Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study.

BACKGROUND: Hypertensive disorders of pregnancy are associated with cardiovascular disease later in life. Given that hypertensive disorders of pregnancy often occur at a relatively young age, there might be an opportunity to use preventive measures to reduce the risk of early cardiovascular disease and mortality. The aim of this study was to assess the risk of cardiovascular mortality in women after a hypertensive disorder of pregnancy. METHODS: In this population-based cohort study, the Netherlands Perinatal Registry (PRN) and the national death registry at the Dutch Central Bureau for Statistics were linked. We analysed women in the Netherlands with a first birth during 1995-2015 to determine the association between cardiovascular mortality and hypertensive disorders of pregnancy (based on recorded diastolic blood pressure or proteinuria, or both). We analysed the association between the highest diastolic blood pressure measured in pregnancy and cardiovascular mortality and constructed survival curves to assess cardiovascular mortality after hypertensive disorders of pregnancy, specifically pre-eclampsia and gestational hypertension. To differentiate between the severity of hypertensive disorders of pregnancy, cardiovascular mortality was assessed in women with a combination of hypertensive disorders of pregnancy with preterm birth (gestational age <37 weeks) and growth restriction (birthweight in the 10th percentile or less). All hazard ratios (HRs)were adjusted for maternal age. FINDINGS: Between Jan 1, 1995, and Dec 31, 2015, the PRN contained 2 462 931 deliveries and 1 625 246 women. In 1 243 890 women data on their first pregnancy were available and were included in this analysis after linkage, with a median follow-up time of 11·2 years (IQR 6·1-16·3). 259 177 (20·8%) women had hypertensive disorders of pregnancy, and of these 45 482 (3·7%) women had pre-eclampsia and 213 695 (17·2%) women had gestational hypertension; 984 713 (79·2%) women did not develop hypertension in their first pregnancy. Compared with women without hypertensive disorders of pregnancy, the risk of death from any cause was higher in women who had hypertensive disorders (HR 1·30 [95% CI 1·23-1·37], p<0·001), pre-eclampsia (1·65 [1·48-1·83]; p<0·0001), and gestational hypertension (1·23 [1·16-1·30]; p<0·0001). Those women with pre-eclampsia had a higher risk of cardiovascular mortality compared with those without any hypertensive disorders of pregnancy (adjusted HR 3·39 [95% CI 2·67-4·29]), as did those with gestational hypertension (2·22 [1·91-2·57]). For women with a history of hypertensive disorders of pregnancy combined with preterm birth (gestational age <37 weeks) and birthweight in the 10th percentile or less, the adjusted HR for cardiovascular mortality was 6·43 (95% CI 4·36-9·47), compared with women without a hypertensive disorder of pregnancy. The highest diastolic blood pressure measured during pregnancy was the strongest risk factor for cardiovascular mortality (for 80-89 mm Hg: adjusted HR 1·47 [95% CI 1·00-2·17]; for 130 mm Hg and higher: 14·70 [7·31-29·52]). INTERPRETATION: Women with a history of hypertensive disorders of pregnancy have a risk of cardiovascular mortality that is 2-3 times higher than that of women with normal blood pressure during pregnancy. The highest measured diastolic blood pressure during pregnancy is an important predictor for cardiovascular mortality later in life; therefore, women who have hypertensive disorders of pregnancy should be given personalised cardiovascular follow-up plans to reduce their risk of cardiovascular mortality. FUNDING: None.

Cardiovascular mortality risk a decade after twin and singleton pregnancies complicated by hypertensive disorders of pregnancy.

OBJECTIVES: To describe the cardiovascular mortality (CVM) risk in women after twin versus singleton pregnancies complicated by hypertensive disorders of pregnancy (HDP). STUDY DESIGN: Retrospective cohort study of nulliparous women with a twin or singleton pregnancy who delivered in the Netherlands between 1995 and 2015. We used data of the Perinatal Registry of the Netherlands and data of the National Death Registry to determine baseline data, the occurrence of HDP and CVM. In the two main analyses we compared twin pregnancies complicated by HDP to 1) singleton pregnancies complicated by HDP and 2) uncomplicated twin pregnancies (i.e. without HDP) of women who delivered within a hospital setting. MAIN OUTCOME MEASURES: CVM risk using cox-proportional hazard models, adjusted for maternal age (aHR). RESULTS: 1,243,231 nulliparous women were included, of which 30,623 (2.5%) had a twin and 1,212,608 (97.5%) had a singleton pregnancy. A total of 9,853 (32.2%) twin pregnancies were complicated by HDP, versus 249,141 (20.6%) singleton pregnancies (p < 0.0001). Within the HDP twin cohort, 14/73 (19.2%) maternal deaths were due to cardiovascular causes, versus 335/1,788 (18.7%) in the HDP singleton cohort and 10/117 (8.6%) in the uncomplicated twin cohort. The corresponding aHR was 2.85 (95% CI 1.26-6.41; p = 0.01) for the HDP twin versus the uncomplicated twin cohort, and 1.05 (95% CI 0.62-1.80; p = 0.85) for the HDP twin versus the HDP singleton cohort. CONCLUSIONS: Women after both twin and singleton pregnancies complicated by HDP are at a similarly increased risk of CVM later in life.

Reproductive risks in 35-year-old adults born very preterm and/or with very low birth weight: an observational study.

Evidence suggests that increased survival over the last decades of very preterm (VPT; gestational age < 32 weeks)- and very low birth weight (VLBW; birth weight < 1500 g)-born infants is not matched by improved outcomes. The objective of our study was to evaluate the reproductive rate, fertility, and pregnancy complications in 35-year-old VPT/VLBW subjects. All Dutch VPT/VLBW infants born alive in 1983 and surviving until age 35 (n = 955) were eligible for a POPS-35 study. A total of 370 (39%) subjects completed a survey on reproductive rate, fertility problems, pregnancy complications, and perinatal outcomes of their offspring. We tested differences in these parameters between the VPT/VLBW subjects and their peers from Dutch national registries. POPS-35 participants had less children than their peers in the CBS registry. They reported more problems in conception and pregnancy complications, including a three times increased risk of hypertension during pregnancy.Conclusion: Reproduction is more problematic in 35-year olds born VPT/VLBW than in the general population, possibly mediated by an increased risk for hypertension, but their offspring have no elevated risk for preterm birth. What is known: At age 28, the Dutch national POPS cohort, born very preterm or with a very low birth in 1983, had lower reproductive rates than the general Dutch population (female 23% versus 32% and male 7% versus 22%). What is new: At age 35, the Dutch POPS cohort still had fewer children than the general Dutch population (female 56% versus 74% and male 40% versus 56%). Females in the POPS cohort had a higher risk of fertility problems and pregnancy complications than their peers in the Dutch national registries, but their offspring had no elevated risk for preterm birth.