Preeclampsia Recurrence and Prevention

Preeclampsia Recurrence and Prevention

Gary A. Dildy III, MD,* Michael A. Belfort, MD, PhD, ‡ and John C. Smulian, MD, MPH

Women with a previous pregnancy complicated by preeclampsia have an increased risk for recurrence in subsequent pregnancies. For severe preeclamptic women in an initial preg- nancy, recurrence rates for any type of preeclampsia are very high, approaching 50% in some studies. Significant maternal and fetal complications are more common in recurrent preeclampsia compared with an initial episode. For women who have experienced a pregnancy complicated by preeclampsia, a systematic evaluation for underlying risk factors may identify a specific pathway suitable for a specific intervention. Although some progress has been made in developing potential therapeutic options to prevent preeclampsia recur- rence, there is a great need for better data to determine who will benefit most from any specific therapy. Semin Perinatol 31:135-141 © 2007 Elsevier Inc. All rights reserved.

KEYWORDS preeclampsia, eclampsia, risk factors, recurrence, prevention, HELLP syndrome

P Preeclampsia Risk Factors

reeclampsia complicates approximately 5% to 10% of

nulliparous pregnancies 1 and is consistently among the

top three causes of maternal death in both developed and Many factors for preeclampsia have been described in the developing countries. 2-4 Two-thirds of cases will be mild and

obstetrical literature, and the majority will persist in subse-

1 quent pregnancies ( Table 1 ). the other third severe in degree. 6 Preeclampsia is considered Preeclampsia tends to be a

a disease of nulliparous women, as it is twice as common in disease of first pregnancy in women with no other obvious risk factors; however, underlying medical conditions with

primigravidas as it is in women who have previously given vascular or renal implications (diabetes mellitus, chronic hy- birth. 5 It is well known that women with a previous preg- pertension) and conditions with increased trophoblast mass nancy complicated by preeclampsia have an increased risk (multifetal gestation or hydrops fetalis) substantially increase for recurrence in subsequent pregnancies. For severe pre- the risk. As preeclampsia is likely a syndrome of multiple

eclamptic women in an initial pregnancy, recurrence rates for etiologies and many underlying factors persist across preg- any type of preeclampsia are very high, approaching 50% in

nancies, a significant risk factor for future preeclampsia is a some studies. Significant maternal and fetal complications

prior history of preeclampsia.

are more common in recurrent preeclampsia compared with an initial episode. Thus, accurate and thorough counseling regarding recurrence risks and potential preventive measures

The Epidemiology of

will assist women and their caregivers to make important

Preeclampsia Recurrence

decisions pertaining to future childbearing.

A number of studies have examined the risk for preeclampsia recurrence in subsequent pregnancies, and all have indicated

a significantly increased risk ( Table 2 ). The highest risks for recurrence are found most consistently when the initial case

was preterm, severe, or complicated by eclampsia, HELLP

*Department of Obstetrics and Gynecology, LSU Health Sciences Center,

New Orleans, LA.

(hemolysis, elevated liver enzymes, and low platelet count)

†Department of Obstetrics and Gynecology, University of Utah Health Sci-

syndrome, or fetal growth restriction. However, good data

ences Center, Salt Lake City, UT.

are still relatively sparse because definitions for preeclampsia

‡Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology

often vary from study to study.

and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ.

Campbell and coworkers studied a population of pregnant

Address reprint requests to Gary A. Dildy III, MD, Maternal Fetal Medicine

women (n ⫽ 29,851) whose first recorded pregnancy oc-

Center, St. Mark’s Hospital, 1140 East 3900 South, Suite 390, Salt Lake

curred between the years 1967 and 1978 in Aberdeen, Scot-

City, Utah 84124. E-mail: Gary.Dildy@HCAhealthcare.com

land and had ⬎2 subsequent pregnancies during that same

0146-0005/07/$-see front matter © 2007 Elsevier Inc. All rights reserved.

doi:10.1053/j.semperi.2007.03.005

G.A. Dildy III, M.A. Belfort, and J.C. Smulian

Table 1 The Strength of the Association of Selected Risk Factors for Preeclampsia*

Risk Factor Associated with Preeclampisa

Reference

OR (95% CI)

Preeclampsia in a previous pregnancy Hnat 18 3.88 (2.98-5.05) Duckitt 48 7.19 (5.85-8.83)

First pregnancy Conde-Agudelo 49 2.38 (2.28-2.49) Duckitt 48 2.91 (1.28-6.61)

Multifetal gestation Sibai 50 2.62 (2.03-3.38) Conde-Agudelo 49 2.10 (1.90-2.32) Duckitt 48 2.93 (2.04-4.21)

Chronic hypertension Conde-Agudelo 49 1.99 (1.78-2.22) Gestational diabetes

Conde-Agudelo 49 1.93 (1.66-2.25) Pregestational diabetes

Duckitt 48 3.56 (2.54-4.99) Vascular and connective tissue disease

Stamilio 51 6.9 (1.1-42.3) Nephropathy Urinary tract infection

Abi-Said 52 4.23 (1.27-14.06) Antiphospholipid antibody syndrome

Robertson 53 2.73 (1.65-4.51) Duckitt 48 9.72 (4.34-21.75)

Genetic factors (eg, thrombophilias)

Robertson 53

Factor V Leiden heterozygosity 2.19 (1.46-3.27) Prothrombin heterozygosity

2.54 (1.52-4.23) MTHFR homozygosity

1.37 (1.07-1.76) Hyperhomocysteinemia

3.49 (1.21-10.11) Obesity (BMI >35 kg/m 2 ) Sibai 1 3.38 (1.91-6.00)

Maternal age >35 years Conde-Agudelo 49 1.67 (1.58-1.77) Family history of preeclampsia

Duckitt 48 2.90 (1.70-4.93) Fetal malformation

Conde-Agudelo 49 1.26 (1.16-1.37) Abnormal maternal serum markers

Dugoff 54

(AFP, hCG, uE3, Inhibin A) Inhibin A >2.0 MOM

2.39 (1.75-3.26) 2 abnormal markers

3.65 (2.79-4.78) African-American race

Tucker 55 1.2 (0.8-1.7) Abbreviations: AFP, alpha fetoprotein; HCG, human chorionic gonadotropin; uE3, unconjugated estriol.

*Presented as odds ratio (OR) and 95% confidence intervals (CI).

time period (n ⫽ 6637). 7 Women were categorized as nor- dent on the outcome of the first pregnancy. If the first preg- motensive (68.0%), mildly preeclamptic (26.3%), protein-

nancy was complicated simply by proteinuric preeclampsia, uric preeclamptic (5.6%), and eclamptic (0.2%). They found

the incidence in the second pregnancy was 7.5%, whereas that the overall incidence of preeclampsia in a second preg-

those who were normotensive in the first pregnancy had a nancy was less than that in a first pregnancy, but was depen-

low rate of proteinuric preeclampsia in the second pregnancy Table 2 Summary of Studies that Present the Risk for Recurrence of Preeclampsia

Author

Study Population

Rate of Recurrence

Campbell 7 Preeclampsia ( n ⴝ 279)

Preeclampsia 7.5%

Sibai 9 Second trimester severe preeclampsia ( n ⴝ 169)

Any preeclampsia 65% <28 weeks 21%

28-36 weeks 21% 37-40 weeks 24%

van Rijn 8 Preeclampsia with delivery <34 weeks

Preeclampsia 25%

Sullivan 12 HELLP ( n ⴝ 161)

Preeclampsia 43% HELLP 27%

Sibai 11 HELLP ( n ⴝ 192)

Preeclampsia 19% HELLP 3%

Chames 13 HELLP with delivery <28 weeks (n ⴝ 62)

Preeclampsia 55% HELLP 6%

Adelusi 14 Eclampsia ( n ⴝ 64)

Eclampsia 16%

Sibai 16 Eclampsia ( n ⴝ 366)

Preeclampsia 22% Eclampsia 2%

Trogstad 17 Preeclampsia singleton ( n ⴝ 19,960)

Preeclampsia 14.1%

Preeclampsia twins ( n ⴝ 325)

Preeclampsia 6.8% Preeclampsia 6.8%

Van Rijn and coworkers studied primiparous women who delivered between 1993 and 2002 at the University Medical Center Utrecht in The Netherlands who had a history of early onset preeclampsia resulting in delivery before 34 weeks of

gestation. 8 Preeclampsia recurred in 25% (30/120) of women in their second pregnancy. Five percent delivered before 34 weeks of gestation and 17% between 34 and 37 weeks of gestation.

Sibai and colleagues 9 reported subsequent pregnancy out- comes in women with severe second trimester preeclampsia. Of these 125 women, 108 had 169 subsequent pregnancies. For the subsequent pregnancies, approximately one-third were normotensive and two-thirds were complicated by pre- eclampsia. Of the women with preeclampsia, approximately one-third developed a recurrence at ⬍28 weeks, one-third at

28 to 36 weeks, and one-third at 37 to 40 weeks.