Maternal age is highly associated with non‐chromosomal congenital anomalies: Analysis of a population‐based case‐control database

Objective The role of maternal age in the development of non‐chromosomal congenital anomalies (NCAs) is under debate. Therefore, the primary aim of this study was to identify the age groups at risk for NCAs. The secondary aim was to perform a detailed analysis of the relative frequency of various anomalies. Design National population‐based study. Setting The Hungarian Case‐Control Surveillance of Congenital Anomalies (CAs) between 1980 and 2009. Population or Sample A cohort of 31 128 cases with confirmed NCAs was compared with Hungary's total of 2 808 345 live births. Methods Clinicians prospectively reported cases after delivery. Data were analysed by non‐linear logistic regression. Risk‐increasing effect of young and advanced maternal age was determined by each NCA group. Main outcome measures These were the total number of NCAs: cleft lip and palate, circulatory, genital, musculoskeletal, digestive, urinary, eye, ear, face, and neck, nervous system, and respiratory system anomalies. Results The occurrence of NCAs in our database was lowest between 23 and 32 years of maternal age at childbirth. The relative risk (RR) of any NCA was 1.2 (95% CI 1.17–1.23) and 1.15 (95% CI 1.11–1.19) in the very young and advanced age groups, respectively. The respective results for the circulatory system were RR = 1.07 (95% CI 1.01–1.13) and RR = 1.33 (95% CI 1.24–1.42); for cleft lip and palate RR = 1.09 (95% CI 1.01–1.19) and RR = 1.45 (95% CI 1.26–1.67); for genital organs RR = 1.15 (95% CI 1.08–1.22) and RR = 1.16 (95% CI 1.04–1.29); for the musculoskeletal system RR = 1.17 (95% CI 1.12–1.23) and RR = 1.29 (95% CI 1.14–1.44); and for the digestive system RR = 1.23 (95% CI 1.14–1.31) and RR = 1.16 (95% CI 1.04–1.29). Conclusion Very young and advanced maternal ages are associated with different types of NCAs. Therefore, screening protocols should be adjusted for these risk groups.