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Keep it in the family: comparing perinatal risks in small-for-gestational-age infants based on population vs within-sibling designs
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University Faculty of Medicine, Montreal, Canada.
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Stockholm, Sweden; Department of Neonatalogy, Karolinska University Hospital, Stockholm, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-1024-5602
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2019 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 48, no 1, p. 297-306Article in journal (Refereed) Published
Abstract [en]

Background: Small-for-gestational-age (SGA) birth is commonly used as a proxy for fetal growth restriction, but also includes constitutionally small infants. Genetic factors account for almost half of the risk of SGA birth. We estimated perinatal risks of SGA birth using both population-based and within-sibling analyses, where the latter by design controls for shared genetic factors and maternal environmental factors that are constant across pregnancies.

Methods: This was a prospective nationwide cohort study of 2 616 974 singleton infants born in Sweden between January 1987 and December 2012, of whom 1 885 924 were full siblings. We estimated associations between severe or moderate SGA (<3rd percentile and 3rd to <10th percentiles, respectively) and risks of stillbirth, neonatal mortality and morbidity, using both population-based and within-sibling analyses. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in stillbirth analyses, whereas relative risks (RRs) were used for analyses of neonatal outcomes.

Results: Compared with non-SGA births (>10th percentile), the HR (95% CI) of stillbirth was 18.5 (95% CI 17.4-19.5) among severe SGA births in the population analysis and 22.5 (95% CI 18.7-27.1) in the within-sibling analysis. In non-malformed infants, RRs for neonatal mortality in moderate and severe SGA infants were similarly increased in both population and within-sibling analyses. In term non-malformed infants (>= 37 weeks), SGA-related RRs of several neonatal morbidities were higher in within-sibling than in population analyses.

Conclusions: Perinatal risks associated with fetal growth restriction are more accurately estimated from analyses of SGA in which genetic factors are accounted for.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 48, no 1, p. 297-306
Keywords [en]
Intrauterine growth restriction, neonatal morbidity, neonatal mortality, sibling analysis, small-for-gestational-age, stillbirth
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:oru:diva-73887DOI: 10.1093/ije/dyy196ISI: 000463862500038PubMedID: 30239740Scopus ID: 2-s2.0-85059285272OAI: oai:DiVA.org:oru-73887DiVA, id: diva2:1306313
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2014-0073 2017-00134The Karolinska Institutet's Research FoundationAvailable from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved

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Ludvigsson, Jonas F.

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