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Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening. The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72–96 h after birth. Three groups based on birth weight were compared: low birth weight (

Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening.The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72-96 h after birth. Three groups based on birth weight were compared: low birth weight (2500 g), appropriate-for-gestational age, and extreme macrosomia (≥5000 g). The comparison was adjusted for possible confounding factors.Compared to appropriate-for-gestational age neonates, both low birth weight and extreme macrosomia were associated with higher levels of glutamic acid. The amino acids alanine and threonine were increased in low birth weight neonates. Free carnitine and some medium- and long-chain acylcarnitines were higher in low birth weight infants. Hydroxybutyrylcarnitine was lower in low birth weight infants, but higher in extremely macrosomic neonates. Acetylcarnitine was higher in low birth weight and extremely macrosomic neonates. Succinylcarnitine was lower and hexadecenoylcarnitine higher in macrosomic newborns.Low birth weight and extremely macrosomic neonates show distinctive differences in their metabolomic profile compared to appropriate-for-gestational age newborns. The differences are not explained by gestational age.The key message of this article is that both low birth weight and extremely macrosomic newborns show dissimilar metabolomic profiles compared to appropriate-for-gestational age neonates. The article contributes to knowledge on what affects evaluation of results in newborn screening. The impact of this article is to provide information on metabolism at both ends of the birth weight range after accounting for confounding factors including gestational age.