The independent and combined influences of small for gestational age and socioeconomic status on newborn metabolite levels.

OBJECTIVES: To determine whether socioeconomic status (SES) and small birthweight for gestational age (SGA) exhibit independent or joint effects on infant levels of 42 metabolites. STUDY DESIGN: Population-based retrospective cohort of metabolic newborn screening information linked to hospital discharge data. SGA infants defined by birthweight <10th percentile for gestational age by sex. SES was determined by a combined metric including education level, participation in the WIC nutritional assistance program, and receiving California MediCal insurance. We performed linear regression to determine the effects of SES independently, SGA independently, and the interaction of SGA and SES on 42 newborn metabolite levels. RESULTS: 736,435 California infants born in 2005-2011 were included in the analysis. SGA was significantly associated with 36 metabolites. SES was significantly associated with 41 of 42 metabolites. Thirty-eight metabolites exhibited a dose-response relationship between SGA and metabolite levels as SES worsened. Fourteen metabolites showed significant interaction between SES and SGA. Eight metabolites showed significant individual and joint effects of SES and SGA: alanine, glycine, free carnitine, C-3DC, C-5DC, C-16:1, C-18:1, and C-18:2. CONCLUSIONS: SES and SGA exhibited independent effects on a majority of metabolites and joint effects on select metabolites. A better understanding of how SES and SGA status are related to infant metabolites may help identify maternal and newborn interventions that can lead to better outcomes for infants born SGA.

Newborn Metabolic Profile Associated with Hyperbilirubinemia With and Without Kernicterus.

Our objective was to assess the relationship between hyperbilirubinemia with and without kernicterus and metabolic profile at newborn screening. Included were 1,693,658 infants divided into a training or testing subset in a ratio of 3:1. Forty-two metabolites were analyzed using logistic regression (odds ratios (ORs), area under the receiver operating characteristic curve (AUC), 95% confidence intervals (CIs)). Several metabolite patterns remained consistent across gestational age groups for hyperbilirubinemia without kernicterus. Thyroid stimulating hormone (TSH) and C-18:2 were decreased, whereas tyrosine and C-3 were increased in infants across groupings. Increased C-3 was also observed for kernicterus (OR: 3.17; 95% CI: 1.18-8.53). Thirty-one metabolites were associated with hyperbilirubinemia without kernicterus in the training set. Phenylalanine (OR: 1.91; 95% CI: 1.85-1.97), ornithine (OR: 0.76; 95% 0.74-0.77), and isoleucine + leucine (OR: 0.63; 95% CI: 0.61-0.65) were the most strongly associated. This study showed that newborn metabolic function is associated with hyperbilirubinemia with and without kernicterus.