Maternal age and birth defects after the use of assisted reproductive technology in Japan, 2004–2010

BACKGROUND Older mothers are becoming more common in Japan. One reason for this is the widespread use of assisted reproductive technology (ART). This study assesses the relationship between maternal age and the risk of birth defects after ART. METHODS Nationwide data on ART between 2004 and 2010 in Japan were analyzed. Diseases that were classified as code Q00-Q99 (ie, congenital malformations, deformations, and chromosomal abnormalities) in the International Classification of Diseases, tenth edition, were selected. There were 219,185 pregnancies and 153,791 live births in total ART. Of these, 1943 abortions, stillbirths, or live births with birth defects were recorded. Percentage of multiple birth defects in total birth defects, the prevalence, crude relative risk and 95% confidence interval per 10,000 pregnancies and per 10,000 live births were analyzed according to the maternal age class (ie, 25-29, 30-34 (reference), 35-39, and 40+ years). RESULTS Multiple birth defects were observed among 14% of the 25-29 year old class, and 8% among other classes when chromosomal abnormalities were excluded. The prevalence of chromosomal abnormalities per pregnancy and per live birth became significantly and rapidly higher in mothers in the age classes of 30-35 and 40+ years. Nonchromosomal birth defects per pregnancy decreased linearly with advanced maternal age, while the number of nonchromosomal birth defects per live birth formed a gradual U-shaped distribution. The prevalence per pregnancy of congenital malformations of the nervous system was significantly lower with advanced maternal age. The relative risk per live birth was significant regarding congenital malformations of the circulatory system for a maternal age of 40+ years. Some other significant associations between maternal age and birth defects were observed. CONCLUSION Maternal age is associated with several birth defects; however, older maternal age in itself does not produce noticeable extra risk for nonchromosomal birth defects overall.