Research Article: Maternal Hypertensive Disorders of Pregnancy and Offspring Risk of Hypertension: A Population-Based Cohort and Sibling Study

Date Published: March 24, 2019

Publisher: Oxford University Press

Author(s): Azra Kurbasic, Abigail Fraser, Ingrid Mogren, Göran Hallmans, Paul W Franks, Janet W Rich-Edwards, Simon Timpka.


Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of hypertension, cardiovascular disease, and type 2 diabetes. Offspring from pregnancies complicated by HDP also have worse cardiometabolic status in childhood and young adulthood, but the offspring risk of clinical hypertension in adulthood is largely unknown.

We studied 13,893 first-born adult offspring (49.4% female) who attended a structured population-based primary care visit (The Västerbotten Health Survey) at age 40 years in Sweden between 1994 and 2013. Data on maternal HDP were collected from a population-based birth register. We investigated the association between maternal HDP and the risk of adult offspring hypertension and worse cardiometabolic risk factor status utilizing multivariable poisson and linear regression models. We also conducted a sibling comparison, which inherently accounted for familial factors shared by siblings (N = 135).

Offspring participants of women with HDP (N = 383, 2.8%) had increased relative risk of hypertension (1.67, 95% confidence interval: 1.38, 2.01) and also higher mean body mass index, systolic blood pressure, diastolic blood pressure, and worse 2-hour 75 g oral glucose tolerance test result at age 40 years. No difference was observed for serum cholesterol. Point estimates for the cardiometabolic risk factors were attenuated in the sibling analyses.

Offspring born to mothers with a history of HDP are on an adverse cardiometabolic trajectory and should be considered as concomitant targets for primordial prevention of hypertension in the maternal post-pregnancy period.

Partial Text

Hypertensive disorders of pregnancy (HDP; including gestational hypertension and pre-eclampsia) are serious complications during pregnancy, and women affected have higher risk of post-pregnancy cardiometabolic disease.1 Furthermore, the children born to these affected women and exposed to maternal HDP also have higher blood pressure2 and body mass index (BMI)3 compared with children born to normotensive mothers. These differences persist in young adulthood4 and might even translate into an increased risk of type 2 diabetes5 and stroke6 later in life. Results from animal models suggest that reduced uterine perfusion and exposure to anti-angiogenic factors during gestation—mimicking pre-eclampsia—can result in higher long-term blood pressure in the offspring, potentially mediated through altered cardiovascular structure and function.7 Yet, a sibling analysis of young adult offspring suggested that the association between maternal HDP and offspring cardiometabolic risk factors might be largely attributable to shared familial factors.4 However, no study has presented clinically measured hypertension data on middle-aged adults born to hypertensive or preeclamptic women and also included analysis of non-exposed siblings.8

We utilized data from standardized population-based preventive care visits in primary care at age 40 years (Västerbotten Health Survey)9,10 and comprehensive population-based registries of deliveries.11 Additional data on education and place of residence were collected via Statistics Sweden. The study was approved by the Regional Ethical Review Board at Lund University (2014/337).

Of the total study sample (N = 13,893), 383 participants (2.8%) were exposed to maternal HDP. At age 40 years, there were no substantial differences in smoking status or education level between participants exposed and not exposed to maternal HDP. Supplementary Table 1 shows the study sample characteristics.

In this study, we for the first time report offspring exposed to maternal HDP during pregnancy to have higher risk of hypertension based on clinical measurements in middle age. Furthermore, we found that exposure to maternal HDP is associated with higher adult blood pressure and BMI. In contrast, we found less evidence of a difference in cardiometabolic health between siblings with differential fetal HDP exposure.

A.K. is currently employed at Leo Pharma A/S, Copenhagen, Denmark.




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