Clinical and environmental influences on metabolic biomarkers collected for newborn screening

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.

Figure 1

Mean concentrations of the essential amino acids, arginine (ARG), leucine (LEU), methionine (MET), phenylalanine (PHE) and valine (VAL) by gestational age. Black bars represent the mean concentration for gestational age ≥ 37 weeks, white bars represent gestational ages 33-36 and gray bars represent gestational ages 24-32 weeks. Standard errors of the mean are given above each bar.

Figure 2

Mean concentrations of thyroid stimulating hormone (TSH) (A) and immunoreactive trypsinogen (IRT) (B) by year. Dotted lines represent the means for winter months (Dec-Feb) and solid lines represent summer months (Jun-Aug). Standard errors are given for each mean.