Metabolic profile of children and neonates born small for gestational age: a systematic review and meta-analysis

The fetal origins of adult disease hypothesis suggests that risk factors from intrauterine environmental exposures affect the fetus' development and increases the risk of specific diseases in later life. Aim of this meta-analysis is to assess the metabolic status of neonates and children who had been small for gestational age (SGA). Four different literature databases were searched for studies comparing neonates and children who had been SGA to neonates and children who had been AGA in terms of glucose, insulin, total cholesterol HDL, LDL and triglycerides. Risk of bias was assessed using newcastle ottawa scale. We estimated the standardised mean difference as effect estimate along with its 95% confidence interval using random effect model separately for neonates and children. In addition, we performed meta-regression analysis including, criteria used for the diagnosis of SGA, children's age and BMI. Moreover, we investigated the correlation between glucose and insulin in the SGA and AGA neonates and children by applying different linear and not linear models. Our search yielded 18546 studies, of which 75 were included in this study. Compared to children who had been AGA, children who had been SGA present with higher levels of insulin (SMD 1.85; 95% CI 0.12 – 3.59), higher levels of triglycerides (SMD 0.14; 95% CI 0.03 – 0.26) and lower levels of HDL (SMD -0.18; 95% CI -0.29 - -0.06). There were no differences between neonates who had been AGA and those who had been SGA. Moreover, neonates and children who had been SGA present non-linear pattern, cubic polynomial correlation between glucose and insulin, while neonates and children who had been SGA present a linear correlation. Children who had been SGA present with aggravated metabolic characteristics compared to children who had been AGA, while both children and neonates who had been SGA present distinct correlation between glucose and insulin compared to children and neonates who had been AGA.