The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.

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.

We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys. Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor. In the original family, we identified a frameshift mutation predicted to result in a truncated protein. In two other families with an incomplete syndrome, we found that affected individuals harbor deletions affecting the 11 or 12 5'-most exons of the gene. The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals. GLIS3 is expressed in the pancreas from early developmental stages, with greater expression in beta cells than in other pancreatic tissues. These results demonstrate a major role for GLIS3 in the development of pancreatic beta cells and the thyroid, eye, liver and kidney.