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Evidence for sex differences in fetal programming of physiological stress reactivity in infancy

Published online by Cambridge University Press:  07 April 2014

Florin Tibu
University of Manchester
Jonathan Hill*
University of Manchester
Helen Sharp
University of Liverpool
Kate Marshall
University of Manchester
Vivette Glover
Imperial College London
Andrew Pickles
King's College London
Address correspondence and reprint requests to: Jonathan Hill, Centre for Developmental Science and Disorders, University of Manchester, Room 3.305, Third Floor, Jean McFarlane Building, University Place, Oxford Road, Manchester M13 9PL, UK; E-mail:


Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

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