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Review
. 2021 Sep 18;10(9):1490.
doi: 10.3390/antiox10091490.

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

Elke van Westering-Kroon  1 , Maurice J Huizing  1 , Eduardo Villamor-Martínez  1   2 , Eduardo Villamor  1
Affiliations
Review

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

Elke van Westering-Kroon et al. Antioxidants (Basel). .

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.

Keywords: bronchopulmonary dysplasia; female advantage; intraventricular hemorrhage; male disadvantage; mortality; necrotizing enterocolitis; oxidative stress; periventricular leukomalacia; preterm birth; retinopathy of prematurity; sex differences.

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Conflict of interest statement

The authors declare no conflict of interest. The views expressed in this paper are those of the authors and do not necessarily reflect the policies of Statistics Netherlands.

Figures

Figure 1
Figure 1
Summary of meta-analyses on the association between obstetric and perinatal characteristics of preterm infants and male sex. CI: confidence interval; K: number of studies; P3: 3rd percentile; P10: 10th percentile; SD: standard deviation.
Figure 2
Figure 2
Summary of meta-analyses on the association between clinical characteristics and outcomes of preterm infants and male sex. BPD: bronchopulmonary dysplasia; CI: confidence interval; IVH: intraventricular hemorrhage; K: number of studies; NEC: necrotizing enterocolitis; PDA: patent ductus arteriosus; PVL: periventricular leukomalacia; ROP: retinopathy of prematurity.
Figure 3
Figure 3
Meta-regression. (A) Plot showing the correlation between the association of male sex with mortality in preterm infants and the median year of birth of each cohort. A total of 24 studies were included (coefficient, −0.009; standard error, 0.004; p = 0.019; R2-analog, 0.37). (B) Plot showing the correlation between the association of male sex with mortality in preterm infants and mean/median gestational age of each cohort. A total of 18 studies were included (coefficient, 0.051; standard error, 0.014; p < 0.001; R2-analog, 0.75).
See this image and copyright information in PMC

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