Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood: a nationwide population-based cohort study
Authors: Yang Liu , Huang Chen , Zhao Min , Lee Priscilla M. Y. , Zhang Cheng , Yu Yongfu , Xi Bo , Li Jiong 
Published: February 2023

Abstract
Background
Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.

Methods
Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring’s age as the time scale.

Results
During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20–1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38–1.78) and gestational diabetes (HR=1.37, 95% CI=1.25–1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98–1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00–1.88) or preeclampsia (HR=1.62, 95% CI=1.41–1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42–2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17–1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06–2.41), 1.29 (1.04–1.59), and 1.38 (1.24–1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85–5.60) than offspring of mothers with HDP or diabetes alone.

Conclusions
Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.