Maternal age and malformations in singleton births

OBJECTIVE: To examine the effect of maternal age on incidence of nonchromosomal fetal malformations. METHODS: Malformations detected at birth or in the newborn nursery were catalogued prospectively for 102,728 pregnancies, including abortions, stillbirths, and live births, from January 1, 1988 to December 31, 1994. Maternal age was divided into seven epochs. Relative risks (RRs) were used to compare demographic variables and specific malformations. The Mantel-Haenszel chi(2) statistic was used to compare age-specific anomalies. Multiple logistic regression analysis was used to adjust for parity. RESULTS: Abnormal karyotypes were significantly more frequent in older women. After excluding infants with chromosomal abnormalities, the incidence of structurally malformed infants also was increased significantly and progressively in women 25 years of age or older. The additional age-related risk of nonchromosomal malformations was approximately 1% in women 35 years of age or older. The odds ratio for cardiac defects was 3.95 in infants of women 40 years of age or older (95% CI 1.70, 9.17) compared with women aged 20-24 years. The risks of clubfoot and diaphragmatic hernia also increased as maternal age increased. CONCLUSION: Advanced maternal age beyond 25 years was associated with significantly increased risk of fetuses having congenital malformations not caused by aneuploidy.