Maternal fever during pregnancy and male offspring reproductive health: A longitudinal cohort study in young Danish males

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Background
Maternal fever during pregnancy has been associated with an increased risk of genital malformations, but the implication for long-term reproductive health in the offspring is unknown.

Objectives
To investigate associations between timing, duration, and temperature of fetal exposure to maternal fever and sons’ semen quality, testicular volume, and levels of reproductive hormones in early adulthood. Further, to examine whether concurrent use of antipyretics and/or antibiotics modified the effect.

Materials and methods
We used the Fetal Programming of Semen Quality cohort consisting of men born to women enrolled in the Danish National Birth Cohort. Self-reported information on maternal fever was collected twice during pregnancy (median 16 and 31 pregnancy weeks) and categorized as any fever during pregnancy, fever during early pregnancy (weeks 1–15), and fever exclusively during late pregnancy (weeks 16–42). Semen quality and concentrations of reproductive hormones were measured at a clinical examination at the age of 18.9 years. We used negative binomial regression to examine the associations, adjusting for maternal age at birth, maternal smoking, family occupational status, and precision variables related to semen quality and hormonal levels, for example, abstinence time.

Results
986 men were included in the study, of which 23% had mothers reporting at least one episode of fever. We found no strong indications of associations between maternal fever during pregnancy and male reproductive health in young men. Concurrent use of antipyretics and antibiotics did not modify the association.

Discussion
Strengths include the large sample size, prospectively collected data, and the adjustment for maternal factors during pregnancy and important precision variables. A limitation is the crude self-reported information on maternal fever.

Conclusion
We found no evidence to support that timing, duration, or temperature of maternal fever during pregnancy has a long-term impact on semen characteristics, testicular volume, or level of reproductive hormones in male offspring
OriginalsprogEngelsk
TidsskriftAndrology
Vol/bind11
Udgave nummer3
Sider (fra-til)523-536
Antal sider14
ISSN2047-2919
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study is a product of the ReproUnion collaboration, co‐financed by the European Union, Interreg Öresund‐Kattegat‐Skagerrak, the Capital Region of Denmark, Region Skåne, and Ferring Pharmaceuticals. In addition, the FEPOS project was funded by the Lundbeck Foundation, Bispebjerg and Frederiksberg Hospital, Helsefonden, Doctor Sofus Carl Emil Friis and Wife Olga Doris Friis Grant, Axel Muusfeldt's Foundation and the A. P. Møller Foundation. The funding sources had no role in the study design, data collection, analyses, interpretation, presentation, or publication.

Funding Information:
The authors wish to thank all participants in the study in addition to the medical laboratory technicians, Marianne Lipka Flensborg and Joan Dideriksen, for managing the study clinics and collection of data. In addition, we thank Cecilia Tingsmark for performing all semen morphology analyses, and Lone Fredslund and Inge Eisensee for data management. The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation and additional support from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation, and other minor grants. Further, this research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation, grant numbers 2010‐11‐12 and 2009‐07‐28.

Publisher Copyright:
© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.

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