Introduction: The age at which women deliver their first child has increased steadily in recent years, particularly in Western societies. Advanced maternal age (≥35 years) is associated with increased maternal and perinatal morbidity and mortality. Little is known about the impact of aging on vascular adaptations to pregnancy that might compromise pregnancy outcome, and whether adult offspring from aged mothers are at an increased risk of cardiovascular disease.
Methods and Results: Aged female Sprague Dawley rats (9 months; approximately equivalent to a 35 year old woman) and young controls (4 months), were mated with young males. Pregnancy outcome was assessed on gestational day (GD)8, GD20, or dams were allowed to deliver. Systolic blood pressure was increased on GD19 in aged rats compared to young rats (young=108.8±5.1 mmHg vs. aged=131.4±5.8 mmHg, P<0.05). Aged dams had a reduced capacity to carry viable pregnancies (young=90% vs. aged=50%), and had reduced litter sizes (young=15.0±0.57 pups vs. aged=8.5±1.6 pups, P<0.01) on GD20. Fetuses from aged dams had a reduced body weight at GD20 (young=3.78±0.1g vs. aged=3.19±0.2g, P<0.05) as well as an increased crown-rump length:abdominal girth ratio – indicative of asymmetric fetal growth restriction (young=0.97±0.0 vs. aged=1.04±0.0), and evidence of hypoxia in the fetus and placenta. Pregnancy in aged dams is impaired early, with implantation sites numbers reduced by 60.7% on GD8 compared to young dams, with evidence of fetal resorption. Using the isolated working heart system, adult offspring (4 months) from aged dams had impaired cardiac recovery following 10-20 min of ischemia. Using wire myography, offspring from aged dams had perturbed relaxation of systemic arteries.
Conclusion: In a rat model of advanced maternal age, pregnancy outcome is impaired and offspring have impaired cardiovascular function, which may increase their susceptibility to cardiovascular disease.