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

Abstract

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.

Fig. 1. Change in hormonal activity during the transition from fetal to postnatal life.

Hormonal activity levels in the newborn undergo changes, caused by the dissociation of the maternal-placental-fetal unit with birth and the maturation of the newborn. PGH placental growth hormone, IGF insulin-like growth factor, GH growth hormone, hPL human placental lactogen, Thyroid thyroid hormones.

Fig. 2. Regulation of fetal growth control.

Fetal growth is regulated by hormonal and nutritional interactions of the maternal-placental-fetal unit. Full lines illustrate the transfer of hormones or nutrients, dotted lines represent the stimulating effect on targets, and the thickness of lines correlates with the intensity of the effect; PGH placental growth hormones, hPL human placental lactogen, IGF insulin-like growth factor, T3  triiodothyronine, T4 thyroxine.

Fig. 3. Hormonal homeostasis of the newborn and postnatal growth.

The hormonal and nutritional withdrawal from the maternal-placental unit after birth leads to changes in hormonal homeostasis of the newborn and affects postnatal growth. AA amino acids, hPL human placental lactogen, IGF insulin-like growth factor, GH growth hormone, T3 triiodothyronine, T4 thyroxine.

Fig. 4. Postnatal growth control in newborns.

The regulation of IGF-1 switches from nutrition to growth hormone control. IGF insulin-like growth factor.