Abstract Objective To study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD). Methods A total of 3 381 samples ruled out of IMD by follow-up were randomly selected from 38931 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 appropriatefor-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=2677), 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 IMDrelated metabolic indices and their influencing factors, while covariance analysis was used to compare the metabolic indices between these groups. Results After 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). Conclusions Low 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.
YI Fang,WANG Ling,WANG Mei et al. Combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases in neonates[J]. CJCP, 2018, 20(5): 352-357.
YI Fang,WANG Ling,WANG Mei et al. Combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases in neonates[J]. CJCP, 2018, 20(5): 352-357.
Garg U, Dasouki M. Expanded newborn screening of inherited metabolic disorders by tandem mass spectrometry:clinical and laboratory aspects[J]. Clin Biochem, 2006, 39(4):315-332.
[3]
Tarini BA, Christakis DA, Welch HG. State newborn screening in the tandem mass spectrometry era:more tests, more falsepositive results[J]. Pediatrics, 2006, 118(2):448-456.
[4]
Ryckman KK, Berberich SL, Shchelochkov OA, et al. Clinical and environmental influences on metabolic biomarkers collected for newborn screening[J]. Clin Biochem, 2013, 46(1-2):133-138.
[5]
Oladipo OO, Weindel AL, Saunders AN, et al. Impact of premature birth and critical illness on neonatal range of plasma amino acid concentrations determined by LC-MS/MS[J]. Mol Genet Metab, 2011, 104(4):476-479.
[6]
Slaughter JL, Meinzen-Derr J, Rose SR, et al. The effects of gestational age and birth weight on false-positive newbornscreening rates[J]. Pediatrics, 2010, 126(5):910-916.
Bennett MJ. Follow-up testing for metabolic diseases identified by expanded newborn screening using tandem mass spectrometry[M]. Washington, DC:The National Academy of Clinical Biochemistry, 2008:12-15.
[11]
Wilson K, Hawken S, Ducharme R, et al. Metabolomics of prematurity:analysis of patterns of amino acids, enzymes, and endocrine markers by categories of gestational age[J]. Pediatr Res, 2014, 75(2):367-373.
[12]
Liu J, Chen XX, Li XW, et al. Metabolomic research on newborn infants with intrauterine growth restriction[J]. Medicine (Baltimore), 2016, 95(17):e3564.
[13]
Alexandre-Gouabau MC, Courant F, Le Gall G, et al. Offspring metabolomic response to maternal protein restriction in a rat model of intrauterine growth restriction (IUGR)[J]. J Proteome Res, 2011, 10(7):3292-3302.
Mandour I, El Gayar D, Amin M, et al. Amino acid and acylcarnitine profiles in premature neonates:a pilot study[J]. Indian J Pediatr, 2013, 80(9):736-744.
[16]
Liu Q, Wu J, Shen W, et al. Analysis of amino acids and acyl carnitine profiles in low birth weight, preterm, and small for gestational age neonates[J]. J Matern Fetal Neonatal Med, 2017, 30(22):2697-2704.
Gucciardi A, Zaramella P, Costa I, et al. Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns[J]. Pediatr Res, 2015, 77(1-1):36-47.
