Respiratory Dysfunction and Newborn Screen Acylcarnitine Profiles Predict Growth Failure in Extremely Low Gestational Age Newborns

Background: Extremely Low Gestational Age Newborns (ELGANs, <29weeks gestation) experience respiratory failure and nutritional deficiencies that are both associated with growth failure. Newborn screen (NBS) metabolites (e.g. acylcarnitine (AC) profiles) have emerged as predictors of important neonatal morbidities, but their associations with neonatal intensive care unit (NICU) exposures and growth rates are not yet established. The objective of this study was to correlate respiratory dysfunction, nutritional intake, and NBS AC profiles over the first 28 days of life (DOL) to growth failure at 36 weeks corrected gestational age (CGA).

Methods: Two ELGAN cohorts (n=127 across 2 centers) had daily recording of nutritional intake and respiratory exposures. Plasma AC profiles (22 compounds) were obtained from New York State (NYS) NBS at approximately DOL 3 and 28. The primary outcome measure (deemed Zchange) was defined as the change in weight Z score from birth to hospital discharge or 36 weeks CGA (Zchange = ZCGA36 – ZDOL0). Three multivariate regression analysis models using robust standard errors were developed looking at various NICU exposures including nutritional intake/route, respiratory dysfunction (cumulative oxygen (O2) exposure, log10OxygenAUC), and AC level univariates and their individual effects on average daily caloric intake and growth failure (expressed as Zchange) in this ELGAN cohort. Some variables were log transformed before analysis.

Results: When modeling for total caloric intake, infants of younger gestational age, those with higher log10OxygenAUC, and those fed a smaller proportion of enteral calories were found to receive less total calories over the first 28 days of life. Higher log10OxygenAUC also had negative impacts on Zchange, while higher DOL 0 weight Z score and increased delivery of enteral fat calories predicted better Zchange. Average 28 day total calories did not impact growth. Of the 22 ACs added to the Zchange model, C14 was independently associated with decreased Zchange.

Conclusion: Elevated cumulative neonatal O2 exposure and a lower percentage of enteral feeding are each individually associated with fewer total calories over the first 28 postnatal days, suggesting that O2 requirements and route of feeding have impacts on total calories delivered, which may reflect clinician hesitancy to enterally feed babies in respiratory distress. Higher C14 and oxygen exposure have independent negative impacts on growth (Zchange) through unclear mechanisms. This study is the first, to our knowledge, to use NBS results to link oxygen exposure with growth failure, thus providing intriguing preliminary data to further interrogate this underutilized clinical information to predict neonatal morbidities.