Hum Reprod Open. 2025 Nov 25;2025(4):hoaf074. doi: 10.1093/hropen/hoaf074. eCollection 2025.
ABSTRACT
STUDY QUESTION: Is maternal pre-existing atherosclerotic cardiovascular disease (ASCVD) associated with neonatal and long-term offspring outcomes?
SUMMARY ANSWER: Maternal pre-existing ASCVD is independently associated with consistent increases in neonatal and early childhood adverse outcomes.
WHAT IS KNOWN ALREADY: Maternal cardiovascular health may influence offspring development through intrauterine and early-life mechanisms. However, the impact of maternal pre-existing ASCVD on neonatal and long-term offspring's neurodevelopmental outcomes remains poorly understood.
STUDY DESIGN SIZE DURATION: We conducted a nationwide cohort study linking maternal and child health data from the Korean National Health Insurance Service between 2005 and 2019.
PARTICIPANTS/MATERIALS SETTING METHODS: Pre-existing ASCVD was defined by diagnostic codes for myocardial infarction, ischemic stroke, or angina prior to conception. Offspring outcomes included neonatal complications (congenital malformations, sepsis, neonatal intensive care unit admission) and neurodevelopmental disorders (developmental delay, seizure, or attention-deficit hyperactivity disorder), with follow-up through 2020. Among 5 461 222 live births (3 640 815 unique mothers), 145 315 (2.7%) were delivered by women with pre-existing ASCVD before pregnancy. Propensity score matching (1:4) was used to adjust for baseline maternal characteristics.
MAIN RESULTS AND THE ROLE OF CHANCE: Offspring of mothers with ASCVD had increased risk of congenital malformations (adjusted odds ratio [aOR] 1.09, 95% CI: 1.07-1.12), neonatal intensive care unit admission (aOR 1.19, 95% CI: 1.16-1.22), and neonatal sepsis (aOR 1.11, 95% CI: 1.07-1.15). The risk of neurodevelopmental disorders was also elevated (adjusted hazard ratio 1.08, 95% CI: 1.07-1.10). The absolute risk differences were consistent regardless of the presence of adverse pregnancy outcomes during pregnancy.
LIMITATIONS REASON FOR CAUTION: As with all observational studies, residual confounding could not be ruled out. Only live births are included.
WIDER IMPLICATIONS OF THE FINDINGS: Maternal pre-existing ASCVD was associated with modest but consistent increases in neonatal and early childhood adverse outcomes. These associations appeared to persist regardless of the presence of adverse pregnancy outcomes, suggesting a possible independent contribution of maternal ASCVD on offspring development. Our findings suggest the importance of identifying and monitoring pregnancies of women with cardiovascular disease and indicate that early neurodevelopmental surveillance may be considered in affected children.
STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC21C0123) and supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2024-00440881). No competing interests are reported.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT06406998.
PMID:41383953 | PMC:PMC12690663 | DOI:10.1093/hropen/hoaf074