Preterm birth is associated with increased mortality and morbidity. However, previous studies have been unable to rigorously examine whether confounding factors cause these associations rather than the harmful effects of being born preterm.
To estimate the extent to which the associations between early gestational age and offspring mortality and morbidity were due to confounds by using a quasi-experimental design, the sibling-comparison approach, and controlling for statistical covariates that varied within families.
Design, Setting, and Participants
A population-based cohort study, combining Swedish registries to identify all individuals born in Sweden from 1973–2008 (n=3,300,708 offspring of 1,736,735 mothers) and link them with multiple outcomes.
Main Outcome Measures
Offspring mortality (during infancy and throughout young adulthood) and psychiatric (psychotic or bipolar disorder, autism, ADHD, suicide attempts, substance use, and criminality), academic (failing grades and educational attainment), and social (partnering, parenthood, low income, social welfare benefits) outcomes through 2009.
In the population, there was a dose-response relation between early gestation and the outcome measures. For instance, extreme preterm birth (23–27 weeks of gestation) was associated with infant mortality (OR=288.1, 95% CI=271.7–305.5), autism (HR=3.2, CI=2.6–4.0), low educational attainment (HR=1.7, CI=1.5–2.0), and social welfare benefits (HR=1.3, CI=1.2–1.5) compared to offspring born at term. The associations between early gestation and mortality and psychiatric morbidity generally were robust when comparing differentially exposed siblings and controlling for statistical covariates, whereas the associations with academic and some social problems were greatly or completely attenuated in the fixed effects models.
The mechanisms responsible for the associations between preterm birth and mortality and morbidity are outcome-specific. Associations between preterm birth and mortality and psychiatric morbidity were largely independent of shared familial confounds and measured covariates, consistent with a causal inference. Some associations, particularly predicting suicide attempt, educational attainment, and social welfare benefits were due to confounding factors, however.