Immune function? A missing link in the gender disparity in preterm neonatal outcomes

Abstract

In neonatology, males exhibit a more severe disease course and poorer prognosis in many pathological states when compared to females. Perinatal brain injury, respiratory morbidity, and sepsis, among other complications, preferentially affect males. Preterm neonates (born <37 weeks gestation) display a particularly marked sexual disparity in pathology, especially at the borders of viability. The sex biases in preterm neonatal outcomes and underlying multifactorial mechanisms have been incompletely explored. Sex-specific clinical phenomena may be partially explained by intrinsic differences in immune function. The distinct immune system of preterm neonates renders this patient population vulnerable, and it is increasingly important to consider biological sex in disease processes and to strive for improved outcomes for both sexes. Areas covered: We discuss the cellular responses and molecular intermediates in immune function which are strongly dependent on sex-specific factors such as the genetic and hormonal milieu of premature birth and consider novel findings in a clinical context. Expert commentary: The role of immune function in the manifestation of sex-specific disease manifestations and outcomes in preterm neonates is a critical prognostic variable. Further mechanistic elucidation will yield valuable translational and clinical information of disease processes in preterm neonates which may be harnessed for modulation.

Institutional Delivery Predisposes to Neonatal Sepsis and Its Associated Factors Among Neonates Admitted to Neonatal Intensive Care Units in Central Gondar Zone Primary Hospitals, Northwest Ethiopia, 2019.

“…Male sex is associated with a higher risk of neurological, pulmonary, cardiovascular and infectious morbidities as well as overall mortality when compared to female infants of similar preterm gestation (29). Important differences in the immune response between male and female preterm neonates have also been noted (31). However, the etiology of sex-speci c differences in disease remains relatively undetermined and is likely multifactorial, with genetic, immunological and hormonal in uences playing key roles (30).…”

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

“…31 These findings are most probably attributed to known sex-based differences in immunity, which are most evident during the early stages of life. [37][38][39] Thus it is reasonable to suspect that the level of IL28B in girls possessing the TT rs12979860/GG rs8099917 haplotype is sufficient to elicit efficiently response to the viral infection giving rise to a mild bronchiolitis as a final clinical outcome. If so, this would indicate that, in the context of both general and RSV bronchiolitis, the TT rs12979860/GG rs8099917 haplotype is protective in girls.…”

Gender disparities in preterm neonatal outcomes

“…Important differences in the immune response between male and female preterm neonates have been noted . In both adult and neonatal populations, experimental, clinical and epidemiological studies indicate improved prognosis for females after a septic challenge .…”

“…Prematurity is significantly correlated to increased inflammatory consequences and comorbidities for the newborn, and it is established that males and females mount differing immune responses to infective stimuli . Differences in clinical outcomes between sexes may represent a complex interaction between immunological, hormonal and genetic factors . In this review, we discuss the differences in clinical outcome between male and female preterm infants, the potential mechanisms underlying these differences and their implications for future research and management.…”