Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies

To evaluate the role of maternal age in the incidence of non-chromosomal congenital anomalies (NCAs) and to pinpoint age groups at higher risk to refine screening protocols.Search performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase.Included were population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women, without restrictions on age range, country, or comorbidities.The PRISMA 2020 guideline and Cochrane Handbook informed the systematic review and meta-analysis. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies.From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (RR 1.31, CI: 1.07-1.61), rising notably after >40 (RR 1.44, CI: 1.25-1.66). The latter changes to 1.25 (CI: 1.08-1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR 1.57, CI: 1.11-2.20) and circulatory system defects (>40, RR 1.94, CI: 1.28-2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR 3.08, CI: 2.74-3.47).The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There's a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.