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OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at

Objective: This study was undertaken to compare rates and severity of gestational hypertension and preeclampsia, as well as perinatal outcomes when these complications develop, between women with twin gestations and those with singleton gestations. Study Design: This was a secondary analysis of prospective data from women with twin (n = 684) and singleton (n = 2946) gestations enrolled in two separate multicenter trials of low-dose aspirin for prevention of preeclampsia. End points were rates of gestational hypertension, rates of preeclampsia, and perinatal outcomes among women with hypertensive disorders. Results: Women with twin gestations had higher rates of gestational hypertension (relative risk, 2.04; 95% confidence interval, 1.60-2.59) and preeclampsia (relative risk, 2.62; 95% confidence interval, 2.03-3.38). In addition, women with gestational hypertension during twin gestations had higher rates of preterm delivery at both P P P = .04). Moreover, when outcomes associated with preeclampsia were compared, women with twin gestations had significantly higher rates of preterm delivery at P P P = .07). In contrast, among women with twin pregnancies, those who remained normotensive had more adverse neonatal outcomes than did those in whom hypertensive complications developed. Conclusions: Rates for both gestational hypertension and preeclampsia are significantly higher among women with twin gestations than among those with singleton gestations. Moreover, women with twin pregnancies and hypertensive complications have higher rates of adverse neonatal outcomes than do those with singleton pregnancies. (Am J Obstet Gynecol 2000;182:938-42.)

Objective: The aim of this study was to determine whether epidural anesthesia during labor increased the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease. Study Design: We performed a secondary retrospective analysis of a subgroup population within a multicenter double-blind trial of low-dose aspirin therapy for women at high risk for development of preeclampsia. Subjects in whom severe hypertensive disease developed were selected. The primary outcomes were the overall frequencies of cesarean delivery among women with severe hypertensive disease who had labor with and without epidural anesthesia. Other maternal and neonatal outcomes were also compared between women who did and did not receive epidural anesthesia. Results: Among the women with severe hypertensive disease (n = 444) 327 had labor. Among the women with severe disease who had labor there was no difference in either the overall cesarean delivery rate (32.1% vs 28.0%; P = .44) or the rate of cesarean delivery for fetal distress or failure to progress (27.8% vs 22.0%; P = .26) between women who did and did not receive epidural analgesia. Women with chronic hypertension were more likely to have a cesarean delivery overall if they received epidural anesthesia, but there was otherwise no difference in the frequencies of cesarean delivery for these indications between women with and without epidural anesthesia within each of the high-risk groups. Pulmonary edema was rare and acute renal failure did not develop in any women. Conclusion: Epidural anesthesia use did not increase the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease. (Am J Obstet Gynecol 1999;181:1096-1101.)

Background Whether low-dose aspirin prevents preeclampsia is unclear. It is not recommended as prophylaxis in women at low risk for preeclampsia but may reduce the incidence of the disease in women at high risk. Methods We conducted a double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeclampsia during a previous pregnancy. The women were enrolled between gestational weeks 13 and 26 and received either 60 mg of aspirin or placebo daily. Results Outcome data were obtained on all but 36 of the 2539 women who entered the study. The incidence of preeclampsia was similar in the 1254 women in the aspirin group and the 1249 women in the placebo group (aspirin, 18 percent; placebo, 20 percent; P = 0.23). The incidences in the aspirin and placebo groups for each of the four hi...

The current literature emphasizes increased risk of adverse outcomes in the presence of proteinuria and hypertension. The objective of this study was to compare the frequency of adverse fetal outcomes in women who developed hypertensive disorders with or without proteinuria.The study design was a secondary analysis of data from women who had preeclampsia in a previous pregnancy (n = 598) who were enrolled in a multicenter trial of aspirin for the prevention of preeclampsia. The women had no history of chronic hypertension or renal disease and were normotensive at study inclusion. The maternal and perinatal outcome variables assessed were preterm delivery at37 and35 weeks of gestation, rate of small-for-gestational-age infants, and abruptio placenta. Data were analyzed by using the chi-square test, and women who remained normotensive or who had mild gestational hypertension were considered as a single group because they had similar outcomes.As compared to mild preeclampsia, women who developed severe gestational hypertension (without proteinuria) had higher rates of both preterm delivery at37 weeks of gestation and small-for-gestational-age infants. In addition, when compared to women with mild preeclampsia, for women with severe gestational hypertension, gestational age and birth weight were significantly lower at delivery (P.003 for both age and birth weight). Moreover, women who developed severe gestational hypertension had higher rates of preterm delivery at37 weeks of gestation (54.2% vs 17.8%, P =.001) and at35 weeks of gestation (25.0% vs 8.4%, P =.0161), and delivery of small-for-gestational-age infants (20.8% vs 6.5%, P =.024) when compared to women who remained normotensive or those who developed mild gestational hypertension. There were no statistically significant differences in perinatal outcomes between the normotensive/mild gestational hypertension and the mild preeclampsia groups. Overall, women who had severe gestational hypertension had increased rates of preterm delivery and delivery of small-for-gestational-age infants than women with mild gestational hypertension or mild preeclampsia. In the presence of severe hypertension, proteinuria did not increase the rates of preterm delivery or delivery of small-for-gestational-age infants.In women who have gestational hypertension or preeclampsia, increased rates of preterm delivery and delivery of small-for-gestational-age infants are present only in those with severe hypertension. In these women, the presence of proteinuria does not influence perinatal outcome.

OBJECTIVE: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. STUDY DESIGN: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. RESULTS: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. CONCLUSIONS: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.

Background: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at highrisk to develop the syndrome. Methods: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results: The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks’ gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions: The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.