OBJECTIVETo study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD).

METHODSA total of 3 381 samples ruled out of IMD by follow-up were randomly selected from 38 931 newborns who participated in the neonatal IMD screening during 2014-2016. The 3 381 neonates were categorized into seven groups according to their gestational age and birth weight: extremely preterm appropriate-for-gestational age (AGA) group (n=12), preterm small-for-gestational age (SGA) group (n=18), preterm AGA group (n=219), preterm large-for-gestational age (LGA) group (n=18), full-term SGA group (n=206), full-term AGA group (n=2 677), and full-term LGA group (n=231). Heel blood samples were collected from each group on postnatal days 3-7 after adequate breastfeeding. Levels of 17 key IMD-related metabolic indices in dried blood spots were measured using tandem mass spectrometry. Spearman′s correlation analysis was used to investigate the relationships between 17 IMD-related metabolic indices and their influencing factors, while covariance analysis was used to compare the metabolic indices between these groups.

RESULTSAfter adjusting the influencing factors such as physiological and pathological status, compared with the full-term AGA group, the extremely preterm AGA, preterm SGA, and preterm AGA groups had significantly reduced levels of leucine\isoleucine\hydroxyproline and valine (P<0.05); the preterm AGA group had a significantly decreased ornithine level (P<0.05); the extremely preterm AGA and preterm AGA groups had a significantly reduced proline level (P<0.05). Besides, the phenylalanine level in the extremely preterm AGA and preterm AGA groups, the methionine level in the preterm SGA group, and the tyrosine level in the preterm AGA group all significantly increased (P<0.05). The increased levels of free carnitine, acetylcarnitine, and propionylcarnitine were found in the preterm SGA and preterm AGA groups. The oleylcarnitine level also significantly increased in the preterm SGA group (P<0.05). Most carnitine indices showed significant differences between the SGA group and the AGA/LGA group in both preterm and full-term infants (P<0.05).

CONCLUSIONSLow gestational age and low birth weight may result in abnormal results in IMD screening. Therefore, gestational age and birth weight should be considered to comprehensively judge the abnormal results in IMD screening.