Obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia are highly prevalent among women of reproductive age and contribute to complications in >30% of pregnancies in Western countries. An accumulating body of evidence suggests that these cardiovascular disorders in women, occurring before and during their pregnancy, can affect the development of the structure, physiology and function of cardiovascular organ systems at different stages during embryonic and fetal development. These developmental adaptations might, in addition to genetics and sociodemographic and lifestyle factors, increase the susceptibility of the offspring to cardiovascular disease throughout the life course. In this Review, we discuss current knowledge of the influence of maternal cardiovascular disorders, occurring before and during pregnancy, on offspring cardiovascular development, dysfunction and disease from embryonic life until adulthood. We discuss findings from contemporary, large-scale, observational studies that provide insights into specific critical periods, evidence for causality and potential underlying mechanisms. Furthermore, we focus on priorities for future research, including defining optimal cardiovascular and reproductive health in women and men before their pregnancy and identifying specific embryonic, placental and fetal molecular developmental adaptations from early pregnancy onwards. Together, these approaches will help stop the intergenerational cycle of cardiovascular disease.
Obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia are highly prevalent among women of reproductive age and complicate >30% of pregnancies in Western countries.
Maternal cardiovascular disorders before and during pregnancy seem to contribute to embryonic and fetal cardiovascular developmental adaptations that predispose to an increased risk of cardiovascular dysfunction and disease in the offspring throughout their life course.
The development of cardiovascular diseases seems to be the result of cumulative effects of cardiovascular adaptations occurring across the life course, and preconception, early pregnancy and infancy seem to be specific critical periods in early life related to future risk of cardiovascular disease.
Future research needs to focus on identifying specific cardiovascular health parameters in both women and men from preconception onwards that are associated with cardiovascular health and disease in offspring, and the mechanisms underlying these associations; use of innovative imaging techniques to study cardiovascular development from embryonic life onwards, novel ‘omics’ approaches to identify functional adaptations, and strong collaborations between cohorts studies worldwide offer opportunities to address these research issues.
The use of innovative imaging techniques to study cardiovascular development from embryonic life onwards as well as novel omics approaches to identify functional adaptations and to interpret findings from cohort studies offer opportunities to address these research issues.
Novel preventative strategies focused on improving cardiovascular health in men and women from preconception onwards might lead to better cardiovascular health in future generations and stop the intergenerational cycle of cardiovascular risk transmission.
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R.G. received funding from the Dutch Diabetes Foundation (grant number 2017.81.002), the Netherlands Organization for Health Research and Development (NWO, ZonMW 543003109; NWO, ZonMw 09150172110034); EU Horizon 2020 research and innovation programme under the ERA-NET Cofund action (grant number 727565), EndObesity (ZonMW 529051026). V.W.V.J received a grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw 05430052110007) and a European Research Council Consolidator Grant (ERC-2014-CoG-648916).
The authors declare no competing interests.
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Gaillard, R., Jaddoe, V.W.V. Maternal cardiovascular disorders before and during pregnancy and offspring cardiovascular risk across the life course. Nat Rev Cardiol (2023). https://doi.org/10.1038/s41569-023-00869-z