Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies - 15/06/24

Doi : 10.1016/j.ajog.2024.05.010

Boglárka Pethő, MD ^a,^b, Szilárd Váncsa, MD, PhD ^b,^d,^e, Alex Váradi ^b,^f,^g, Gergely Agócs, PharmD, PhD ^b,^c, Ákos Mátrai, MD ^a,^b, Franciska Zászkaliczky-Iker ^a,^b, Zita Balogh ^a,^b, Ferenc Bánhidy, MD, PhD ^a,^b, Péter Hegyi, MD, PhD ^b,^d,^e, Nándor Ács, MD, PhD ^a,^b,^⁎
^a Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
^b Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
^c Institute of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
^d Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
^e Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
^f Department of Metagenomics, University of Debrecen, Debrecen, Hungary
^g Department of Laboratory Medicine, University of Pécs, Pécs, Hungary

^∗Corresponding author: Nándor Ács, MD, PhD.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 15 June 2024

Abstract

Background

Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature.

Objective

To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols.

Study Design

A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies.

Results

From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [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).

Conclusion

The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is 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.

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Key words : aging, congenital abnormalities, maternal age, nonchromosomal anomalies, pregnancy, screening

Plan

Assessment of risk of bias

Data synthesis

Results

Study selection

Study characteristics

Risk of bias assessment

Synthesis of results

Comment

Principal findings and comparison with existing literature

Strengths and limitation

Conclusions and implication

	The authors report no conflict of interest.
	Ethical approval: No ethical approval was required for this systematic review with meta-analysis, as all data were already published in peer-reviewed journals. No patients were involved in the design, conduct or interpretation of our study.
	The datasets used in this study can be found in the full-text articles included in the systematic review and meta-analysis.
	Cite this article as: 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. Am J Obstet Gynecol 2024;XXX:XX–XX.