hypertension in pregnancy guidelines

8/13/2019 Hypertension in Pregnancy guidelines

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INPREGNANCYHYPERTENSION


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Hypertension in Pregnancywas developed by the Task Force on

Hypertension in Pregnancy. The information inHypertension in

Pregnancy should not be viewed as a body of rigid rules. The guidelines

are general and intended to be adapted to many dierent situations,taking into account the needs and resources particular to the locality,the institution, or the type of practice. Variations and innovations thatimprove the quality of patient care are to be encouraged rather than

restricted. The purpose of these guidelines will be well served if they

provide a rm basis on which local norms may be built.

Library of Congress Cataloging-in-Publication Data

American College of Obstetricians and Gynecologists. Task Force on Hypertension in Pregnancy, author. Hypertension in pregnancy / developed by the Task Force on Hypertension in Pregnancy. p. ; cm.

Includes bibliographical references. ISBN 978-1-934984-28-4 I. American College of Obstetricians and Gynecologists, issuing body. II. Title. [DNLM: 1. Hypertension, Pregnancy-InducedPractice Guideline. WQ 244] RG575.5 618.3'6132dc23

2013022521

Copyright 2013 by the American College of Obstetricians and Gynecologists,409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920. All rightsreserved. No part of this publication may be reproduced, stored in a retrievalsystem, or transmitted, in any form or by an means, electronic, mechanical,photocopying, recording, or otherwise, without prior written permission fromthe publisher.

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Contents

Task Force on Hypertension in Pregnancy v

Endorsements vii

Foreword ix

Executive Summary 1

Chapter 1: Classification of Hypertensive Disorders 13

PreeclampsiaEclampsia 13

Chronic Hypertension 14

Chronic Hypertension With Superimposed Preeclampsia 14 Gestational Hypertension 14

Postpartum Hypertension 15

Chapter 2: Establishing the Diagnosis of Preeclampsia and Eclampsia 17

Preeclampsia 17

Eclampsia 19

Chapter 3: Prediction of Preeclampsia 21

Denition of an Ideal Predictive Test 21 Epidemiology of and Risk Factors for Preeclampsia 21

Prediction of Preeclampsia Using Uterine Artery Doppler Velocimetry 22 Prediction of Preeclampsia Using Biomarkers 22 Prediction of Adverse Outcomes in Patients With Gestational Hypertension and

Preeclampsia 23

Clinical Considerations 23

Chapter 4: Prevention of Preeclampsia 27

Antiplatelet Agents 27

Antioxidant Supplementation With Vitamin C and Vitamin E 28 Other Nutritional Interventions 28

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Dietary Salt Intake 29

Lifestyle Modications 29

Chapter 5: Management of Preeclampsia and HELLP Syndrome 31

Antepartum Management 31

Intrapartum Management 34

Severe Preeclampsia 36

Route of Delivery in Preeclampsia 40

Eclampsia 40

HELLP Syndrome 41

Anesthetic Considerations 42

Postpartum Hypertension and Preeclampsia 43

Chapter 6: Management of Women With Prior Preeclampsia 47

Preconception Management 47

Antepartum Management 49

Chapter 7: Chronic Hypertension in Pregnancy and Superimposed Preeclampsia 51 Chronic Hypertension in Pregnancy 51

Superimposed Preeclampsia 61

Management of Women With Chronic Hypertension in the Postpartum Period 65

Chapter 8: Later-Life Cardiovascular Disease in Women With Prior Preeclampsia 71

Chapter 9: Patient Education 73

Importance of Patient Education 73

Patient Education Strategies 74

Patient Education Barriers 75

Chapter 10: State of the Science and Research Recommendations 79

Fundamental Advances in the Understanding of Preeclampsia 79 Summary of Fundamental Research Recommendations by the Task Force 83

iv CONTENTS


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v

Task Force on Hypertension in Pregnancy

James M. Roberts, MD, Chair

Investigator Magee-Womens Research InstituteProfessor, Department of Obstetrics, Gynecology and

Reproductive Sciences, Epidemiology and ClinicalTranslational Research

University of Pittsburgh

Pittsburgh, PA

Phyllis A. August, MD, MPH

Professor of Medicine in Obstetrics and Gynecology

New York PresbyterianWeill Cornell PhysiciansNew York, NY

George Bakris, MD

Professor of Medicine

Director, Comprehensive Hypertension CenterUniversity of Chicago

Chicago, IL

John R. Barton, MD

Director, Maternal-Fetal MedicineBaptist Health LexingtonLexington, KY

Ira M. Bernstein, MD

John VanSicklen Maeck Professor and ChairDepartment of Obstetrics, Gynecology andReproductive Sciences

Senior Associate Dean for Research

University of VermontBurlington, VT

Maurice Druzin, MD

Professor of Obstetrics and Gynecology and

Maternal-Fetal Medicine

Stanford University

Stanford, CA

Robert R. Gaiser, MD

Professor of Anesthesiology and Critical Care

University of Pennsylvania

Philadelphia, PA

Joey P. Granger, PhD

Billy S. Guyton Distinguished Professor

Professor of Physiology and Medicine

Director, Center for Excellence in Cardiovascular-Renal Research

Dean, School of Graduate Studies in Health SciencesUniversity of Mississippi Medical Center

Jackson, MS

Arun Jeyabalan, MD, MS

Associate Professor, Department of Obstetrics,Gynecology and Reproductive Sciences

University of Pittsburgh

Pittsburgh, PA

Donna D. Johnson, MD

Lawrence L. Hester Professor and Chair

Department of Obstetrics and Gynecology

Medical University of South Carolina

Charleston, SC


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vi TASK FORCE ON HYPERTENSION IN PREGNANCY

S. Ananth Karumanchi, MD

Associate Professor of Medicine

Beth Israel Deaconess Medical Center

Harvard Medical School

Boston, MA

Marshall D. Lindheimer, MD

Professor Emeritus, Departments of Obstetrics &Gynecology, Medicine, and Committee on ClinicalPharmacology and Pharmacogenomics

University of Chicago

Chicago, IL

Michelle Y. Owens, MD, MS

Associate Professor

Vice-Chair of Obstetrics and GynecologyUniversity of Mississippi Medical Center

Jackson, MS

George R. Saade, MDProfessor, Department of Obstetrics and GynecologyDirector, Division of Maternal-Fetal MedicineUniversity of Texas Medical BranchGalveston, TX

Baha M. Sibai, MD

Professor, Department of Obstetrics, Gynecology andReproductive Sciences

University of Texas Health Science CenterHouston, TX

Catherine Y. Spong, MD

Director, Extramural ResearchEunice Kennedy Shriver National Institute of Child

Health and Human Development, NationalInstitutes of Health

Bethesda, MD

Eleni Tsigas

Executive DirectorPreeclampsia Foundation

Melbourne, FL

James N. Martin Jr, MD

Ex Ocio Task Force MemberPast President, American College of Obstetricians

and Gynecologists and American Congress of

Obstetricians and Gynecologists (20112012)

Vice Chair, Research and Academic Development

Director, Division of Maternal-Fetal MedicineUniversity of Mississippi Medical CenterJackson, MS

American College of Obstetricians and Gynecologists

Staff

Gerald F. Joseph Jr, MD, Vice President of PracticeActivities

Nancy OReilly, MHSAlyssa Politzer

Sarah Son, MPHKarina Ngaiza

Conflict of Interest Disclosures

The following task force members reported no nancial relationships or potential conicts of interest to disclose:James M. Roberts, MD; Ira M. Bernstein, MD; Maurice Druzin, MD; Robert R. Gaiser, MD; Joey P. Granger, PhD;

Arun Jeyabalan, MD; Donna D. Johnson, MD; Marshall Lindheimer, MD; Michelle Y. Owens, MD, MS;George R. Saade, MD; Catherine Y. Spong, MD; and Eleni Tsigas.

George Bakris, MD, has Investigator Initiated grants from Takeda and CVRx paid directly to the Universityof Chicago. He received a salary for being National Clinical Trial Principal Investigator for Medtronic (15%),Relypsa (15%) (the percentage is salary support.) He is a consultant for Takeda, Abbott, CVRx, Johnson& Johnson, Eli Lilly, Daichi-Sankyo, Boerhinger-Ingelheim, and the U.S. Food and Drug Administration. He is aneditor for the American Journal of Nephrology and the Hypertension section of UpToDate, and an associate editorfor Diabetes Care and Nephrology Dialysis and Transplantation. John R. Barton, MD, provides research supportto Alere and Beckman Coulter. S. Ananth Karumanchi, MD, has served as consultant to Beckman Coulter, Rocheand Siemens; has a nancial interest in Aggamin Therapeutics LLC, Co; and is an inventor on patents related topreeclampsia biomarkers held by Beth Israel Deaconess Medical Center. Baha M. Sibai, MD, is a consultantfor Alere Womens Health who is investigating a biomarker for preeclampsia.


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Endorsements

The following professional organizations have reviewed, endorsed, and support this report:

American Academy of Physician Assistants

American Academy of Neurology*

American College of Occupational and Environmental Medicine

American Optometric Association

American Osteopathic Association

American Society of Hypertension

Preeclampsia Foundation

Society for Maternal-Fetal Medicine

vii

*The American Academy of Neurology has armed the value of this report. Please see the American Academy ofNeurology Guideline Endorsement Policy for further information.


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Foreword

Hypertensive disorders of pregnancy, including pre-eclampsia, complicate up to 10% of pregnancies

worldwide, constituting one of the greatest causes ofmaternal and perinatal morbidity and mortality

worldwide. In early 2011, as the 62nd President Electof the American College of Obstetricians and Gyne-

cologists (the College) and the American Congress of

Obstetricians and Gynecologists, I decided to makethis issue a Presidential Initiative for the following

reasons:

The incidence of preeclampsia has increased by

25% in the United States during the past two

decades (1).

Preeclampsia is a leading cause of maternal and

perinatal morbidity and mortality, with an estimated50,00060,000 preeclampsia-related deaths peryear worldwide (2, 3).

For every preeclampsia-related death that occurs

in the United States, there are probably 50100other women who experience near miss signi-cant maternal morbidity that stops short of death

but still results in signicant health risk and healthcare cost (4,5).

What can be considered less-than-optimal" care ofpatients with preeclampsia and other hypertensive

disorders of pregnancy reportedly occurs with some

frequency worldwide, contributing to maternal andperinatal injury that might have been avoidable (6).

Hypertensive disorders of pregnancy are major

contributors to prematurity.

Preeclampsia is a risk factor for future cardiovascu-

lar disease and metabolic disease in women.

Despite considerable research, the etiology of pre-eclampsia remains unclear.

Within the past 10 years, substantial advances inthe understanding of preeclampsia pathophysiology

as well as increased eorts to obtain evidence toguide therapy have emerged. However, this infor-mation has not translated into improved clinical

practice.

New best practice recommendations are greatly

needed to guide clinicians in the care of women

with all forms of preeclampsia and hypertension

that occur during pregnancy, particularly womenwith acute severe hypertension and superimposed

preeclampsia. Also needed is a system for continu-

ally updating these guidelines and integrating them

into daily obstetric practice.

Identication of patients with severe forms of pre-eclampsia continues to challenge clinicians.

Improved patient education and counseling strate-gies are needed to convey more eectively thedangers of preeclampsia and hypertension and the

importance of early detection to women with vary-

ing degrees of health literacy.

Research on preeclampsia and other hypertensive

disorders of pregnancy in both the laboratory and

clinical arenas requires continued emphasis and

funding.

ix


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x FOREWORD

To address these important issues, the Task Forceon Hypertension in Pregnancy, composed of 17 expertsin the elds of obstetrics, maternalfetal medicine,hypertension, internal medicine, nephrology, anesthe-siology, physiology, and patient advocacy, was createdand charged with three tasks: 1) summarize the cur-

rent state of knowledge about preeclampsia and other

hypertensive disorders in pregnancy by reviewing and

grading the quality of the extant world literature;2) translate this information into practice guidelines

for health care providers who treat obstetric patients

aected by these disorders; and 3) identify and priori-tize the most compelling areas of laboratory and clini-

cal research to bridge gaps in our current knowledge.

Members of the task force met three times over 9

months during 2011 and 2012 at the College head-

quarters in Washington, DC. They spent countless

additional hours writing and deliberating to achieveconsensus on the practice recommendations that fol-

low in the Executive Summary.I am deeply grateful to each member of the Task

Force on Hypertension in Pregnancy for their hard

work and dedication to this important endeavor.

References

1. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in

the rates of preeclampsia, eclampsia, and gestational hyper-tension, United States, 19872004. Am J Hypertens2008;21:5216. [PubMed]^

2. World Health Organization. The world health report:2005: make every mother and child count. Geneva: WHO;2005. Available at: http://www.who.int/whr/2005/whr

2005_en.pdf. Retrieved March 20, 2013.^

3. Duley L. Maternal mortality associated with hypertensive

disorders of pregnancy in Africa, Asia, Latin America andthe Caribbean. Br J Obstet Gynaecol 1992;99:54753.

[PubMed]^

In addition, I would like to give special thanks toDr. James M. Roberts of the University of Pittsburghs

Magee-Womens Research Institute for his superbleadership of the task force and to Nancy OReilly,Senior Director of Practice Bulletins, and Dr. Gerald F.Joseph Jr, Vice President of Practice Activities, at theCollege for their support throughout the process.

Eorts are now underway to achieve global consen-sus on best practice guidelines for the diagnosis and

management of preeclampsia and other hypertensive

disorders of pregnancy. It is my fervent hope that the

work of the Task Force on Hypertension in Pregnancy

serves as a springboard to these eorts and ultimatelytranslates into improved obstetric care for patients

with preeclampsia and other hypertensive disorders of

pregnancy in this country and throughout the world.

James N. Martin Jr, MDImmediate Past President

The American College of Obstetricians and Gynecologists

20122013

The American Congress of Obstetricians and Gynecologists

20122013

4. Callaghan WM, Mackay AP, Berg CJ. Identication of

severe maternal morbidity during delivery hospitaliza-tions, United States, 19912003. Am J Obstet Gynecol2008;199:133.e18. [PubMed][Full Text]^

5. Kuklina EV, Ayala C, Callaghan WM. Hypertensive disor-ders and severe obstetric morbidity in the United States.

Obstet Gynecol 2009;113:1299306.[PubMed][Obstet-rics & Gynecology]^

6. van Dillen J, Mesman JA, Zwart JJ, Bloemenkamp KW,van Roosmalen J. Introducing maternal morbidity audit

in the Netherlands. BJOG2010;117:41621. [PubMed][Full Text]^
http://www.ncbi.nlm.nih.gov/pubmed/18437143http://www.who.int/whr/2005/whr2005_en.pdfhttp://www.who.int/whr/2005/whr2005_en.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/1525093http://www.ncbi.nlm.nih.gov/pubmed/18279820http://www.sciencedirect.com/science/article/pii/S0002937807023320http://www.ncbi.nlm.nih.gov/pubmed/19461426http://journals.lww.com/greenjournal/Fulltext/2009/06000/Hypertensive_Disorders_and_Severe_Obstetric.16.aspxhttp://journals.lww.com/greenjournal/Fulltext/2009/06000/Hypertensive_Disorders_and_Severe_Obstetric.16.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/20105161http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2009.02480.x/fullhttp://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2009.02480.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20105161http://journals.lww.com/greenjournal/Fulltext/2009/06000/Hypertensive_Disorders_and_Severe_Obstetric.16.aspxhttp://journals.lww.com/greenjournal/Fulltext/2009/06000/Hypertensive_Disorders_and_Severe_Obstetric.16.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/19461426http://www.sciencedirect.com/science/article/pii/S0002937807023320http://www.ncbi.nlm.nih.gov/pubmed/18279820http://www.ncbi.nlm.nih.gov/pubmed/1525093http://www.who.int/whr/2005/whr2005_en.pdfhttp://www.who.int/whr/2005/whr2005_en.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/18437143


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Executive Summary

The American College of Obstetricians and

Gynecologists (the College) convened a task

force of experts in the management of hyper-tension in pregnancy to review available data

and publish evidence-based recommendations for clin-

ical practice. The Task Force on Hypertension in Preg-

nancy comprised 17 clinicianscientists from the eldsof obstetrics, maternalfetal medicine, hypertension,internal medicine, nephrology, anesthesiology, physi-ology, and patient advocacy. This executive summaryincludes a synopsis of the content and task force rec-

ommendations of each chapter in the report and is in-

tended to complement, not substitute, the report.Hypertensive disorders of pregnancy remain a

major health issue for women and their infants in the

United States. Preeclampsia, either alone or superim-posed on preexisting (chronic) hypertension, presentsthe major risk. Although appropriate prenatal care,with observation of women for signs of preeclampsia

and then delivery to terminate the disorder, hasreduced the number and extent of poor outcomes,serious maternalfetal morbidity and mortality still

occur. Some of these adverse outcomes are avoidable,whereas others can be ameliorated. Also, althoughsome of the problems that face neonates are related

directly to preeclampsia, a large proportion are sec-ondary to prematurity that results from the appropri-

ate induced delivery of the fetuses of women who are

ill. Optimal management requires close observation

for signs and premonitory ndings and, after establish-ing the diagnosis, delivery at the optimal time for bothmaternal and fetal well-being. More recent clinical evi-

dence to guide this timing is now available. Chronic

hypertension is associated with fetal morbidity in the

form of growth restriction and maternal morbidity

manifested as severely increased blood pressure (BP).

However, maternal and fetal morbidity increase dra-matically with the superimposition of preeclampsia.

One of the major challenges in the care of women with

chronic hypertension is deciphering whether chronic

hypertension has worsened or whether preeclampsia

has developed. In this report, the task force providessuggestions for the recognition and management of

this challenging condition.

In the past 10 years, there have been substantialadvances in the understanding of preeclampsia as well

as increased eorts to obtain evidence to guide therapy.Nonetheless, there remain areas on which evidence isscant. The evidence is now clear that preeclampsia is

associated with later-life cardiovascular (CV) disease;however, further research is needed to determine howbest to use this information to help patients. The task

force also has identied issues in the management ofpreeclampsia that warrant special attention. First, isthe failure by health care providers to appreciate the

multisystemic nature of preeclampsia. This is in part

1


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2 EXECUTIVE SUMMARY

due to attempts at rigid diagnosis, which is addressedin the report. Second, preeclampsia is a dynamic pro-cess, and a diagnosis such as mild preeclampsia(which is discouraged) applies only at the moment the

diagnosis is established because preeclampsia by

nature is progressive, although at dierent rates.Appropriate management mandates frequent reevalu-

ation for severe features that indicate the actions out-

lined in the recommendations (which are listed after

the chapter summaries). It has been known for many

years that preeclampsia can worsen or present for the

rst time after delivery, which can be a major scenariofor adverse maternal events. In this report, the taskforce provides guidelines to attempt to reduce mater-

nal morbidity and mortality in the postpartum period.

The Approach

The task force used the evidence assessment and rec-

ommendation strategy developed by the Grading of

Recommendations Assessment, Development andEvaluation (GRADE) Working Group (available at www.gradeworkinggroup.org/index.htm). Because of itsutility, this strategy has been adapted worldwide by alarge number of organizations. With the GRADE Work-ing Group approach, the function of expert task forcesand working groups is to evaluate the available evi-

dence regarding a clinical decision that, because of lim-ited time and resources, would be dicult for theaverage health care provider to accomplish. The expert

group then makes recommendations based on the evi-dence that are consistent with typical patient values

and preferences. The task force evaluated the evidence

for each recommendation, the implications, and thecondence in estimates of eect. With this combination,the available information was evaluated and recom-

mendations were made. In this report, the condencein estimates of eect (quality) of the available evidenceis judged as very low, low, moderate, or high.

Recommendations are practices agreed to by the

task force as the most appropriate course of action;

they are graded as strong or qualied. A strong recom-mendation is one that is so well supported that it

would be the approach appropriate for virtually all

patients. It could be the basis for health care policy. A

qualied recommendation is also one that would bejudged as appropriate for most patients, but it mightnot be the optimal recommendation for some patients

(whose values and preferences dier, or who have dif-ferent attitudes toward uncertainty in estimates of

eect). When the task force has made a qualied rec-ommendation, the health care provider and patientare encouraged to work together to arrive at a decision

based on the values and judgment and underlying

health condition of a particular patient in a particular

situation.

Classification of Hypertensive Disordersof Pregnancy

The task force chose to continue using the classicationschema rst introduced in 1972 by the College andmodied in the 1990 and 2000 reports of the WorkingGroup of the National High Blood Pressure Education

Program. Similar classications can be found in theAmerican Society of Hypertension guidelines, as wellas College Practice Bulletins. Although the task force

has modied some of the components of the classica-tion, this basic, precise, and practical classication wasused, which considers hypertension during pregnancy

in only four categories: 1) preeclampsiaeclampsia,2) chronic hypertension (of any cause), 3) chronichypertension with superimposed preeclampsia, and4) gestational hypertension. Importantly, the follow-ing components were modied. In recognition of thesyndromic nature of preeclampsia, the task force haseliminated the dependence of the diagnosis on pro-

teinuria. In the absence of proteinuria, preeclampsia isdiagnosed as hypertension in association with throm-

bocytopenia (platelet count less than 100,000/microli-ter), impaired liver function (elevated blood levels ofliver transaminases to twice the normal concentra-

tion), the new development of renal insuciency (ele-

vated serum creatinine greater than 1.1 mg/dL or adoubling of serum creatinine in the absence of other

renal disease), pulmonary edema, or new-onset cere-bral or visual disturbances (see Box E-1). Gestationalhypertension is BP elevation after 20 weeks of gesta-

tion in the absence of proteinuria or the aforemen-

tioned systemic ndings, chronic hypertension ishypertension that predates pregnancy, and superim-

posed preeclampsiais chronic hypertension in associa-

tion with preeclampsia.

Establishing the Diagnosis of

Preeclampsia or EclampsiaThe BP criteria are maintained from prior recommenda-

tions.Proteinuriais dened as the excretion of 300 mgor more of protein in a 24-hour urine collection. Alter-

natively, a timed excretion that is extrapolated to this24-hour urine value or a protein/creatinine ratio of at

least 0.3 (each measured as mg/dL) is used. Because of

the variability of qualitative determinations (dipstick

test), this method is discouraged for diagnostic useunless other approaches are not readily available. If


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EXECUTIVE SUMMARY 3

this approach must be used, a determination of 1+ isconsidered as the cuto for the diagnosis of protein-uria. In view of recent studies that indicate a minimal

relationship between the quantity of urinary protein

and pregnancy outcome in preeclampsia, massive pro-teinuria (greater than 5 g) has been eliminated from

the consideration of preeclampsia as severe. Also,because fetal growth restriction is managed similarly

in pregnant women with and without preeclampsia, ithas been removed as a nding indicative of severe pre-

eclampsia (Table E-1).

Prediction of Preeclampsia

A great deal of eort has been directed at the identi-cation of demographic factors, biochemical analytes,or biophysical ndings, alone or in combination, topredict early in pregnancy the later development of

preeclampsia. Although there are some encouraging

ndings, these tests are not yet ready for clinical use.

TASK FORCE RECOMMENDATION

Screening to predict preeclampsia beyond obtain-ing an appropriate medical history to evaluate for

risk factors is not recommended.

Quality of evidence: Moderate

Strength of recommendation: Strong

Prevention of Preeclampsia

It is clear that the antioxidants vitamin C and vitamin Eare not eective interventions to prevent preeclampsia

or adverse outcomes from preeclampsia in unselected

women at high risk or low risk of preeclampsia. Calci-

um may be useful to reduce the severity of preeclamp-

sia in populations with low calcium intake, but thisnding is not relevant to a population with adequatecalcium intake, such as in the United States. Theadministration of low-dose aspirin (6080 mg) to pre-

vent preeclampsia has been examined in meta-analy-ses of more than 30,000 women, and it appears thatthere is a slight eect to reduce preeclampsia and

adverse perinatal outcomes. These ndings are notclinically relevant to low-risk women but may be rele-vant to populations at very high risk in whom the num-

ber to treat to achieve the desired outcome will be

substantially less. There is no evidence that bed rest or

salt restriction reduces preeclampsia risk.

TASK FORCE RECOMMENDATIONS

For women with a medical history of early-onset pre-

eclampsia and preterm delivery at less than 34 0/7

weeks of gestation or preeclampsia in more than

one prior pregnancy, initiating the administration ofdaily low-dose (6080 mg) aspirin beginning in the

late rst trimester is suggested.*

Quality of evidence: Moderate

Strength of recommendation: Qualied

*Meta-analysis of more than 30,000 women in randomizedtrials of aspirin to prevent preeclampsia indicates a smallreduction in the incidence and morbidity of preeclampsiaand reveals no evidence of acute risk, although long-termfetal eects cannot be excluded. The number of women totreat to have a therapeutic eect is determined by preva -lence. In view of maternal safety, a discussion of the use ofaspirin in light of individual risk is justied.

BOX E-1. Severe Features of Preeclampsia(Any of these findings) ^

Systolic blood pressure of 160 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher

on two occasions at least 4 hours apart while the patient is on bed rest (unless antihypertensivetherapy is initiated before this time)

Thrombocytopenia (platelet count less than 100,000/microliter)

Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes(to twice normal concentration), severe persistent right upper quadrant or epigastric pain unrespon-sive to medication and not accounted for by alternative diagnoses, or both

Progressive renal insufficiency (serum creatinine concentration greater than 1.1 mg/dL or a doublingof the serum creatinine concentration in the absence of other renal disease)

Pulmonary edema

New-onset cerebral or visual disturbances


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The close monitoring of women with gestational

hypertension or preeclampsia without severe fea-

tures, with serial assessment of maternal symptomsand fetal movement (daily by the woman), serialmeasurements of BP (twice weekly), and assess-ment of platelet counts and liver enzymes (weekly)

is suggested.

Quality of evidence:Moderate

Strength of recommendation:Qualied

For women with gestational hypertension, monitor-ing BP at least once weekly with proteinuria assess-

ment in the oce and with an additional weeklymeasurement of BP at home or in the oce is sug-gested.

Quality of evidence:ModerateStrength of recommendation:Qualied

For women with mild gestational hypertension or

preeclampsia with a persistent BP of less than

160 mm Hg systolic or 110 mm Hg diastolic, it issuggested that antihypertensive medications not be

administered.



For women with gestational hypertension or pre-

eclampsia without severe features, it is suggested

that strict bed rest not be prescribed.*

Quality of evidence:Low


* The task force acknowledged that there may be situations

in which dierent levels of rest, either at home or in thehospital, may be indicated for individual women. Theprevious recommendations do not cover advice regard-

ing overall physical activity and manual or oce work.

Women may need to be hospitalized for reasons otherthan bed rest, such as for maternal and fetal surveillance.The task force agreed that hospitalization for maternal

and fetal surveillance is resource intensive and should be

considered as a priority for research and future recom-

mendations.

For women with preeclampsia without severe fea-

tures, use of ultrasonography to assess fetal growthand antenatal testing to assess fetal status is sug-

gested.



If evidence of fetal growth restriction is found in

women with preeclampsia, fetoplacental assess-ment that includes umbilical artery Doppler veloci-

metry as an adjunct antenatal test is recommended.

Quality of evidence:ModerateStrength of recommendation:Strong


preeclampsia without severe features and no indi-

cation for delivery at less than 37 0/7 weeks of ges-

tation, expectant management with maternal andfetal monitoring is suggested.




preeclampsia without severe features at or beyond

37 0/7 weeks of gestation, delivery rather than con-tinued observation is suggested.



For women with preeclampsia with systolic BP of

less than 160 mm Hg and a diastolic BP less than

110 mm Hg and no maternal symptoms, it is sug-gested that magnesium sulfate not be administered

universally for the prevention of eclampsia.



For women with severe preeclampsia at or beyond

34 0/7 weeks of gestation, and in those with un-stable maternal or fetal conditions irrespective of

gestational age, delivery soon after maternal stabili-zation is recommended.


Strength of recommendation:Strong

For women with severe preeclampsia at less than

34 0/7 weeks of gestation with stable maternal and

fetal conditions, it is recommended that continuedpregnancy be undertaken only at facilities with

adequate maternal and neonatal intensive care

resources.



For women with severe preeclampsia receiving

expectant management at 34 0/7 weeks or less ofgestation, the administration of corticosteroids forfetal lung maturity benet is recommended.

Quality of evidence:High


EXECUTIVE SUMMARY 5


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For women with preeclampsia with severe hyper-

tension during pregnancy (sustained systolic BP

of at least 160 mm Hg or diastolic BP of at least

110 mm Hg), the use of antihypertensive therapyis recommended.



For women with preeclampsia, it is suggested that adelivery decision should not be based on the

amount of proteinuria or change in the amount of

proteinuria.



For women with severe preeclampsia and before

fetal viability, delivery after maternal stabilization isrecommended. Expectant management is not rec-ommended.



It is suggested that corticosteroids be administered

and delivery deferred for 48 hours if maternal and

fetal conditions remain stable for women with

severe preeclampsia and a viable fetus at 33 6/7

weeks or less of gestation with any of the following:

preterm premature rupture of membranes

labor

low platelet count (less than 100,000/microliter)

persistently abnormal hepatic enzyme concentra-tions (twice or more the upper normal values)

fetal growth restriction (less than the fth per-centile)

severe oligohydramnios (amniotic uid indexless than 5 cm)

reversed end-diastolic ow on umbilical arteryDoppler studies

new-onset renal dysfunction or increasing renal

dysfunction



It is recommended that corticosteroids be given if

the fetus is viable and at 33 6/7 weeks or less of

gestation, but that delivery not be delayed after ini-tial maternal stabilization regardless of gestational

age for women with severe preeclampsia that is

complicated further with any of the following:

uncontrollable severe hypertension

eclampsia

pulmonary edema

abruptio placentae

disseminated intravascular coagulation

evidence of nonreassuring fetal status

intrapartum fetal demise



For women with preeclampsia, it is suggested that

the mode of delivery need not be cesarean delivery.The mode of delivery should be determined by fetal

gestational age, fetal presentation, cervical status,and maternal and fetal conditions.



For women with eclampsia, the administration ofparenteral magnesium sulfate is recommended.



For women with severe preeclampsia, the adminis-

tration of intrapartumpostpartum magnesium sul-fate to prevent eclampsia is recommended.



For women with preeclampsia undergoing cesarean

delivery, the continued intraoperative administra-tion of parenteral magnesium sulfate to prevent

eclampsia is recommended.



For women with HELLP syndrome and before the

gestational age of fetal viability, it is recommendedthat delivery be undertaken shortly after initial

maternal stabilization.



6 EXECUTIVE SUMMARY


17/99

For women with HELLP syndrome at 34 0/7 weeks

or more of gestation, it is recommended that deliv-ery be undertaken soon after initial maternal stabi-

lization.


For women with HELLP syndrome from the gesta-

tional age of fetal viability to 33 6/7 weeks of gesta-

tion, it is suggested that delivery be delayed for24 48 hours if maternal and fetal condition re-

mains stable to complete a course of corticosteroids

for fetal benet.*



*Corticosteroids have been used in randomized controlled

trials to attempt to improve maternal and fetal condition.

In these studies, there was no evidence of benet toimprove overall maternal and fetal outcome (although

this has been suggested in observational studies). There is

evidence in the randomized trials of improvement of

platelet counts with corticosteroid treatment. In clinical

settings in which an improvement in platelet count is con-

sidered useful, corticosteroids may be justied.

For women with preeclampsia who require analge-

sia for labor or anesthesia for cesarean delivery and

with a clinical situation that permits sucient timefor establishment of anesthesia, the administrationof neuraxial anesthesia (either spinal or epiduralanesthesia) is recommended.


For women with severe preeclampsia, it is suggestedthat invasive hemodynamic monitoring not be used

routinely.



For women in whom gestational hypertension, pre-eclampsia, or superimposed preeclampsia is diag-nosed, it is suggested that BP be monitored in thehospital or that equivalent outpatient surveillance

be performed for at least 72 hours postpartum and

again 710 days after delivery or earlier in women

with symptoms.



For all women in the postpartum period (not just

women with preeclampsia), it is suggested that dis-charge instructions include information about the

signs and symptoms of preeclampsia as well as the

importance of prompt reporting of this information

to their health care providers.



For women in the postpartum period who present

with new-onset hypertension associated with head-

aches or blurred vision or preeclampsia with severe

hypertension, the parenteral administration of mag-nesium sulfate is suggested.



For women with persistent postpartum hyperten-

sion, BP of 150 mm Hg systolic or 100 mm Hg dia-stolic or higher, on at least two occasions that are atleast 46 hours apart, antihypertensive therapy issuggested. Persistent BP of 160 mm Hg systolic or

110 mm Hg diastolic or higher should be treated

within 1 hour.



Management of Women With

Prior Preeclampsia

Women who have had preeclampsia in a prior preg-nancy should receive counseling and assessments

before their next pregnancy. This can be initiated at thepostpartum visit but is ideally accomplished at a pre-

conception visit before the next planned pregnancy.During the preconception visit, the previous pregnancyhistory should be reviewed and the prognosis for the

upcoming pregnancy should be discussed. Potentially

modiable lifestyle activities, such as weight loss andincreased physical activity, should be encouraged. Thecurrent status of medical problems should be assessed,including laboratory evaluation if appropriate. Medical

problems such as hypertension and diabetes should be

brought into the best control possible. The eect ofmedical problems on the pregnancy should be dis-

cussed. Medications should be reviewed and their

administration modied for upcoming pregnancy. Folicacid supplementation should be recommended. If a

woman has given birth to a preterm infant during a

preeclamptic pregnancy or has had preeclampsia in

more than one pregnancy, the use of low-dose aspirinin the upcoming pregnancy should be suggested.

EXECUTIVE SUMMARY 7


18/99

Women with a medical history of preeclampsia shouldbe instructed to return for care early in pregnancy.

During the next pregnancy, early ultrasonographyshould be performed to determine gestational age, andassessment and visits should be tailored to the prior

pregnancy outcome, with frequent visits beginningearlier in women with prior preterm preeclampsia. The

woman should be educated about the signs and symp-

toms of preeclampsia and instructed when and how to

contact her health care provider.


For women with preeclampsia in a prior pregnancy,preconception counseling and assessment is sug-

gested.


Strength of recommendation: Qualied

Chronic Hypertension and

Superimposed Preeclampsia

Chronic hypertension (hypertension predating preg-

nancy), presents special challenges to health care pro-viders. Health care providers must rst conrm thatthe BP elevation is not preeclampsia. Once this is estab-

lished, if the BP elevation has not been previously eval-uated, a workup should be performed to documentthat BP is truly elevated (ie, not white coat hyperten-sion) and to check for secondary hypertension and

end-organ damage. The choice of which women totreat and how to treat them requires special consider-

ations during pregnancy, especially in light of emerg-ing data that suggest lowering BP excessively mighthave adverse fetal eects.

Perhaps the greatest challenge is the recognition of

preeclampsia superimposed on chronic hypertension, acondition that is commonly associated with adverse

maternal and fetal outcomes. Recommendations are

provided to guide health care providers in distinguish-

ing women who may have superimposed preeclampsia

without severe features (only hypertension and protein-

uria) and require only observation from women who

may have superimposed preeclampsia with severe fea-

tures (evidence of systemic involvement beyond hyper-

tension and proteinuria) and require intervention.


For women with features suggestive of secondary

hypertension, referral to a physician with expertisein treating hypertension to direct the workup is sug-

gested.



For pregnant women with chronic hypertension

and poorly controlled BP, the use of home BP moni-toring is suggested.



For women with suspected white coat hypertension,the use of ambulatory BP monitoring to conrm thediagnosis before the initiation of antihypertensive

therapy is suggested.



It is suggested that weight loss and extremely low-sodium diets (less than 100 mEq/d) not be used for

managing chronic hypertension in pregnancy.



For women with chronic hypertension who are

accustomed to exercising, and in whom BP is wellcontrolled, it is recommended that moderate exer-cise be continued during pregnancy.



For pregnant women with persistent chronic hyper-

tension with systolic BP of 160 mm Hg or higher or

diastolic BP of 105 mm Hg or higher, antihyperten-sive therapy is recommended.




and BP less than 160 mm Hg systolic or 105 mm Hg

diastolic and no evidence of end-organ damage, it issuggested that they not be treated with pharmaco-

logic antihypertensive therapy.



8 EXECUTIVE SUMMARY


19/99


treated with antihypertensive medication, it issuggested that BP levels be maintained between

120 mm Hg systolic and 80 mm Hg diastolic and

160 mm Hg systolic and 105 mm Hg diastolic.



For the initial treatment of pregnant women with

chronic hypertension who require pharmacologic

therapy, labetalol, nifedipine, or methyldopa arerecommended above all other antihypertensive

drugs.



For women with uncomplicated chronic hyperten-

sion in pregnancy, the use of angiotensin-converting

enzyme inhibitors, angiotensin receptor blockers,renin inhibitors, and mineralocorticoid receptorantagonists is not recommended.



For women of reproductive age with chronic hyper-

tension, the use of angiotensin-converting enzymeinhibitors, angiotensin receptor blockers, renininhibitors, and mineralocorticoid receptor antago-nists is not recommended unless there is a compel-

ling reason, such as the presence of proteinuricrenal disease.



For women with chronic hypertension who are at

a greatly increased risk of adverse pregnancy out-

comes (history of early-onset preeclampsia and

preterm delivery at less than 34 0/7 weeks of

gestation or preeclampsia in more than one prior

pregnancy), initiating the administration of dailylow-dose aspirin (6080 mg) beginning in the late

rst trimester is suggested.*


Strength of recommendation:Qualied* Meta-analysis of more than 30,000 women in randomizedtrials of aspirin to prevent preeclampsia indicates a small

reduction in the incidence and morbidity of preeclampsia

and reveals no evidence of acute risk, although long-termfetal eects cannot be excluded. The number of women totreat to have a therapeutic eect is determined by preva -lence. In view of maternal safety, a discussion of the useof aspirin in light of individual risk is justied.

For women with chronic hypertension, the use ofultrasonography to screen for fetal growth restric-

tion is suggested.


Strength of recommendation:Qualied If evidence of fetal growth restriction is found in

women with chronic hypertension, fetoplacental as-sessment to include umbilical artery Doppler veloci-

metry as an adjunct antenatal test is recommended.



For women with chronic hypertension complicated

by issues such as the need for medication, otherunderlying medical conditions that aect fetaloutcome, or any evidence of fetal growth restric-tion, and superimposed preeclampsia, antenatalfetal testing is suggested.



For women with chronic hypertension and no addi-

tional maternal or fetal complications, delivery be-fore 38 0/7 weeks of gestation is not recommended.



For women with superimposed preeclampsia who

receive expectant management at less than 34 0/7weeks of gestation, the administration of cortico-

steroids for fetal lung maturity benet is recom-mended.



For women with chronic hypertension and superim-

posed preeclampsia with severe features, the admin-istration of intrapartumpostpartum parenteral

magnesium sulfate to prevent eclampsia is recom-

mended.



For women with superimposed preeclampsia with-

out severe features and stable maternal and fetal

conditions, expectant management until 37 0/7weeks of gestation is suggested.



EXECUTIVE SUMMARY 9


20/99

Delivery soon after maternal stabilization is recom-

mended irrespective of gestational age or full corti-

costeroid benet for women with superimposedpreeclampsia that is complicated further by any of

the following:

uncontrollable severe hypertension

eclampsia

pulmonary edema

abruptio placentae

disseminated intravascular coagulation

nonreassuring fetal status


Strength of the recommendation: Strong

For women with superimposed preeclampsia with

severe features at less than 34 0/7 weeks of gesta-

tion with stable maternal and fetal conditions, it is

recommended that continued pregnancy should beundertaken only at facilities with adequate mater-

nal and neonatal intensive care resources.


Strength of evidence:Strong

For women with superimposed preeclampsia with

severe features, expectant management beyond34 0/7 weeks of gestation is not recommended.


Strength of the recommendation:Strong

Later-Life Cardiovascular Disease in

Women With Prior Preeclampsia

Over the past 10 years, information has accumulatedindicating that a woman who has had a preeclamptic

pregnancy is at an increased risk of later-life CV disease.This increase ranges from a doubling of risk in all cas-

es to an eightfold to ninefold increase in women with

preeclampsia who gave birth before 34 0/7 weeks of

gestation. This has been recognized by the American

Heart Association, which now recommends that apregnancy history be part of the evaluation of CV riskin women. It is the general belief that preeclampsia

does not cause CV disease, but rather preeclampsia

and CV disease share common risk factors. Awarenessthat a woman has had a preeclamptic pregnancy

might allow for the identication of women not previ-ously recognized as at-risk for earlier assessment and

potential intervention. However, it is unknown if thiswill be a valuable adjunct to previous information. If

this is the case, would the current recommendation ofassessing risk factors for women by medical history,lifestyle evaluation, testing for metabolic abnormali-ties, and possibly inammatory activation at age 40

years provide all of the information that would be

gained by knowing a woman had a past preeclamptic

pregnancy? Would it be valuable to perform thisassessment at a younger age in women who had a

past preeclamptic pregnancy? If the risk was identi-

ed earlier, what intervention (other than lifestylemodication) would potentially be useful and wouldit make a dierence? Are there risk factors that couldbe unmasked by pregnancy other than conventional

risk factors? Further research is needed to determine

how to take advantage of this information relating

preeclampsia to later-life CV disease. At this time, thetask force cautiously recommends lifestyle modica-tion (maintenance of a healthy weight, increasedphysical activity, and not smoking) and suggests earlyevaluation for the most high-risk women.


For women with a medical history of preeclampsia

who gave birth preterm (less than 37 0/7 weeks of

gestation) or who have a medical history of recur-

rent preeclampsia, yearly assessment of BP, lipids,fasting blood glucose, and body mass index is sug-gested.*



*Although there is clear evidence of an association be-

tween preeclampsia and later-life CV disease, the valueand appropriate timing of assessment is not yet estab-

lished. Health care providers and patients should make

this decision based on their judgment of the relative value

of extra information versus expense and inconvenience.

Patient Education

Patient and health care provider education is key to

the successful recognition and management of pre-

eclampsia. Health care providers need to inform

women during the prenatal and postpartum periods

of the signs and symptoms of preeclampsia and stress

the importance of contacting health care providers if

these are evident. The recognition of the importance

of patient education must be complemented by the

recognition and use of strategies that facilitate the

successful transfer of this information to women with

varying degrees of health literacy. Recommended

strategies to facilitate this process include using plain

nonmedical language, taking time to speak slowly,reinforcing key issues in print using pictorially based

information, and requesting feedback to indicate thatthe patient understands, and, where applicable, herpartner.

10 EXECUTIVE SUMMARY


21/99


It is suggested that health care providers convey

information about preeclampsia in the context ofprenatal care and postpartum care using proven

health communication practices.

Quality of evidence: Low


The State of the Science and

Research Recommendations

In the past 10 years, striking increases in the under-standing of the pathophysiology of preeclampsia have

occurred. Clinical research advances also have em-

erged that have provided evidence to guide therapy. It

is now understood that preeclampsia is a multisystem-

ic disease that aects all organ systems and is far morethan high BP and renal dysfunction. The placenta isevident as the root cause of preeclampsia. It is with the

delivery of the placenta that preeclampsia begins to

resolve. The insult to the placenta is proposed as an

immunologically initiated alteration in trophoblast

function, and the reduction in trophoblast invasionleads to failed vascular remodeling of the maternal

spiral arteries that perfuse the placenta. The resulting

reduced perfusion and increased velocity of blood

perfusing the intervillous space alter placental func-

tion. The altered placental function leads to mater-

nal disease through putative primary mediators,

including oxidative and endoplasmic reticulum stress

and inammation, and secondary mediators thatinclude modiers of endothelial function and angio-genesis. This understanding of preeclampsia patho-

physiology has not translated into predictors or

preventers of preeclampsia or to improved clinical

care. This has led to a reassessment of this conceptual

framework, with attention to the possibility that pre-eclampsia is not one disease but that the syndrome

may include subsets of pathophysiology.

Clinical research advances have shown approaches

to therapy that work (eg, delivery for women with ges-tational hypertension and preeclampsia without

severe features at 37 0/7 weeks of gestation) or do not

work (vitamin C and vitamin E to prevent preeclamp-

sia). However, there are few clinical recommendationsthat can be classied as strong because there arehuge gaps in the evidence base that guides therapy.

These knowledge gaps form the basis for research rec-ommendations to guide future therapy.

Conclusion

The task force provides evidence-based recommenda-

tions for the management of patients with hyperten-

sion during and after pregnancy. Recommendations

are graded as strong or qualied based on evidence ofeectiveness weighed against evidence of potentialharm. In all instances, the nal decision is made by thehealth care provider and patient after consideration of

the strength of the recommendations in relation to the

values and judgments of the individual patient.

EXECUTIVE SUMMARY 11


22/99


23/99


24/99

14 CLASSIFICATION OF HYPERTENSIVE DISORDERS

liver function (elevated blood levels of liver transami-

nases to twice the normal concentration), the newdevelopment of renal insuciency (elevated serumcreatinine greater than 1.1 mg/dL or a doubling of

serum creatinine in the absence of other renal dis-

ease), pulmonary edema, or new-onset cerebral orvisual disturbances.

Hypertensionis dened as either a systolic BP of140 mm Hg or greater, a diastolic BP of 90 mm Hgor greater, or both. Hypertension is consideredmild until diastolic or systolic levels reach or exceed110 mm Hg and 160 mm Hg, respectively. It is recom-mended that a diagnosis of hypertension require at

least two determinations at least 4 hours apart,although on occasion, especially when faced withsevere hypertension, the diagnosis can be conrmedwithin a shorter interval (even minutes) to facilitate

timely antihypertensive therapy.Proteinuria is diagnosed when 24-hour excretionequals or exceeds 300 mg in 24 hours or the ratio ofmeasured protein to creatinine in a single voided urine

measures or exceeds 3.0 (each measured as mg/dL),termed the protein/creatinine ratio. As discussed in

Chapter 2 Establishing the Diagnosis of Preeclampsiaand Eclampsia, qualitative dipstick readings of 1+suggest proteinuria but have many false-positive and

false-negative results and should be reserved for use

when quantitative methods are not available or rapid

decisions are required.

Eclampsia is the convulsive phase of the disorder

and is among the more severe manifestations of thedisease. It is often preceded by premonitory events,such as severe headaches and hyperreexia, but it canoccur in the absence of warning signs or symptoms.

Specic biochemical markers have been linked toincreased morbidity in hypertensive complications of

pregnancy (eg, hyperuricemia), but these should notbe used for diagnosis. Although some label preeclamp-

sia as less severe or more severe, or mild andsevere, these are not specic classications, and theconsideration of preeclampsia as mild should beavoided. The task force recommends that the term

mild preeclampsia be replaced by preeclampsia

without severe features. These points are more exten-sively discussed in Chapter 2 Establishing the Diagno-sis of Preeclampsia and Eclampsia.

Chronic Hypertension

During pregnancy, chronic hypertension is dened ashigh BP known to predate conception or detected

before 20 weeks of gestation. Previously, some sug-gested that when high BP is rst diagnosed in the rst

half of pregnancy and normalizes postpartum, thediagnosis should be changed to transient hyperten-sion of pregnancy. However, because dischargerecords are rarely modied, the task force recom-mends against instituting this latter terminology.

Chronic Hypertension With

Superimposed Preeclampsia

Preeclampsia may complicate all other hypertensive

disorders, and in fact the incidence is four to ve timesthat in nonhypertensive pregnant women (4). In such

cases, prognosis for the woman and her fetus is worsethan either condition alone. Although evidence from

renal biopsy studies suggests that the diagnosis of

superimposed preeclampsia may be often erroneous

(5), the diagnosis is more likely in the following seven

scenarios: women with hypertension only in early ges-tation who develop proteinuria after 20 weeks of ges-

tation and women with proteinuria before 20 weeks of

gestation who 1) experience a sudden exacerbation ofhypertension, or a need to escalate the antihypertensivedrug dose especially when previously well controlled

with these medications; 2) suddenly manifest other

signs and symptoms, such as an increase in liver enzymesto abnormal levels; 3) present with a decrement in

their platelet levels to below 100,000/microliter;4) manifest symptoms such as right upper quadrant

pain and severe headaches; 5) develop pulmonary

congestion or edema; 6) develop renal insuciency

(creatinine level doubling or increasing to or above 1.1mg/dL in women without other renal disease); and 7)

have sudden, substantial, and sustained increases inprotein excretion.

If the only manifestation is elevation in BP to levels

less than 160 mm Hg systolic and 110 mm Hg diastolic

and proteinuria, this is considered to be superim-posed preeclampsia without severe features. The

presence of organ dysfunction is considered to be

superimposed preeclampsia with severe features. For

classication purposes, both variants are termedsuperimposed preeclampsia, but management isguided by the subcategory (analogous to preeclamp-

sia with severe features and preeclampsia withoutsevere features).

Gestational Hypertension

Gestational hypertension is characterized most often by

new-onset elevations of BP after 20 weeks of gestation,often near term, in the absence of accompanying pro-teinuria. The failure of BP to normalize postpartum

requires changing the diagnosis to chronic hypertension.


25/99

CLASSIFICATION OF HYPERTENSIVE DISORDERS 15

Outcomes in women with gestational hypertension

usually are quite successful, although some of thesewomen experience BP elevations to the severe levelwith outcomes similar to women with preeclampsia

(6). The cause of this entity is unclear, but many ofthese women have preeclampsia before proteinuria

and other organ manifestations have occurred. Thus,gestational hypertension, even when BP elevations aremild, requires enhanced surveillance.

Gestational hypertension, although transient innature, may also be a sign of future chronic hyperten-sion. Thus, even when benign, it is an importantmarker regarding follow-up and preventive medicine

decisions (7).

Postpartum Hypertension

It is important to remember that preeclampsiaincluding preeclampsia with severe systemic organinvolvement and seizurescan rst develop in thepostpartum period. Because early hospital discharge is

the current practice in the United States, this man-dates instruction of women at discharge from the hos-

pital to be aware of symptoms (eg, severe headache,visual disturbances, or epigastric pain) that should bereported to a health care provider.

Although not recommended in this classicationschema, the task force calls attention to a phenome-non once labeled late postpartum hypertension, adisorder that was more frequently diagnosed when

women in the postpartum period routinely remainedhospitalized for as long as 2 weeks. It was dened aswomen with normotensive gestations who develop

hypertension (usually mild) in a period that ranges

from 2 weeks to 6 months postpartum. Blood pressure

remains labile for months postpartum, usually normal-izing by the end of the rst year. Little is known of thisentity, and, like gestational hypertension, it may be apredictor of future chronic hypertension.

References

1. Report of the National High Blood Pressure Education

Program Working Group on High Blood Pressure in Preg-nancy. Am J Obstet Gynecol 2000;183:S1S22.

[PubMed][Full Text]^

2. Lindheimer MD, Taler SJ, Cunningham FG. Hyperten-sion in pregnancy. J Am Soc Hypertens 2010;4:6878.

[PubMed]^

3. Diagnosis and management of preeclampsia and eclamp-

sia. ACOG Practice Bulletin No. 33. American College of

Obstetricians and Gynecologists. Obstet Gynecol 2002;99:15967. [PubMed][Obstetrics & Gynecology]^

4. Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebano M,Thom E, et al. Low-dose aspirin to prevent preeclampsiain women at high risk. National Institute of Child Health

and Human Development Network of Maternal-Fetal-

Medicine Units. N Engl J Med 1998;338:7015.


5. Fisher KA, Luger A, Spargo BH, Lindheimer MD. Hyper-tension in pregnancy: clinical-pathological correlations

and remote prognosis. Medicine (Baltimore) 1981;60:

26776.^

6. Buchbinder A, Sibai BM, Caritis S, Macpherson C, Hauth J,Lindheimer MD, et al. Adverse perinatal outcomes aresignicantly higher in severe gestational hypertension

than in mild preeclampsia. National Institute of ChildHealth and Human Development Network of Maternal-

Fetal Medicine Units. Am J Obstet Gynecol 2002;186:

6671. [PubMed][Full Text]^

7. Williams D. Long-term complications of preeclampsia.Semin Nephrol 2011;31:11122. [PubMed]^
http://www.ncbi.nlm.nih.gov/pubmed/10920346http://www.sciencedirect.com/science/article/pii/S0002937800408203http://www.ncbi.nlm.nih.gov/pubmed/20400051http://www.ncbi.nlm.nih.gov/pubmed/16175681http://journals.lww.com/greenjournal/Fulltext/2002/01000/ACOG_Practice_Bulletin_No__33__Diagnosis_and.28.aspxhttp://journals.lww.com/greenjournal/Fulltext/2002/01000/ACOG_Practice_Bulletin_No__33__Diagnosis_and.28.aspxhttp://journals.lww.com/greenjournal/Fulltext/2002/01000/ACOG_Practice_Bulletin_No__33__Diagnosis_and.28.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/9494145http://www.nejm.org/doi/full/10.1056/NEJM199803123381101#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11810087http://www.sciencedirect.com/science/article/pii/S0002937802024882http://www.ncbi.nlm.nih.gov/pubmed/21266269http://www.ncbi.nlm.nih.gov/pubmed/21266269http://www.sciencedirect.com/science/article/pii/S0002937802024882http://www.ncbi.nlm.nih.gov/pubmed/11810087http://www.nejm.org/doi/full/10.1056/NEJM199803123381101#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/9494145http://journals.lww.com/greenjournal/Fulltext/2002/01000/ACOG_Practice_Bulletin_No__33__Diagnosis_and.28.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/16175681http://www.ncbi.nlm.nih.gov/pubmed/20400051http://www.sciencedirect.com/science/article/pii/S0002937800408203http://www.ncbi.nlm.nih.gov/pubmed/10920346


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27/99

Establishing the Diagnosis of

Preeclampsia and Eclampsia

CHAPTER

2

Specic criteria must be met to establish thediagnosis of preeclampsia, preeclampsia withsevere features, and eclampsia. More recentcriteria for the denition of preeclampsia have

been established based on their association with ad-

verse clinical outcomes. Several preexisting criteria forpreeclampsia with severe features have been eliminat-

ed based largely on whether evidence suggests that

their presence should outline clinical management in

the preterm setting.

Preeclampsia

DenitionPreeclampsia is a syndrome that chiey includes thedevelopment of new-onset hypertension in the second

half of pregnancy. Although often accompanied by

new-onset proteinuria, preeclampsia can be associatedwith many other signs and symptoms, including visualdisturbances, headaches, epigastric pain, and the rapiddevelopment of edema.

Diagnostic criteria include the development of

hypertension, dened as a persistent systolic bloodpressure (BP) of 140 mm Hg or higher, or a diastolicBP of 90 mm Hg or higher after 20 weeks of gestation

in a women with previously normal blood pressure (1,2) (Table 2-1). The optimal measurement of BP is

made with the patient comfortably seated, legsuncrossed, and the back and arm supported, so that

the middle of the cu on the upper arm is at the levelof the right atrium (the midpoint of the sternum). The

patient should be instructed to relax and not talkduring the measurement procedure; ideally, 5 minutesshould elapse before the rst reading is taken. If ele-

vated on initial assessment, the BP measurementshould be repeated after several minutes to attempt to

eliminate spuriously elevated BP determinations (3).

It is worth noting that measurement of BP taken in the

upper arm with the woman in the left lateral position

will falsely lower BP readings because the blood pres-

sure cu will be above the heart when these readingsare made. This approach is discouraged.

Hypertension does not mean that a patient has pre-

eclampsia; other criteria are required. In most cases,this will be new-onset proteinuria, but in the absence ofproteinuria that meets or exceeds the diagnostic thresh-old, any of the following can establish the diagnosis:new-onset thrombocytopenia, impaired liver function,renal insuciency, pulmonary edema, or visual or cere-bral disturbances. Proteinuria is dened by the excre-tion of 300 mg or more of protein in a 24-hour urine

collection (or this amount extrapolated from a timedcollection) (4). Alternatively, a protein/creatinine ratioof at least 0.3 (each measured as mg/dL) is an equiva-

lent acceptable threshold for the diagnosis to be estab-

lished because this ratio has been demonstrated to

match or exceed a 24-hour urine protein collection of300 mg (5). A dipstick reading of 1+ also suggests

17

^


28/99

18 ESTABLISHING THE DIAGNOSIS OF PREECLAMPSIA AND ECLAMPSIA

proteinuria, but because this qualitative method hasmany false-positive and false-negative results, it shouldbe used for diagnosis only when quantitative methods

are not available. Alternatively, the diagnosis may beestablished by the presence of hypertension as denedpreviously in association with thrombocytopenia (plate-

let count less than 100,000/microliter), impaired liverfunction (elevated blood concentrations of liver trans-

aminases to twice the normal concentration), the newdevelopment of renal insuciency (serum creatinineconcentration greater than 1.1 mg/dL or a doubling of

the serum creatinine concentration in the absence of

other renal disease), pulmonary edema, or new-onsetcerebral or visual disturbances. Proteinuria is not abso-

lutely required for the diagnosis of preeclampsia (6).

Preeclampsia with the absence of severe manifesta-

tions often has been characterized as mild. It shouldbe noted that this characterization can be misleading;

even in the absence of severe disease (dened in thischapter), morbidity and mortality are signicantlyincreased. Therefore, the task force recommends thatthe term preeclampsia without severe features beused instead. Some pregnant women present with a

specic constellation of laboratory ndingshemoly-sis, elevated liver enzymes, and low platelet countthat has been labeled HELLP syndrome. This

constellation of laboratory ndings is often considereda preeclamptic subtype. The segregation of HELLP

syndrome from thrombotic thrombocytopenic purpura

may be helped by the measurement of serum lactatedehydrogenase when additional criteria for pre-

eclampsia are absent (7).

Prediagnostic Findings WarrantingIncreased SurveillanceSome maternal symptoms, even in the absence of aconrmed diagnosis of preeclampsia, should promptthe obstetric care provider to closely evaluate mater-

nal status for specic signs of preeclampsia. Theseinclude the new onset of headache or visual distur-

bances, as well as abdominal pain, particularly in theright upper quadrant, or epigastric pain.

Additional ndings that warrant close observationfor the subsequent development of preeclampsia

include fetal growth restriction or new-onset protein-

uria in the second half of pregnancy (8, 9). Elevationsin BP during pregnancy (comparing late pregnancy

with early pregnancy) that exceed 15 mm Hg diastolicor 30 mm Hg systolic are common in uncomplicated

pregnancies (10). Nevertheless, women who demon-strate this degree of elevation in BP warrant closeobservation, as suggested by the National High Blood

TABLE 2-1.Diagnostic Criteria for Preeclampsia ^

Blood pressure Greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hgdiastolic on two occasions at least 4 hours apart after 20 weeks of gestation in awoman with a previously normal blood pressure

Greater than or equal to 160 mm Hg systolic or greater than or equal to 110 mm Hgdiastolic, hypertension can be confirmed within a short interval (minutes) to facilitatetimely antihypertensive therapy

and

Proteinuria Greater than or equal to 300 mg per 24 hour urine collection (or this amountextrapolated from a timed collection)

or

Protein/creatinine ratio greater than or equal to 0.3*

Dipstick reading of 1+ (used only if other quantitative methods not available)

Or in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:

Thrombocytopenia Platelet count less than 100,000/microliter

Renal insufficiency Serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serumcreatinine concentration in the absence of other renal disease

Impaired liver function Elevated blood concentrations of liver transaminases to twice normal concentration

Pulmonary edema

Cerebral or visualsymptoms

* Each measured as mg/dL.


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ESTABLISHING THE DIAGNOSIS OF PREECLAMPSIA AND ECLAMPSIA 19

Pressure Education Program Working Group (2).Additionally, biochemical markers can be associatedwith poorer outcomes in women in whom preeclamp-

sia has been diagnosed. These markers may have value

in the management of specic patients, but they do notcontribute to establishing the diagnosis. Among these

markers is uric acid concentration (11). It is important

to note that these ndings warn that preeclampsia maybe impending, which may inuence patterns of clinicalobservation, but the ndings do not support the initia-tion of specic interventions in and of themselves.

Although clinically evident edema or rapid weight

gain, or both, may raise the clinical suspicion for pre-eclampsia, it is not a diagnostic criterion. Nondepen-dent edema occurs in 1015% of women who remain

normotensive throughout pregnancy, and it is neithera sensitive nor specic sign of preeclampsia (12).

Assessing the Severity of PreeclampsiaSome clinical ndings increase the risk of morbidityand mortality in the setting of preeclampsia and, whenpresent, segregate preeclampsia into a more severecategory (13). The more severe forms of preeclampsia

are characterized by the certain ndings in womenmeeting the basic criteria for diagnosing the disorder

(Box 2-1). Additionally, women who have met the basiccriteria for preeclampsia with systolic BP levels of 140

160 mm Hg or diastolic BP levels of 90110 mm Hg,along with new evidence of thrombocytopenia,impaired liver dysfunction, renal insuciency, pulmo-

nary edema, or visual loss or cerebral disturbance, alsoshould be considered as having severe disease.

In view of recent studies that indicate a minimal rela-

tionship between the quantity of urinary protein and

pregnancy outcome in preeclampsia, massive protein-uria (greater than 5 g) has been eliminated from the

consideration of preeclampsia as severe. Also, becausefetal growth restriction is managed similarly in pregnant

women with and without preeclampsia, it has beenremoved as a nding indicating severe preeclampsia.

Eclampsia

Eclampsia is dened as the presence of new-onsetgrand mal seizures in a woman with preeclampsia.

Eclampsia can occur before, during, or after labor.Other causes of seizures in addition to eclampsia

include a bleeding arteriovenous malformation, rup-tured aneurysm, or idiopathic seizure disorder. Thesealternative diagnoses may be more likely in cases in

which new-onset seizures occur after 4872 hours

postpartum or when seizures occur during use of

antiepileptic therapy with magnesium sulfate.

References

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2. Report of the National High Blood Pressure Education

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3. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J,Hill MN, et al. Recommendations for blood pressuremeasurement in humans and experimental animals: Part1: blood pressure measurement in humans: a statement

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BOX 2-1. Severe Features of Preeclampsia(Any of these findings)^

Systolic blood pressure of 160 mm Hg or higher, or diastolic

blood pressure of 110 mm Hg or higher on two occasions at

least 4 hours apart while the patient is on bed rest (unless

antihypertensive therapy is initiated before this time)

Thrombocytopenia (platelet count less than 100,000/microliter)

Impaired liver function as indicated by abnormally elevated

blood concentrations of liver enzymes (to twice normal

concentration), severe persistent right upper quadrant or

epigastric pain unresponsive to medication and not accounted

for by alternative diagnoses, or both

Progressive renal insufficiency (serum creatinine concentration

greater than 1.1 mg/dL or a doubling of the serum creatinineconcentration in the absence of other renal disease)

Pulmonary edema

Cerebral or visual disturbances
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Prediction of Preeclampsia

CHAPTER

3

Agreat deal of eort has been directed at theidentication of demographic factors, bio-chemical analytes, or biophysical ndings,alone or in combination, to predict early

in pregnancy the later development of preeclampsia.

Evidence relating to the reliability of prediction tests

for preeclampsia is reviewed as follows.

Definition of an Ideal Predictive TestThe utility of a predictive test will depend on the over-

all prevalence of the disease (1). Although sensitivity

and specicity have been used to assess how well a testis able to identify patients with a disease, they do notfocus on the meaning of a single test result. In this

respect, the best way to assess the value of a specictest result is by use of likelihood ratios (2). The likeli-

hood ratio (LR) of a particular test result is the propor-

tion of participants with the target condition who have

a positive test result relative to the proportion without

the target condition who have the same test result.

Because the incidence of preeclampsia is relativelylow, screening tests with positive test results requirehigh LRs to adequately predict the diseases probabil-

ity, and tests with negative results require low LRs tocondently exclude the disorder. Thus, useful predic-tion for preeclampsia would require a high LR (greater

than 10) for a positive test as well as a low LR for a

negative result (less than 0.2). Even the most reliable

prediction test will only have clinical utility if eective

preventive approaches and therapeutic interventions

are available or if close follow-up after prediction

demonstrates improved maternal or fetal outcomes.

Epidemiology of and Risk Factors

for Preeclampsia

A number of clinical circumstances, summarized inBox 3-1, increase the risk of preeclampsia (3). The riskof preeclampsia is increased twofold to fourfold if a

patient has a rst-degree relative with a medical his-tory of the disorder and is increased sevenfold if pre-

eclampsia complicated a previous pregnancy (3, 4).Multiple gestation is an additional risk factor; triplet

gestation is a greater risk than twin gestation. Classic

cardiovascular risk factors also are associated with

increased probability of preeclampsia, as are maternalage older than 40 years, diabetes, obesity, and preex-isting hypertension. The increased prevalence of

chr

hypertension in pregnancy guidelines

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