Is there evidence of separate inflammatory or metabolic forms of preeclampsia?

OBJECTIVES: To examine whether high insulin resistance versus high inflammation identifies subtypes of preeclampsia. METHODS: A cytokine panel, glucose and insulin were measured in 37 preeclampsia plasma samples. Wilcoxon rank sum assessed median concentration of HOMA(IR) by pro-inflammatory:anti-inflammatory ratio. Regression stratifying by BMI and preterm birth was conducted. RESULTS: There was no difference in median HOMA(IR) by the pro-inflammatory:anti-inflammatory ratio (p = 0.16). No subsets scatterplot clusters emerged. A positive correlation between HOMAlog and the ratio was significant (p = 0.04). CONCLUSIONS: No dichotomous subsets of preeclampsia by inflammation versus insulin resistance were detected. Contrary to our hypothesis, insulin resistance was higher as inflammation increased in preeclampsia.

Cigarette smoking during pregnancy: chromosome translocations and phenotypic susceptibility in mothers and newborns.

The effects of maternal cigarette smoking during pregnancy on structural chromosome aberrations were evaluated in peripheral lymphocytes from 239 mothers and their 241 newborns to determine whether smoking during pregnancy, genetic susceptibility, and race are associated with chromosome aberrations including translocations. Demographic information and cigarette smoking data were obtained via questionnaire. There were 119 Caucasian Americans, 118 African Americans, and 2 Asian Americans. The average maternal age was 24.9+/-5.8 (mean+/-S.D.) years. Thirty-nine percent of the Caucasian Americans and 45.4% of the African Americans self-reported that they were active smokers during the index pregnancy. The average number of cigarettes smoked per day was 2.65+/-5.75 and 1.37+/-3.17 for Caucasian and African American mothers, respectively. Peripheral blood lymphocytes from the mother and from the fetal side of the placenta were evaluated for chromosome aberrations by whole chromosome painting. Aliquots from the same blood samples were also used to assess genetic susceptibility with an in vitro bleomycin challenge assay. Spontaneous translocation frequencies in both maternal and newborn lymphocytes were not associated with cigarette smoking, socioeconomic status, or education. The absence of a smoking effect may be attributable to the low level of cigarette usage in these subjects. The average bleomycin-induced damage in the maternal and newborn populations was 0.37+/-0.27 and 0.15+/-0.14 breaks per cell, respectively, a difference that was highly significant (p<0.0001). In newborns there was a positive association between bleomycin sensitivity and the frequencies of aberrations as measured by chromosome painting: p

Maternal cereal consumption and adequacy of micronutrient intake in the periconceptional period.

OBJECTIVE: To assess the adequacy of periconceptional intake of key micronutrients for perinatal health in relation to regular cereal consumption of pregnant women. DESIGN, SETTING AND SUBJECTS: Low-income pregnant women (n 596) in Pittsburgh, Pennsylvania, USA, who enrolled in a cohort study at <20 weeks' gestation. These women reported usual dietary intake in the three months around conception on an FFQ. Cereal consumers were women who reported consuming any dry cereal at least three times per week. High risk for nutrient inadequacy was defined as intake less than the Estimated Average Requirement. RESULTS: About 31 % of the women regularly consumed cereal. After adjusting for energy intake, race/ethnicity, marital status, breakfast consumption and supplement use, cereal eaters had significantly higher intakes of folate, Fe, Zn, Ca, fibre and vitamins A, C, D and E (all P < 0.01) and were approximately two to six times more likely to have intakes in the highest third of the distribution for folate, Fe, Zn, Ca, vitamins A and D, and fibre (all P < 0.01) than cereal non-eaters. Cereal consumption was also associated with reductions of 65-90 % in the risk of nutrient inadequacies compared with non-consumption (all P < 0.01). CONCLUSIONS: Encouraging cereal consumption may be a simple, safe and inexpensive nutrition intervention that could optimize periconceptional intake for successful placental and fetal development.

Increased myeloperoxidase in the placenta and circulation of women with preeclampsia.

Myeloperoxidase (MPO) is a hemoprotein normally released from activated monocytes and neutrophils. Traditionally viewed as a microbicidal enzyme, MPO also induces low-density lipoprotein oxidation, activates metalloproteinases, and oxidatively consumes endothelium-derived NO. The elevated plasma MPO level is a risk factor for myocardial events in patients with coronary artery disease. Patients with preeclampsia display evidence of the inflammation and endothelial dysfunction associated with oxidative stress in the circulation, vasculature, and placenta. We hypothesized that MPO levels in the circulation and placental extracts from women with preeclampsia would be greater than levels in women with normal pregnancies. Placental extracts were prepared from placental villous biopsies from preeclamptic (n=27) and control (n=43) placentas. EDTA plasma samples were obtained from gestationally age-matched preeclamptic and control normal pregnancies. MPO concentrations were measured by ELISA. Immunohistochemistry was used to determine MPO localization in the placenta. MPO levels in placental extracts from women with preeclampsia were significantly higher than the levels in normal control subjects (546+/-62 versus 347+/-32 ng/mL; P=0.025). MPO was found in the floating villi and basal plate of placentas with a greater staining in the basal plates from preeclampsia placentas compared with normal pregnancies. Plasma MPO levels were 3-fold higher in patients with preeclampsia compared with normal control subjects (36.6+/-7.6 versus 11.0+/-3.1 ng/mL; P=0.003). In conclusion, MPO levels are significantly increased in the circulation and placenta of women with preeclampsia. We speculate that MPO may contribute to the oxidative damage reported in the endothelium and placenta of women with preeclampsia.

Cigarette smoke exposure and angiogenic factors in pregnancy and preeclampsia.

BACKGROUND: Cigarette smoking during pregnancy is paradoxically associated with a reduced risk of developing preeclampsia. Both smoking and preeclampsia are associated with alterations in circulating angiogenic factors. The objective of this study was to investigate the relationship between cigarette smoking and the angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in pregnant women with and without preeclampsia. METHODS: Plasma sFlt-1, PlGF, and cotinine were measured using enzyme-linked immunosorbent assay in 125 women with uncomplicated pregnancies (controls) and 58 women with preeclampsia. RESULTS: In uncomplicated pregnancies, maternal sFlt-1 concentrations were lower in smokers compared to nonsmokers (779.6 (487.5-1,140.8) vs. 1,116.5 (793.6-1,905.2) pg/ml, P < 0.005). Preeclamptic women who smoked also demonstrated a trend toward lower concentrations of sFlt-1 compared to nonsmokers (3,423.0 (2,183.4-5,689.0) vs. 5,504.9 (3,418.0-6,361.3) pg/ml, P = 0.07). Maternal PlGF concentrations were higher in smokers with uncomplicated pregnancies (398.4 (165.2-621.7) vs. 191.4 (104.6-446.8) pg/ml); however, this was not a statistically significant difference (P = 0.07). PlGF concentrations were not different in preeclamptic smokers compared to nonsmokers. The sFlt/PlGF ratio was significantly lower in smokers with uncomplicated pregnancies, but not in smokers with preeclampsia compared to nonsmokers. CONCLUSIONS: Cigarette smoking is associated with lower maternal sFlt-1 concentrations during pregnancy and preeclampsia. On the basis of these data, cigarette smoke exposure may decrease the risk of preeclampsia in part by moderating the anti-angiogenic phenotype observed in the syndrome.

Postpartum adiponectin concentration, insulin resistance and metabolic abnormalities among women with pregnancy-induced disturbances.

The authors compared postpartum adiponectin levels among women with prior pregnancy-induced disturbances and assessed their association with homeostasis model assessment for insulin resistance (HOMA-IR), the metabolic syndrome (MS), and the Framingham risk score (FRS). Women delivering in 1998 through 2001 and who had gestational diabetes mellitus (n=22), gestational hypertension (n=32), or preeclampsia (n=34) were examined 1 to 2 years after delivery and were grouped-matched to controls (n=29) by age and prepregnancy body mass index. HOMA-IR was increased, adiponectin values were decreased, and there was a higher MS prevalence in women with prior gestational diabetes mellitus (all P<.05). Adiponectin levels were inversely related to HOMA-IR (r=-0.45; P<.0001) and FRS (r=-0.25; P=.007), and a significant trend for decreasing adiponectin values with increased number of MS components was noted (P trend <.0001). Adiponectin concentration remained a significant correlate of FRS and MS irrespective of pregnancy history; a concentration <10.5 microg/mL provided the optimal cutoff to distinguish those with or without MS. Thus, a lower postpartum adiponectin concentration identifies women at increased cardiovascular risk regardless of pregnancy history.

A comparison of circulating TNF-alpha in obese and lean women with and without preeclampsia.

OBJECTIVES: We hypothesized that TNF-alpha would be higher in obese versus lean women with preeclampsia. METHODS: Total plasma TNF-alpha was measured in a nested case-control study of 123 nulliparous lean and obese control women and women with preeclampsia. RESULTS: Adjusted mean TNF-alpha concentrations were 0.97 +/- 0.11 (pg/mL +/- SEM) in lean controls, 1.01 +/- 0.10 in obese controls, 1.43 +/- 0.11 in lean women with preeclampsia and 1.16 +/- 0.11 in obese women with preeclampsia. Pregnancy outcome was the single predictor of TNF-alpha concentration in the general linear regression model (p = 0.04). CONCLUSION: TNF-alpha concentration was higher in preeclampsia compared with control subjects. Obesity was not associated with higher TNF-alpha concentrations in either preeclampsia or control subjects.

Elevated asymmetric dimethylarginine concentrations precede clinical preeclampsia, but not pregnancies with small-for-gestational-age infants.

OBJECTIVE: The purpose of this study was to investigate maternal plasma concentrations of asymmetric dimethylarginine (ADMA) in mid pregnancy and at the time of disease in women who experience preeclampsia, compared with women with uncomplicated pregnancies and women with small-for-gestational-age infants. STUDY DESIGN: Plasma samples were collected at mid-pregnancy and at the time of delivery from 31 women with uncomplicated pregnancies, from 12 women with small-for-gestational-age infants, and from 15 women with preeclampsia. ADMA and L-arginine concentrations were measured using high-pressure liquid chromatography. RESULTS: Maternal ADMA concentrations were elevated at mid pregnancy and remained elevated at delivery in women who later experienced preeclampsia (0.45 +/- 0.09 micromol/L) compared with women with uncomplicated pregnancies (0.34 +/- 0.08 micromol/L; P < .01) and with women with small-for-gestational-age infants (0.33 +/- 0.06 micromol/L; P < .01). CONCLUSION: Maternal ADMA concentrations are higher in mid pregnancy in women who experience preeclampsia, compared with women with uncomplicated pregnancies and small-for-gestational-age infants. Elevated ADMA concentration before clinical onset of preeclampsia suggests a role of this nitric oxide synthase inhibitor in the pathophysiologic condition of preeclampsia.

Early pregnancy lipid concentrations and spontaneous preterm birth.

OBJECTIVE: Women who deliver preterm infants may be at increased risk for cardiovascular disease, perhaps related to dyslipidemia. STUDY DESIGN: In a nested case control study of women with spontaneous preterm birth, cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were evaluated. Lipid concentrations and gestational changes, as well as risk for preterm birth, were evaluated in women who delivered <34 (n = 23), >or=34-<37 (n = 67), and >or=37 weeks (n = 199). RESULTS: High cholesterol or triglycerides or=34-<37 weeks, respectively. Overweight women who delivered <34 weeks had particularly elevated early pregnancy concentrations of cholesterol and low-density lipoprotein; lean women with moderate preterm birth had elevated triglycerides. There was a reduced triglyceride response in the first half of pregnancy among women who delivered <34 weeks. CONCLUSION: Our results indicate the presence of dyslipidemia in women with spontaneous preterm birth.

Maternal leptin across pregnancy in women with small-for-gestational-age infants.

OBJECTIVE: We hypothesized that women with small-for-gestational-age (SGA) neonates would have lower concentrations of leptin compared to women with appropriately grown infants (AGA). STUDY DESIGN: This is a nested case-control study of normotensive nulliparous women. Cases (n = 28) delivered SGA < 10 percentile and controls (n = 77) delivered AGA. Maternal plasma leptin concentrations were compared at 18, 28, and 40 weeks' gestation via repeated measures. RESULTS: Maternal leptin concentrations at 18 weeks were correlated with prepregnancy BMI (r = 0.69, P < .0001) and early pregnancy waist circumference (r = 0.59, P < .0001). After adjustment for maternal body composition, leptin was lower across pregnancy in women with SGA compared to AGA neonates (13.6 vs 15.2 ng/mL at 18 weeks; 13.6 vs 17.3 ng/mL at 28 weeks; 16.6 vs 20.7 ng/mL at 40 weeks; P = .04). CONCLUSION: Maternal leptin was correlated with maternal adiposity; however, after adjustment for body composition, leptin was lower across pregnancy in women with SGA.

Periconceptional multivitamin use reduces the risk of preeclampsia.

The objective was to assess the independent effect of regular periconceptional multivitamin use on the risk of preeclampsia. Pregnant women (n=1,835) enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001) at less than 16 weeks' gestation were asked whether they regularly used multivitamins or prenatal vitamins in the past 6 months. Women were classified as users or nonusers. The unadjusted prevalence of preeclampsia was 4.4% in nonusers and 3.8% in users. After adjustment for race/ethnicity, marital status, parity, prepregnancy physical activity, and income in a multiple logistic regression model, regular use of multivitamins was associated with a 45% reduction in preeclampsia risk compared with nonuse (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.32, 0.95). Prepregnancy overweight modified this effect. After confounder adjustment, lean multivitamin users had a 71% reduction in preeclampsia risk compared with lean nonusers (OR=0.29, 95% CI: 0.12, 0.65). In contrast, there was no relation between multivitamin use and preeclampsia among overweight women (OR=1.08, 95% CI: 0.52, 2.25). A sensitivity analysis for unmeasured confounding by fruit and vegetable intake supported these conclusions. If confirmed by others, these results suggest that regular use of a multivitamin supplement in the periconceptional period may help to prevent preeclampsia, particularly among lean women.

The absence of interaction between drug metabolizing enzyme genotypes and maternal lifestyle factors on glycophorin A somatic mutation frequency levels in newborns.

Prenatal exposure to carcinogens results in newborn DNA damage which in turn is associated with impaired health conditions in both childhood and adulthood. The present study aimed to evaluate whether phase I and II biotransformation enzyme genetic polymorphisms in combination with environmental exposures during pregnancy result in elevated levels of newborn DNA damage. Maternal peripheral and umbilical cord blood samples from 406 mother/newborn pairs were genotyped for a panel of phase I/II metabolic enzymes (CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2) responsible for the metabolism of tobacco and lifestyle-related mutagens and carcinogens. DNA damage was measured by somatic cell mutation frequency at the glycophorin A (GPA) locus in newborns. No association with elevated somatic cell mutation frequency was observed between the combination of maternal/newborn genotypes and cigarette smoke or lifestyle exposures. The observed variation in newborn GPA frequency might be due to either environmental factors not assessed in this study or inter-individual differences in alternative metabolic or DNA repair pathways.

Inflammation and triglycerides partially mediate the effect of prepregnancy body mass index on the risk of preeclampsia.

The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors conducted a nested case-control study of 55 preeclamptic women and 165 pregnant controls from the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001). Serum samples collected at < or = 20 weeks' gestation were analyzed for levels of C-reactive protein and triglycerides. The adjusted odds ratio (AOR) from a multivariable conditional logistic regression model assessing the total effect of body mass index on preeclampsia risk was compared with the AOR from the same model after results were controlled for C-reactive protein, triglycerides, and confounding factors (direct-effects model). The percentage of the total effect that was mediated through inflammation and triglycerides was calculated as 100 - [ln(direct-effects AOR)/ln(total-effects AOR)]. In the total-effects model, 4- and 8-unit increases in body mass index were associated with 1.7-fold (95% confidence interval (CI): 1.3, 2.3) and 2.9-fold (95% CI: 1.6, 5.2) increases in preeclampsia risk, whereas in the direct-effects model, these AORs were 1.4 (95% CI: 1.0, 1.9) and 2.0 (95% CI: 1.0, 3.8), respectively. Inflammation was a more important mediator than triglycerides. These findings suggest that approximately one third of the total effect of body mass index on preeclampsia risk is mediated through inflammation and triglyceride levels.

Maternal plasma homocysteine concentrations are not increased in twin pregnancies.

OBJECTIVE(S): We tested the hypothesis that twin pregnancies would lead to increased maternal plasma homocysteine. We further hypothesized that twin pregnancies complicated by preeclampsia would have increased plasma homocysteine compared to twin pregnancies without preeclampsia and normal singleton pregnancies. METHODS: Plasma was collected at delivery from 127 nulliparous subjects: 57 women with normal singleton pregnancies, 39 women with singleton and preeclampsia, 17 women with uncomplicated twin pregnancies, and 14 women with twins and preeclampsia. Subjects were group matched for prepregnancy body mass index (BMI) and race. Plasma homocysteine was analyzed by high pressure liquid chromatography (HPLC) with fluorescence detection, and plasma folic acid was measured by radio immunoassay (RIA). RESULTS: The mean plasma concentration of homocysteine was significantly increased in all women with preeclampsia (7.4+/-2.9 microM) compared to all normal pregnant women (5.9+/-2.1 microM, p=0.002). However, homocysteine was not significantly increased in all women with twins (6.7+/-2.1 microM) compared to all women with singleton pregnancies (6.5+/-2.7 microM, p=0.61). In addition, women with twins and preeclampsia did not have increased homocysteine (6.8+/-2.1 microM) compared to women with twins and normal pregnancy (6.7+/-2.1 microM, p=0.72). As expected, because of extra supplementation, plasma folic acid was significantly increased in women with twins (27.9+/-11.6 ng/mL) compared to women with singleton pregnancies (20.8+/-8.5 ng/mL, p=0.0003). However, folic acid was not different between preeclamptics and controls (23.5+/-10.8 vs. 21.9+/-9.2 ng/mL respectively, p=0.36). Lastly, there was a significant inverse correlation between homocysteine and folic acid among all the subjects (r2=- 0.053, p< 0.01), and this correlation persisted in the women with singleton pregnancies (r2=- 0.078, p< 0.01), but was lost in the twins (r2=- 0.073, p=0.14). CONCLUSIONS: With contemporary management including increased folic acid supplementation, plasma homocysteine is not increased in twin pregnancies with or without preeclampsia.

Association between allelic variants in cytokine genes and preeclampsia.

OBJECTIVE: The purpose of this study was to examine the relationship between cytokine genotypes and preeclampsia. STUDY DESIGN: We conducted a case-control study that examined cytokine genotypes among 150 primiparous preeclamptic women and 661 primiparous, normotensive women. Analyses were adjusted for age, prepregnancy cigarette smoking, and education. RESULTS: Preeclamptic white women were more likely than normotensive white women to carry the up-regulating tumor necrosis factor-alpha-308 A/A (odds ratio, 4.1; 95% CI, 1.1-15.3) genotype. Both black and white women with preeclampsia were more likely than normotensive control subjects to carry the interleukin-1alpha-producing-4845 G/G genotype (black odds ratio, 11.6; 95% CI, 1.5-89.3; white odds ratio, 1.7; 95% CI, 0.7-3.9), -889 C/C genotype (black odds ratio, 5.1; 95% CI, 0.6-41.6; white odds ratio, 1.9; 95% CI, 0.8-4.7), and the interleukin-1alpha-4845/interleukin-1alpha-889/interleukin-1beta-3957 GCC/GCC haplotype (black odds ratio, 3.4; 95% CI, 1.3-8.7; white odds ratio, 2.1; 95% CI, 1.4-3.2). CONCLUSION: Cytokine genotypes were associated with preeclampsia and may identify women who are at high risk for preeclampsia.

S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: effects in pregnancy and preeclampsia plasma.

S-nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO) in plasma. In preeclampsia, a pregnancy-specific disorder associated with endothelial dysfunction, we previously found significant elevations in plasma SNO-Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg, copper [Cu]) are necessary for release of NO from S-nitrosothiols. We propose that vasodilator effects of SNO-Alb, mediated by release of NO, are fully realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO-Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled plasma from normal or preeclamptic pregnancies were examined in isolated mouse arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or SH-Alb at physiologically relevant concentrations. When free Cu was added in excess (10 mumol/L), NO release was not dependent on Asc. However, when Cu was added at lower (physiological) levels, NO release was dependent on Asc. The addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated arteries >90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1+/-4.7%, whereas normal pregnancy plasma caused 11.9+/-4.2% relaxation (P=0.007). These data indicate that SNO-Alb alone or in plasma can act as a potent vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb.

Barrier methods, length of preconception intercourse, and preeclampsia.

BACKGROUND: The immune maladaptation theory suggests that tolerance to paternal antigens, resulting from prolonged exposure to sperm, protects against the development of preeclampsia. We tested whether barrier contraception and shorter sexual experience with the father of the pregnancy would increase the risk of preeclampsia. METHODS: Of 2211 women delivering singleton births after enrollment in a pregnancy cohort study, 85 (3.8%) developed preeclampsia as defined by antepartum systolic blood pressure > or = 140 or diastolic blood pressure > or = 90 plus proteinuria. At a mean of 10.2 weeks of gestation, all women in the cohort were asked about preconception contraception and timing of first sexual intercourse with the father of the pregnancy. Odds ratios (OR) comparing cases with preeclampsia to the rest of the cohort were adjusted for age, smoking, parity, and body mass index (BMI). RESULTS: Women using barrier contraception prior to conception were no more likely than women not using barrier contraception to develop preeclampsia (adjusted OR 1.0, 95% CI 0.6-1.6). In unadjusted analyses, a prolonged time to conception was associated with preeclampsia (OR 1.9), however, after adjustment, the association was less prominent (OR 1.6) and after stratification by contraception method, the link between time to conception and preeclampsia was eliminated. CONCLUSION: These data do not support the immune maladaptation theory of preeclampsia.

Differential distribution of allelic variants in cytokine genes among African Americans and White Americans.

Racial disparities in health are largely unexplained. Because many diseases causing premature mortality among African Americans are mediated by the immune system, the authors explored the race-specific distribution of allelic variants in cytokine genes known to stimulate inflammation. The authors studied women seeking prenatal care and delivering singletons in uncomplicated first births at a US hospital in 1997-2001. A total of 179 African-American women and 396 White women were evaluated for functionally relevant allelic variants in cytokine genes. African-American women were significantly more likely to carry allelic variants known to up-regulate proinflammatory cytokines; odds ratios increased with allele dose. Odds ratios for African Americans versus Whites in genotypes up-regulating proinflammatory interleukin (IL) 1 (IL1A-4845G/G, IL1A-889T/T, IL1B-3957C/C, and IL1B-511A/A) ranged from 2.1 to 4.9. The proinflammatory cytokine interleukin-6 IL6-174 G/G genotype was 36.5 times (95% confidence interval (CI): 8.8, 151.9) more common among African Americans. Genotypes known to down-regulate the antiinflammatory interleukin-10 (IL10-819 T/T and IL10-1082 A/A) were elevated 3.5-fold (95% CI: 1.8, 6.6) and 2.8-fold (95% CI: 1.6, 4.9) in African Americans. Cytokine genotypes found to be more common in African-American women were consistently those that up-regulate inflammation.

Family history of hypertension, heart disease, and stroke among women who develop hypertension in pregnancy.

OBJECTIVE: To assess familial cardiovascular risk factors in women developing hypertension in pregnancy. METHOD: Of 2211 women delivering live births after enrollment in a pregnancy cohort study, 85 (3.8%) developed preeclampsia (antepartum systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 plus proteinuria) and 142 (6.4%) developed transient hypertension of pregnancy (antepartum blood pressure elevation without proteinuria). At a mean of 10.2 weeks' gestation, women were asked about first-degree family members with heart disease or stroke, hypertension, diabetes, renal disease, or any of these, which defined familial cardiovascular risk. RESULTS: After adjustment for age and body size, having two or more family members, versus no family members, with cardiovascular risk imparted a 1.9-fold (95% confidence interval [CI] 1.1, 3.2) elevated risk for developing preeclampsia and a 1.7-fold (95% CI 1.1, 2.6) risk for developing transient hypertension of pregnancy. Having two or more family members with hypertension also imparted a significant, two-fold elevation in risk of preeclampsia and transient hypertension of pregnancy, and having two or more family members with heart disease or stroke imparted a 3.2-fold (95% CI 1.4, 7.7) elevation in the risk for preeclampsia. CONCLUSION: A strong family history of aggregate cardiovascular risk increased the likelihood for developing preeclampsia and transient hypertension of pregnancy. These findings support the theory that a preexisting tendency to cardiovascular risk, and particularly hypertension, increases a women's susceptibility to developing hypertension in pregnancy.