Metabolic-endocrine disruption due to preterm birth impacts growth, body composition, and neonatal outcome.

Despite optimized nutrition, preterm-born infants grow slowly and tend to over-accrete body fat. We hypothesize that the premature dissociation of the maternal-placental-fetal unit disrupts the maintenance of physiological endocrine function in the fetus, which has severe consequences for postnatal development. This review highlights the endocrine interactions of the maternal-placental-fetal unit and the early perinatal period in both preterm and term infants. We report on hormonal levels (including tissue, thyroid, adrenal, pancreatic, pituitary, and placental hormones) and nutritional supply and their impact on infant body composition. The data suggest that the premature dissociation of the maternal-placental-fetal unit leads to a clinical picture similar to panhypopituitarism. Further, we describe how the premature withdrawal of the maternal-placental unit, neonatal morbidities, and perinatal stress can cause differences in the levels of growth-promoting hormones, particularly insulin-like growth factors (IGF). In combination with the endocrine disruption that occurs following dissociation of the maternal-placental-fetal unit, the premature adaptation to the extrauterine environment leads to early and fast accretion of fat mass in an immature body. In addition, we report on interventional studies that have aimed to compensate for hormonal deficiencies in infants born preterm through IGF therapy, resulting in improved neonatal morbidity and growth. IMPACT: Preterm birth prematurely dissociates the maternal-placental-fetal unit and disrupts the metabolic-endocrine maintenance of the immature fetus with serious consequences for growth, body composition, and neonatal outcomes. The preterm metabolic-endocrine disruption induces symptoms resembling anterior pituitary failure (panhypopituitarism) with low levels of IGF-1, excessive postnatal fat mass accretion, poor longitudinal growth, and failure to thrive. Appropriate gestational age-adapted nutrition alone seems insufficient for the achievement of optimal growth of preterm infants. Preliminary results from interventional studies show promising effects of early IGF-1 supplementation on postnatal development and neonatal outcomes.

Fat and Fat-Free Mass of Preterm and Term Infants from Birth to Six Months: A Review of Current Evidence.

To optimize infant nutrition, the nature of weight gain must be analyzed. This study aims to review publications and develop growth charts for fat and fat-free mass for preterm and term infants. Body composition data measured by air displacement plethysmography (ADP) and dual energy X-ray absorptiometry (DXA) in preterm and term infants until six months corrected age were abstracted from publications (31 December 1990 to 30 April 2019). Age-specific percentiles were calculated. ADP measurements were used in 110 studies (2855 preterm and 22,410 term infants), and DXA was used in 28 studies (1147 preterm and 3542 term infants). At term age, preterm infants had higher percent-fat than term-born infants (16% vs. 11%, p < 0.001). At 52 weeks postmenstrual age (PMA), both reached similar percent-fat (24% vs. 25%). In contrast, at term age, preterm infants had less fat-free mass (2500 g vs. 2900 g) by 400 g. This difference decreased to 250 g by 52 weeks, and to 100 g at 60 weeks PMA (5000 g vs. 5100 g). DXA fat-free mass data were comparable with ADP. However, median percent-fat was up to 5% higher with DXA measurements compared with ADP with PMA > 50 weeks. There are methodological differences between ADP and DXA measures for infants with higher fat mass. The cause of higher fat mass in preterm infants at term age needs further investigation.