Metabolic syndrome in children and adolescents born premature and small-for-gestational age: A scenario of Developmental Origins of Health and Disease (DOHaD)

Metabolic syndrome, also known as syndrome X, which was first described in the 1950s, is a disorder characterized by central obesity, hypertension, hyperglycemia, and dyslipidemia. With insulin resistance being one of the pathogenetic factors, it predisposes individuals to the development of type 2 diabetes mellitus and cardiovascular disease.1Reaven G.M. Banting lecture 1988. Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607Crossref PubMed Scopus (11139) Google Scholar However, metabolic syndrome in children and adolescents has no universally accepted definition. The majority of current definitions have been adapted from the adult criteria developed by the National Cholesterol Education Program.2Ford E.S. Li C. Defining the metabolic syndrome in children and adolescents: will the real definition please stand up?.J Pediatr. 2008; 152: 160-164Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar A direct link between prenatal nutrition and late-onset coronary heart disease was proposed by Barker in 1986.3Barker D.J. Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.Lancet. 1986; 1: 1077-1081Abstract PubMed Scopus (1891) Google Scholar Later, he advocated the earliest theory of fetal origins of adult disease, which has been denoted as the "Barker's hypothesis." Since Barker's initial findings, the results have been replicated in diverse populations from Europe, Asia, North America, Africa, and Australia. Based on this hypothesis, the concept of DOHaD (Developmental Origins of Health and Disease) highlights not only the fetal origins of metabolic syndrome but also the important impact of postnatal growth and other factors on later metabolic outcomes. Infants born small-for-gestational age (SGA) and exhibiting a rapid increase in weight during early childhood (the so-called "catch-up growth") have been reported to have a significantly increased risk of developing metabolic syndrome.4Lévy-Marchal C. Czernichow P. Small for gestational age and the metabolic syndrome: which mechanism is suggested by epidemiological and clinical studies?.Horm Res. 2006; 65: 123-130Crossref PubMed Scopus (96) Google Scholar In this issue of Pediatrics and Neonatology, Huang et al. have reported a population-based cohort study examining the association of preterm birth and SGA with metabolic outcomes in children and adolescents.5Huang Y.T. Lin H.Y. Wang C.H. Su B.H. Lin C.C. Association of preterm birth and small for gestational age with metabolic outcomes in children and adolescents: a population-based cohort study from Taiwan.Pediatr Neonatol. 2018; 59: 147-153Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar The authors observed that children and adolescents who were preterm and SGA at birth have a higher overall risk of developing metabolic disease, which included hypertension, diabetes, and hyperlipidemia. They also showed that the risk of developing hypertension, diabetes, and hyperlipidemia is increased in these former preterm and SGA cohorts. Interestingly, when compared with preterm and comparison cohorts, the cumulative incidence of metabolic disease increased dramatically between the age of 2 and 6 years in the SGA cohort (Fig. 1, lower panel in Ref. 5Huang Y.T. Lin H.Y. Wang C.H. Su B.H. Lin C.C. Association of preterm birth and small for gestational age with metabolic outcomes in children and adolescents: a population-based cohort study from Taiwan.Pediatr Neonatol. 2018; 59: 147-153Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). It is not known whether these infants have catch-up growth before the age of 2 years. Nevertheless, this study still has few limitations, including 1) the accuracy of diagnosing hypertension, diabetes, and dyslipidemia in children and adolescents using International Classification of Diseases (ICD) codes from the claims database, 2) the relatively short-term follow-up, 3) no further detailed growth profiles regarding the presence of a "catch-up growth" in these high-risk cohorts, and 4) born with an SGA or a preterm status is not a synonym of being born with low birth weight or intrauterine growth retardation. In conclusion, further studies with a longer follow-up duration are required to confirm whether there is a tendency to develop metabolic syndrome in these study cohorts. Such studies must also provide detailed postnatal growth profiles to confirm whether this problem occurs in accordance with the concept of DOHaD. The author declares that he has no financial or non-financial conflicts of interest related to the subject matter or materials discussed in the manuscript.