The Peter Pan paradigm

You may delay, but time will notBenjamin FranklinUSA Founding FatherThe fragility of the developmental process is well known with estimates as high as 70% of conceptions lost in early pregnancy [1]. Genetic defects are known to produce numerous changes in both metabolic and morphologic characteristics of the fetus [2]. The choreography of genes necessary for successful fetal development is amply demonstrated by embryonic lethal [3] and other phenotypes [4-8] in knockout mouse models. Thus, genetic defects introduced in the developmental cascade contribute to structural malformations. But organogenesis requires the genetic choreography to occur not just in sequence but also during a sensitive time period. What happens when the genes regulating the developmental time clock [9,10] are mutated or delayed by epigenetic factors? Can the organ continue to develop outside the fetal environment and if not, what are the consequences of retaining fetal characteristics in an adult?The best model for addressing these questions related to organogenesis and timing is the premature infant. Modern neonatology has extended viability to 23 weeks in the 40 week human gestation, but what are the consequences of completing less than 60% of gestation on the human fetus? The obvious immediate consequences seen in any neonatal unit include poor lung function, intestinal deficiencies, immune system deficiencies, and poor renal function. These immediate problems combined with therapies used to combat them can lead to significant morbidity and mortality in the premature infant.Infants surviving the immediate organ deficiencies and therapies of premature birth, however, do not grow into healthy adult. Rather, numerous epidemiological and clinical observations have shown that prematurity is associated with many adult onset diseases (Table 1). The epidemiologic basis for late or adult-onset diseases, following either premature birth or low birth weight, includes poor pre-natal maternal nutrition