Preterm birth and mortality in adulthood: a systematic review

Preterm birth (gestational age < 37 weeks) has a worldwide prevalence of nearly 11%, and >95% of preterm infants who receive modern neonatal and pediatric care now survive into adulthood. However, improved early survival has been accompanied by long-term increased risks of various chronic disorders, prompting investigations to determine whether preterm birth leads to higher mortality risks in adulthood. A systematic review identified eight studies with a total of 6,594,424 participants that assessed gestational age at birth in relation to all-cause or cause-specific mortality at any ages ≥18 years. All six studies that included persons born in 1967 or later reported positive associations between preterm birth and all-cause mortality in adulthood (attained ages, 18-45 years). Most adjusted relative risks ranged from 1.2 to 1.6 for preterm birth, 1.1 to 1.2 for early term birth (37-38 weeks), and 1.9 to 4.0 for extremely preterm birth (22-27 weeks), compared with full-term birth (variably defined but including 39-41 weeks). These findings appeared independent of sociodemographic, perinatal, and maternal factors (all studies), and unmeasured shared familial factors in co-sibling analyses (assessed in four studies). Four of these studies also explored cause-specific mortality and reported associations with multiple causes, including respiratory, cardiovascular, endocrine, and neurological. Two smaller studies based on an earlier cohort born in 1915-1929 found no clear association with all-cause mortality but positive associations with selected cause-specific mortality. The overall evidence indicates that premature birth during the past 50 years is associated with modestly increased mortality in early to mid-adulthood.