If vaginal delivery is planned and the cervix is unfavourable. then cervical ripening should be used to increase the chance a successful vaginal delivery. (Grade A) 5. (Grade C) . Women with long standing hypertension should be evaluated for end-organ disease including cardiomegaly. 2. Nifedipine PA (intermediate release) tablets (10–20 mg PO BID-TID. Vaginal delivery should be considered unless a cesarean section is required for the usual obstetric indication. max 120 mg/day) Methyldopa and labetalol are the first line antihypertensive therapies. (Level I. (Grade A) 7. c. (Grade B) 6. creatinine clearance and 24 hour urine protein are encouraged. (Grade B) 4. Baseline ultrasound at 18-20 weeks and repeat scan at 28-32 weeks to monitor fetal growth and to check amniotic fluid volume. max 180 mg/day) or XL (slow release) preparation (20–60 mg PO OD. If with growth restriction or superimposed preeclampsia. (Grade A) 3. Grade A) Obstetric Management 1. Antenatal fetal surveillance should include umbilial artery Doppler velocimetry. When some but not all these parameters are present. MD HELLP Syndrome Definition • The acronym HELLP was created by Louis Weinstein in 1982 to describe a subset of severe preeclampsia/eclampsia with microangiopathic hemolytic anemia. Abruptio Placnta) Ma. evidence of hepatic dysfunction (AST and/or ALT > 70 IU/L).5 . and hemolysis (total serum LDH > 600 IU/L). (2) hepatic dysfunction with AST 70 IU/L or greater.000/ml or less. and class 3 includes patients with mild thrombocytopenia (platelets >100. • The Mississippi Triple Class System (Martin 1999)3 divides patients into 3 classes based on their platelet counts: class 1 requires severe thrombocytopenia (platelets < 50. MD and Sol M. and abnormal liver function tests presenting with right upper quadrant/epigastric pain. to guide therapeutic intervention and assess outcomes. or bilirubin 1. and evidence of hemolysis (total serum LDH > 600 IU/L). (3) evidence of hemolysis with an abnormal peripheral smear in addition to either total serum LDH 600 IU/L or greater. Complications of Pregnancy Induced Hypertension (HELLP. (H = hemolysis. disrupted or destroyed erythrocytes on peripheral smear. liver-targetted acute inflammatory condition and disordered immunologic process. Strand et al4 postulated that placenta- derived proteins are shed into the maternal circulation which damage hepatic cells. moderate to severe thrombocytopenia.000 to < 100.000/ml ). suggesting that HELLP syndrome is a placenta-instigated.000 but < 150. Acu.000/ml). EL = elevated liver enzymes.000/ml. class 2 requires similar criteria except thrombocytopenia is moderate ( >50. Luisa S. nausea and vomiting. • The Tennessee Classification (Sibai 1986)2 defines “complete” HELLP syndrome if all the following criteria are met: (1) moderate to severe thrombocytopenia with platelets 100. Pangan. the term “partial” or “incomplete” HELLP is used. Pathophysiology • The pathophysiology of HELLP remains unclear.2 mg/dL or greater. and LP = low platelets)1 • Two classification systems have been created to stratify patients’ risks for significant maternal morbidity. mild hepatic dysfunction (AST and/or ALT > 40 IU/L). (Level II.13 • The most important symptom is severe epigastric/right upper quadrant pain.9 • A patient with severe preeclampsia who suddenly develops severe writhing epigastric/upper abdominal pain. or magnetic resonance imaging (MRI).3. Rupture of a subcapsular liver hematoma is one of the most dreaded. computed tomography (CT). or .Clinical Presentation • Usually develops suddenly in the third trimester or immediate postpartum. hepatic imaging with transabdominal ultrasound. (Grade B) • There is a consensus of opinion that prompt delivery is indicated if the syndrome develops beyond 34 weeks gestation. life-threatening complication of the HELLP syndrome. Other causes of death are cardiac arrest.6.11 • HELLP usually resolves within a week postpartum. treatment consists of prophylaxis against convulsions with magnesium sulfate.10 Management • Liver function tests and platelet counts should be done in all preeclamptic women. sepsis.8 • Onset of disease occurs antepartum in 70 %.3. or earlier if there is multiorgan dysfunction. and constitutes an obstetric emergency. however. very high LDH. If suspected. found in 100% of Weinstein’s original series of 29 advanced cases.6. can be performed.5. stabilization of maternal condition.1. may have hepatic hematoma or rupture.25 • 60 % of maternal mortalities occur with class 1 disease and the most common cause is cerebral hemorrhage/stroke. DIC. AST and/or uric acid levels. Progression is usually rapid with 35-50 % decrease in platelets per day and rise in AST and ALT until 24 – 48 hours postpartum when levels begin to recover. Patients are usually seen complaining of malaise (90%).14 • Significant maternal morbidity occurs with worsening thrombocytopenia. control of hypertension. or nonreassuring fetal status. suspected abruption placentae.16 (Grade C) • Aggressive high dose corticosteroid therapy has been advocated to improve maternal and neonatal outcome in HELLP. liver infarction or hermorrhage. and then delivery. and postpartum in 30 % of cases. on the management of women with HELLP syndrome before 34 weeks gestation when the maternal condition is stable except for mild to moderate abnormalities in blood tests with a reassuring fetal condition.16 (Level III. renal failure. epigastric or right upper quadrant pain (90%).29.15 Hypertension and proteinuria may be mild and may not directly correlate with laboratory parameters. Intravenous dexamethasone 10-12 mg every 12 hours. and some with non-specific viral-like symptoms. disseminated intravascular coagulopathy. In these situations. renal failure. especially with suspected HELLP. Grade B) • There is no general agreement. often heralds rapidly progressive disease. ARDS. Grade B) • Best managed in a center with intensive care facilities for hepatologic. hepatic rupture and hypoxic encephalopathy. or nausea or vomiting (50%). hematologic and obstetric emergencies.7. Aggressive high dose corticosteroids can increase the platelet count to 75.000/mm3 and no evidence of end-organ damage.29 The 4 randomized trials were not placebo controlled. renal failure. Isler CM.16-23. and possible vaginal delivery. there was a shorter average platelet count recovery and less duration of hospitalization in those who received dexamethasone (4. Hypertension in pregnancy.180:1373-84. choice of historical controls and/or clinical outcome reported. Blake PG. placebo-controlled clinical trials. Martin JN Jr. . Blake PG. Gastroenterology 2004.29 Hence a Cochrane review (2004) concluded that there is insufficient evidence to determine whether corticosteroid use in HELLP syndrome decreases major maternal and perinatal morbidity. the threshold deemed adequate to undertake regional anesthesia (from 0% to 42%). Mann A. until delivery. 6.000/mm3 . Grade B) • Epidural or spinal anesthesia is the preferred anesthesia for patients with preeclampsia. Martin JN Jr. were given with reported improvement in laboratory values. 3. (Level III. Mabie BC. Am J Obstet Gynecol 1999. McCaul JF. Thornton S. 2. and low platelet count: a severe consequence of hypertension in pregnancy.28 (Level II.p. Martin JN Jr. Terrone DA. do not support routine use of this regimen for all HELLP cases. Magann EF. no differences in serious maternal morbidity such as need for transfusion. Although improved laboratory values and urine output were obtained in the patients given dexamethasone. Rinehart K. The natural history of HELLP syndrome: patterns of disease progression and regression. Saade GR. elevated liver enzymes. Martin RW. of the Fonseca cases.27 Most of these studies are retrospective and have critical design flaws. mainly in inclusion criteria.000/mm3 ). with the largest sample sizes to date.126:849-58. Grade B) • Most of the patients could be discharged after 4-8 days hospitalization. a subgroup analysis according to severity of disease. shorter hospital stay and an increased use of regional anesthesia. and additional 3 more doses after delivery.6 versus 10. induction of labor. and low platelets in severe preeclampsia-eclampsia. Strand D. 5. on the use of high dose dexamethasone to improve maternal outcome in patients with HELLP syndrome. The spectrum of severe preeclampsia: comparative analysis by HELLP sybdrome classification. et. Hess LW. Am J Obstet Gynecol 1991. • Replacement of clotting factors with frozen plasma and factor concentrates. Sibai BM. Am J Obstet Gynecol 1986. elevated liver enzymes. both randomized.4 days). Syndrome of hemolysis. showed that among the patients with Class 1 HELLP (platelet counts less than 50. Blessing M. HELLP sybdrome: the scope of disease and treatment. Strand S. Amon E. 4. However. Placenta-derived CD95 ligand causes liver damage in HELLP syndrome.164:1500-13.000/mm3 should be given as needed. Weinstein L. double-blind. al.24 • The results of two recent studies. or serous hepatic complications were shown.25 References 1. 2003.155:501-9. pulmonary edema. improvement in blood pressure.27. editors. Perry KG. Fonseca25 and Katz26. Oxford: Marcel Dekker. Seufert R. intramuscular betamethasone 10-12 mg every 12 hours. May WL. and to enable cervical ripening. Am J Obstet Gynecol 1982. Chap 7. In: Belfort MA. Ryan GM.141-88. if the platelet count is greater than 100. el-Nazer A. Magann EF. Maternal-perinatal outcome associated with the syndrome of hemolysis. Lotz J. Taslimi MM.142:159-67. and platelet transfusion for counts below 50. Sibai BM. Am J Obstet Gynecol 2004. Isler CM.198:283. Bass JD. A prospective randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP syndrome. Bruinse HW. Effects of postpartum corticosteroids in patients with HELLP syndrome. Obstet implications of antepartum corticosteroid therapy for HELLP syndrome. Am J Obstet Gynecol 2005. Magann EF. elevated liver enzymes and low platelet count. Sullivan DL. Rath W. Am J Obstet Gynecol 2004. Faridi A. 17. Vigil-DeGracia P. Bowes WA Jr. Sener T. Postpartum recovery after severe preeclampsia and HELLP sybdrome. 19. Ozalp S. Obstet Gynecol 2004.103:981-91. and low platelets syndrome.193:1587-90. controversies.12:310-3. Makkonen N. J Perinat Med 1996. The HELLP syndrome (hemolysis. and low platelet count) syndrome: impact on the rate of regional anesthesia. Thorp JM. Figueroa JN. Catano C. 2004:CD002076 Oxford: Updates Software. Briery CM. Arias F. 27. The natural history of thrombocytopenia associated with preeclampsia.163:1142-3. Martin JN Jr. Okur A. Rose CH. 13. Am J Obstet Gynecol 1998. Am J Obstet Gynecol 1994. Pinto eSilva JL. Diagnosis. 12. Postpartum dexamethasone for women with hemolysis.24:641-9. Chouhan SP. Understanding and managing HELLP syndrome: the integral role of aggressive glucocorticoids for mother and child. 20.181:924-8. Postpartum corticosteroids: accelerated recovery fom HELLP syndrome. and management of the syndrome of hemolysis. Maternal morbidity and mortality in 442 pregnancies with hemolysis. . Moodley J.59:217-21. Int J Gynaecol Obstet 1997. elevated liver enzymes.162:311-6. Fonseca JE. Bass D. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a double blind. Chouhan SP.191:S41. O’brien JM. Rozas L. Martin JN Jr. Dexamethasone to improve maternal outcome in women with hemolysis. Sibai BM.193:1591-8. Usta I. placebo-controlled. van Runnard Heimel PH. Z Gerburstschilfe 1996. Differential HELLP syndrome diagnosis. Rose CH. Garcia-Caceres E. Subcapsular liver hematoma in HELLP syndrome: evaluation of diagnostic and therapeutic options – A unicenter study. 28. Maternal benefit of corticosteroid therapy in patients with HELLP (hemolysis. Mosley CA. Milligan DA. Harris RL. Contemp Ob Gyn 1999. 24. Harju M. and low platelets (HELLP syndrome). Martin JN Jr. Martin JN Jr.190:106-112. Int J Gynaecol Obstet 1997. Neeser E. Maternal mortality associated with HELLP syndrome. 25. May WL. Franx A. Martin JN Jr.171:1148-53. Am J Obstet Gynecol 2006. Catanzarite VA. Am J Obstet Gynecol 1990. Am J Obstet Gynecol 2002. (Cochrane Review) In: The Cochrane Library. Perry KG Jr.200:88-95. High-dose dexamethasone:a promising therapeutic option for HELLP. Meydrech EF. Cushman J.171:1154-8. Matchaba P.e8. Martin JN Jr. Magann EF.169:1000-6.184:1332-7. Dexamethasone in the postpartum treatment of HELLP syndrome. and low platelets): much ado about nothing? Am J Obstet Gynecol 1990. 29.195:914-34. levated liver enzymes. Sneider JM. randomized clinical trial. Shumate SA. de Amorin MMR. 18. Sibai BM. Am J Obstet Gynecol 2005. elevated liver enzymes. Salama M. Rinehart BK. Satchwell SL. 10. Cousins LM. Mendez F. Hass H. 23. Becker HD. 16. Magann EF. Friedman SA. 22. randomized clinical trial. Koopman C. Magann EF. Am J Obstet Gynecol 1993. Magann EF.186:457-9. Kirkinen P. 9. Antepartum corticosteroids: disease stabilization in patients with HELLP syndrome. Obstet Gynecol 2004. Lauders CF. 15. Wicke C. Bots ML. Am J Obstet Gynecol 1994. Severe preeclampsia with fulminant and extreme elevationof aspartate aminotransferase and lactate dehydrogenase levels: high risk for maternal death. Rodegerdts EA. placebo- controlled. Barton JR. Terrone DA. elevated liver enzymes.7. 21. Katz VL. Martin JN Jr. 26. 14. Am J Obstet Gynecol 2008.61:141-8. Issue 4. Yalcin OT. Sibai BM. Martin RW. Martin RW. Am J Perinatol 1995. Thigpen BD. A randomized placebo controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term: maternal and neonatal complications. elevated liver enzymes. and low platelets (HELLP) syndrome: a double-blind. Flesch I.104:1011-4. Katz L.e1-283. Barrilleaux PS. Isler CM. Corticosteroids for HELLP syndrome in pregnancy. Ramadan MK. Barton JR. Pereira PL.44:55-65. Juisjes AJM. 8. Steinberg SM. Bofill JA. Mercer BM. Am J Obstet Gynecol 2001. 11. and escapes through the cervix into the vagina. and III. or case series). The levels of available evidence for the diagnosis and management of abruptio placenta are mostly II-1. Abruptio Placenta Definition Placental abruption is defined as premature separation of a normally implanted placenta. case-control. Clinical Importance Placental abruption has a wide spectrum of clinical significance. Premature separation of the placenta before delivery may deprive the fetus of oxygen and nutrition. Maternal complications include antepartum and postpartum hemorrhage. disseminated intravascular coagulation (DIC) and acute renal failure. Approximately 0. while in partial abruption. only a portion of the placenta is detached from the uterine wall. the severity of hypertension does not necessarily correlate with the incidence of abruption. Total abruption involves the entire placenta. it is also often an indication for iatrogenic preterm delivery. and less commonly. fetal hypoxia and/or exsanguination. and growth restriction. There are no trials to assess any intervention for prevention of abruption or its complications. whereas its effect on the fetus is determined both by its severity and the gestational age at which it occurs. Although placental abruption is an important cause of spontaneous preterm birth.” in which case blood tracks between the membranes and the decidua. to massive abruption leading to fetal death and severe maternal morbidity.5 – 1% of all pregnancies are complicated by placental abruption. preterm delivery. varying from cases with minor bleeding and little or no consequences. in which case it typically leads to fetal death. However. maternal death. cohort. with no obvious external bleeding.e. because approximately one half of the excess perinatal deaths are associated with early delivery. The less common “concealed” abruption occurs when blood accumulates behind the placenta. need for blood transfusions. Abruption may be “revealed. Most large studies with abruption have examined the risk factors for this condition. hysterectomy. Hypertensive diseases in pregnancy are strongly associated with placental abruption. Abruption may be implicated in up to 10% of preterm births. Majority of the studies published in English are observational (i. . Fetal complications include a high perinatal mortality. II-2. This high perinatal mortality is largely due to preterm delivery. leading to long-term handicap among survivors. The maternal effect of abruption depends primarily on its severity. There are no randomized controlled studies that have specifically studied abruption. Studies dealing on management strategies for abruptio are usually limited by small sample size. The severity of symptoms depends on the location of the abruption. Labor typically proceeds fairly rapidly in cases of abruption. There is a correlation between the extent of placental separation and the risk of stillbirth. Vintzileos AM.8 RR. reduced variability. or a sinusoidal fetal heart rate pattern. Hagerstown (MD). There may be acute fetal distress.1 Mild and Severe Preeclampsia ++ 0. Diagnosis The diagnosis of placental abruption is made primarily on clinical presentation. OR. editor. These estimates are the ranges of RR or OR found in independent studies. Evidence and Strength of Association Linking Major Risk Factors with Placental Abruption Based on Published Studies Risk Factors Strength of Evidence RR or OR Chronic hypertension ++ 1.Table 1.4 -4. The classically described symptoms of placental abruption are vaginal bleeding and abdominal pain. with stillbirth occurring in most cases in which there is greater than 50% placental separation. It is also possible to have severe abruption without neither or just of one of these signs. Symptoms may vary. In some cases. there is uterine hypertonus with associated high-frequency. fetal demise. Placental abruption. Lippincott. Clinical Presentation The clinical presentation of abruption varies widely from totally asymptomatic cases to those where there is fetal death with severe maternal morbidity. in cases of concealed abruption associated with fetal death. and in cases where more than 50% of the placenta has separated. evidence of abruption may be found on ultrasonographic examination of asymptomatic patients. Rarely fetal death due to abruption may occur with no other symptoms or signs. Williams & Wilkins. the result of disseminated intravascular coagulopathy. especially when the placental location is posterior. leading to oliguria and renal failure. low. Gynecology and obstetrics.8 – 5.5 Chronic hypertension with Preeclampsia +++ 7. More infrequently. © 2003 Lippincott Williams & Wilkins. there may be maternal hypovolemic shock. In: Sciarra J. The amount of vaginal bleeding correlates poorly with the degree of abruption. Backache may be the only symptom. Typically. The uterus is frequently tender and may feel hard on palpation. A variety of fetal heart rate patterns have been described in association with abruption. There may be recurrent late or variable decelerations. Finally. Vol 2. 2003. and the degree of abruption. Abruptio placenta must be considered whenever bleeding occurs in the second half of pregnancy. Reprinted from Yeo L. the first clinical sign may be of evidence of abnormal bleeding. In addition. odds ratio. relative risk. abruption may present as idiopathic preterm labor. whether it is revealed or concealed. Ananth CV. bradycardia. Placental abruption may be associated with acute tubular necrosis and acute cortical necrosis. depending on how much of the placenta has separated and the age of .amplitude uterine contractions. uterine contractions >5 / 10 minutes (17%). About 10 % of abruption present with only concealed bleeding. when the ultrasonogram seems to show an abruption. urinary tract infections. with the worst prognosis occurring in retroplacental abruptions. appendicitis. Fetal distress 5. However. the likelihood of extensive separation causing fetal death is increased remarkably. uterine-abdominal tenderness/back pain (66%). No vaginal bleeding to mild bleeding 2. Occasionally the presenting sign is fetal death. a Kleihauer-Betke test allows quantification of feto-maternal transfusion to guide dosing of Rh-immune globulin in Rh-negative women. Ultrasound is primarily useful in ruling out other causes of third trimester bleeding. Maintaining a high index of suspicion even in the absence of the “classic” signs of shock is warranted. uterine hypertonus (17%). Before a pelvic examination can be performed safely. ovarian pathology. However. magnetic resonance imaging (MRI) may help better define the location of the placenta and the presence pf abrutpion. fetal non-reassuring testing (60%). The differential diagnosis includes all causes of abdominal pain and bleeding. Classification Class 1 – mildest type. Importantly. If clinical circumstances of ultrasound findings are confusing. A negative test should not be used to rule out abruption. The Kleihauer-Betke test has limited usefulness in the diagnosis of abruption. and muscular pain. Moderate to severe uterine tenderness with possible tetanic contractions 3. No fetal distress Class 2 – moderate. Nyberg and colleagues in a retrospective review of 69 cases of abruption. The classic presentation of abruption is the presence of painful cramps or contractions with dark red or bright red vaginal bleeding after the 20th week of pregnancy. found that fetal mortality correlated with the ultrasonographically estimated percentage of abruption and with the location. No vaginal bleeding to mild bleeding 2. Slightly tender uterus 3. Ultrasonography may also predict prognosis in abruption. preterm labor. Maternal tachycardia with orthostatic changes in BP and HR 4. No coagulopathy 5. Normal maternal BP and HR 4. These include placenta previa. an ultrasonographic examination should be performed to exclude placenta previa. Do not perform a digital examination on a pregnant patient with vaginal bleeding without first ascertaining the location of the placenta. a negative ultrasonogram does not rule out an abruption. With delay. 27% 1. fibroid degeneration. 48% 1. Severity of abruption often depends on how quickly the woman is seen following symptom onset. Low fibrinogen levels present . nor does a positive test necessarily confirm abruption. the likelihood that there is indeed an abruption is extremely high.gestation it occurs. Frequency of the clinical findings in women with placental abruption are the following: vaginal bleeding (76%). Fetal death Management The goals in the management of abruption are to assess. 6. Very painful tetanic uterus 3. prompt cesarean delivery is indicated. otherwise induction of labor should be considered. 3. Both mother and fetus should be monitored closely during labor. 8. Obtain intravenous access using 2 large-bore IV lines. the fetus should be delivered promptly. Labor. should maternal compromise occur. desirable in cases of severe abruption. or persistent late decelerations. 24% 1. conservative management. because total placental detachment could occur without warning. Begin external fetal monitoring for both fetal heart rate and contractions. The main question is whether vaginal delivery can be achieved without fetal or maternal death or severe morbidity. loss of variability. expectant management for mild (grade 1) abruption may allow time for glucocorticoid administration. Coagulopathy 5.Class 3 – severe. physical examination. if <34 weeks. may not be appropriate in milder cases of abruption. cesarean delivery should be performed promptly. with the goal of vaginal delivery. control and restore the amount of blood lost and to deliver a viable infant to prevent coagulation disorders. Begin blood transfusion if patient is hemodynamically unstable after fluid resuscitation. When there is partial placental abruption and the maternal and fetal status are reassuring. Institute crystalloid resuscitation. Maternal or fetal compromise necessitates delivery. The management of placental abruption depends on the presentation. it is important to individualize management on a case-by-case basis. When both maternal and fetal status are reassuring. More aggressive management. A decision to delivery interval of </= 20 minutes is associated with a substantial reduction in neonatal morbidity and mortality in cases of fetal bradycardia. In cases in which there is evidence of fetal compromise and delivery is not imminent. if established. and the degree of maternal and fetal compromise. the patient may be managed . is reasonable. No vaginal bleeding to heavy bleeding 2. Maternal shock 4. should be allowed to progress. Administer Rh immune globulin is patient is Rh-negative. Correct coagulopathy. However. Admission is required if abruptio placenta is considered. The following should be performed once it is diagnosed: 1. 4. with bradycardia. Should the fetal heart rate tracing become non-reassuring. Because the presentation is widely variable. History. 2. the gestational age. Foley catheter should be placed and the hourly urine output should be monitored closely. Type and cross-match blood. Similarly. Prompt delivery is indicated if the pregnancy is at or near term. 7. 5. laboratory and ultrasonographic studies guide management. the uterus is contracting vigorously. which may be masked because the patient may be normotensive due to . no evidence of maternal or fetal compromise. and it is important to stabilize the patient and to correct any coagulation derangement during surgery. 3. and urine output. It may be possible to discharge these patients to outpatient management if the fetal status is reassuring once they have remained stable for several days. Patients should be delivered in a center with adequate neonatal facilities and the parents should be counseled by a neonatologist regarding potential treatments and out. or a prior classical cesarean delivery. and occasionally hysterectomy may be necessary. amount of blood loss. clinicians frequently underestimate this.conservatively. Amniotomy is not proven to decrease bleeding from spiral arteries and reduce the entry of thromboplastin into the maternal circulation. it cannot be overemphasized that these patients require extremely close monitoring. it is reasonable. Blood should be drawn for complete blood count and coagulation studies at regular intervals until the patient is stable. . It is prudent to involve an anesthesiologist in the patient’s care early. Preterm birth is the leading cause of perinatal death in women with abruption. regardless of gestational age. some cases of abruption may be associated with severe preeclampsia.rapid delivery typically by cesarean is indicated. Bleeding from surgical incisions in the presence of DIC may be difficult to control. to allow the patient to have a vaginal delivery. In most cases. to prolong gestation. evidence of fetal non-reassuring testing. When labor does not progress rapidly. 2. If the fetus is reasonably mature. often with DIC – vaginal delivery is indicated if patient is stable. Severe abruption (grade 3). fetal demise. Typically. Amniotomy is frequently sufficient to speed up delivery. In cases where the gestational age is between 24 and 34 weeks. because there is a significant risk of fetal death.comes for the neonate. There is no evidence that oxytocin might predispose to DIC by enhancing entry of thromboplastin into the maternal circulation. Meticulous attention should be paid the amount of blood loss. as long as the mother is stable. it is desirable. if possible. There is a significant risk of coagulopathy and hypovolemic shock. the intact sac may facilitate cervical dilatation. fetal malpresentation. steroids should be administered to promote fetal lung maturation. Moderate abruption (grade 2. in the absence of other con. the patient should be monitored closely. and to optimize perinatal outcomes. with particular attention paid to vital signs. and labor rapidly progresses. cesarean delivery may be necessary to avoid worsening of the coagulopathy. In addition. rupture of the membranes may hasten delivery. The uterus may be hypotonic. Intravenous access should be established and blood and coagulation factors should be replaced aggressively. If the fetus is immature. In cases of severe abruption with fetal death. vaginal delivery is indicated.traindications. Oxytocin is given in standard doses to effect vaginal delivery if there has been no previous uterine surgery and there are no rhythmic superimposed contractions noted. Finally. Prolonged hospitalization and monitoring may be necessary. and in cases in which there is feto-pelvic disproportion. and blood loss should be monitored closely. After delivery. However. The mode of delivery is dependent primarily on the condition of the mother and the fetus: 1. for mild abruption (grade I). the uterus should be observed closely to ensure that it remains contracted and is not increasing in size. In such cases. complete blood count and coagulation indices should be checked.hypovolemia. especially sympathomimetics such as terbutaline. In all cases. the patients may benefit from close volume status monitoring. maternal and infant outcomes can be optimized through attention to the risks and benefits of conservative management. The extensive extravasation of blood into the uterine musculature. Thus. It is not an indication for hysterectomy Tocolysis It is generally taught that tocolytics.4 . and intake. blood or blood volume should be replaced. including patients with suspected stable placental abruption before 35 weeks gestation. output. seldom interferes with myometrial contractions to cause atony. in some cases. a few retrospective cohort and case– control studies have evaluated the use of tocolytics (including sympathomimetics) in the presence of bleeding in the second half of pregnancy. coagulopathy should be corrected. and renal function should be monitored. Algorithm for the management of placental abruption in term or near term (A) and preterm births (B). ongoing evaluation of fetal and maternal well-being. there should be a high index of suspicion for severe preeclampsia in patients with abruption not resulting from an obvious cause such as trauma or cocaine use. However. However. early recognition of hypovolemia. and adequate blood replacement. and through expeditious delivery where appropriate. a condition known as Couvelaire’s uterus. Based on these reports tocolytics may be used in caution in stable women remote from term who Most cases of placental abruption cannot be predicted or prevented. are contraindicated in the presence of vaginal bleeding. because side effects such as tachycardia could mask the clinical signs of blood loss. . Ananth CV. Placental abruption. Glantz C. al. Savitz DA. Pupkin MJ. 23rd edition. Kaufmann P. Mack LA. Crenshaw MC Jr. 5. p 193-200. Obstet Gynecol 2006.282: 1646–51. 4th ed. Saller DN Jr. Heppard M.10:125–8. Towers CV. Bernischke K. Obstetric evidence based guidelines by Vincenzo Berghella.108:1005-1016. 6. Shuman WP. et. Cunningham L. p 761-769. Pathology of the human placenta. 2000. JAMA 1999. Wilson DA. Nyberg DA. Placental abruption and adverse perinatal outcomes. Interventions for treating placental abruption.References 1. . 8. Neilson JP. 2. 2007. AJR Am J Roentgenol 1987. Sonographic spectrum of placental abruption. Cochrane Database Syst Rev 2009. 7. 9.180:1572–8. Nagey DA. Lapinski RH. J Perinatol 1990. Purnell L. 10. Clinical utility of sonography in the diagnosis and treatment of placental abruption.21:837–40. Williams Obstetrics. Berkowitz GS. New York (NY): Springer. 3. J Ultrasound Med 2002. Ananth CV.148:161–4. Is tocolysis safe in the management of third-trimester bleeding? Am J Obstet Gynecol 1999. Oyelese Y. 4. Cyr DR. Tocolysis in the management of third trimester bleeding. Pircon RA. 2010. based on clinical experience. There is fair evidence to support the recommendation that the practice be D excluded in the management of hypertensive complications of pregnancy. There is insufficient evidence to recommend for or against the inclusion of C the practice in the management of hypertensive complications of pregnancy. There is fair evidence to support the recommendation of the practice in the B management of hypertensive complications of pregnancy. descriptive III studies and case reports or reports of expert committees. A good practice point (GPP) is a recommendation for best practice based GPP on the experience of the Task Force. There is good evidence to support the recommendation that the practice be E excluded in the management of hypertensive complications of pregnancy. preferably from more than one center or research group Evidence obtained from multiple time series with or without the II-3 intervention. ! GRADE DEFINITION There is good evidence to support the recommendation of the practice in A the management of hypertensive complications of pregnancy. ! ! ! . Opinions of respected authorities. APPENDIX LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION LEVEL DEFINITION I Evidence obtained from at least one properly randomized controlled trial Evidence obtained from well-designed controlled trials without II-1 randomization Evidence obtained from well-designed cohort or case-control analytic II-2 studies.