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Paternal age, risk of congenital anomalies, and birth outcomes: a population-based cohort study

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Abstract

The objective of the study was to explore the impact of paternal age on the risk of congenital anomalies and birth outcomes in infants born in the USA between 2016 and 2021. This retrospective cohort study used data from the National Vital Statistics System (NVSS) database, a data set containing information on live birth in the USA between 2016 and 2021. Newborns were divided into four groups based on their paternal age (< 25, 25–34, 35–44, and > 44 years) and using the 25–34 age group as a reference. The primary outcomes were congenital anomalies involving structural anomalies and chromosome anomalies. Secondary outcomes were preterm birth, low birth weight, severe neonatal perinatal asphyxia, and admission to neonatal intensive care units (NICU). A multivariable logistic regression model was used to analyze the association between paternal age and outcomes. Overall, 17,764,695 live births were included in the final analyses. After adjusting confounding factors, advanced paternal age > 44 years was associated with increased odds of congenital anomalies (adjusted odds ratio (aOR) = 1.17, 95%CI 1.12–1.21) compared with the 25–34 age group, mainly for the chromosomal anomalies (aOR = 1.59, 95%CI 1.40–1.78) but not the structure anomalies (aOR = 1.03, 95%CI 0.97–1.09). The risk of preterm delivery, low birth weight, and NICU hospitalization in their infants was increased by advanced parental age as well.

  Conclusion: Advanced paternal age increases the risk of congenital anomalies, especially chromosomal anomalies in their offspring, implying prenatal genetic counseling is required.

What is Known:

• There's a rising trend of advanced paternal age, which is associated with an increased likelihood of premature birth and low birth weight in their offspring. However, the exploration between paternal age and congenital abnormalities in offspring was limited and contradictory.

What is New:

• Infants with a paternal age > 44 years were more likely to be born with congenital anomalies, especially chromosomal anomalies.

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Data Availability

The data that support the findings of this study are available from the National Vital Statistics System at https://www.cdc.gov/nchs/data_access/vitalstatsonline.htm.

Abbreviations

aOR:

Adjusted odds ratio

BMI:

Body mass index

CAs:

Congenital anomalies

ChAs:

Chromosome anomalies

CI:

Confidence interval

DNA:

Deoxyribonucleic acid

NICU:

Neonatal intensive care unit

NVSS:

National Vital Statistics System

PA:

Paternal age

SAs:

Structural anomalies

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Author information

Authors and Affiliations

  1. Department of Neonatology, National Children’s Medical Center (Shanghai), Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, China

    Xinghe Bu, Wenjing Ye & Jianguo Zhou

Authors
  1. Xinghe Bu
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  2. Wenjing Ye
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  3. Jianguo Zhou
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Contributions

All authors contributed to the final draft during the writing and reviewing of the paper. Specific contributions are as follows. It was JZ who developed the conceptual framework and supervised the writing process. The first draft of the manuscript was written by XB and all authors commented on previous versions of the manuscript. XB and JZ provided statistical and methodological advice on the use of routine vital event data and potential sources of bias. The overall management of the population cohort is performed by XB and WY, as well as ensuring that the reports are accurate. JZ conceived the original concepts for the paper.

Corresponding author

Correspondence to Jianguo Zhou.

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Since the data used in the study was publicly available and the study involved no human subjects, the Children’s Hospital of Fudan University Institutional Review Board waived the informed consent requirement.

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The authors confirm that the work described has not been published before; that it is not under consideration for publication elsewhere; that its publication has been approved by all co-authors; and that its publication has been approved (tacitly or explicitly) by the responsible authorities at the institution where the work is carried out.

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The authors declare no competing interests.

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Bu, X., Ye, W. & Zhou, J. Paternal age, risk of congenital anomalies, and birth outcomes: a population-based cohort study. Eur J Pediatr 182, 3519–3526 (2023). https://doi.org/10.1007/s00431-023-05025-w

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