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

Arch Dis Child Fetal Neonatal Ed. 2021 Jan;106(1):17-24. doi: 10.1136/archdischild-2020-318832. Epub 2020 May 25.


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.

Keywords: mortality; multiple births; neonatology; outcomes research; twins.

MeSH terms

  • Bronchopulmonary Dysplasia / mortality
  • Cerebral Intraventricular Hemorrhage / mortality
  • Developed Countries
  • Female
  • Gestational Age
  • Hospital Mortality / trends*
  • Humans
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Infant, Premature, Diseases / mortality*
  • Infant, Very Low Birth Weight
  • Leukomalacia, Periventricular / mortality
  • Male
  • Retinopathy of Prematurity / mortality
  • Retrospective Studies
  • Severity of Illness Index
  • Sex Factors
  • Twins