Male infant born alive 1.25 X more likely if sufficient Vitamin D - Oct 2019

THE ROLE OF MATERNAL PRECONCEPTION VITAMIN D STATUS IN HUMAN OFFSPRING SEX RATIO.

Presented at American Society for Reproductive Medicine Conference O-63 Monday, October 14, 2019 11:15 AM

Alexandra C. Purdue-Smithe, PhD,a Keewan Kim, PhD,a Carrie J. Nobles, PhD,a Enrique F. Schisterman, PhD,a Karen C. Schliep, PhD,b Neil J. Perkins, PhD,a Lindsey A. Sjaarda, PhD,c Josh Freeman, MPH,a Sonia L. Robinson, PhD,d Jeannie G. Radoc, BS,a James L. Mills, MD, MS,a Robert M. Silver, MD,b Sunni L. Mumford, PhDe aNICHD, Bethesda, MD; bUniversity of Utah, Salt Lake City, UT; cEpidemiology Branch, DIPHR, NICHD, NIH, Bethesda, MD; dNational Institutes of Child Health and Human Development, Bethesda, MD; eNational Institute of Child Health and Human Development, Bethesda, MD.

OBJECTIVE: Experimental data suggests that maternal inflammation is specifically detrimental to the implantation or survival of male embryos, which may contribute to sex ratio reduction on the population scale. However, it is currently unknown whether other factors associated with both pregnancy and inflammation, such as vitamin D status, are associated with altered offspring sex ratio. Our objective was to therefore evaluate the association of preconception serum 25-hydroxyvitamin D levels [25(OH)D] and male live birth among reproductive-age women attempting pregnancy.
DESIGN: This was a prospective secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial, which included 1,228 reproductive-age women attempting to conceive.

MATERIALS AND METHODS: 25(OH)D and high sensitivity C-reactive protein (hsCRP) levels were measured in serum at baseline. Participants were classified as vitamin D sufficient versus insufficient [25(OH)D >30 vs. <30 ng/mL]. Fetal sex was ascertained by medical record abstraction among live births and by chromosomal analysis among clinical pregnancy losses. We estimated unadjusted and adjusted relative risks (RRs) and 95% confidence intervals (CIs) for male live birth and pregnancy with a male fetus according to preconception vitamin D status using generalized estimating equations of log-binomial regression with robust standard errors.

RESULTS: Among 1,094 women who completed follow-up, the proportion of male live births was 24% (n=136) and 30% (n=156) in the vitamin D insufficient and sufficient groups, respectively. In multivariable models, women in the

• vitamin D sufficient group were 25% (RR = 1.25; 95% CI = 1.02, 1.52) more likely to have a live-born male infant compared to the insufficient group.

These associations were stronger among women with high versus low levels of preconception hsCRP (>1.95 ng/mL: RR = 1.44;95% CI - 1.01,2.05, versus % 1.95 ng/mLRR - 1.08; 95% CI - 0.81,1.43), a marker of systemic low-grade inflammation.
In analyses utilizing available karyotype data from clinical pregnancy losses, sufficient versus insufficient vitamin D was also positively associated with pregnancy with a male fetus (RR — 1.21; 95% CI — 1.01, 1.46). Estimates were stronger among women with high versus low levels of hsCRP (>1.95 ng/mL: RR — 1.34; 95% CI — 0.96,1.88 versus % 1.95 ng/mLRR — 1.12; 95% CI — 0.90,1.39), though not statistically significant.

CONCLUSIONS: Our findings that preconception vitamin D status is positively associated with male live birth and pregnancy with a male fetus, particularly among women with elevated inflammation, suggest that sufficient levels of preconception vitamin D may mitigate maternal inflammation that would otherwise be detrimental to the implantation or survival of male conceptuses in utero. These findings highlight the importance of vitamin D in reproduction and implicate a novel factor associated with altered offspring sex ratio in humans.

SUPPORT: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424, and HHSN267200603426)

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Sex ratio varies with season of conception in Modena Italy- April 2003

The male disadvantage and the seasonal rhythm of sex ratio at the time of conception
Human Reproduction 18(4):885-7, DOI: 10.1093/humrep/deg185
Angelo CagnacciAngelo CagnacciA RenziSerenella AranginoSerenella Arangino
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In accordance with a presumed greater fragility of male versus female pregnancies, we tested whether sex ratio (male/female ratio) of vital pregnancies is higher in seasons more favourable for reproduction. A retrospective study was performed on 14,310 births which had occurred in our institute between 1995-2001. For each single pregnancy the time of conception was calculated by the last menstrual period recall and confirmed or redefined by ultrasound in 95.8% of cases. The sex ratio of 199,454 pregnancies which had occurred in the Modena County between 1936-1998 was also stratified according to the month of birth. Sex ratio of institutional deliveries was 0.511 and was identical to that obtained from the County registry. Sex ratio at birth did not show a significant seasonal variation. By contrast, sex ratio calculated at time of conception showed a seasonal rhythm, with amplitude of 2.4% and peak values in October (confidence interval: +/-43 days). The rhythm was in phase with the rhythm of conception that showed peak values in September (confidence interval: +/-37 days) and an amplitude of 7%. The superimposition of the phase of sex ratio and conception rhythms supports the contention that more males than females are conceived in seasons with more favourable reproductive conditions.