New Insights in Thyroid Function in Preterm Infants

Korte inhoud:THs are indispensable for fetal development in general, and in particular for the developing brain, where they play an important role in neurogenesis, myelination, dendrite proliferation and synaptogenesis. Until mid-gestation, the fetus is completely dependent on maternal TH supply and the placenta plays a central role in this maternal-fetal TH transfer. From around 20 weeks of gestation, the fetal TH system starts to function, but it is only after birth that the newborns' TH system acts completely autonomously. Preterm infants often present with THOP, a temporary decrease in circulating TH levels without the expected increase in the pituitary secreted TSH. THOP is already topic of debate for several decades: both the clinical relevance as therapeutic approaches are subject of discussion. This demonstrates the complexity of this phenomenon. The aim of this PhD project was to gain more insight in THOP. Chapter 1, the general introduction of this thesis, gave an overview of the general aspects of TH metabolism and actions, underlined the importance of THs in fetal maturation and brain development and discussed the challenges of pregnancy towards maternal thyroid economy and mechanisms of maternal-fetal TH transfer in normal circumstances. Subsequently, the focus shifted towards complicated pregnancies. Histological features of the placenta in conditions of chronic utero-placental hypoxia were described and the current knowledge about the impact of these conditions on placental TH transport and metabolism were discussed. Since preterm birth is the result of a complicated pregnancy, and preterm infants present with THOP, this chapter ended with an overview of the knowledge about the etiology of THOP, and discussed controversies about both the impact of THOP on the infants' neurodevelopment and therapeutic approaches. In Chapter 2, the aim and objectives of the thesis were outlined. Chapter 3 investigated the first hypothesis: in preterm birth, the underlying pregnancy complication affects the trans-placental supply of THs to the fetus and therefore, this complication predisposes the preterm infant to THOP. Similar to histological placental compensation mechanisms, there were indications of maternal and placental compensation mechanisms in TH metabolism in conditions of pregnancy-associated vascular complications in order to provide the fetus under chronic distress with an increased amount of T3, compared to complicated pregnancies, resulting in spontaneous preterm birth. There were no indications that the etiology of preterm birth was compromising the preterm infants' TH status at birth. In Chapter 4, the evolution of circulating TH levels during the first week of life in preterm infants was studied. It remains questionable which ranges for circulating TH levels in preterm infants are optimal in relation to gestation and postnatal ages. By studying the evolution of circulating TH levels during the first week of life and expressing it as ∆, i.e. the difference between the end of the first week of life and cord blood, we developed a novel approach in assessing THOP, independent of predefined reference values. By this approach, we found that immaturity is the most important contributing factor to THOP, since negative trends in the evolution of TH levels were most prevalent in ELGANs, whereby infants with GA of 24-25 weeks were most affected. Besides, the use of dopamine was another risk factor for these negative trends. Not a negative evolution in the prohormone T4, but in the active hormone T3 was negatively affecting the infants' neurodevelopment at the corrected age of 9 months, but this impact could not be demonstrated anymore at the corrected age of 24 months. In Chapter 5, this novel approach of THOP to the evaluation of TH action in the preterm infants' brain was applied by performing a pilot study about the impact of THOP on functional brain development with EEG measurements. We hypothesized that since THOP is present in a time-frame where important TH-dependent processes occur, brain development is affected and this is reflected by alterations in EEG complexity at term age. Although the study had a retrospective design with limitations, there were indications that EEG might be a helpful tool in studying the impact of THOP on brain development of the preterm infant. The results of this thesis might help to develop further research strategies to obtain more insight in the underlying mechanisms and impact of THOP and to design possible future therapeutic trials.

Jaar van publicatie:2019

Toegankelijkheid:Open