American Journal of Epidemiology Advance Access originally published online on July 31, 2008
American Journal of Epidemiology 2008 168(6):665; doi:10.1093/aje/kwn180
American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.
RE: "BROTHERS AND REDUCTION OF THE BIRTH WEIGHT OF LATER-BORN SIBLINGS"
William H. James
The Galton Laboratory, University College London, London NW 1 2 HE, United Kingdom
(e-mail: whjames{at}waitrose.com)
In a recent Journal article, Nielsen et al. reported that later-born siblings (of both sexes) with preceding brothers weighed significantly less at birth compared with controls with no preceding brothers. The authors suggested that this phenomenon might be explained by "maternal immune reactions directed against the H-Y antigens initiated during pregnancies with boys" (1, p. 480).
This association between birth weights of later siblings and the sex of their preceding siblings is susceptible to an alternative explanation: there are independent associations of each with maternal testosterone levels. Substantial quantities of data have been adduced to support the hypothesis that mammalian (including human) hormone levels around the time of conception are associated with the sex of the resulting offspring, high levels of testosterone (in either parent) being associated with the subsequent production of sons (2, 3). Moreover, high testosterone levels in pregnant women at 17 and 33 weeks of gestation are reportedly associated with fetal growth restriction in utero (4). This latter association is apparently causal because administering testosterone to pregnant ewes reportedly leads to significantly reduced birth weights of lambs of both sexes (5). This potential explanation regarding the data of Nielsen et al. (1) suggests that proponents of the maternal immune hypothesis should present direct immunologic data to support their idea.
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ACKNOWLEDGMENTS
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Conflict of interest: none declared.
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References
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- Nielsen HS, Mortensen L, Nygaard U, et al. Brothers and reduction of the birth weight of later-born siblings. Am J Epidemiol (2008) 167:480–4.[Abstract/Free Full Text]
- James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. J Theor Biol (1996) 180:271–86.[CrossRef][Web of Science][Medline]
- James WH. Further evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. Hum Reprod (2004) 19:1250–6.[Abstract/Free Full Text]
- Carlsen SM, Jacobsen G, Romundstad P. Maternal testosterone levels during pregnancy are associated with offspring size at birth. Eur J Endocrinol (2006) 155:365–70.[Abstract/Free Full Text]
- Manikkam M, Crespi EJ, Doop DD, et al. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology (2004) 145:790–8.[Abstract/Free Full Text]

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