Preterm Birth, Long-term Survival, and Fertility

Abstract

To the Editor: In their cohort study of more than 1 million Norwegians identified from the Medical Birth Registry, Dr Swamy and colleagues reported that preterm birth was associated with diminished long-term survival and reproduction. These findings are consistent with a growing body of evidence supporting the hypothesis of a fetal or developmental origin of adult disease. However, we are concerned that the results could be confounded by a more dominant influence of low birth weight, which often accompanies preterm birth. Elucidating the relative influences of low birth weight vs prematurity is important because these 2 parameters reflect different underlying mechanisms (ie, poor in utero growth vs maternal infections, respectively) and require different maternal interventional strategies. Maternal and neonatal health programs, particularly in developing countries, need to determine which modifiable perinatal factor might have the greatest effect on adult health, as this will influence public health strategies. The authors also report that preterm birth was associated with apparent reduced fertility, as assessed from offspring records. A possible confounder of these findings is genetic influences; ie, the same genetic factors could predispose to preterm birth and to reduced reproductive potential. Such genetic effects are difficult to disentangle, but the large data set may permit nested twin substudies, which have proven valuable in minimizing confounding from genetic and environmental factors. Additional analyses to stratify or adjust for the effects of birth weight and, if feasible, to conduct supplementary analysis in nested twin studies may provide further insights into underlying mechanisms of fetal origins of adult diseases.