What may Pygmies teach us about short stature in very preterm infants?

Abstract

Short stature is frequently observed in preterm infants until adulthood. Linear growth represents predominantly protein, lean mass, and bone mass accretion and indicates organ growth, which is dependent on the growth hormone-somatomedin axis. Weight gain represents total body mass, including fat mass, and indicates the balance between energy intake and expenditure, which is dependent on the glucose-insulin axis. Although the causes of preterm weight retardation are known and have been extensively studied, the origins and consequences of linear growth retardation in this population have not been fully investigated. The objective of this article is to discuss the striking similarities observed between the evolutionary strategies of Pygmies and the neonatal adaptive strategies of preterm infants that we noted during our investigations to understand the origin of postnatal linear growth retardation in preterm infants. Humans show considerable variations in height. In our contemporary setting, Efe huntergatherers in the Ituri Rainforest (Democratic Republic of Congo) are the shortest people studied in the world.3 The origin of Pygmy short stature has been an enigma until very recently and, in our experience, knowledge about it provides fundamental data for understanding neonatal evolutionary biology. Pygmies are born with a normal length and weight for their gestational age, as are preterm infants without intrauterine growth retardation. Based on this, it is possible to rule out genetic and prenatal causes of linear growth deficiency. During postnatal life, Pygmies grow in an isolated ecosystem with limited resources and face recurrent gastrointestinal infections due to lack of access to drinking water, leading to sustained systemic inflammation (SSI) with permanently elevated serum levels of C-reactive protein. There is plenty evidence linking SSI caused by recurrent infections with the presence of short stature and growth hormone resistance in both Pygmies and children from poverty-stricken communities. Similarly, preterm infants grow in isolation in incubators undergoing invasive procedures that promote the development of complications, such as sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia, leading to SSI associated with short stature.