Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study

Objective Infant boys have worse outcomes than girls. In twins, the 'male disadvantage' has been reported to extend to female co-twins via a 'masculinising' effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins. Design Retrospective cohort study Setting Eleven countries participating in the International Network for Evaluating Outcomes of Neonates. Patients Liveborn twins admitted at 23-29 weeks' gestation in 2007-2015. Main outcome measures We examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above). Results Among 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively. Conclusions Sex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants.