Preconception stress and the secondary sex ratio in a population-based preconception cohort

This prospective cohort study provides evidence suggesting that paternal lifetime history of physician-diagnosed anxiety disorders may influence sex allocation in offspring, resulting in an excess of male births.

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Volume 107, Issue 3, Pages 714–722


Jisuk Bae, M.D., Ph.D., Courtney D. Lynch, Ph.D., M.P.H., Sungduk Kim, Ph.D., Rajeshwari Sundaram, Ph.D., Katherine J. Sapra, Ph.D., M.P.H., Germaine M. Buck Louis, Ph.D., M.S.



To examine the association between preconception parental stress and the secondary sex ratio, defined as the ratio of males to females at birth.


A population-based preconception cohort.


Not applicable.


A total of 235 couples who were enrolled before conception in Michigan and Texas between 2005 and 2009 and who had a singleton birth during the follow-up period. Couples were interviewed separately at baseline to obtain information on perceived stress (Cohen's Perceived Stress Scale) and lifetime history of physician-diagnosed anxiety and/or mood disorders. Female partners were also trained to collect basal saliva samples for the measurement of salivary stress markers, alpha-amylase and cortisol.



Main Outcome Measure(s)

Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each stress marker.


After adjusting for potential confounders, we observed a 76% increase in the risk of fathering a male infant (RR 1.76; 95% confidence interval 1.17–2.65) in men diagnosed with anxiety disorders compared with those who were not diagnosed. When lifetime history of physician-diagnosed anxiety disorders was modeled jointly for the couple, the association was slightly strengthened (RR 2.03; 95% confidence interval 1.46–2.84).


This prospective cohort study suggests that paternal lifetime history of physician-diagnosed anxiety disorders may be associated with an increase in the secondary sex ratio, resulting in an excess of male births.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

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