Maternal age factors in nonchromosomal congenital anomalies in offspring

Infants born to mothers who are very young or those with advanced age are at increased risk of nonchromosomal congenital anomalies (NCAs), according to the results of a meta-analysis.

Researchers searched multiple online databases for population-based studies in which the impact of maternal age on the incidence of NCAs was assessed. There were no restrictions on age range, country, or comorbidities.

The search yielded 15,547 studies, of which 72 were included in the meta-analysis. Of the studies, 37 were from the American continent, 17 were from Europe, 14 were from Asia, three were from Australia, and one was from Africa. The systematic review and meta-analysis were conducted according to the PRISMA 2020 guidelines and Cochrane Handbook.

Pooled data showed that maternal age >35 years was associated with an increased risk of NCA (risk ratio [RR], 1.31, 95 percent confidence interval [CI], 1.07–1.61). The risk substantially increased at a maternal age of >40 years (RR, 1.44, 95 percent CI, 1.25–1.66) but was attenuated when the co-occurrence of chromosomal aberrations was excluded (RR, 1.25, 95 percent CI, 1.08–1.46).

Of note, advanced maternal age (>40 years) was strongly associated with specific anomalies such as cleft lip/palate (RR, 1.57, 95 percent CI, 1.11–2.20) and circulatory system defects (RR, 1.94, 95 percent CI, 1.28–2.93).

On the other hand, maternal age <20 years was associated with gastroschisis (RR, 3.08, 95 percent CI, 2.74–3.47).

The findings underscore a need for age-specific prenatal screening protocols to better detect NCAs, given the current trend of delayed childbearing. More studies are warranted to fully understand the impact of maternal age on the prevalence of rarer NCAs.