Maternal Hypertensive Disorder of Pregnancy and Mortality in Offspring From Birth to Young Adulthood: National Population-Based Cohort Study

Abstract

ABSTRACT Worldwide, hypertensive disorders of pregnancy (HDPs) affect up to 10% of pregnancies. It has been associated with adverse pregnancy and birth outcomes, as well as diseases in the offspring later in life, such as metabolic syndrome, and neurodevelopmental and psychiatric disorders. It has been proposed that maternal HDPs may increase the susceptibility of offspring to disease through multiple pathways, such as placental dysfunction, a hypoxic-ischemic environment in pregnancy, abnormal inflammatory levels, and epigenetic changes. However, there is a scarcity of evidence to support this association. The aim of this study was to examine the association between maternal HDPs with mortality in offspring from birth to young adulthood. This was a population-based cohort study based on data from Danish national health registries. Included were all live births in Denmark between 1978 and 2018. Excluded were those with a birth weight <500 g and gestational age at birth <22 weeks and those who died on the day of birth. Live-born individuals were followed from the date of birth until the date of death, emigration, or December 31, 2018, whichever came first. Maternal HDP was categorized as eclampsia, preeclampsia, or hypertension. Overall, 4.2% of 2,437,718 live-born offspring were exposed prenatally to maternal HDP, including 2.8% exposed to preeclampsia or eclampsia and 1.4% to hypertension. During follow-up of up to 41 years (median, 19.4 [interquartile range 9.7–28.7] years), there were 781 deaths (58.94 per 100,000 person years) among offspring exposed to preeclampsia, 17 deaths (133.73 per 100,000) among those exposed to eclampsia, 223 deaths (44.38 per 100,000) among those exposed to hypertension, and 19,119 deaths (41.99 per 100,000) among those not exposed to HDP. The HDP-exposed cohort had a higher cumulative incidence of all-cause mortality than the nonexposed cohort (2.06% [95% confidence interval {CI}, 1.82%–2.34%] vs 1.69% [95% CI, 1.65%–1.73%]), a 0.37% difference (95% CI, 0.11%–0.64%). The HDP-exposed cohort also had a 26% higher risk (hazard ratio, 1.26 [95% CI, 1.18–1.34]) of all-cause mortality than nonexposed offspring. The risks of all-cause mortality were 29% in those exposed to preeclampsia (1.29 [95% CI, 1.20–1.38]), 118% in those exposed to eclampsia (2.88 [95% CI, 1.79–4.63]), and 12% in those exposed to hypertension (1.12 [95% CI, 0.98–1.28]). There were increased risks for cause-specific mortality in the HDP-exposed cohort, including from digestive diseases (2.09 [95% CI, 1.27–3.43]); conditions originating in the perinatal period (2.04 [95% CI, 1.81–2.30]); endocrine, nutritional, and metabolic diseases (1.56 [95% CI, 1.08–2.27]); and cardiovascular diseases (1.52 [95% CI, 1.08–2.13]). In conclusion, maternal HDP was associated with increased risks of all-cause mortality, as well as cause-specific deaths, including digestive diseases; conditions originating in the perinatal period; endocrine, nutritional, and metabolic diseases; and cardiovascular disease.