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Advanced paternal age and stillbirth rate: a nationwide register-based cohort study of 944,031 pregnancies in Denmark

  • PERINATAL EPIDEMIOLOGY
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Abstract

Advanced paternal age has been associated with a variety of rare conditions and diseases of great public health impact. An increased number of de novo point mutations in sperm with increasing age have been suggested as a mechanism, which would likely also affect fetal viability. We examined the association between paternal age and stillbirth rate in a large nationwide cohort. We identified all pregnancies in Denmark from 1994 to 2010 carried to a gestational age of at least 22 completed weeks (n = 944,031) as registered in national registers and linked to individual register data about the parents. The hazard ratio of stillbirth according to paternal age was estimated, adjusted for maternal age in 1-year categories, year of outcome, and additionally parental educational levels. The relative rate of stillbirth (n = 4946) according to paternal age was found to be J-shaped with the highest hazard ratio for fathers aged more than 40 years when paternal age was modelled using restricted cubic splines. When modelled categorically, the adjusted hazard ratios of stillbirth were as follows: <25, 1.16 (95% confidence interval, CI 1.01–1.34); 25–29, 1.03 (95% CI 0.95–1.11); 35–39, 1.16 (95% CI 1.07–1.26); 40–44, 1.41 (95% CI 1.26–1.59); 45–49, 1.20 (95% CI 0.97–1.49); 50+, 1.58 (95% CI 1.18–2.11), compared with fathers aged 30–34 years. These estimates attenuated slightly when further adjusted for parental education. Our study showed that paternal age was associated with the relative rate of stillbirth in a J-shaped manner with the highest hazard ratios among fathers aged more than 40 years.

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Funding

This work was supported by the Department of Public Health, University of Copenhagen, a Ph.D. grant from the Faculty of Health and Medical Sciences, University of Copenhagen, and the Medical Research Council [grant number MC_UU_12013/1-9].

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Authors and Affiliations

  1. Section of Social Medicine, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, 1014, Copenhagen K, Denmark

    Stine Kjaer Urhoj, Laust Hvas Mortensen & Anne-Marie Nybo Andersen

  2. Section of Biostatistics, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, 1014, Copenhagen K, Denmark

    Per Kragh Andersen

  3. Methods and Analysis, Statistics Denmark, Sejrøgade 11, 2100, Copenhagen Ø, Denmark

    Laust Hvas Mortensen

  4. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK

    George Davey Smith

Authors
  1. Stine Kjaer Urhoj
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Corresponding author

Correspondence to Stine Kjaer Urhoj.

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The authors declare that they have no conflict of interest.

Ethical approval

Statistics Denmark linked information from the registers using a unique identification number which was concealed before releasing the data for analysis, complying with privacy protection rules. The study was approved by the Danish data protection agency. No additional ethical approval or informed consent was acquired according to Danish legislation, since this study used routine register data.

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Urhoj, S.K., Andersen, P.K., Mortensen, L.H. et al. Advanced paternal age and stillbirth rate: a nationwide register-based cohort study of 944,031 pregnancies in Denmark. Eur J Epidemiol 32, 227–234 (2017). https://doi.org/10.1007/s10654-017-0237-z

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  • DOI: https://doi.org/10.1007/s10654-017-0237-z

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