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Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity



Identifying preterm infants at risk for mortality or major morbidity traditionally relies on gestational age, birth weight, and other clinical characteristics that offer underwhelming utility. We sought to determine whether a newborn metabolic vulnerability profile at birth can be used to evaluate risk for neonatal mortality and major morbidity in preterm infants.


This was a population-based retrospective cohort study of preterm infants born between 2005 and 2011 in California. We created a newborn metabolic vulnerability profile wherein maternal/infant characteristics along with routine newborn screening metabolites were evaluated for their association with neonatal mortality or major morbidity.


Nine thousand six hundred and thirty-nine (9.2%) preterm infants experienced mortality or at least one complication. Six characteristics and 19 metabolites were included in the final metabolic vulnerability model. The model demonstrated exceptional performance for the composite outcome of mortality or any major morbidity (AUC 0.923 (95% CI: 0.917–0.929). Performance was maintained across mortality and morbidity subgroups (AUCs 0.893–0.979).


Metabolites measured as part of routine newborn screening can be used to create a metabolic vulnerability profile. These findings lay the foundation for targeted clinical monitoring and further investigation of biological pathways that may increase the risk of neonatal death or major complications in infants born preterm.


  • We built a newborn metabolic vulnerability profile that could identify preterm infants at risk for major morbidity and mortality.

  • Identifying high-risk infants by this method is novel to the field and outperforms models currently in use that rely primarily on infant characteristics.

  • Utilizing the newborn metabolic vulnerability profile for precision clinical monitoring and targeted investigation of etiologic pathways could lead to reductions in the incidence and severity of major morbidities associated with preterm birth.

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Fig. 1: Reference for race/ethnicity is white and the reference for education is >12 years.


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Data from the California Prenatal and Newborn Screening Programs were obtained through the California Biobank Program (Screening Information System request no. 476). Data were obtained with an agreement that the California Department of Public Health is not responsible for the results or conclusions drawn by the authors of this publication. This work was supported by the California Preterm Birth Initiative within the University of California, San Francisco (UCSF).

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S.P.O., E.E.R., R.J.B., K.K.R., and L.L.J.-P. contributed to the conception and design, acquisition of data, or analysis and interpretation of data. All authors contributed to drafting the manuscript or revising it critically for important intellectual content All authors also gave final approval of the version to be published.

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Correspondence to Scott P. Oltman.

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No authors have any financial ties to products in the study or potential/perceived conflicts of interest.

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The State of California granted a waiver of consent for this study.

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Oltman, S.P., Rogers, E.E., Baer, R.J. et al. Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity. Pediatr Res 89, 1405–1413 (2021).

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