Abstract
BACKGROUND: Assessing gestational age by ultrasound can introduce a systematic bias due to sex differences in early growth. METHODS: This cohort study included data on 1,314,602 births recorded in the Swedish Medical Birth Register. We compared rates of prematurity-related adverse outcomes in male infants born early term (gestational week 37-38) or late preterm (gestational week 35-36), in relation to female infants, between a time period when pregnancy dating was based on the last menstrual period (1973-1978), and a time period when ultrasound was used for pregnancy dating (1995-2010), in order to assess the method's influence on outcome by fetal sex. RESULTS: As expected, adverse outcomes were lower in the later time period, but the reduction in prematurity-related morbidity was less marked for male than for female infants. After changing the pregnancy dating method, male infants born early term had, in relation to female infants, higher odds for pneumothorax (Cohort ratio [CR] 2.05; 95 % confidence interval [CI] 1.33-3.16), respiratory distress syndrome of the newborn (CR 1.99; 95 % CI 1.33-2.98), low Apgar score (CR 1.26; 5 % CI 1.08-1.47), and hyperbilirubinemia (CR 1.12; 95 % CI 1.06-1.19), when outcome was compared between the two time periods. A similar trend was seen for late preterm male infants. CONCLUSION: Misclassification of gestational age by ultrasound, due to size differences, can partially explain currently reported sex differences in early term and late preterm infants' adverse neonatal outcomes, and should be taken into account in clinical decisions and when interpreting study results related to fetal sex.