A study published in Clinical Chemistry establishes the first reference intervals for newborn steroid hormones and amino acids that play key roles in child development. 

The research could lead to earlier diagnosis and more effective treatment of numerous developmental disorders, including pediatric cancer, diabetes, and congenital adrenal hyperplasia, and could aid in detecting neonatal exposure to harmful endocrine-disrupting chemicals. 

The development of reference intervals in this population has been limited by access to samples from geographically diverse populations of healthy children. This is particularly true of newborns, in whom it is difficult to obtain the volumes of blood needed to perform reference interval studies. 

To address this challenge, AACC’s Pediatric Reference Range Committee used dried blood spots (DBS) from 310 newborns in the National Institutes of Health’s National Children’s Study biobank. The samples were identified by age, birthweight, sex, and geographic location. Researchers analyzed the samples for 25 amino acids and four steroid hormones using liquid chromatography-tandem mass spectrometry, with nonparametric statistical approaches to generate the 2.5th–97.5th percentile distributions for newborns. They then used paired plasma/DBS specimens to mathematically transform DBS reference intervals to corresponding plasma intervals. 

“The strengths of these data include the large sample of the youngest children and a level of geographic heterogeneity not previously achieved,” said committee co-chair and 2016 AACC president Patricia Jones, PhD, DABCC, FACB, who is a professor of pathology at the University of Texas Southwestern Medical Center in Dallas. Dennis Dietzen, PhD, DABCC, FACB, who directs the core laboratory and metabolic genetics laboratory at St. Louis Children’s Hospital in Missouri and is AACC’s 2018 president, co-chaired the committee with Jones. 

The committee found that 10 of 25 DBS amino acid distributions were dependent on sex, with little correlation with age, birthweight, or geographic location over the first 4 days of life. 

They also found that newborn steroid distributions were generally negatively correlated with age and birthweight over the first 4 days of life, with no relation to geographic location. However, testosterone concentrations displayed sex dependence. 

The reference interval data highlighted in the paper, Jones said, “is the first step to providing the best biochemical parameters of healthy growth and development and enabling better recognition and detection of abnormal adrenal, reproductive, and metabolic pathology.”