ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. Volume 105, Issue 4, April 2020, Pages e1561–e1568, PMID: 32126138

Newborn screening techniques are being used to detect an increasing number of inborn errors of metabolism. The application of tandem mass spectroscopy has allowed for high-throughput simultaneous quantification of acylcarnitine species and amino acids. Established patterns of metabolites are characteristic of specific acylcarnitine and amino acid disorders. However, the way a specimen is collected and handled, the condition of the infant and mother, as well as any treatments, all lead to both false-positive and false-negative results. While macrosomia is an established complication in offspring of obese and diabetic mothers and both macrosomia and maternal obesity are independent risk factors for future obesity, there is little evidence on the possible influence of newborn macrosomia on the accuracy of newborn screening.

The authors accessed data on 139 702 newborns, including 7806 with macrosomia (birth weight 4000–8000 g) and 131 896 non-macrosomic newborns (2500–3999 g). Macrosomic infants were more likely to be male than female (consistent with the typical sex difference in birth weights). Macrosomic infants had higher levels of certain carnitine and acylcarnitine species which interfered with the accuracy of newborn screening test, giving more false positive results.

These observations are interesting and suggest subtle biological differences in the context of macrosomia but the underlying reasons are not clear. Some of these biomarkers might reflect mitochondrial dysfunction and incomplete beta-oxidation (how fatty acids are used in the cell) as observed in obesity-related diseases. A previous study (1) reported that large for gestational age infants have an acylcarnitine and carnitine profile which is characteristic of childhood and adult obesity. Thus, it would be of interest to follow up the macrosomic infants with false positive markers to see if this pattern predicts higher risks of obesity, type 2 diabetes and the metabolic syndrome.

Reference:

1. Snchez-Pintos P, de Castro MJ, Roca I, Rite S, L.pez M, Couce ML. Similarities between acylcarnitine profiles in large for gestational age newborns and obesity. Sci Rep. 2017;7(1):16267.