Small for gestational age and risk of childhood mortality : A Swedish population study

Background: Small for gestational age (SGA) has been associated with increased risks of stillbirth and neonatal mortality, but data on long-term childhood mortality are scarce. Maternal antenatal care, including globally reducing the risk of SGA birth, may be key to achieving the Millennium Development Goal of reducing under-5 mortality. We therefore aimed to examine the association between SGA and mortality from 28 days to <18 years using a population-based and a sibling control design. Methods and findings: In a Swedish population study, we identified 3,795,603 non-malformed singleton live births and 2,781,464 full siblings born from January 1, 1973, to December 31, 2012. We examined the associations of severe (<3rd percentile) and moderate (3rd to <10th percentile) SGA with risks of death from 28 days to <18 years after birth. Children born SGA were first compared to non-SGA children from the population, and then to non-SGA siblings. The sibling-based analysis, by design, features a better control for unmeasured factors that are shared between siblings (e.g., socioeconomic status, lifestyle, and genetic factors). Hazard ratios (HRs) were calculated using Cox proportional hazards and flexible parametric survival models. During follow-up (1973-2013), there were 10,838 deaths in the population-based analysis and 1,572 deaths in sibling pairs with discordant SGA and mortality status. The crude mortality rate per 10,000 person-years was 5.32 in children born with severe SGA, 2.76 in children born with moderate SGA, and 1.93 in non-SGA children. Compared with non-SGA children, children born with severe SGA had an increased risk of death in both the population-based (HR = 2.58, 95% CI = 2.38-2.80) and sibling-based (HR = 2.61, 95% CI = 2.19-3.10) analyses. Similar but weaker associations were found for moderate SGA in the population-based (HR = 1.37, 95% CI = 1.28-1.47) and sibling-based (HR = 1.38, 95% CI = 1.22-1.56) analyses. The excess risk was most pron
Funding Agency:Karolinska Institutet