“Masculinizing” Effect on Respiratory Morbidity in Girls From Unlike-Sex Preterm Twins: A Possible Transchorionic Paracrine Effect

Abstract

OBJECTIVES. Preterm male infants are at a disadvantage when compared with female infants regarding the incidence of respiratory and neurologic morbidity and mortality. At term, female infants from unlike-sex twin pairs have birth weights that are closer to their male co-twins than to girls from like-sex twin pairs. We hypothesized that if the male disadvantage is mediated via factors that affect fetal lung development, there may be a potential effect on the incidence of respiratory distress syndrome and its complications in female infants from unlike-sex pairs. PATIENTS AND METHODS. In this population-based study we used data from the Israel Neonatal Network, which included data from 8858 very low birth weight (500–1500 g) infants of 24 to 34 weeks' gestation. The incidence of morbidity and mortality was compared in male and female infants from singletons and like-sex and unlike-sex twin pairs. Multivariable analyses were used, accounting for relevant confounding variables. RESULTS. Male singletons and like-sex twins were at increased risk for mortality, respiratory distress syndrome, pneumothorax, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, and periventricular leukomalacia. However, in unlike-sex twin pairs, no difference was seen in the incidence of respiratory morbidity between male and female twins. The male disadvantage was maintained for mortality and periventricular-intraventricular hemorrhage. CONCLUSIONS. These findings suggest that the difference in morbidity and mortality between male and female premature infants represents a male disadvantage as opposed to a female advantage and that this disadvantage may be transferred from boys to girls in unlike-sex twin pairs, perhaps via an intrauterine paracrine effect.