Sex Differences in Infant Mortality: A Population Data Linkage Study of Brazilian Male-Female Twin Pairs

Abstract

Introduction Epidemiological studies of twin pairs provide researchers with the opportunity to better understand the roles of genetics and the environment on human traits and health conditions. Twin births are also of interest for public health, given they are five times more likely to be of low birth weight and preterm compared to singletons. Male twin newborns are at high risk of mortality, although the causes of such disadvantage are still largely unknown. Objectives and Approach We deterministically linked population birth to death records of twins born in Brazil from 2012–2016, and probabilistically linked twins within pairs through a bespoke algorithm. We studied male-female twin pairs to investigate sex differences in infant mortality stratified by early neonatal (0–6 days), late neonatal (7–27 days) and late infant (28–365 days) deaths. We used conditional logistic regression to estimate odds ratios (OR) for male sex, adjusting for birth weight and matching for familial factors by design. Results Our algorithm successfully matched 101,382 twin pairs, 28,558 were male-female pairs included in the study. Average birthweight was 100g greater for males compared with females. We found that males were at higher risk of infant mortality than their female co-twins even after adjusting for birth weight and familial factors (aOR = 1.42, 95% CI: 1.22–1.66). The aORs for neonatal death increased from those born at less than 28 weeks to those born at 28–31, 32–26 and 37+ weeks: 1.47 (1.02–2.13), 1.73 (1.17–2.57), 1.99 (1.17–3.38), and 3.35 (1.29–8.73), respectively. Conclusion / Implications Male twins have greater risk of infant and neonatal mortality compared with female co-twins, more so the higher the gestational age. Unmeasured familial and maternal factors may influence the role of birth weight in the association between sex and poor early life outcomes.