Clinical and Environmental Influences on Metabolic Biomarkers Collected for Newborn Screening

Overview

Journal Clin Biochem

Specialty Biochemistry

Date 2012 Sep 27

PMID 23010448

Citations 39

Authors

Kelli K Ryckman

Stanton L Berberich

Oleg A Shchelochkov

Daniel E Cook

Jeffrey C Murray

Affiliations

Soon will be listed here.

Abstract

Objectives: Identifying common clinical and environmental factors that influence newborn metabolic biomarkers will improve the utilization of metabolite panels for clinical diagnostic medicine.

Design And Methods: Environmental effects including gender, season of birth, gestational age, birth weight, feeding method and age at time of collection were evaluated for over 50 metabolites collected by the Iowa Neonatal Metabolic Screening Program on 221,788 newborns over a six year period.

Results: We replicated well known observations that low birth weight and preterm infants have higher essential amino acids and lower medium and long chain acylcarnitine levels than their term counterparts. Smaller, but still significant, differences were observed for gender and timing of sample collection, specifically the season in which the infant was born. Most intriguing were our findings of higher thyroid stimulating hormone in the winter months (P<1×10(-40)) which correlated with an increased false positive rate of congenital hypothyroidism in the winter (0.9%) compared to summer (0.6%). Previous studies, conducted globally, have identified an increased prevalence of suspected and confirmed cases of congenital hypothyroidism in the winter months. We found that the percentage of unresolved suspected cases were slightly higher in the winter (0.3% vs. 0.2%).

Conclusions: We identified differences in metabolites by gestational age, birth weight, gender and season. Some are widely reported such as gestational age and birth weight, while others such as the effect of seasonality are not as well studied.

Citing Articles

Unbalanced long-chain fatty acid beta-oxidation in newborns with cystic fibrosis and congenital hypothyroidism.

Pinnaro C, Ryckman K, Uc A, Norris A Mol Genet Metab Rep. 2025; 42:101182.

PMID: 39816991 PMC: 11732690. DOI: 10.1016/j.ymgmr.2024.101182.

Abnormal biochemical indicators of neonatal inherited metabolic disease in carriers.

Guo F, Zhou L, Zhang F, Yu B, Yang Y, Liu Z Orphanet J Rare Dis. 2024; 19(1):145.

PMID: 38575986 PMC: 10996179. DOI: 10.1186/s13023-024-03138-5.

Association of Maternal Age and Blood Markers for Metabolic Disease in Newborns.

Xie Y, Peng G, Zhao H, Scharfe C Metabolites. 2024; 14(1).

PMID: 38276295 PMC: 10821442. DOI: 10.3390/metabo14010005.

Late-onset cblC defect: clinical, biochemical and molecular analysis.

Ding S, Ling S, Liang L, Qiu W, Zhang H, Chen T Orphanet J Rare Dis. 2023; 18(1):306.

PMID: 37770946 PMC: 10536707. DOI: 10.1186/s13023-023-02890-4.

Real world external validation of metabolic gestational age assessment in Kenya.

Hawken S, Ward V, Bota A, Lamoureux M, Ducharme R, Wilson L PLOS Glob Public Health. 2023; 2(11):e0000652.

PMID: 36962760 PMC: 10021775. DOI: 10.1371/journal.pgph.0000652.

References

Chace D, Spitzer A . Altered metabolism and newborn screening using tandem mass spectrometry: lessons learned from the bench to bedside. Curr Pharm Biotechnol. 2011; 12(7):965-75. DOI: 10.2174/138920111795909104. View

van der Kamp H, Oudshoorn C, Elvers B, van Baarle M, Otten B, Wit J . Cutoff levels of 17-alpha-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J Clin Endocrinol Metab. 2005; 90(7):3904-7. DOI: 10.1210/jc.2004-2136. View

Virtanen M, Maenpaa J, Pikkarainen J, Pitkanen L, Perheentupa J . Aetiology of congenital hypothyroidism in Finland. Acta Paediatr Scand. 1989; 78(1):67-73. DOI: 10.1111/j.1651-2227.1989.tb10889.x. View

Nakamizo M, Toyabe S, Asami T, Akazawa K . Seasonality in the incidence of congenital hypothyroidism in Japan. J Paediatr Child Health. 2005; 41(7):390-1. DOI: 10.1111/j.1440-1754.2005.00644_1.x. View

Chace D, DiPerna J, Mitchell B, Sgroi B, Hofman L, Naylor E . Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem. 2001; 47(7):1166-82. View

Therrell Jr B, Berenbaum S, Simmank J, Korman K, Prentice L, Gonzalez J . Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics. 1998; 101(4 Pt 1):583-90. DOI: 10.1542/peds.101.4.583. View

Kwon C, Farrell P . The magnitude and challenge of false-positive newborn screening test results. Arch Pediatr Adolesc Med. 2000; 154(7):714-8. DOI: 10.1001/archpedi.154.7.714. View

Kelleher A, Clark R, Steinbach M, Chace D, Spitzer A . The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates. J Perinatol. 2008; 28(4):270-4. DOI: 10.1038/jp.2008.5. View

Kaye C, Accurso F, La Franchi S, Lane P, Hope N, Sonya P . Newborn screening fact sheets. Pediatrics. 2006; 118(3):e934-63. DOI: 10.1542/peds.2006-1783. View

10.

. Using tandem mass spectrometry for metabolic disease screening among newborns. A report of a work group. MMWR Recomm Rep. 2004; 50(RR-3):1-34. View

11.

Atzori L, Antonucci R, Barberini L, Locci E, Cesare Marincola F, Scano P . 1H NMR-based metabolomic analysis of urine from preterm and term neonates. Front Biosci (Elite Ed). 2011; 3(3):1005-12. DOI: 10.2741/e306. View

12.

Laroche D, Travert G . Abnormal frequency of delta F508 mutation in neonatal transitory hypertrypsinaemia. Lancet. 1991; 337(8732):55. DOI: 10.1016/0140-6736(91)93377-l. View

13.

Pang S, Shook M . Current status of neonatal screening for congenital adrenal hyperplasia. Curr Opin Pediatr. 1997; 9(4):419-23. DOI: 10.1097/00008480-199708000-00018. View

14.

Atzori L, Antonucci R, Barberini L, Griffin J, Fanos V . Metabolomics: a new tool for the neonatologist. J Matern Fetal Neonatal Med. 2009; 22 Suppl 3:50-3. DOI: 10.1080/14767050903181500. View

15.

Fanos V, Barberini L, Antonucci R, Atzori L . Metabolomics in neonatology and pediatrics. Clin Biochem. 2011; 44(7):452-454. DOI: 10.1016/j.clinbiochem.2011.03.006. View

16.

Varness T, Allen D, Hoffman G . Newborn screening for congenital adrenal hyperplasia has reduced sensitivity in girls. J Pediatr. 2005; 147(4):493-8. DOI: 10.1016/j.jpeds.2005.04.035. View

17.

Turgeon C, Magera M, Allard P, Tortorelli S, Gavrilov D, Oglesbee D . Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem. 2008; 54(4):657-64. DOI: 10.1373/clinchem.2007.101949. View

18.

Reuter S, Evans A, Chace D, Fornasini G . Determination of the reference range of endogenous plasma carnitines in healthy adults. Ann Clin Biochem. 2008; 45(Pt 6):585-92. DOI: 10.1258/acb.2008.008045. View

19.

Borum P . Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults. Am J Clin Nutr. 1987; 46(3):437-41. DOI: 10.1093/ajcn/46.3.437. View

20.

Kloosterboer M, Hoffman G, Rock M, Gershan W, Laxova A, Li Z . Clarification of laboratory and clinical variables that influence cystic fibrosis newborn screening with initial analysis of immunoreactive trypsinogen. Pediatrics. 2009; 123(2):e338-46. DOI: 10.1542/peds.2008-1681. View