Intrauterine Growth Restriction: New Insight from the Metabolomic Approach

Abstract

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn's short- and long-term health. Ever since the first suggestion of the "thrifty phenotype hypothesis" in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies' trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics-a relatively new field of '-omics' research-can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an "early" pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice.

Keywords: biomarkers; fetal growth restriction; intrauterine growth restriction; mass spectrometry; metabolomics; newborn; nuclear magnetic resonance spectroscopy; small for gestational age.

Figure 1

Summary of current knowledge on the short- and long-term consequences of intrauterine growth restriction. The fetus’ prenatal exposure to undernutrition and hypoxia induce hemodynamic and metabolic adjustments, as well as changes in hormones and adipokines. IGF-1: Insuline-like growth factor; ACTH: adrenocorticotropic hormone.