The metabolic signature of diabetes on newborn screening

Abstract

The work presented in this thesis represents various uses of NBS data to draw correlations between the metabolic profile of the newborn infant and various antecedent events in the pregnancy (GDM, maternal medication exposure) or later outcomes in the child (development of type 1 diabetes). Chapter 1 outlines the background of diabetes, GDM and NBS, and briefly discusses the overlap in clinical presentation between diabetes and inborn errors of metabolism and provides a short summary of the metabolite derangements common to both. Chapter 2 is published as a narrative review with a systematic review of the literature performed as part of the review. In addition to outlining the paucity of published work regarding NBS and diabetes to date, it discusses seminal literature on the metabolomics of diabetes (GDM, type 2 and type 1 diabetes) on cord blood of infants and compares NBS dried blood spots (DBS) with cord blood as a sample in diabetes research. Chapter 3 discusses the newborn screening results of the infants born to mothers who developed early GDM (<20 weeks) and were treated early, in comparison to infants from pregnancies with risk factors for GDM and infants from GDM pregnancies diagnosed and treated according to current standard. Significant findings were elevations of tyrosine in the late GDM group (p=0.01), immunoreactive trypsinogen in the early treatment group (p=0.02) and methionine in the high risk (but no GDM) group (p=0.04) as compared to age-matched NBS controls. Chapter 4 discusses the NBS results of infants born to mothers with GDM treated with metformin as compared to infants born to mothers treated with diet and exercise and infants with no diabetes exposure. Metformin use was associated with elevations of short, medium and long- chain acylcarnitines (<0.001) as compared to diet and exercise treatment.

Date of Award	2021
Original language	English
Awarding Institution	Western Sydney University
Supervisor	David Simmons (Supervisor)