Hormonal Factors in the Morbidities Associated with Extreme Prematurity and the Potential Benefits of Hormonal Supplement

Abstract

Cortisol and thyroid hormones are known to modulate the maturation of various fetal organ systems, enzymes, and biochemical pathways. The cortisol furnished by the structural and biochemical immature fetal adrenal gland renders the extremely premature infants relatively cortisol deficient in comparison with the term newborns. The premature infants also have elevated fetal androgens, the production of which persists until ≈42 weeks of postconceptional age. The androgens produced by the fetal adrenal cortex and the müllerian inhibiting substance produced by the fetal testis have antiglucocorticoid and inhibitory effects on human fetal lung growth and maturation in vitro. Hypothalamic-pituitary-thyroid axis and thyroid function are also immature in extreme prematurity. In addition, there is reduced tissue thyroid hormone responsiveness. Superimposed on this is the reduced thyroid function seen in non-thyroidal illness in which elevated cytokine levels have been implicated. Repeated courses of antenatal steroids and high-dose postnatal dexamethasone appear to be deleterious to lung and brain development. This may be through inhibition of cell replication and catabolism as well as decreased thyroid-stimulating hormone secretion and reduced peripheral conversion of T₄ to T₃. Furthermore, dexamethasone has been found to enhance neurosteroid production in the immature brain, potentially altering brain development. Considered together, the relative cortisol deficiency/androgen excess and reduced thyroid function as well as prolonged high-dose postnatal dexamethasone therapy in these infants may be important factors in their high degree of morbidity. We propose to restrict antenatal steroids to a single course and hypothesize that the overall outcome of low-gestation infants would be improved with (1) hydrocortisone (i.v./p.o.) supplement at a fixed dose of 0.5 mg/kg birth weight every 12 h in infants <30 weeks of gestation from birth till 32 weeks of postconceptional age and (2) T₃ (i.v./p.o.) supplement at a fixed dose of 0.4 µg/kg birth weight every 12 h in those <27 weeks of gestation from birth till 32 weeks of postconceptional age.

Clinical importance of hypothyroxinemia in the preterm infant and a discussion of treatment concerns

“…Although the administration of thyroid hormone has been reported to be associated with hypocortisolism [114], in our study cortisol levels were similar throughout the hospitalization in treated and placebo participants [69]. Similar findings were reported by Valerio et al [115].…”

Nutritionally Regulated Hormonal Factors in Prolonged Postnatal Growth Retardation and Its Associated Adverse Neurodevelopmental Outcome in Extreme Prematurity

“…We have previously examined the role of cortisol and thyroid hormone deficiency as contributing hormonal factors in both short-and long-term morbidities associated with extreme prematurity, including neurodevelopmental disadvantage, and proposed hydrocortisone and T 3 supplements from birth [228]. In this subsequent review, having examined the role of low serum concentration of IGF-I, a nutritionally regulated hormonal factor, in growth retardation and its associated adverse effect on neurodevelopmental outcome, we propose to increase the dietary protein intake from birth and increase the protein:calorie ratio to 3.6 g/100 kcal at a daily overall calorie intake of "125 kcal/kg in enterally fed infants born at !30 weeks of gestation.…”

Growth in 10- to 12-Year-Old Children Born at 23 to 25 Weeks' Gestation in the 1990s: A Swedish National Prospective Follow-up Study

“…Interaction of the nutritional and endocrine factors that govern early growth in infants born prematurely is not perfectly understood. Differences in levels of many circulating hormones between preterm and term infants have been reported, [51][52][53][54] linking them to the early growth failure in premature infants. 54 We need to address the specific issues of whether postnatal growth failure is related to nutritional factors and how fast these infants should grow (including catch-up growth).…”