Advanced maternal age at first delivery as a female-specific cardiovascular risk modifier: a systematic review of long-term coronary and cardiovascular outcomes
A Mcmorrow, G B Bruno, T K KiernanAbstract
Background
Advanced maternal age (AMA) refers to pregnancy ≥ 35 years at delivery, and is subcategorized as very AMA (VAMA, ≥ 40 years) and extremely AMA (EAMA, ≥ 45 years). While AMA is associated with obstetric and peripartum cardiovascular complications, its long-term implications for coronary risk remain incompletely characterised. With rising maternal age across Europe (EU mean 31.2 years (Eurostat)) clarifying if delayed childbearing confers sustained vulnerability to long-term adverse cardiovascular (CV) events has implications for risk assessment tools.
Aim
To evaluate whether AMA at first delivery is independently associated with long-term coronary or CV outcomes and if it may represent a female-specific CV risk modifier.
Methods
Following PRISMA guidelines, we searched, on February 16th 2026, for original articles in PubMed, Embase, Scopus, EBSCOhost, and Cochrane from January 2006 onwards, using terms: ‘Advanced maternal age’ (OR ‘maternal age at first delivery’ OR ‘maternal age at first birth’ OR ‘delayed childbearing’ OR (‘maternal age’ AND ‘first birth’) AND (‘acute coronary syndrome’ OR ‘myocardial infarction’ OR ‘STEMI’ OR ‘NSTEMI’ OR ‘coronary artery disease’ OR ‘coronary heart disease’ OR ‘ischemic heart disease’ OR ‘cardiovascular mortality’). After screening 100 studies, 15 abstracts were reviewed, and 4 were included; quality was appraised with the LEGEND tool.
Results
Four studies met inclusion criteria, including three prospective cohort studies and one large cross-sectional analysis comprising >150,000 women across Japan and the United States. Two Japanese prospective cohorts demonstrated a significant association between AMA at first delivery and increased long-term CV mortality (adjusted HRs 1.22–1.33), which persisted after adjustment for demographic, lifestyle, and reproductive factors. In contrast, a large U.S. cohort found no independent association between AMA and incident CV disease after multivariable adjustment, suggesting socioeconomic confounding. A U.S. cross-sectional study reported a U-shaped association between age at first birth and CV disease, with both early and later maternal age associated with increased odds of CV disease.
Conclusion
AMA at first delivery demonstrates a modest but population-dependent association with long-term CV mortality, with consistent trends observed in Asian cohorts and attenuated association in U.S. populations after socioeconomic adjustment. Although most available data relate to composite CV outcomes rather than coronary-specific events, the observed heterogeneity suggests delayed childbearing may function as a context-dependent female-specific CV risk modifier rather than a direct causal determinant. These findings support further evaluation of reproductive timing within population-specific CV risk stratification frameworks. European cohort validation is warranted in view of this critical gap in coronary risk stratification for women of AMA in Europe.PRISMA Diagram for AMA and Coronary Outcome