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.