Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss.
BACKGROUND
Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, we assessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA.


METHODS
Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with 1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% CI and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration - a marker of systemic inflammation.


RESULTS
Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% CI: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LDA vs. 43% in placebo, ITT RR = 1.36, 95% CI: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% CI: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspring yielded similar results.


CONCLUSIONS
Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos.


BACKGROUND
ClinicalTrials.gov NCT00467363.


BACKGROUND
Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.
Rose G
RG
Radin
Sunni L
SL
Mumford
Robert M
RM
Silver
Laurie L
LL
Lesher
Noya
N
Galai
David
D
Faraggi
Jean
J
Wactawski-Wende
Janet M
JM
Townsend
Anne M
AM
Lynch
Hyagriv N
HN
Simhan
Lindsey A
LA
Sjaarda
Neil J
NJ
Perkins
Shvetha M
SM
Zarek
Karen C
KC
Schliep
Enrique F
EF
Schisterman
D000022:Abortion, Spontaneous / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D050498:Live Birth; D008297:Male; D011247:Pregnancy; D012737:Sex Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin