The Need to Address Sex as a Biological Variable in Neonatal Clinical Studies.
The Need to Address Sex as a Biological Variable in Neonatal Clinical Studies.
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需要将性别作为新生儿临床研究中的生物变量。
DOI：
10.1016/j.jpeds.2022.11.021
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Eichenwald,Eric
中科院分区：
文献类型：
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作者：
Lingappan,Krithika;Alur,Pradeep;Eichenwald,Eric
男性已被确定为早产儿死亡的危险因素。1、2、3、4尽管男性早产儿的死亡率、呼吸窘迫综合征(RDS)和支气管肺发育不良(BPD)下降得更快，但他们出院前的死亡率、RDS、坏死性小肠结肠炎、迟发性败血症、严重脑室出血(IVH)、严重早产儿视网膜病变(ROP)和BPD的风险仍显著高于男性早产儿。5韩国、加拿大、日本、奥地利和瑞士的新生儿队列中也报告了早产男婴死亡率增加的类似结果。3、6、7、8、9在一项荟萃分析中，32项研究中有26项显示早产男性死亡率增加，而6项研究报告没有性别差异。10越来越多的证据表明，性别在疾病结局、病理生理学和治疗反应中作为生物变量的作用，突显了新生儿临床和转化试验中的差距。这篇评论强调了已经证明了不同性别在结果上的差异的研究。我们承认，这里没有讨论的其他研究未能证明所讨论的结果中的性别差异。然而，大多数新生儿研究没有足够的能力来检测关键结果中特定性别的差异，这可能导致对生物学性别和结果之间的关键交互作用的报告不足。我们剖析了这些观察结果是如何由基线的性别差异或对常见新生儿治疗(如产前和出生后的类固醇和吲哚美辛)的适应或反应造成的。我们认为，这些数据提高了评估按生物性别分层的治疗反应的迫切需要。在新生儿学的临床和转译研究中，生物性别应该被认为是一个基本因素，可以推动易感性、病理生理学、治疗反应和结果。
Male sex has been identified as a risk factor associated with mortality in preterm neonates. 1, 2, 3, 4 Even though male preterm neonates have shown faster declines in mortality, respiratory distress syndrome (RDS), and bronchopulmonary dysplasia (BPD), they still have a significantly higher risk of mortality before hospital discharge, RDS, necrotizing enterocolitis, late-onset sepsis, severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), and BPD. 5 Similar results of increased mortality in premature male neonates have been reported from neonatal cohorts from Korea, Canada, Japan, Austria, and Switzerland. 3, 6, 7, 8, 9 In one meta-analysis, 26 of the 32 studies showed increased mortality in premature males, while 6 reported no sex difference. 10The increasing evidence of the role of sex as a biological variable in disease outcome, pathophysiology, and response to therapy has highlighted the gap in neonatal clinical and translational trials. This commentary highlights studies that have demonstrated sex-specific differences in outcomes. We acknowledge that other studies not discussed here, fail to demonstrate sex differences in the outcomes discussed. However, most neonatal studies are not adequately powered to detect sex-specific differences in key outcomes, which likely lead to underreporting of critical interactions between biological sex and outcomes. We dissect how these observations may result from sex differences at baseline or with adaptation or response to common neonatal therapies such as antenatal and postnatal steroids, and indomethacin. We argue that these data raise the critical need to assess therapeutic responses stratified by biological sex. Biological sex should be recognized as an essential factor that can drive susceptibility, pathophysiology, response to therapy, and outcomes in clinical and translational studies in neonatology.