Low Apgar score and asphyxia complications at birth and risk of longer-term cardiovascular disease: a nationwide population-based study of term infants

BACKGROUND: Most follow-up studies have focused on the long-term consequences of asphyxia at birth on the brain. The aim of this study was to investigate associations between low Apgar score and asphyxia-related complications and subsequent risks of cardiovascular diseases (CVD) in childhood and early adulthood. METHODS: This population-based cohort study included 2,826,424 non-malformed singleton births, born at term (≥37 weeks’ gestation) between 1988 and 2018 in Sweden. Primary exposure was a composite of asphyxia-related complications, defined as a) Apgar score 0–3 at 1-min; or b) Apgar score 0–3 at 5-min; or c) neonatal seizures (including hypoxic ischemic encephalopathy). Using Cox regression, we estimated the risk of CVD after 1 year of age, defined as stroke, coronary heart disease, heart failure, and atrial fibrillation. RESULTS: Overall, there were 4165 cases with cardiovascular diseases. Individuals with asphyxia-related complications had adjusted hazard ratios (95% confidence intervals) of 1.90 (1.54 to 2.34) for cardiovascular disease, 2.29 (1.74 to 3.03) for stroke, 2.17 (1.37 to 3.42) for heart failure, and 1.38 (0.87 to 2.17) for atrial fibrillation. Hazard ratios for CVD were elevated among individuals with Apgar score 0–3 at 1 and 5 min, and those with neonatal seizures. Compared with unexposed individuals, neonatal seizures were associated with 5 times higher rates of stroke and heart failure, respectively. INTERPRETATION: Asphyxia-related complications and its neonatal complications, especially low Apgar score and neonatal seizures, are associated with increased risks of CVD in childhood and early adulthood, although the absolute risk of CVD is low in young age. FUNDING: 10.13039/501100004359Swedish Research Council and the 10.13039/501100003793Swedish Heart-Lung Foundation