Abstract
Objective This study aims to determine if advanced maternal age (AMA) is a risk factor for
major congenital anomalies, in the absence of aneuploidy.
Study Design Retrospective cohort study of all patients with a singleton gestation presenting
for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses
were excluded. Study groups were defined by maternal age ≤ 34 and ≥ 35 years. The
primary outcome was the presence of one or more major anomalies diagnosed at the second
trimester ultrasound. Univariable and multivariable logistic regression analyses were
used to estimate the risk of major anomalies in AMA patients.
Results Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in
the incidence of major fetal anomalies with increasing maternal age until the threshold
of age 35 (p < 0.001). Being AMA was significantly associated with an overall decreased risk for
major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52–0.66).
The subgroup analysis demonstrated similar results for women ≥ 40 years of age.
Conclusion AMA is associated with an overall decreased risk for major anomalies. These findings
may suggest that the “all or nothing” phenomenon plays a more robust role in embryonic
development with advancing oocyte age, with anatomically normal fetuses being more
likely to survive.
Keywords
advanced maternal age - aneuploidy - congenital anomalies - fetal structural malformation
