Maternal age is highly associated with non-chromosomal congenital anomalies: Analysis of a population-based case-control database

Boglárka Pethő; Ákos Mátrai; Gergely Agócs; Dániel Sándor Veres; Andrea Harnos; Szilárd Váncsa; Ferenc Bánhidy; Péter Hegyi; Nándor Ács

doi:10.1111/1471-0528.17461

Maternal age is highly associated with non-chromosomal congenital anomalies: Analysis of a population-based case-control database

BJOG. 2023 Sep;130(10):1217-1225. doi: 10.1111/1471-0528.17461. Epub 2023 Apr 3.

Authors

Boglárka Pethő^{1

2}, Ákos Mátrai^{1

2

3}, Gergely Agócs^{2

4}, Dániel Sándor Veres^{2

4}, Andrea Harnos^{2

5}, Szilárd Váncsa^{2

6

7}, Ferenc Bánhidy^{1

2}, Péter Hegyi^{2

6

7}, Nándor Ács^{1

2}

Affiliations

¹ Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary.
² Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
³ Faculty of Health Sciences, University of Pécs, Pécs, Hungary.
⁴ Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
⁵ Department of Biostatics, University of Veterinary Medicine Budapest, Budapest, Hungary.
⁶ Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary.
⁷ Institute for Pancreatic Diseases, Semmelweis University, Budapest, Hungary.

PMID: 37012679
DOI: 10.1111/1471-0528.17461

Abstract

Objective: The role of maternal age in the development of non-chromosomal congenital anomalies (NCAs) is under debate. Therefore, the primary aim of this study was to identify the age groups at risk for NCAs. The secondary aim was to perform a detailed analysis of the relative frequency of various anomalies.

Design: National population-based study.

Setting: The Hungarian Case-Control Surveillance of Congenital Anomalies (CAs) between 1980 and 2009.

Population or sample: A cohort of 31 128 cases with confirmed NCAs was compared with Hungary's total of 2 808 345 live births.

Methods: Clinicians prospectively reported cases after delivery. Data were analysed by non-linear logistic regression. Risk-increasing effect of young and advanced maternal age was determined by each NCA group.

Main outcome measures: These were the total number of NCAs: cleft lip and palate, circulatory, genital, musculoskeletal, digestive, urinary, eye, ear, face, and neck, nervous system, and respiratory system anomalies.

Results: The occurrence of NCAs in our database was lowest between 23 and 32 years of maternal age at childbirth. The relative risk (RR) of any NCA was 1.2 (95% CI 1.17-1.23) and 1.15 (95% CI 1.11-1.19) in the very young and advanced age groups, respectively. The respective results for the circulatory system were RR = 1.07 (95% CI 1.01-1.13) and RR = 1.33 (95% CI 1.24-1.42); for cleft lip and palate RR = 1.09 (95% CI 1.01-1.19) and RR = 1.45 (95% CI 1.26-1.67); for genital organs RR = 1.15 (95% CI 1.08-1.22) and RR = 1.16 (95% CI 1.04-1.29); for the musculoskeletal system RR = 1.17 (95% CI 1.12-1.23) and RR = 1.29 (95% CI 1.14-1.44); and for the digestive system RR = 1.23 (95% CI 1.14-1.31) and RR = 1.16 (95% CI 1.04-1.29).

Conclusion: Very young and advanced maternal ages are associated with different types of NCAs. Therefore, screening protocols should be adjusted for these risk groups.

Keywords: ageing; congenital abnormalities; maternal age; non-chromosomal anomalies; pregnancy; screening.

MeSH terms

Case-Control Studies
Cleft Lip*
Cleft Palate* / epidemiology
Cleft Palate* / genetics
Congenital Abnormalities* / epidemiology
Data Collection
Female
Humans
Maternal Age