172 Chapter 8 The “Developmental Origins of Health andDisease” hypothesis states that exposure to so called insults in critical periods of development influences later health outcomes. (1) For preterm infants the extra-uterine third trimester is such a critical period and postnatal growth restriction is an insult which has been associated with potentially severe adverse health outcomes. Limiting postnatal growth restriction could therefore be a key factor in improving long-term outcomes of preterm infants. Nutrition in relation to the endocrine regulation of preterm growth and body composition It is known that nutrition potentiates growth and has a direct effect on the endocrine axis.(2) In preterm infants, however, there seems to be a certain time frame in which nutrition can exert a significant impact on the endocrine axis. In line with previous studies, our findings as described in chapter 4 suggest that the influence of nutrition on the endocrine axis increases, in particular IGF-I, with increasing postmenstrual age. (3) This could imply that less nutrient intake is required to potentiate an effect on the endocrine axis and subsequently on growth at higher postmenstrual ages. Hypothesizing, this could be due to a rise in growth factors which exert more influence on growth as their levels rise with increasing postmenstrual age. Indeed, initially serum IGF-I levels in preterm infants are low and start showing an increase between 30 and 32 weeks postmenstrual age. (2) As described in chapter 5 in our study population as well as other extremely and very preterm study cohorts (4), an increase in growth SD scores is seen from 30 to 32 weeks postmenstrual age. This gain in growth SD scores coincides with the rise in IGF-I levels. Therefore, it could be speculated that at this point IGF-I levels pass a certain threshold and are now able to direct growth. Hypothesizing from this point onwards nutrient enrichment could be decreased. Since IGF-I seems to potentiate growth from this point an excess of nutrients could lead to fat deposition and an unfavourable body composition. Or it could cause rapid growth which has been associated with adverse cardiometabolic outcomes in later life.(5) Originally the NUTRIE study was designed as a randomized controlled trial comparing preterm infants fed limited energy- and nutrient-enriched formula from 32 weeks postmenstrual age onwards with preterm infants fed standard fully enriched preterm starters formula.(6) This would have enabled us to investigate whether in the light of growth, body composition and neurodevelopment indeed less nutrient enrichment is required once IGF-I passes the threshold concentration. Due to the establishment of a human milk bank in our centre, there was a large increase in human milk use. Therefore it was no longer possible to complete the original trial design. Instead, we carried out an observational study. This resulted in a detailed collection of data on nutritional intake and growth which enabled a good exploration of potential associations with health outcomes. However, to reduce total blood sampling volumes, we sampled IGF-I at a low frequency
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