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Association of Rheumatologic Disease With Preeclampsia

Wolfberg, Adam J., MD, MPH*†; Lee-Parritz, Aviva, MD; Peller, Allyson J., MPH§; Lieberman, Ellice S., MD, DrPH

doi: 10.1097/01.AOG.0000126279.87151.e1
Original Research

OBJECTIVE: To determine whether maternal rheumatologic disease is associated with an increased risk of adverse obstetric or neonatal outcomes.

METHODS: Using an institutional database, we identified all women with diagnosed rheumatologic disease (n = 114) who delivered a baby at our institution during a 33-month period. We compared the incidence of adverse obstetric and neonatal outcomes among these women with the incidence among women without rheumatologic diseases (n = 18,534).

RESULTS: Women with rheumatologic diseases were more likely to have preeclampsia than women without rheumatologic disease (8.8% versus 2.3%, P < .001) Women with rheumatologic diseases were also at increased risk of preterm delivery (15.2% versus 7.8%, P = .002) and small-for-gestational-age infants (8.0% versus 3.1%, P = .001) compared with women without rheumatologic disease.

CONCLUSION: The finding that women with rheumatologic diseases are at increased risk of adverse obstetric outcomes suggests a need for heightened clinical vigilance and further research into the common pathophysiologic correlates.


Pregnant women with rheumatologic diseases are at increased risk of having preeclampsia.

From the *Department of Obstetrics and Gynecology, Brigham and Women's Hospital, and †Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston; ‡Department of Obstetrics and Gynecology, Boston Medical Center, Boston University School of Medicine, Boston; §Genetics and Teratology Unit, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston; and ¶Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Grant Sponsor: National Birth Defects Prevention Study, the National Center for Environmental Health, Centers for Disease Control and Prevention through a grant to the Massachusetts Center for Birth Defects Research and Prevention, Massachusetts Department of Public Health.

Address reprint requests to: Adam Wolfberg, MD, MPH, Department of OB/GYN, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115; e-mail:

Received December 5, 2003. Received in revised form February 13, 2004. Accepted February 18, 2004.

A number of reports have examined rheumatologic diseases during pregnancy. Most investigations are among women with systemic lupus erythematosis (SLE), which has been associated with fetal loss rates between 11% and 46%,1,2 prematurity, and small-for-gestational-age (SGA) birth. For pregnant women with SLE, the reported risk of preterm delivery and SGA is higher among those who become pregnant after being diagnosed with SLE than among those who become pregnant and are subsequently diagnosed with SLE.3–5 In contrast, the association of scleroderma, rheumatoid arthritis, and other rheumatologic conditions with fetal loss, prematurity, and SGA birth is less consistent.6–8

There are limited data regarding the association of rheumatologic diseases with hypertension and preeclampsia. Yasmeen et al5 found that the incidence of hypertensive disorders in pregnancy was higher among women with SLE than among those without SLE, based on an analysis of a large state database. However, the rates of hypertensive disorders among women with SLE (2.9%) and those without SLE (0.4%) in that report are both well below the commonly accepted rates of gestational hypertension and preeclampsia.9 A study of pregnant patients in Norway with rheumatologic diseases found an increased incidence of preeclampsia among women with SLE, systemic sclerosis, Sjögren's syndrome, polymyositis, and dermatomyositis, but the association was not consistent over the study period.10

Given the limited data available, we sought to determine whether there was an increased rate of preeclampsia among women with rheumatologic diseases.

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We used a research database of antepartum and intrapartum variables collected on all deliveries at our institution during selected time periods, specifically December 1994 to August 1995 and the calendar years 1998 and 2000. The time periods represent those when prenatal and intrapartum data were abstracted for our database. We then identified all pregnant women who were noted in their medical record to have been diagnosed with SLE, rheumatoid arthritis, or another rheumatologic disorder and compared them with pregnant women who did not have a rheumatologic disease. We also identified women who had been diagnosed with antiphospholipid antibody syndrome (n = 21) and compared them with women without a rheumatologic disease. If a woman had 2 or more pregnancies during the study period, we used the most recent pregnancy for our analysis. A woman was considered to have an autoimmune disease if she had been diagnosed by her doctor and the diagnosis was recorded in the medical record. Diagnoses were not verified by serologic testing. There is a small amount of overlap, with 5 of 114 subjects carrying the diagnosis of more than 1 autoimmune disorder. Women in our database were then linked with a surveillance database of congenital anomalies to compare the prevalence of anomalies between the groups.11 This database is easily linked to the obstetric data by infant medical record number; the database has a high detection rate for anomalies (93%) based on validation studies.12

We excluded women with multiple pregnancies, women transferred to our institution intrapartum, and women with diseases that are associated with preeclampsia or other adverse obstetric or neonatal outcomes, such as diabetes, thyroid disease, and infection with cytomegalovirus or parvovirus.

Information about women's prenatal course, chronic hypertension diagnosed before pregnancy, preeclampsia, intrauterine growth restriction (IUGR), SGA, intrauterine fetal demise, and coexisting medical conditions was collected. To isolate the association of preeclampsia with rheumatologic diseases, we excluded women with a diagnosis of chronic hypertension, defined as history of hypertension before pregnancy and reported in the patient's chart. We also excluded women diagnosed with hypertension during the first 20 weeks of pregnancy because hypertension that early in pregnancy could represent a preexisting hypertensive disorder rather than preeclampsia.

Preeclampsia was defined as new-onset hypertension after 20 weeks of pregnancy (systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg) accompanied by proteinuria and/or evidence of organ involvement. Only patients diagnosed with preeclampsia before labor were included; we excluded women diagnosed with preeclampsia during labor to avoid overdiagnosing preeclampsia by mistakenly including women with a single isolated elevated blood pressure reading. An SGA infant was defined as one with birth weight below the 5th percentile, by using a United States population reference.13

Statistical comparisons were performed with χ2 or Fisher exact test, as appropriate. Logistic regression analysis was used to evaluate the association of rheumatologic conditions with preeclampsia while controlling for maternal age. The overall association was evaluated in a logistic analysis where any rheumatologic disease (yes/no) was the outcome variable. Separate logistic regressions were also performed by examining the association of each rheumatologic condition with preeclampsia. P < .05 was considered statistically significant.

The protocol was approved by our institutional review board.

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Women with rheumatologic diseases were no more likely to be multiparous than the women in the control group (55.2% versus 55.1% P = .9) and were not more likely to be older than 39 years (6.4% versus 4.3%, P = .3). The mean age of women with rheumatologic disease was 31.8 compared with 30.7 years for women in the control group (P = .04).

There was an almost 4-fold greater risk of preeclampsia among the overall group of women with rheumatologic diseases than among those without rheumatologic diseases (8.8% versus 2.3%; relative risk 4.3; 95% confidence interval 2.2, 8.2). When examined separately, SLE, rheumatoid arthritis, other rheumatologic diseases grouped together, and antiphospholipid antibody syndrome were each associated with a 3- to 5-fold higher rate of preeclampsia, although only the associations with SLE and the other rheumatologic diseases grouped together reached statistical significance. After adjusting for maternal age, the overall association between all rheumatologic diseases and preeclampsia remained highly significant. When examined separately, only SLE and antiphospholipid antibody syndrome were significantly associated with preeclampsia in the regression analyses (Table 1).

Table 1

Table 1

Women with rheumatologic disorders were at a greater risk than women without rheumatologic disease of having chronic hypertension (5.6% versus 1.2%, P < .001), SGA infants (8.0% versus 3.1%), and preterm delivery (15.2% versus 7.8%, P = .002). There was a somewhat higher rate of IUGR in women with rheumatologic disease, although the difference did not reach statistical significance (P = .1) There was no increased risk of intrauterine fetal demise or congenital anomalies among women with rheumatologic disease compared with women without rheumatologic disease (Table 2).

Table 2

Table 2

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We found a nearly 4-fold increase in the incidence of preeclampsia in the overall group of women with autoimmune disease. The increase was of similar magnitude for all of the individual diseases that we examined, although only the association with SLE consistently reached statistical significance, probably because of the larger number of women in that group. Our data add evidence that SLE is associated with an increased incidence of preeclampsia.

Our data demonstrate a consistent, increased incidence of preeclampsia in all rheumatologic diseases. We find it reassuring that the rate of preeclampsia among women without rheumatologic diseases was consistent with population estimates of the disease (2–7%),9 suggesting a valid diagnosis of preeclampsia among all women studied. This finding contrasts with one of the other studies that suggests an association between SLE and preeclampsia but reports a prevalence of preeclampsia below the generally accepted rates for patients both with and without SLE.5

Our data also show that women with rheumatologic diseases have an approximately 2-fold greater risk of adverse pregnancy outcomes including preterm delivery, SGA, and IUGR than women without rheumatologic diseases.

We show an increased rate of chronic hypertension among women with rheumatologic disorders, a finding that is not surprising, given that hypertension has been associated with rheumatologic disorders in patients who are not pregnant.

The reason for the association of IUGR and SGA with rheumatologic disease is unclear. A possible explanation may be found in a common autoimmune process linking the patient's pregnancy (a process of autoimmune tolerance), rheumatologic disease, and preeclampsia, and consequently compromising the uteroplacental unit. Further research to elucidate the commonalities between these conditions may be fruitful.

Our study does have certain limitations. To the extent that women with rheumatologic diseases may undergo heightened prenatal attention and blood-pressure screening, they may be more likely to be diagnosed with preeclampsia than patients with uncomplicated pregnancies whose elevated blood pressure or proteinuria go unnoticed. In addition, the fact that proteinuria is a common finding in SLE and a diagnostic criterion for preeclampsia complicates interpretation of our results. Whether the finding of proteinuria makes patients with SLE more likely to be diagnosed with preeclampsia or less likely to be diagnosed with preeclampsia because their proteinuria is attributed to SLE is unclear.

Clinically, these findings suggest that women with rheumatologic diseases deserve extremely close monitoring during the antepartum and intrapartum periods. From a pathophysiologic perspective, however, these data suggest the possibility of a common autoimmunologic link between preeclampsia and rheumatologic disorders that is worthy of further research.

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© 2004 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.