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.