Risk Of Recurrent Preeclampsia Research Articles

Pre-eclampsia in a first pregnancy and subsequent pregnancy outcomes: a nationwide cohort study

BackgroundFor women whose first pregnancy was complicated by pre-eclampsia (PE), particularly if severe and requiring early birth, the risk of recurrence and maternal and neonatal outcomes at subsequent birth are...

Risk of recurrent preeclampsia (PRE) in a consecutive pregnancy cohort

Previous preeclampsia (PRE) is a risk factor for recurrence of PRE in future pregnancies. However, the magnitude of the recurrence risk in contemporaneous population-based cohorts is not well quantified. We evaluated the risk of recurrent PRE following PRE in prior pregnancy in a large database of consented and enrolled participants with two consecutive pregnancies during the study period.

The interval between births and the risk of recurrent preeclampsia among predominantly high risk women in urban tertiary care center

Women with a history of preeclampsia have a higher risk of recurrent preeclampsia. This study sought to ascertain the relationship between the interbirth interval and the risk of recurrent preeclampsia and difference in angiogenic markers between the two groups. Data was collected from an ongoing cohort study of women with hypertensive disorders of pregnancy (HDP) enrolled at the admission to the labor and delivery floor. From this dataset, multigravida women with a prior diagnosis of preeclampsia were identified and compared to women with no prior history of preeclampsia. Of the 375 women with HDP who were predominantly African American, 245 were multigravida and 44 (18.0%) had a prior history of preeclampsia. Women with prior preeclampsia had an earlier gestational age of delivery, higher rates of preterm delivery and a higher incidence of preeclampsia with severe features (56.8% vs 29.8%) in the index pregnancy (p-values≤0.001) than those without. The median number of years between history of preeclampsia in previous pregnancy and current pregnancy was 6years (IQR 3, 8). Among patients with a prior history of preeclampsia, the interbirth interval was not associated with severe preeclampsia (p=0.60) and there was no difference in angiogenic factors between patients with a prior history of preeclampsia compared to those without. In this study, the duration of the interbirth interval was not identified as a risk factor of developing severe preeclampsia in a subsequent pregnancy and angiogenic factors are not a reflection of maternal predisposition to recurrent preeclampsia.

Comparison of three definitions of metabolic syndrome and relation to risk of recurrent preeclampsia

ABSTRACT Objective. To determine the prevalence of metabolic syndrome in formerly preeclamptic women according to three definitions of metabolic syndrome (World Health Organization [WHO], International Diabetes Federation [IDF], and Third Adult Treatment Panel updated [ATPIII]), to evaluate agreement amongst definitions and to compare the risk of recurrent preeclampsia. Methods. In 197 women with a history of preeclampsia, we determined presence of metabolic syndrome using WHO, IDF, and ATPIII criteria. We evaluated agreement amongst definitions by using Kappa statistics. The prevalence of recurrent preeclampsia was compared between women with and without inter-pregnancy metabolic syndrome, according to the three definitions. Results. A total of 40 (20%), 46 (23%), and 31 (16%) of women with previous preeclampsia were classified as having metabolic syndrome postpartum according to WHO, IDF, and ATPIII criteria, respectively. Agreement among criteria was considered substantial between WHO and IDF (κ = 0.64, 95% CI 0.53–0.79), WHO and ATPIII (κ = 0.74, 95% CI 0.62–0.86), and IDF and ATPIII (κ = 0.66, 95% CI 0.51–0.77). The prevalence of recurrent preeclampsia was 45% versus 17% in women with and without inter-pregnancy metabolic syndrome according to the WHO definition (P < 0.001), 26% versus 21% according to the IDF criteria (P = 0.16), and 39% versus 20% according to the ATPIII definition (P = 0.02). Conclusions. Agreement among WHO, IDF, and ATPIII criteria of metabolic syndrome in women after preeclampsia is considered substantial. The risk of recurrent preeclampsia is almost one out of two in women with inter-pregnancy metabolic syndrome according to the WHO criteria.

Abstract 15564: What Pre-pregnancy, Pregnancy, and Inter-pregnancy Cardiometabolic Factors Contribute to Increased Risk of Recurrent Preeclampsia?: A Longitudinal Analysis in the Boston Birth Cohort

Introduction: Women with recurrent preeclampsia represent a group at uniquely high risk for maternal and perinatal morbidity, as well as future cardiovascular complications. The aim of this study is to examine the association of cardiometabolic risk factors with recurrent preeclampsia in the subsequent pregnancy. Methods: The Boston Birth Cohort is a racially/ethnically diverse birth cohort with over 8500 women. We identified 618 women with repeat pregnancies. Of those, 78 women had preeclampsia in the index pregnancy, and of those, 33 had recurrent preeclampsia in the subsequent pregnancy. We used log-binomial regression to examine the association between pre-pregnancy, pregnancy, and inter-pregnancy cardiometabolic risk factors (e.g., obesity, hypertension, diabetes mellitus, preterm birth, low birth weight, and gestational diabetes mellitus) and recurrent risk of preeclampsia. Results: Among the 78 women who had preeclampsia in their index pregnancy, the recurrence rate of preeclampsia was 42.3%. Several maternal risk factors were associated with this recurrent risk. Compared to women with pre-(index) pregnancy normal weight, the risk of recurrent preeclampsia was 3 times higher for women with pre-(index) pregnancy overweight (RR 3.0 [95% CI: 1.4 to 6.6]) or obesity (RR 3.1 [95% CI: 1.5 to 6.7). Compared to women without new inter-pregnancy chronic hypertension, women with new inter-pregnancy chronic hypertension had a 2-fold higher risk of recurrent preeclampsia (RR 2.4 [95% CI: 1.5 to 3.9]). Conclusions: Pre-(index) pregnancy obesity and new inter-pregnancy chronic hypertension was highly associated with recurrent preeclampsia in the subsequent pregnancy. Clinical and public health programs focused on reducing preconception obesity and reducing risk of hypertension in both the pre-pregnancy and inter-pregnancy periods may help reduce recurrent preeclampsia, which, in turn may help prevent or reduce subsequent cardiovascular disease.

Recurrence risk of preeclampsia in a linked population-based cohort: Effects of first pregnancy maximum diastolic blood pressure and gestational age.

To estimate preeclampsia occurrence and recurrence risk in the 2nd pregnancy and analyze associated risk factors such as 1st pregnancy maximum diastolic blood pressure (maxDBP) and gestational age at delivery (GA). Linked cohort of 1st and 2nd pregnancies of 272,551 women from the Dutch Perinatal Registry collected between 2000 and 2007. We defined preeclampsia as hypertension (maxDBP ≥90 mmHg or documented hypertension) plus proteinuria (≥300 mg/24 h) and analyzed its 2nd pregnancy occurrence with logistic regression. Early and late onset preeclampsia were defined by delivery before and after the 34th week, respectively. Preeclampsia prevalences in the 1st and 2nd pregnancies were 2.5% and 0.9%, respectively. Women with prior preeclampsia had a 10.5% risk of recurrence. For women with term 1st pregnancies and maxDBP <80 mmHg, the 2nd pregnancy preeclampsia rate was 0.2% (95% CI 0.17%-0.23%), while for those whom presented maxDBP ≥110 mmHg it was 4.2% (95% CI 3.6%-4.8%). First pregnancy late onset preeclampsia was associated with increased preeclampsia recurrence risk proportional to 1st pregnancy maxDBP: in women with a maxDBP between 100 and 109 mmHg the recurrence risk was 8.3%, while for women with a maxDBP ≥110 mmHg this risk was 11% (difference 2.7%; 95% CI 1.0%-4.4%). In 1st pregnancy early onset preeclampsia corresponding rates were 14.8% and 19.3% (difference 4.5%; 95% CI -1.3%-9.7%). Preeclampsia recurrence risk is 10%. Preeclampsia risk in the 2nd pregnancy increases proportionally to 1st pregnancy maxDBP. Earlier onsets of 1st pregnancy preeclampsia further increase recurrence risk.

Placental weight in the first pregnancy and risk for preeclampsia in the second pregnancy: A population-based study of 186 859 women

ObjectiveTo study whether placental weight in the first pregnancy is associated with preeclampsia in the second pregnancy.Study designIn this population-based study, we included all women with two consecutive singleton pregnancies reported to the Medical Birth Registry of Norway during 1999–2012 (n = 186 859). Placental weight in the first pregnancy was calculated as z-scores, and the distribution was divided into five groups of equal size (quintiles). We estimated crude and adjusted odds ratios with 95% confidence intervals for preeclampsia in the second pregnancy according to quintiles of placental weight z-scores in the first pregnancy. The 3rd quintile was used as the reference group.ResultsAmong women without preeclampsia in the first pregnancy, 1.4% (2507/177 149) developed preeclampsia in the second pregnancy. In these women, the risk for preeclampsia in the second pregnancy was associated with placental weight in the first pregnancy in both lowest (crude odds ratio (cOR) 1.30, 95% confidence interval (CI); 1.14–1.47) and highest quintile (cOR 1.20, 95% CI; 1.06–1.36). The risk associated with the highest quintile of placental weight was confined to term preeclampsia. Among women with preeclampsia in the first pregnancy, 15.7% (1522/9710) developed recurrent preeclampsia, and the risk for recurrent preeclampsia was associated with placental weight in lowest quintile in the first pregnancy (cOR 1.30, 95% CI; 1.10–1.55). Adjustment for interval between pregnancies, maternal diabetes, age, and smoking in the first pregnancy did not alter these estimates notably.ConclusionPlacental weight in the first pregnancy might help to identify women who could be at risk for developing preeclampsia in a second pregnancy.

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia

The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September2014. The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52-0.95). Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.

H1. Persistent maternal cardiac dysfunction after preeclampsia identifies patients at risk for recurrent pre-eclampsia

Objective: The purpose of our study was to assess cardiac function in non-pregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia.Methods: Seventy-five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case control study and submitted to echocardiographic examination in the non-pregnant state 12–18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term.Results: Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the non-pregnant state, patients with recurrent preeclampsia compared to controls and non-recurrent preeclampsia had lower stroke volume (63 ± 14 mL versus 73 ± 12 mL and 70 ± 11 mL, p < 0.05), cardiac output (4.6 ± 1.2 L versus 5.3 ± 0.9 L and 5.2 ± 1.0 L, p < 0.05), higher E/E’ ratio (11.02 ± 3.43 versus 7.34 ± 2.11 versus 9.03 ± 3.43, p < 0.05), and higher total vascular resistance (1638 ± 261 dyne·s·cm−5 versus 1341 ± 270 dyne·s·cm−5 and 1383 ± 261 dyne·s·cm−5, p < 0.05). Left ventricular mass index was higher in both recurrent and non-recurrent preeclampsia compared to controls (30.0 ± 6.3 g/m2.7 and 30.4 ± 6.8 g/m2.7 versus 24.8 ± 5.0 g/m2.7, p < 0.05). Conclusions: Signs of diastolic dysfunction and different left ventricular characteristics are present in the non-pregnant state before a second pregnancy with recurrent preeclampsia. Previous preeclamptic patients with non-recurrent preeclampsia show left ventricular structural and functional features intermediate with respect to controls and recurrent preeclampsia.

47 Quantifying recurrence risk of preeclampsia in a population-based cohort: Effects of first pregnancy maximum diastolic pressure

Introduction Preeclampsia (PE) is a major source of maternal and fetal morbidity that affects 2.5–3.0% of all pregnancies. Recurrence estimates range from 0% to 67%. Such a wide range imposes a difficult challenge in counseling future pregnancies, and so a better assessment of pertinent risk factors for recurrence in the individual patient is required. Objective We aim to estimate the recurrence risk of preeclampsia (PE) in the 2nd pregnancy and investigate the influence of first pregnancy maximum diastolic pressure and additional risk factors. Methods We studied a linked cohort of 1st and 2nd pregnancies of 272.551 women from the Dutch Perinatal Registry collected between 2000 and 2007. We defined PE as hypertension (diastolic blood pressure >90 mmHg) plus proteinuria (>300 mg/24 h), included recorded PE cases and analysed the PE recurrence rate using logistic regression. To avoid potential listwise deletion bias, multiple imputation of missing maximum diastolic blood pressure data was used. Gestational and maternal ages, multiple pregnancy, chronic hypertension, diabetes, ethnicity and socioeconomic status were considered as covariates. Results The overall PE prevalences in the 1st and 2nd pregnancies were 2.4% and 0.9%, respectively. In the 2nd pregnancy the prevalence of PE was 10.4% for women with prior preeclampsia. Early onset PE in the 1st pregnancy with delivery before the 34th week was associated with increased recurrence risk proportional to the maximum diastolic blood pressure (DBP) in the 1st pregnancy: for DBP between 90 and 100 mmHg the recurrence risk was 15% (95% CI 11.1–20.6%) while for DBP above 110 mmHg the risk was 26.6% (95% CI 21.6–32.3%). For women with increased maximum DBP but no history of preeclampsia the corresponding rates were 2.2% (95% CI 2.0–2.4%) and 6.3% (95% CI 5.3–7.5%). Conclusion The overall chance of recurrence of preeclampsia is 10.4%. Early onset preeclampsia complicated by severe hypertension increases this rate to about one in four. Severe hypertension in the 1st pregnancy in women that did not present preeclampsia is a major risk factor for preeclampsia in the following pregnancy. This knowledge can improve patient and physician awareness of the individual risks of occurrence and recurrence of preeclampsia which are fundamental for the proper management of subsequent pregnancies.

54 Can we prevent recurrent pre-term preeclampsia?

Preterm preeclampsia (PTPE) (<34 weeks of gestation) is a life-threatening complication of pregnancy with a high recurrence rate (20–60%). Low dose aspirin (ASA) may prevent recurrence, and some trials suggest that low molecular weight heparin (LMWH) and ASA together is more effective but results are inconclusive. We report the recurrence rate of PE in women with prior PTPE and the impact of therapy on fetal birth weight (BW) and gestational age at delivery (GA). We prospectively followed 41 women with PTPE in a prior pregnancy throughout 53 subsequent pregnancies. Women were screened for genetic and acquired thrombophilias and treated with either ASA or LMWH and ASA as determined by treating physicians. Maternal and fetal outcomes in subsequent pregnancies were ascertained including preeclampsia (PE), GA, and BW. The mean (±SD) age of the women was 36 ± 5 years at the time of their subsequent pregnancy, and BMI was 25.6 ± 5.4kg/m2. 66% were white, 5% black and 15% Hispanic. Genetic thrombophilias were detected in 91% and acquired thrombophilias in 36%. Thirteen women (25%) were not treated with ASA or LMWH, 12 (23%) received ASA alone, and 27 (52%) received LMWH ± ASA. PE recurred in 6 pregnancies (11%) and PTPE in 5 (9%). In subsequent pregnancies BW was higher (1473 ± 743 g prior pregnancy vs. 2880 ± 778 g in the subsequent pregnancies, p < 0.001), and GA at delivery was later (29 ± 4 weeks vs. 36 ± 4 weeks, p < 0.001). PE recurrence was numerically higher in the untreated group compared to those treated with ASA alone, or LMWH ± ASA (3/13 vs. 1/12 or 2/27). BW and GA increased similarly in subsequent pregnancies in all groups although women treated with LMWH ± ASA had a greater increase in GA (8.8 vs. 4.4 weeks, p = 0.021). The risk of recurrent PE or PTPE in women with prior PTPE was lower than reported in prior studies. BW and GA at delivery were significantly better in subsequent pregnancies. We found a trend towards a decreased incidence of PE and greater prolongation of pregnancy in those treated with LMWH ± ASA compared to no treatment or ASA alone. We propose an appropriately designed clinical trial to determine the benefits/risks of LMWH in women at risk for PTPE.

Clinical Implications

Clinical Implications

646: The recurrence risk of preeclampsia in subsequent pregnancies in northern Tanzania: a registry–based prospective cohort study

SpyghmoCor device (AtCor Medical Inc. USA), incorporating software that analyzes direct applanation tonometry. Aortic waveforms were constructed and arterial compliance surrogates, AP and AIx-75 (standardized to pulse of 75), were derived. An operator index of 80 assured consistency. After delivery the subject’s chart was reviewed to obtain final diagnosis. The AP and Aix-75 values were compared to final diagnosis. Statistical analyses were performed using ANOVA and Tukey multiple comparison tests and ROC curves were created in SAS 9.2. RESULTS: 151 women were recruited with an average gestational age of 35.6 weeks. 76.2% of the cohort had comorbidities: GHTN(33.9%), CHTN(41.7%), asthma(7.8%), diabetes(5.2%), other (11.3%). Readings with operator index 80 were eliminated; 136 were analyzed. 44% of the cohort was diagnosed with preeclampsia (mild 63.6%, severe 12.1%, superimposed 24.2%); these 59 AP and 54 Aix-75 readings were compared to the final diagnosis. AP and AIx-75 readings were significantly correlated to the diagnosis of preeclampsia (p .005 and p .004 respectively). AP readings were significant in diagnosing severe preeclampsia (p 0.03) and in distinguishing preeclampsia from chronic hypertension (p 0.03). ROC curves were constructed; an AP value of 9.5 and an AIx-75 value of 27.1 were 80% sensitive in predicting the diagnosis of preeclampsia, but specificity was only 40%; area under AP and AIx-75 curves were 0.62, and 0.65, respectively. CONCLUSION: Applanation tonometry may be a useful adjunct in making the diagnosis of preeclampsia, particularly in individuals in whom the diagnosis is not clear. However test characteristics of the AP and AIx-75 are not as high as desired.

Secular trends in the epidemiology of pre‐eclampsia throughout 40 years in Norway: prevalence, risk factors and perinatal survival

Pre-eclampsia is a leading complication of pregnancy, associated with maternal and neonatal morbidity. The present study describes the epidemiology of pre-eclampsia in Norway, with data from the Medical Birth Registry of Norway, covering 40 years. We aimed at describing time trends in prevalence, selected risk factors and perinatal mortality. We also analysed time trends in recurrence risk of total pre-eclampsia and pre-eclampsia with preterm delivery. A total of 2,416,501 women giving birth during 1967-2008 were included. Prevalence of pre-eclampsia increased from 1967 to 1999 and decreased thereafter, with an overall prevalence of 3%. Rates increased more over time among younger than older women, resulting in a significantly lower excess risk of pre-eclampsia associated with high maternal age in later years. For example, relative risk (RR) of pre-eclampsia among primiparae aged ≥35 relative to <25 years changed from 2.4 [95% confidence interval (CI) 2.1, 2.7] in 1967-1976 to 1.2 [95% CI 1.1, 1.3] in 1999-2008. For recurrence risk, subsequent pregnancies to a mother were linked, with the mother being the unit of analysis. Recurrence risk of pre-eclampsia was high, particularly recurrence of preterm pre-eclampsia, with overall RR close to 50 of a second pregnancy with pre-eclampsia and preterm birth compared with women without pre-eclampsia in first pregnancies. Finally, stillbirth associated with pre-eclampsia decreased more than neonatal mortality over time, and in the last 5 years only a moderate excess risk of stillbirth and neonatal death was observed.

Prepregnancy Low-Plasma Volume and Predisposition to Preeclampsia and Fetal Growth Restriction

To estimate whether recurrence risks of preeclampsia, preterm birth, and fetal growth restriction relate to prepregnancy plasma volume. We conducted a retrospective cohort study in 580 formerly preeclamptic women and a control group. In all women we measured plasma volume (iodine-human serum albumin indicator dilution method) in the nonpregnant state. One hundred seventy-eight normotensive (formerly preeclamptic) women had a subsequent pregnancy within the study period (1996-2008). Odds ratios (ORs) for recurrent preeclampsia, preterm birth, and small for gestational age (SGA) neonates were estimated, using multivariable logistic regression with adjustment for confounders. Plasma volumes were lower in women who developed recurrent preeclampsia (1,241±158 mL/m², 17% lower compared with women in the control group) than in women without recurrent preeclampsia (1,335±167 mL/m², 11% lower compared with women in the control group). Logistic regression analysis demonstrated that each 100-mL/m difference in plasma volume was associated with an OR of 0.6 (95% confidence interval [CI] 0.5-0.8) to develop recurrent preeclampsia in subsequent pregnancy. Risk of preterm delivery (before 37 weeks of gestation) depended on preeclampsia in subsequent pregnancy, the adjusted hazard ratio for preterm birth was 0.9 (95% CI 0.7-1.1) for each 100-mL/m² change in plasma volume. Risk of delivering an SGA neonate was independent of recurrent preeclampsia. Each 100-mL/m² change in plasma volume was associated with an adjusted OR of 0.8 (95% CI 0.5-0.9) to deliver an SGA neonate in subsequent pregnancy. The risk of recurrent preeclampsia and fetal growth restriction in subsequent pregnancy relates inversely and linearly to prepregnancy plasma volume.

Recurrent Preeclampsia

To estimate whether the risk of recurrent preeclampsia is affected by interpregnancy change in body mass index (BMI). We conducted a population-based cohort study using Missouri maternally linked birth certificates for 17,773 women whose first pregnancies were complicated by preeclampsia. The women were placed into three groups: those who decreased their BMIs, those who maintained their BMIs, and those who increased their BMIs between their first two pregnancies. The primary outcome was recurrent preeclampsia in the second pregnancy. Adjusted risk ratios and 95% confidence intervals were calculated using Poisson regression analysis. The overall rate of recurrent preeclampsia in women who decreased their BMIs between pregnancies was 12.8% (risk ratio 0.70, confidence interval 0.60-0.81) compared with 14.8% if BMI was maintained and 18.5% in those who increased their BMIs (risk ratio 1.29, confidence interval 1.20-1.38). Within the normal weight, overweight, and obese weight categories, women who decreased BMI between pregnancies were less likely to experience recurrent preeclampsia. Women in all weight categories who increased their BMIs between pregnancies were more likely to experience recurrent preeclampsia. Interpregnancy weight reduction decreases the risk of recurrent preeclampsia and should be encouraged in women who experience preeclampsia. II.

764: Differential gene expression in first trimester human placenta from women at high risk for recurrent preeclampsia

764: Differential gene expression in first trimester human placenta from women at high risk for recurrent preeclampsia

763: Levels of oxidized proteins are higher in first trimester human placenta from women at high risk for recurrent preeclampsia

763: Levels of oxidized proteins are higher in first trimester human placenta from women at high risk for recurrent preeclampsia

Recurrence risk of preeclampsia in twin and singleton pregnancies.

The etiology of preeclampsia is unknown. The relatively high risk of recurrence of preeclampsia in subsequent pregnancies to the same mother suggests a genetic basis for the disease, but the mode of inheritance is uncertain. We compare the risk of preeclampsia in second pregnancies for mothers whose first preeclamptic pregnancy was either a singleton or a twin pregnancy. The crude and adjusted recurrence risks of preeclampsia in twin and singleton pregnancies were estimated in a population-based register including the first and second pregnancies of 550218 women registered in the Medical Birth Registry of Norway, 1967-1998. The recurrence risk of preeclampsia in second pregnancy for women with a singleton pregnancy with preeclampsia the first time was 14.1% (95% CI: 13.6-14.6). For women with a first time twin pregnancy the recurrence risk was lower, 6.8% (CI: 4.3-10.1), P < 0.001. Thus, the crude excess risk for recurrent preeclampsia was 7.3% (95% CI: 4.5-10.0) in women with a first time singleton as compared to women with a first time twin pregnancy. The recurrence risk of preeclampsia is lower when the first pregnancy was a twin as compared to a singleton pregnancy. This observation is consistent with a polygenic liability model.

Maternal-Fetal Flow, Negative Events, and Preeclampsia

The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (P=0.0002) and allele frequency (P<0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (P=0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. The current study shows that the ACE I/D polymorphism affects uteroplacental and umbilical flows and the recurrence of an adverse pregnancy outcome in women with history of preeclampsia.