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

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Ludvigsson, Jonas F.
dc.contributor.author Lu, Donghao
dc.contributor.author Hammarström, Lennart
dc.contributor.author Cnattingius, Sven
dc.contributor.author Fang, Fang
dc.date.accessioned 2019-04-03T15:51:46Z
dc.date.available 2019-04-03T15:51:46Z
dc.date.issued 2018-12-18
dc.identifier.citation Ludvigsson, J. F., Lu, D., Hammarström, L., Cnattingius, S., & Fang, F. (2018). Small for gestational age and risk of childhood mortality: A Swedish population study. PLoS Medicine, 15(12), e1002717. doi:10.1371/journal.pmed.1002717
dc.identifier.issn 1549-1676
dc.identifier.uri https://hdl.handle.net/20.500.11815/1094
dc.description Publisher's version (útgefin grein)
dc.description.abstract 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 pronounced between 28 days and <1 year of age but remained throughout childhood. The greatest risk increase associated with severe SGA was noted for deaths due to infection and neurologic disease. Although we have, to our knowledge, the largest study sample so far addressing the research question, some subgroup analyses, especially the analysis of cause-specific mortality, had limited statistical power using the sibling-based approach. Conclusions We found that SGA, especially severe SGA, was associated with an increased risk of childhood death beyond the neonatal period, with the highest risk estimates for death from infection and neurologic disease. The similar results obtained between the population- and sibling-based analyses argue against strong confounding by factors shared within families.
dc.description.sponsorship This work was supported by the Swedish Research Council for Health, Working Life and Welfare (grant number 2017-00134; https://forte.se/en/) and the Karolinska Institutet (Partial Financing of New Doctoral Student to DL, Senior Researcher Award and Strategic Research Area in Epidemiology Award to FF, and Distinguished Professor Award to SC; https://ki.se/en/startpage). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.extent e1002717
dc.language.iso en
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartofseries Plos Medicine;15(12)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Death rates
dc.subject Child health
dc.subject Birth
dc.subject Pregnancy
dc.subject Sweden
dc.subject Cohort studies
dc.subject Labor and delivery
dc.subject Meðganga
dc.subject Fæðing
dc.subject Fósturlát
dc.subject Fósturgallar
dc.title Small for gestational age and risk of childhood mortality: A Swedish population study
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.version Peer Reviewed
dc.identifier.journal Plos Medicine
dc.identifier.doi 10.1371/journal.pmed.1002717
dc.relation.url http://dx.plos.org/10.1371/journal.pmed.1002717
dc.contributor.department Miðstöð í lýðheilsuvísindum (HÍ)
dc.contributor.department The Centre of Public Health Sciences (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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