Insights into the pathophysiology of catch-up compared with non-catch-up growth in children born small for gestational age: an integrated analysis of metabolic and transcriptomic data

Abstract

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4-9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

“…These findings parallel results from insulin resistant adults (36). Other groups have observed positive associations between accelerated postnatal weight gain and plasma LPC14:0 and glutamine, and inverse associations with urine myoinositol (128, 129). …”

Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat

“…Stevens et al investigated the metabolic profiling of children born SGA that exhibited catch-up growth. Compared with noncatch-up SGA children, catch-up SGA children had greater BMI z-scores, insulin-like growth factor-I (IGF-I) levels, and fasting glucose levels, but lower adiponectin values at age 4-9 y, suggesting a greater risk of cardiometabolic diseases (26). In another study, Deng et al investigated insulin resistance in term SGA children with catch-up growth, and found that the insulin resistance values of the homeostatic model assessment (HOMA-IR) were significantly higher in term catch-up SGA children than in term non-catch-up SGA and term appropriate for gestational age (AGA) children (27).…”

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease

“…In the present time, no studies have been performed in prepubertal children with GHD. The only available data on the use of metabolomics in the pediatric population include a selected group of children with other growth disorders, including newborns with intrauterine growth retardation [56] or in children born small for gestational age [57]. …”

“…Metabolic profiling demonstrated a fourfold decrease in urine myoinositol in children with catch-up compared with children with no catch-up growth, and this was associated with an increase in growth factor and IGF-I signaling, along with increased insulin levels in children with catch-up growth, thus implying a possible role of specific metabolic profiles that may relate to cardiometabolic risk [57]. …”