ABSTRACT: Although birth defects affect 3% of births, causes are not known for about 66% of cases. Both younger and older maternal age may increase risks for well-known birth defects. The aim of this study was to use current data obtained across the United States to assess the association between maternal age and the risk for birth defects of unknown etiology.
The National Birth Defects Prevention Study (NBDPS) is a population-based, case-control study that includes case infants identified through birth defect surveillance systems. Case infants have at least 1 of more than 30 types of major structural birth defects. Control infants have no major birth defects. Mothers were contacted 6 weeks to 24 months after their estimated delivery date (EDD). A standardized telephone interview was conducted to ascertain exposures and behaviors 3 months before and during pregnancy and to obtain information on demographic and lifestyle factors and pregnancy history. Maternal age at EDD was categorized as less than 20, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and 40 years or older. Logistic regression models adjusted for maternal race/ethnicity, education, body mass index, folic acid use, smoking, gravidity, and parental age difference were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) relative to the 25- to 29-year age group.
The NBDPS contains interviews from mothers of 23,333 case infants and 8494 control infants for 1997 to 2007. The final sample included 20,377 case and 8169 control infants. The mean and median maternal ages at EDD for case and control mothers were the same at 27.5 years and at 27 years, respectively. Case and control mothers were demographically similar within each age category. The proportion of smokers was 2.5 times higher in mothers younger than 20 years compared with mothers 40 years old; the use of folic acid–containing supplements increased with increasing maternal age. For maternal age younger than 20 years, positive associations were observed for total anomalous pulmonary venous return (aOR, 2.3), amniotic band sequence (aOR, 2.4), and gastroschisis (aOR, 6.1). For the group of mothers 40 years or older, positive associations were observed for tetralogy of Fallot (aOR, 2.2), perimembranous ventricular septal defect (aOR 2.5), atrial septal defect not otherwise specified (aOR, 2.5), and ventricular septal defect plus atrial septal defect association (aOR, 2.9). Noncardiac defects observed in group of mothers 40 years or older were esophageal atresia (aOR, 2.9; 95% CI, 1.7–4.9), hypospadias (aOR, 2.0; 95% CI, 1.4–3.0), and craniosynostosis (aOR, 1.6). For those younger than 20 years, birth defects associated with reduced aORs were cataracts and lens defects (aOR, 0.5), perimembranous ventricular septal defect (aOR, 0.7), left ventricular outflow tract obstruction (aOR, 0.6), coarctation of the aorta (aOR, 0.5), hypospadias (aOR, 0.6), and craniosynostosis (aOR, 0.6). The only birth defect with a reduced aOR seen with increasing maternal age was gastroschisis. For the 30- to 34-year and 35- to 39-year age groups, the aORs were 0.5 and 0.2, respectively; this defect did not appear in the group of mothers 40 years or older.
Modifications in lifestyle factors can help to improve infant outcomes. Regardless of age, women who optimize their health before conception and are aware of information on all risks and potential preventions can reduce their risks for birth defects.
National Center on Birth Defects and Developmental Disabilities (S.K.G., C.B., O.D., R.F.G., S.A.R., J.R.), and Epidemic Intelligence Service (S.K.G.), Centers for Disease Control and Prevention, Atlanta, GA