University of Oulu

Katriina Heikkilä, Johanna Metsälä, Anna Pulakka, Sara Marie Nilsen, Mika Kivimäki, Kari Risnes, Eero Kajantie, Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study, The Lancet Public Health, Volume 8, Issue 9, 2023, Pages e680-e690, ISSN 2468-2667,

Preterm birth and the risk of multimorbidity in adolescence : a multiregister-based cohort study

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Author: Heikkilä, Katriina1,2,3; Metsälä, Johanna1; Pulakka, Anna1,4;
Organizations: 1Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
2Department of Public Health, University of Turku, Turku, Finland
3Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
4Research Unit of Population Health, University of Oulu, Oulu, Finland
5Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
6Centre for Health Care Improvement, St. Olavs Hospital, Trondheim, Norway
7Department of Mental Health for Older People, Faculty of Brain Sciences, University College London, London, UK
8Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
9Children's Clinic, St. Olavs Hospital, Trondheim, Norway
10Clinical Medicine Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Elsevier, 2023
Publish Date: 2023-10-13


Background: Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10–18 years).

Methods: We used population-wide data from Finland (1 187 610 adolescents born 1987–2006) and Norway (555 431 adolescents born 1998–2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23–27 weeks (extremely preterm), 28–31 weeks (very preterm), 32–33 weeks (moderately preterm), 34–36 weeks (late preterm), 37–38 weeks (early term), 39–41 weeks (term, reference category) and 42–44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10–18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence.

Findings: Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19–2·39) for two health outcomes (PAF 9·0%; 8·3–9·6), and 4·22 (3·66–4·87) for four health outcomes (PAF 22·7%; 19·4–25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose–response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets.

Interpretation: Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10–18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care.

Funding: European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

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Series: The Lancet. Public health
ISSN: 2468-2667
ISSN-E: 2468-2667
ISSN-L: 2468-2667
Volume: 8
Issue: 9
Pages: e680 - e690
DOI: 10.1016/S2468-2667(23)00145-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: This study and EK were supported by the European Union Horizon 2020 (733280 Research on European Children and Adults Born Preterm), the Academy of Finland (315690), the Foundation for Pediatric Research, the Sigrid Jusélius Foundation, the Signe and Ane Gyllenberg Foundation, and Finska Läkaresällskapet. KH was supported by the Foundation for Pediatric Research and the Signe and Ane Gyllenberg Foundation. AP was supported by the Juho Vainio Foundation and the Signe and Ane Gyllenberg Foundation. SMN was supported by Felles forskningsutvalg (joint research committee) of Helseforetak (Health Trust), St Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (30223 2022). MK was supported by the Wellcome Trust (221854/Z/20/Z), the Medical Research Council (R024227, S011676), the National Institute on Aging (National Institutes of Health, R01AG056477, R01AG062553), and the Academy of Finland (350426).
Copyright information: © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.