Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study

Abstract

Background

The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited.

Methods and findings

We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia ( n = 68,387), gestational hypertension ( n = 18,603), and pregestational hypertension ( n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare.

Conclusions

Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Abstract

Chen Huang and co-workers study associations between maternal hypertensive disorders and cardiovascular disease in offspring.

Author summary

Why was this study done?

• The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades in developed countries.

• Maternal hypertensive disorders of pregnancy (HDP) is associated with an increased risk of congenital heart disease and a number of risk factors of CVD in offspring.

• Little is known about whether and to what extent prenatal exposure to HDP affects the development of early-onset CVD in offspring from birth to adolescence and beyond.

What did the researchers do and find?

• We conducted a population-based cohort study that included all 2,491,340 live births in Denmark from 1977 to 2018 and followed them from birth to early adulthood (up to 40 years).

• We found that individuals born to mothers with HDP had a 23% increased risk of early-onset CVD in offspring, especially of those mothers with a history of CVD (67% increased risk) or diabetes (56% increased risk).

What do these findings mean?

• Offspring born to mothers with HDP, especially mothers with CVD or diabetes, are at an increased risk of early-onset CVD from birth to early adulthood.

• These findings suggest that better management of maternal HDP, particularly in early phase of pregnancy, may improve cardiovascular health of children and adolescents and beyond, in terms of reducing the risk of early-onset CVD.

• Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring in early decades of life.