The Reduced Thyroid Function of the Premature Newborn: Relation With Molecular Changes in the Placenta and Maternal Thyroid Hormone Status and Neurodevelopmental Implications

Transient hypothyroxinemia of prematurity (THOP) is a typical entity of the preterm infant, affecting the majority of preterm infants, born less than 30 weeks of gestational age. It is defined as a temporary postnatal reduction from cord values in serum levels of T4 and FT4, but with normal thyroid-stimulating hormone (TSH) levels.The etiology of THOP is complex and multifactorial. Loss of maternal T4, limited postnatal thermogenesis, hypothalamic-pituitary immaturity, limited thyroid gland reserve, persistent fetal thyroid hormone metabolism and predisposition to nonthyroidal illness syndrome are several factors that contribute in less or more intensity to THOP.The association between THOP and poor neurodevelopmental outcome is well established and several therapeutic clinical trials have been set up. However, there is currently no evidence for prophylactic or therapeutic supplementation with thyroxine (T4) for premature infants with THOP. One study of van Wassenaer et al. showed a beneficial effect of treatment of THOP in a subgroup of preterm infants with gestational age less than 28 weeks, but a reverse effect in the group with a gestational age of 29 weeks. This is an illustration of the limited comprehension of the pathophysiology of THOP. Although studies about THOP usually involves the preterm infants born at 33 weeks or earlier, one study of Paul et al. showed a decreased thyroid function in late preterm and term infants with respiratory distress syndrome as function of severity of illness. Unpublished data of our center showed also the presence of THOP, although less frequent, in the group of late preterm infants. Other data about this group of preterm infants are scarce. During the first half of pregnancy, the fetus is completely dependent of maternal thyroid hormone supply and the fetal thyroid gland starts thyroid hormone secretion from about 17-19 weeks of gestational age. Conditions of maternal (sub)clinical hypothyroidism are associated with compli