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Neonatal multimorbidity and the phenotype of premature aging in preterm infants

Pediatric Research volume 97, pages 2258–2266 (2025)Cite this article

Abstract

Multimorbidity is the co-occurrence of multiple chronic health problems, associated with aging, frailty, and poor functioning. Children born preterm experience more multimorbid conditions in early life compared to term-born peers. Though neonatal multimorbidity is linked to poor health-related quality of life, functional outcomes, and peer group participation, gaps in our theoretical understanding and conceptualization remain. Drawing from life course epidemiology and the Developmental Origins of Heath and Disease models, we offer a framework that neonatal multimorbidity reflects maturational vulnerability posed by preterm birth. The impact of such vulnerability on health and development may be further amplified by adverse exposures and interventions within the environment of the neonatal intensive care unit. This can be exacerbated by disadvantaged home or community contexts after discharge. Uncovering the physiologic and social antecedents of multiple morbid conditions in the neonatal period and their biological underpinnings will allow for more accurate risk-prediction, counseling, and care planning for preterm infants and their families. According to this framework, the maturational vulnerability to multimorbidity imparted by preterm birth and its negative effects on health and development are not predetermined or static. Elucidating pathways of early biologic and physical aging will lead to improvements in care and outcomes.

Impact

  • Multimorbidity is associated with significant frailty and dysfunction among older adults and is indicative of early physiologic aging.

  • Preterm infants commonly experience multimorbidities in the newborn period, an underrecognized threat to long-term health and development.

  • We offer a novel framework incorporating multimorbidity, early cellular aging, and life course health development to innovate risk-prediction, care-planning, and therapeutics.

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Funding

NICHD K23 HD088695.

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Authors and Affiliations

  1. Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, USA

    Jonathan S. Litt

  2. Department of Pediatrics, Harvard Medical School, Boston, USA

    Jonathan S. Litt & Mandy Brown Belfort

  3. Department of Social and Behavioral Sciences, Harvard TH Chan School of Public Health, Boston, USA

    Jonathan S. Litt & Henning Tiemeier

  4. Department of Pediatrics, Brigham and Women’s Hospital, Boston, USA

    Mandy Brown Belfort

  5. Department of Environmental Health, Emory University, Atlanta, USA

    Todd M Everson

  6. Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, USA

    Sebastien Haneuse

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  1. Jonathan S. Litt
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  2. Mandy Brown Belfort
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  3. Todd M Everson
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  4. Sebastien Haneuse
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  5. Henning Tiemeier
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All authors participated in the conception, organization, and reasoning of this review article. Dr. Litt drafted the manuscript. All co-authors provided comprehensive comments and contributed to manuscript editing. All authors approved the final version of the manuscript for publication.

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Litt, J.S., Belfort, M.B., Everson, T.M. et al. Neonatal multimorbidity and the phenotype of premature aging in preterm infants. Pediatr Res 97, 2258–2266 (2025). https://doi.org/10.1038/s41390-024-03617-2

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