Maternal age linked to higher risk of nonchromosomal congenital anomalies

Maternal age linked to higher risk of nonchromosomal congenital anomalies | Image Credit: © Mangostar - © Mangostar - stock.adobe.com.

Nonchromosomal congenital anomalies (NCAs) are significantly more common in patients with both very young and advanced maternal age (AMA), according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Congenital anomalies are defined as abnormalities occurring during intrauterine life. They have been linked to 25.3 to 38.8 million lost disability-adjusted life years worldwide, making them the largest cause of morbidity and mortality in infants.²

An association has been reported between maternal age and the risk of congenital anomalies, with data indicating an increase in risk among women with an AMA of 35 years or older.¹ However, this data is mainly based on chromosomal abnormalities (CAs), with little information about the association with NCAs available.

To determine the association between maternal age and NCAs, investigators conducted a systematic review and meta-analysis. Data was obtained through systematic searches of the MEDLINE, Cochrane Library, and Embase databases.

Eligible articles included population-based studies comparing NACs among pregnant women based on maternal age groups. The rate of total NACs was reported as the primary outcome, while secondary outcomes included structural defects of different organ systems.

Exclusion criteria included not reporting the exact number of NACs in different age groups, having CAs as the target outcome, and being a case-control or cohort study, case series, or case report. Three independent review authors performed study selection, first based on title, then abstract, and finally full text.

Data extraction was also performed by the 3 authors, with the decision based on a consensus during disagreements, or through a fourth author when necessary. Relevant data included first author, year of publication, study population, study period, study site, study design, demographic data, number of patients in each age group, NCAs in age groups, and risk of bias data.

The reference group was mothers aged 20 to 30 years. Very young mothers were those aged under 20 years, while AMA was defined as being aged 35 years or older. The rate of NCAs was also evaluated in mothers aged over 40 years.

There were 72 studies included in the final analysis, 37 of which were from the American continent, 17 from Europe, 14 from Asia, 3 from Australia, and 1 from Africa. Thirty-six studies were conducted on a national level, 34 at a subnational level, and 2 at a multinational level. High heterogeneity was reported for most studies.

An increased risk of NCAs was reported among patients aged over 35 years and over 40 years, with relative risks (RRs) of 1.31 and 1.44, respectively. A positive correlation was identified between NCA risk and maternal age, with the risk increasing each year.

No association was reported between maternal age and congenital nervous system malformations. However, AMA was linked to diseases of the circulatory system, with an RR of 1.94 for patients aged over 40 years. For an age of under 20 years, the RR was 0.87.

AMA was also linked to an increased risk of cleft lip and cleft palate. An RR of 1.57 was reported among patients aged over 40 years. Additionally, the RRs for cleft palate were 1.78 and 1.77 among patients aged over 35 years and over 40 years, respectively. For the digestive system, the RR was 2.16 for a maternal age over 40 years.

These results indicated a positive correlation between AMA and NCA risk. Investigators recommended additional screening methods be utilized in high-risk age groups.

Reference

1. Pethő B, Váncsa S, Váradi A, et al. Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies. American Journal of Obstetrics & Gynecology. 2024;231(5):490-500. doi:10.1016/j.ajog.2024.05.010
2. Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197-223. doi:10.1016/S0140-6736(12)61689-4