Familial Patterns of Preterm Delivery: Maternal and Fetal Contributions

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Preterm delivery before 37 completed weeks’ gestation is the commonest reason for infant death in the United States, and continues to become more frequent in the United States and elsewhere. Previous delivery of a preterm infant is a strong risk factor for a recurrence. The investigators used data from the Medical Birth Registry of Norway in the years 1967–2004 to identify 191,282 mothers and 127,830 fathers who later had at least 1 singleton infant. The risk of preterm delivery of firstborn infants was calculated by stratifying parents according to whether or not they themselves had been born before term. The study was limited to parents who had been singleton births and their singleton offspring. Preterm births were those occurring between 22 and 36 weeks’ gestation, while “early” preterm births took place from 22 to 34 weeks’ gestation. Of all parents analyzed, 3.9% had themselves been preterm births. The rate of preterm delivery among all firstborn offspring was 5.5%, and the risk was higher if the parents themselves been delivered preterm. The risk of preterm birth was 8.5% of births of mothers born preterm, compared with 5.5% if the mother had been born at term (relative risk [RR], 1.54; 95% confidence interval [CI], 1.42–1.67). The comparable figures for fathers were 6.0% and 5.3%, respectively (RR, 1.12; 95% CI, 1.01–1.25). The contrast between mothers and fathers was more marked when analyzing “early” preterm births. Using less than 35 weeks as the outcome in the second generation, the risk of early preterm delivery depended strongly on the degree of the mother’s own preterm birth. Mothers born before 28 weeks’ gestation had a 3-fold increase in the risk of delivering early. No such trend was noted for preterm fathers. These findings suggest that paternal genes have little or no effect on the risk of preterm delivery. It would appear that fetal genes inherited from either patient do not make a major contribution. The increased risk of preterm delivery in mothers who themselves had been born preterm is consistent with inheritable maternal phenotypes that increase the risk of preterm delivery.