BMJ  2007;334:486-487 (10 March), doi:10.1136/bmj.39141.622917.80

Editorials

Ratio of boys to girls at birth

Is not related to the time taken to conceive, or exposure to environmental agents

In 2005, the BMJ published a paper suggesting that subfertile couples were more likely than fertile couples to have boys.¹ This observation was offered as support of the hypothesis that sperm bearing Y chromosomes swim faster through viscous cervical mucous. In the flurry of letters that followed, other researchers reported that their data did not support the sex ratio finding.² Furthermore, the sperm swimming hypothesis was exposed as a persistent myth.³

In this week's BMJ, Joffe and colleagues⁴ pool data from several large fecundity studies, further confirming the lack of association between secondary sex ratio (boys to girls at birth) and time to pregnancy. On this point, we are confident the authors are correct. However, their hypothesis that the sex ratio could be a marker of adverse effects on the male reproductive system is less certain. They suggest that a slight decline over time in the secondary sex ratio could represent deterioration in male reproductive health. But does it?

The sex ratio at birth is a prevalence measure. Firstly, it reflects the relative number and fertilising capacity of sperm bearing X and Y chromosomes that reach the ovum in the female genital tract, and secondly it reflects the relative survival of male and female conceptuses in early pregnancy. In human semen, the number of spermatozoa with X and Y chromosomes is equal. However, from the time that pregnancy is clinically recognised (around six weeks after last menstrual period), males are the more prevalent. What happens in those early weeks to create this male excess? It is not known whether this results from a higher fertilising capability of spermatozoa bearing Y chromosomes, or a preferential loss of female fetuses during fertilisation, implantation, and early embryogenesis.⁵ It seems unlikely that males are the better survivors during this period, given the excess mortality of males throughout the rest of pregnancy (and for a long time thereafter).

Added to this mystery are the few factors that are known to be associated with sex ratio. The proportion of males decreases with increasing parental age, and it is higher in white people than in black people.⁶ Studies of inter-racial marriages indicate that the race difference is determined by paternal factors,⁵ but the mechanisms are unknown.

Changes have occurred in the secondary sex ratio over time, although they are very small. During the past 60 years, the proportion of male babies decreased from 51.54% to 51.38% in Europe (a shift of fewer than two babies in 10 000 from male to female).⁷ In the United States the sex ratio increased between 1959 and 1971 (from 51.17% to 51.30% males) and then decreased to 51.14% in 2002.⁶

One of the most quoted areas of research on sex ratio is the effects of toxic exposures.⁸ However, the evidence that reproductive toxicants interfere with the sex ratio is weak or circumstantial, and the mechanisms involved are conjectural.⁹ For example, DBCP (1,2-dibromo-3-chloropropane) is a powerful male reproductive toxicant that can cause complete sterility. DBCP is regarded as a prime example of a toxicant that changes the secondary sex ratio. To our knowledge, however, this claim is based on one small study.¹⁰ Similarly, while positive studies may have been reported, there is no compelling or consistent evidence that well established reproductive hazards such as tobacco smoke, ionising radiation, or inorganic lead have any impact on the sex ratio of offspring.¹¹

Why then does sex ratio continue to attract so much scientific attention? One reason may be that it is so easy to measure. Literally 1000s of studies include information on sex of offspring. With so many opportunities for analysing data, it is hardly surprising that striking findings emerge. When they do, imaginative researchers have no trouble constructing plausible biological mechanisms to explain their findings. Such hypotheses often assume a life of their own (as with sperm bearing Y chromosomes being faster swimmers), even as the original observations fail for lack of confirmation.

This is not to say that the secondary sex ratio is of no interest. One of the most important reproductive trends of this new century may be the rising secondary sex ratio in China, where today 117 boys are born for every 100 girls.¹² This enormous deficit of females has disturbing implications for future societal stresses in China—and thus for the rest of the world. But in terms of the sex ratio being a barometer of male reproductive health, we remain doubtful. The sex ratio is an endpoint particularly vulnerable both to false positive reports and fanciful interpretation. Positive findings should be treated with scepticism.

¹ Department of Occupational Medicine, Aarhus University Hospital, DK 8000 Aarhus, Denmark, ² Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA

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Competing interests: None declared.

Provenance and peer review: Commissioned; not externally peer reviewed.

References

1. Smits LJ, de Bie RA, Essed GG, van den Brandt PA. Time to pregnancy and sex of offspring: cohort study. BMJ 2005;331:1437-8.[Free Full Text]
2. Olsen J, Weijin Z, Jin LZ. Time to pregnancy and sex ratio of offspring. Electronic response to Smits LJ, et al. Time to pregnancy and sex of offspring: cohort study. BMJ 2005. www.bmj.com/cgi/eletters/331/7530/1437#124413
3. Grant VJ. Entrenched misinformation about X- and Y-sperm. Electronic response to Smits LJ, et al. Time to pregnancy and sex of offspring: cohort study. BMJ 2006. www.bmj.com/cgi/eletters/331/7530/1437#130012
4. Joffe M, Bennett J, Best N, Jensen TK. Sex ratio and time to pregnancy: analysis of four large European population surveys. BMJ 2007 doi: 10.1136/bmj.39097.508426.BE[Abstract/Free Full Text]
5. Boklage CE. The epigenetic environment: secondary sex ratio depends on differential survival in embryogenesis. Hum Reprod 2005;20:583-7.[Abstract/Free Full Text]
6. Mathews TJ, Hamilton BE. Trend analysis of the sex ratio at birth in the United States. Natl Vital Stat Rep 2005;53:1-17.[Medline]
7. Martuzzi M, Di Tanno ND, Bertollini R. Declining trends of male proportion at birth in Europe. Arch Environ Health 2001;56:358-64.[ISI][Medline]
8. Weijin Z, Olsen J. Offspring sex ratio as an indicator of reproductive hazards. Occup Environ Med 1996;53:503-4.[ISI][Medline]
9. Trasler J. Paternal exposures: altered sex ratios. Teratology 2000;62:77-8.[CrossRef][ISI][Medline]
10. Potashnik G, Porath A. Dibromochloropropane (DBCP): a 17-year reassessment of testicular function and reproductive performance. J Occup Environ Med 1995;37:1287-92.[CrossRef][ISI][Medline]
11. Heron J, Ness A. Lack of association between smoking behavior and the sex ratio of offspring in the Avon longitudinal study of parents and children. Fertil Steril 2004;81:700-2.[CrossRef][ISI][Medline]
12. Wu Z, Viisainen K, Hemminki E. Determinants of high sex ratio among newborns: a cohort study from rural Anhui province, China. Reprod Health Matters 2006;14:172-80.[CrossRef][ISI][Medline]

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