Radin Rose G, Mumford Sunni L, Silver Robert M, Lesher Laurie L, Galai Noya, Faraggi David, Wactawski-Wende Jean, Townsend Janet M, Lynch Anne M, Simhan Hyagriv N, Sjaarda Lindsey A, Perkins Neil J, Zarek Shvetha M, Schliep Karen C, Schisterman Enrique F
J Clin Invest. 2015 Sep;125(9):3619-26. doi: 10.1172/JCI82357. Epub 2015 Aug 17.
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.
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.
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.
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.
ClinicalTrials.gov NCT00467363.
Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.
多项证据表明，男性胚胎可能比女性胚胎更容易出现炎症紊乱；因此，抗炎药物，如低剂量阿司匹林（LDA），可能会改变性别比例。在此，我们评估了LDA对男性活产和男性后代的影响，通过基因评估纳入了妊娠丢失情况（n = 56），这是一项孕前LDA的平行设计、区组随机、安慰剂对照试验的一部分。
参与者（615人接受LDA治疗，613人接受安慰剂治疗）年龄在18至40岁之间，有1至2次既往妊娠丢失史。我们估计了意向性分析（ITT）风险比（RR）和95%置信区间（CI），并评估了与基线高敏C反应蛋白（hsCRP）血清浓度的相互作用——全身炎症的一个标志物。
在完成随访的1078名女性中（535人接受LDA治疗，543人接受安慰剂治疗），男性活产的ITT RR等于1.31（95% CI：1.07 - 1.59）。随着hsCRP三分位数增加，安慰剂组出生时男性比例下降，而LDA对男性活产的影响增加（第一三分位数：LDA组48%为男性，安慰剂组为52%，ITT RR = 0.97, 95% CI: 0.70 - 1.35；第二三分位数：LDA组57%为男性，安慰剂组为43%，ITT RR = 1.36, 95% CI: 0.98 - 1.90；第三三分位数：LDA组53%为男性，安慰剂组为35%，ITT RR = 1.70, 95% CI: 1.13 - 2.5；P相互作用 = 0.03）。对怀有男性后代妊娠的分析得出了类似结果。
孕前开始使用LDA可恢复有1至2次既往妊娠丢失史女性的男性活产数量以及怀有男性后代的妊娠数量。此外，我们的数据表明LDA可调节炎症，否则炎症会降低男性胚胎的受孕率或存活率。
ClinicalTrials.gov NCT00467363。
美国国立卫生研究院尤妮斯·肯尼迪·施赖弗国家儿童健康与人类发展研究所的内部研究项目。
