Offspring sex ratios and the causes of placental pathology: the case of placental abruption

William H. James

The Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK

Dear Sir,

Many disorders of pregnancy are associated with skewed offspring sex ratios (proportions of males). Significant excesses of boys are associated with abruptio placenta, placenta praevia, fatty liver of pregnancy and pre-eclampsia: significant excesses of girls are associated with placenta accreta and extra-uterine pregnancy (James, 1995Go). The causes of these sex ratio skews are not established. However I have hypothesized that maternal hormone concentrations around the time of conception causally affect the sex of the resulting offspring, high concentrations of oestrogen being associated with boys, and low concentrations with girls (James, 1996Go). So I suggested that each of these characteristic sex ratios is partially caused by a distinct hormone profile which is also partially responsible for the later associated pathology (James, 1995Go). In that paper I adduced further external evidence to support the notions that high oestrogen concentrations are partially responsible for placenta praevia, pre-eclampsia and fatty liver of pregnancy: and that low concentrations of oestrogen are associated with placenta accreta and extrauterine pregnancy. A similar argument was used to devise a testable endocrine explanation of the excess of daughters associated with hyperemesis gravidarum (James, 2001Go).

Though I cited data on the (high) offspring sex ratio associated with abruptio placenta (James, 1995Go), I offered no suggestion on its cause. The purpose of the present note is to acknowledge that abruptio placenta is not similarly explained (viz by an endocrine profile which also explains the associated offspring sex ratio). Ananth et al. (2001) gave data on more than 7.6 million US births, 1995 and 1996 (Ananth et al., 2001Go). The sex ratio (proportion male) of the abruptio cases was 0.546, a value that is significantly higher than the US live birth sex ratio in those years. However these authors also note that abruptio placenta is very highly associated with gestational age, being about 25 times more commonly associated with infants of 20–27 weeks gestation than with those at term. This feature alone is sufficient to explain the high sex ratio because pre-term births are disproportionately of boys (Cooperstock and Campbell, 1996Go). In short, the association of placenta abruptio with sex ratio seems secondary to associations of both with duration of gestation. So—in contrast to the other pathologies mentioned above—the unusual sex ratio associated with abruptio placenta apparently throws no light on its causes.

It should be mentioned that the hypothesized hormonal causes of some of the pathologies above could be tested by examining the extent to which hormone concentrations control Fallopian tube motility and infiltration by extravillous trophoblast in the placental bed.

References

Ananth, C.V., Smulian, J.C., Demissie, K. et al. (2001) Placental abruption among singleton and twin births in the United States: risk factor profiles. Am. J. Epidemiol., 153, 771–778[Abstract/Free Full Text]

Cooperstock, M. and Campbell, J. (1996) Excess males in preterm birth: interactions with gestational age, race and multiple birth. Obstet. Gynecol., 88, 189–193[Abstract/Free Full Text]

James, W.H. (1995) Sex ratios of offspring and the causes of placental pathology. Hum. Reprod., 10, 1403–1406[Abstract]

James, W.H. (1996) Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. J. Theor. Biol., 180, 271–286[ISI][Medline]

James, W.H. (2001) The associated offspring sex ratios and cause(s) of hyperemesis gravidarum. Acta Obstet. Gynaecol, Scand., 80, 378–379[ISI][Medline]





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