All-Cause Mortality of Low Birthweight Infants in Infancy, Childhood, and Adolescence: Population Study of England and Wales

BACKGROUND: Low birthweight (LBW) is associated with increased mortality in infancy, but its association with mortality in later childhood and adolescence is less clear. We investigated the association between birthweight and all-cause mortality and identified major causes of mortality for different birthweight groups. METHODS AND FINDINGS: We conducted a population study of all live births occurring in England and Wales between 1 January 1993 and 31 December 2011. Following exclusions, the 12,355,251 live births were classified by birthweight: 500–1,499 g (very LBW [VLBW], n = 139,608), 1,500–2,499 g (LBW, n = 759,283), 2,500–3,499 g (n = 6,511,411), and ≥3,500 g (n = 4,944,949). The association of birthweight group with mortality in infancy (<1 y of age) and childhood/adolescence (1–18 y of age) was quantified, with and without covariates, through hazard ratios using Cox regression. International Classification of Diseases codes identified causes of death. In all, 74,890 (0.61%) individuals died between birth and 18 y of age, with 23% of deaths occurring after infancy. Adjusted hazard ratios for infant deaths were 145 (95% CI 141, 149) and 9.8 (95% CI 9.5, 10.1) for the VLBW and LBW groups, respectively, compared to the ≥3,500 g group. The respective hazard ratios for death occurring at age 1–18 y were 6.6 (95% CI 6.1, 7.1) and 2.9 (95% CI 2.8, 3.1). Male gender, the youngest and oldest maternal age bands, multiple births, and deprivation (Index of Multiple Deprivation score) also contributed to increased deaths in the VLBW and LBW groups in both age ranges. In infancy, perinatal factors, particularly respiratory issues and infections, explained 84% and 31% of deaths in the VLBW and LBW groups, respectively; congenital malformations explained 36% and 23% in the LBW group and ≥2,500 g groups (2,500–3,499 g and ≥3,500 g groups combined), respectively. Central nervous system conditions explained 20% of deaths in childhood/adolescence in the VLBW group, with deaths from neoplasms and external conditions increasingly prevalent in the 1,500–2,499 g and ≥2,500 g birthweight groups. The study would have benefited had we had access to information on gestational age and maternal smoking, but since the former is highly correlated with birthweight and the latter with deprivation, we believe that our findings remain robust despite these shortcomings. CONCLUSIONS: LBW is associated with infant and later child and adolescent mortality, with perinatal factors and congenital malformations explaining many of the deaths. By understanding and ameliorating the influences of upstream exposures such as maternal smoking and deprivation, later mortality can be decreased by reducing the delivery of vulnerable infants with LBW.