Male Disadvantage in Oxidative Stress-Associated Complications of Prematurity: A Systematic Review, Meta-Analysis and Meta-Regression

Abstract

A widely accepted concept is that boys are more susceptible than girls to oxidative stress-related complications of prematurity, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL). We aimed to quantify the effect size of this male disadvantage by performing a systematic review and meta-analysis of cohort studies exploring the association between sex and complications of prematurity. Risk ratios (RRs) and 95% CIs were calculated by a random-effects model. Of 1365 potentially relevant studies, 41 met the inclusion criteria (625,680 infants). Male sex was associated with decreased risk of hypertensive disorders of pregnancy, fetal distress, and C-section, but increased risk of low Apgar score, intubation at birth, respiratory distress, surfactant use, pneumothorax, postnatal steroids, late onset sepsis, any NEC, NEC > stage 1 (RR 1.12, CI 1.06–1.18), any IVH, severe IVH (RR 1.28, CI 1.22–1.34), severe IVH or PVL, any BPD, moderate/severe BPD (RR 1.23, CI 1.18–1.27), severe ROP (RR 1.14, CI 1.07–1.22), and mortality (RR 1.23, CI 1.16–1.30). In conclusion, preterm boys have higher clinical instability and greater need for invasive interventions than preterm girls. This leads to a male disadvantage in mortality and short-term complications of prematurity.

Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation

“…Genetic factors, including sex, influence the development of EPT 42 . It is well known that boys are more vulnerable to oxidative stress‐related complications of prematurity than girls 43 …”

Endotypes of Prematurity and Phenotypes of Bronchopulmonary Dysplasia: Toward Personalized Neonatology

“…In addition to differences in GA, our meta-analyses also showed that chorioamnionitis was associated with higher rates of antenatal corticosteroids [ 47 ] and that HDP was associated with higher frequencies of female fetuses [ 48 ]. These two factors may modulate the role of the endotype on the development of respiratory complications [ 49 , 50 , 51 ] and require further investigation. Finally, we also analyzed the association of chorioamnionitis, HDP, and SGA/IUGR with the risk of developing respiratory distress syndrome (RDS).…”

The Impact of Oxidative Stress of Environmental Origin on the Onset of Placental Diseases

“…Elevated OS can induce complications in pregnancy progression, leading to long-term effects on both the mother and the fetus. These links were recently reviewed for recurrent pregnancy loss (RPL) [ 1 ], prematurity [ 2 ], intra-uterine growth restriction (IUGR) [ 3 ], diabetes [ 4 ], and preeclampsia, PE [ 5 ].…”