Sex differences in the effects of prematurity and/or low birthweight on neurodevelopmental outcomes: systematic review and meta-analyses

Plain Language SummaryEarly life environmental conditions and adversities affect health into adulthood. For example, it is well-known that premature birth and low birthweight have long-lasting effects on the development and functioning of the brain, affecting various aspects of academic performance, intelligence, and the risk of behavioural problems including depression, anxiety, aggression, impulsivity, and inattention. However, it is not clear if these effects differ between boys and girls. We searched for studies examining the effects of prematurity and/or of low birthweight on cognitive abilities and behavioural problems in children measured at 1 year of age or older, and identified 75 relevant studies. Combining the results of studies found that prematurity/low birthweight decreased measures of intelligence and increased the incidence of behavioural problems, as expected. However, there was no indication that the effects of prematurity/low birthweight consistently differed between males and females, and there were no specific traits where boys appeared to be more or less susceptible to the effects of prematurity/low birthweight than girls. While sex and gender influence health, and in many cases will influence the effects of early life conditions on health, our study shows that prematurity and low birthweight have similar long-term effects on intelligence and behaviour in boys and girls. BackgroundPremature birth and/or low birthweight have long-lasting effects on cognition. The purpose of the present systematic review is to examine whether the effects of prematurity and/or low birth weight on neurodevelopmental outcomes differ between males and females.MethodsWeb of Science, Scopus, and Ovid MEDLINE were searched for studies of humans born premature and/or of low birthweight, where neurodevelopmental phenotypes were measured at 1 year of age or older. Studies must have reported outcomes in such a way that it was possible to assess whether effects were greater in one sex than the other. Risk of bias was assessed using both the Newcastle-Ottawa scale and the National Institutes of Health Quality assessment tool for observational cohort and cross-sectional studies.ResultsSeventy-five studies were included for descriptive synthesis, although only 24 presented data in a way that could be extracted for meta-analyses. Meta-analyses found that severe and moderate prematurity/low birthweight impaired cognitive function, and severe prematurity/low birthweight also increased internalizing problem scores. Moderate, but not severe, prematurity/low birthweight significantly increased externalizing problem scores. In no case did effects of prematurity/low birthweight differ between males and females. Heterogeneity among studies was generally high and significant, although age at assessment was not a significant moderator of effect. Descriptive synthesis did not identify an obvious excess or deficiency of male-biased or female-biased effects for any trait category. Individual study quality was generally good, and we found no evidence of publication bias.ConclusionsWe found no evidence that the sexes differ in their susceptibility to the effects of severe or moderate prematurity/low birthweight on cognitive function, internalizing traits or externalizing traits. Result heterogeneity tended to be high, but this reflects that one sex is not consistently more affected than the other. Frequently stated generalizations that one sex is more susceptible to prenatal adversity should be re-evaluated.