The Inconstancy of Human Sex Ratios at Birth

27 05 2010

To the Editor:

When human sex ratio (proportion male) at birth is categorized by some demographic variables (maternal age, paternal age, parity etc) it is, as confirmed by Ein-Mor et al (1) ‘remarkably constant.’ However I have adduced evidence that sex ratio shows substantial variation when it is categorized by selected other variables, e.g., adverse paternal chemical exposures (dioxin, dibromochloropropane, fungicides, methylmercury, vinclozolin, borates, alcohol and smoking); paternal pathology (HLA B 15 positivity, non-Hodgkin’s lymphoma, testicular cancer and hepatitis B status) and adverse paternal occupational exposures (professional driving or diving, astronaut and non-ionizing radiation) (2).

Moreover offspring sex ratio reportedly varies substantially (both upwards and downwards) with a number of obstetric pathologies (dermatoses of pregnancy, extrauterine pregnancy, fatty liver of pregnancy, hyperemesis gravidarum, placenta accreta, placenta praevia, and pre-eclampsia) and with a number of maternal pathologies (celiac disease, cytomegalovirus status, hepatitis B status, measles, non-Hodgkin’s lymphoma, polycystic ovary syndrome, and schizophrenia) (2). I showed in that paper that much of this variation may be reconciled with the hypothesis that offspring sex ratio is partially controlled by parental hormone levels around the time of conception. So it is notable that the one highly significant finding reported by Ein-Mor et al (1) – variation of offspring sex ratio with duration of gestation – may also be explained by that hypothesis.

These authors reported a monotonic decline in sex ratio with duration of gestation. However when very large quantities of data are examined (e.g. the annual U.S. natality records, each of which is roughly one hundred times the size of the sample of Ein-Mor (1)), it is clear that the regression of sex ratio on duration of gestation is U-shaped, not simply monotonic declining. Such a phenomenon occurred in these records for every single year 1966-76 inclusive (3). I have also shown in a meta-analysis that the regression of sex ratio on time of insemination within the cycle is U-shaped (4). Lastly, I have shown by a simple mathematical model, that the U-shaped regression at conception (which ex hypothesi is due to the mid-cycle luteal surge) is apparently responsible for the U-shaped regression at birth several months later (3). So the highly significant finding of Ein-Mor et al (1) is potentially explained.

In short, sex ratio at birth varies substantially with some variables, and there is strong evidence (in regard to some of these) that this variation is mediated by parental hormone concentrations around the time of conception. Evidence for the hypothesis has been summarized (5).

Dr. William H. James
The Galton Laboratory
Department of Genetics, Evolution and Environment
University College London
London, United Kingdom

References
1. Ein-Mor E, Mankuta D, Hochner-Celnikier D, Hurwitz A, Haimov-Kochman R. Sex ratio is remarkably constant. Fertil Steril 2010;93:1961-5.

2. James WH. Offspring sex ratios at birth as markers of paternal endocrine disruption. Env Res 2006;100:77-85.

3. James WH. Cycle day of insemination, sex ratio of offspring and duration of gestation. Ann Hum Biol 1994;21:263-6.

4. James WH. Analysing data on the sex ratio of human births by cycle day of conception. Hum Reprod 2000;15:1206-7.

5. James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. J Endocrinol 2008;198:3-15.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.05.044

The Authors Respond:

The sex ratio at birth is an important demographic indicator that is determined by the number of male births relative to the number of female births. The sex ratio at birth affects critical demographic measures, such as the ‘‘doubling-time’’ of a population which rises as the ratio of males to females at birth increases. Moreover, data about the sex ratio at birth is necessary to understanding trends in infant morbidity and mortality, since male infants are more susceptible to illness and have higher infant mortality rates (1).

The sex ratio at birth has been used to assess the impact of environmental factors on the endocrine system and reproductive health of humans. Currently, ‘‘sex control/selection’’ is being discussed across the nation, using sex ratio data to assist with the understanding of these apparent practices. And finally, there is the first most frequently heard question asked of new parents, ‘‘is it a boy or a girl?’’(2)

W.H. James commented that parental exposure to chemicals, paternal pathologies and occupation may affect the sex ratio at birth. While these observations may be intriguing as well as alluding towards potential biological mechanisms determining the sex ratio, they may still be in function in only a small scale of the population (3).

Our study “Sex ratio is remarkably constant” reported for the first time the male to female proportion in the Israeli population (4). The 1.05 male/female ratio that was found in our research matches the ratio found in several other European and American analyses (2). Our birth cohort covers three and a half years. It is possible that if we had examined a much longer period we would have found fluctuations in the sex ratio over the years. As for the contribution of specific factors to the sex ratio, the scale of our study (n=35,837) seems large enough for these various factors to be assimilated.

We summarize that on a larger scale sex ratio at birth is constant although may vary with some variables, that have not been investigated in our study.

References
1. Drevenstedt GL, Crimmins EM, Vasunilashorn S, Finch CE. The rise and fall of excess male infant mortality. Proc Natl Acad Sci U S A. 2008 ;105(13):5016-21.

2. Mathews TJ, Hamilton BE. Trend analysis of the sex ratio at birth in the United States. National vital statistics reports; vol 53 no 20. Hyattsville, Maryland: National Center for Health Statistics. 2005.

3. James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. J Endocrinol 2008;198:3-15.

4. Ein-Mor E, Mankuta D, Hochner-Celnikier D, Hurwitz A, Haimov-Kochman R. Sex ratio is remarkably constant. Fertil Steril 2010;93:1961-5.

Eliana Ein-Mor, M.Sc.
Ronit Haimov-Kochman, M.D.
Department of Obstetrics and Gynecology
Hadassah Hebrew University Medical Center
Jerusalem, Israel

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.05.043


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