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Advanced maternal age (AMA) is a well-established risk factor for fetal chromosomal abnormalities secondary to defects in cell division; however, the relationship between AMA and major congenital anomalies remains unknown. The objective of this study was to determine if AMA is an independent risk factor for major congenital anomalies diagnosed at the time of second trimester anatomic survey, in the absence of aneuploidy.
This is a retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over an 18 year period. Cases of aneuploidy were excluded. Study groups were defined by maternal age <35 versus ≥35 years. The primary outcome was the presence of one or more major fetal anomalies diagnosed at second trimester ultrasound. Univariate and multivariate logistic regression analyses were used to estimate the risk of major fetal anomalies in women who were AMA. The distribution of fetal anomalies by organ system was also compared between the study groups.
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) AMA was significantly associated with an overall decreased risk for major fetal anomalies (aOR 0.59, 95% CI 0.52-0.66) after controlling for potential confounders. Specifically, the incidence of central nervous system (CNS), renal, and abdominal wall anomalies were decreased in women ≥35 years. This was contrasted by the similar rate of cardiac anomalies between the study groups. (Table).
∗Adjusted for alcohol use, gestational diabetes, pre-gestational diabetes, and African American race; †Adjusted for gestational diabetes, pre-gestational diabetes, and African American race; ¶Adjusted for tobacco use, parity, and African American race.