Vol. 38, No.5, 1995 Printed in U.S.A.Intrauterine growth retardation, or being small for gestational age (SGA), has a life-long impact on a fetus's potential for development and survival. The incidence and relative risk of short stature in children born SGA were studied using a Swedish healthy full-term (37-43 wk of gestation) singleton birth cohort (n = 3650) from Goteborg, followed from birth to final height at about 18 y of age. Most infants, defined as SGA on the basis of a birth length less than -2 standard deviation scores (SDS) below the mean (SGA L infants), showed catch-up growth during the first 6 mo after birth, and by 1 Y only 13.4% of the SGA L infants were below -2 SDS in height. This percentage decreased further during childhood to reach a value of 7.9% at 18 y of age. Although most SGA L infants have catch-up growth in early life, those who do not constitute 21% of short, prepubertal children. At 18 Y of age, 22% of the total short population were short at birth « -2 SDS), whereas when birth weight was used to define SGA, only 14% of the 18-y-old short population were light at birth. SGA L infants were found to have a 7-fold higher risk for short final stature (relative risk, 7.1; 95% confidence interval,

Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.

Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.

These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

Background: Growth charts and child growth assessment have become prime global instruments in child health practice over the 30 years. An updated, continuous growth standard that bridges size at birth values with postnatal growth values can improve child growth screening and monitoring.