Response to Therapeutic Interventions in the NICU: Role of Sex as a Biological Variable

Abstract

Sex as a biological variable plays a critical role in the pathophysiology of specific diseases and can have a potential impact on the response to therapies and disease outcomes. Sex-specific differences have been reported in prematurity-related outcomes, suggesting that preterm infants exhibit differences in biological predisposition or resilience to disease. Furthermore, striking differences in response to common neonatal therapies such as antenatal and postnatal steroids, indomethacin, and other nonpharmacologic agents raise the critical need to assess therapeutic responses stratified by biological sex. Very few clinical and translational studies in neonates report outcomes by sex, even though most account for biological sex at enrollment. Sex-specific differences in the newborn may arise from baseline or adaptive differences in male and female preterm neonates. In the current era of precision medicine and the increasing interest in tailoring risk-based therapy to patients, data from neonatal clinical studies should be disaggregated by sex and reported for informing studies with a larger sample size or meta-analyses.