Endocrine and metabolic consequences of being born small- or large-for-gestational age: a review

ABSTRACT

In this review article, the genetics of size at birth, prenatal metabolic programming and the endocrine and metabolic consequences of abnormal size at birth are discussed. In addition, the relevance of fetal origin of adult disease in developing countries and the public health implication as well as future perspectives are also discussed. Being born either small- or large-for-gestational age affects such children and adults in several ways. These include increased risk of type 2 diabetes mellitus, metabolic syndrome, oxidative stress, persistent reduction in growth, cardiovascular disease, osteoporosis and premature pubarche as well as adrenarche. Individuals with abnormal size at birth who experienced rapid growth in the first three years of life have the greatest risk for future metabolic abnormalities. The mechanisms involved in prenatal (fetal) metabolic programming in infants with abnormal size at birth are just beginning to be explored. Both the “thrifty genes” and the “thrifty phenotype” could result in adverse health consequences later in life on exposure to plentiful nutrition. The most important epigenetic reactions affecting genetic transcription are acetylation and methylation. However, the major challenge at this point in time is to link such alterations with modifications in gene expression and ultimately, with metabolic abnormalities encountered in adult life. Thus, developmental origins of health and disease (DOHaD) represent a relatively new frontier of research and with time, some of the discrepancies may be resolved.