Genetic score associations with birthweight in preterm-born infants compared with term-born infants

ObjectiveIn preterm infants, lower birthweight correlates with a higher risk of neonatal complications. Understanding the factors influencing birthweight in these infants is important as it may guide future antenatal and perinatal care. Genetic variants account for at least one-quarter of variation in birthweight in term-born infants, but the genetic contribution to birthweight in preterm infants is not well understood. We aimed to compare genetic score associations with birthweight in a well-powered sample of preterm infants with those in term-born infants. Study designWe used linear regression to test the association between birth weight and fetal genetic scores for birthweight (BW-GS) in a total of 1,416 preterm, singleton and 15,253 term, singleton infants. Analyses, adjusted for ancestry principal components were performed within each of 4 datasets and meta-analysed. ResultsIn term-born infants: a 1 SD higher BW-GS was associated with a 1.20 (95% CI 1.10-1.29) SD higher birthweight. In preterm infants, there was also strong evidence of association, but with a smaller effect size (0.76SD (0.41-1.11) higher birthweight per 1-SD higher BW-GS). In preterms, when stratifying by gestational duration, we found that the associations strengthened with increasing gestational duration. ConclusionsGenetic scores composed of variants identified in term-born infants also influenced birthweight in preterm infants. However, the associations had smaller effects in preterms and were weaker at earlier gestations. This suggests that while many of the same genetic factors influence birthweight in preterm and term-born infants, other factors (environmental, placental, different genetic) may be more important in preterms. Future well-powered studies are required to investigate this.