Maternal Age-Specific Risk of Nonchromosomal Anomalies

Abstract

With a continuing rise in the average maternal age in industrialized societies, accurate data are needed on maternal age-related obstetric risks. Although it is well known that the risk of fetal aneuploidy increases along with maternal age, it is unclear whether older mothers are at increased risk of having a fetus with nonchromosomal congenital anomalies (NCA). Much of the data on the risk data for NCA among older European mothers are either difficult to interpret or come from studies with small sample size, and little data are available on the overall risk of NCA in younger (teenage) mothers. This population-based prevalence study compared the age-specific risk of NCA among mothers in 15 European countries. Data from 1.75 million infants born between 2000 and 2004 were obtained from the EUROCAT database, a network of population-based congenital anomaly registers in 15 European countries. The primary outcome measures were the prevalence of NCA at increasing maternal ages and the relative risk (RR) of any NCA and 84 standard NCA subgroups. Included among the 38,958 cases of NCA were live births, fetal deaths ≥20 weeks’ gestation, and pregnancy terminations following prenatal diagnosis of malformation. The highest crude prevalence of all NCAs was among mothers <20 years old (26.5 per 1000 births). With increasing maternal age, the overall prevalence of NCA decreased: the crude prevalence per 1000 births for mothers 20 to 24, 25 to 29, 30 to 34, 35 to 39, and 40 to 44 years was 23.8, 22.5, 21.5, 21.4, and 22.6, respectively. Compared to mothers age 25 to 29, the RR of NCA adjusted for country was 1.11 (95% confidence interval [CI], 1.06–1.17) for mothers age <20 years, 0.99 (95% CI, 0.96–1.02) for mothers age 35 to 39, and 1.01 (95% CI, 0.95–1.07) for mothers age 40 to 44. There was significant variation in the pattern of maternal age-related risk between countries: the RR was higher for teenage mothers in France, Ireland, and Portugal, whereas the RR was higher for older mothers in Germany and Poland. The maternal age-specific RR was also different for specific NCAs among the 84 subgroups analyzed. Mothers <20 years old were at a significantly greater risk of nervous system abnormalities including anencephaly, tricuspid atresia, digestive system anomalies including gastroschisis, and maternal infection syndromes. Older mothers aged from 35 to 39 and 40 to 44 years were at a significantly greater risk of encephalocele, esophageal atresia, thanatophoric dwarfism, and fetal alcohol syndrome (all values P < 0.01). These findings indicate that, while teenage mothers are at increased risk of having offspring with NCAs, older maternal age is a negligible risk factor for NCAs overall, although the risk of a few specific anomalies appears to increase with age.