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Male Disadvantage in Oxidative Stress-Associated Complications of Prematurity: A Systematic Review, Meta-Analysis and
Elke van Westering-Kroon1, Maurice J Huizing1, Eduardo Villamor-Martínez1,2
1Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), 6229HA Maastricht, The Netherlands.
Insights
Preterm boys face higher risks for serious health issues like bronchopulmonary dysplasia and necrotizing enterocolitis compared to preterm girls. This study quantifies the male disadvantage in mortality and short-term complications of prematurity.
Area of Science:
- Neonatal Medicine
- Perinatal Health
- Pediatric Physiology
Background:
- Oxidative stress is widely believed to affect males more than females, leading to higher susceptibility to prematurity complications.
- Common complications include bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL).
Purpose of the Study:
- To quantify the effect size of the male disadvantage in prematurity complications.
- To systematically review and meta-analyze cohort studies on sex differences in adverse outcomes among preterm infants.
Main Methods:
- Systematic review and meta-analysis of cohort studies.
- Inclusion of 41 studies comprising 625,680 infants.
- Calculation of risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model.
Main Results:
- Male sex was associated with increased risk for low Apgar score, intubation at birth, respiratory distress, surfactant use, pneumothorax, postnatal steroids, late-onset sepsis, NEC (RR 1.12), severe IVH (RR 1.28), moderate/severe BPD (RR 1.23), severe ROP (RR 1.14), and mortality (RR 1.23).
- Conversely, male sex showed a decreased risk for hypertensive disorders of pregnancy, fetal distress, and Cesarean section.
- Preterm boys exhibited greater clinical instability and required more invasive interventions.
Conclusions:
- Preterm male infants experience a significant disadvantage in mortality and short-term complications compared to preterm females.
- The findings highlight sex-based differences in vulnerability to adverse outcomes following premature birth.
- Clinical management strategies may need to consider sex-specific risks in preterm infants.
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.
