Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: perinatal influences and impact on neurodevelopment

Abstract

Background For several decades, transient hypothyroxinemia of prematurity (THOP) has been a topic of debate. The pathophysiology is incompletely understood and consensus on the therapeutic approach is lacking. This study aimed at gaining a better insight into the pathogenesis by studying the trends in thyroid hormone (TH) levels during the first week of life. Methods This single-center prospective observational study analyzed the plasma levels of total thyroxine (T4) and free thyroxine (fT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) in cord blood and at the end of the first week of life in 120 preterm infants (gestational age [GA] <37 weeks). The change over time was calculated (delta, ∆). The impact of perinatal and subsequently postnatal variables on ∆ was studied by hierarchical multiple regression. The impact of ∆ on the neurodevelopmental outcome at the corrected ages of 9 and 24 months, measured by the Bayley Scales of Infant Development (BSID)-II, was assessed by logistic regression. Results ∆fT4 levels were negatively affected by GA and use of dopamine, whereas only GA was associated with low ∆T3 levels. Negative ∆fT4 levels were present in 75% of the extremely low-for-gestational-age infants, whereas 23.5% had a negative ∆T3 level. There was an increased risk for an abnormal mental developmental score (<85) with decreasing ∆T3 at 9 months, corrected age, but not at 24 months. Conclusions A negative evolution in circulating TH levels is principally an immaturity phenomenon, whereas dopamine can further suppress the hypothalamic-pituitary-thyroid axis. There is at least a temporary negative effect of this evolution on the infants’ neurodevelopment.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls

“…Few studies had examined cord blood T3 and infant neurodevelopment. A previous study on preterm infants found that a decrease between cord blood T3 and infant serum T3 levels at the end of the first week of life was associated with an increased risk of disturbed mental (44). In this study, a "U"-shaped relationship was found between cord blood FT3 levels and scores in the communication domain in girls.…”

Thyroid hormone increases fatty acid use in fetal ovine cardiac myocytes

“…In agreement with previous investigations (Graham & Huang, 2021; Sayre & Lechleiter, 2012), this study suggests that rising T 3 levels in utero contribute to increased maximal capacity for oxidative metabolism, concurrent with the other maturational changes stimulated by T 3 . Cardiac metabolic dysfunction may be a consequence in preterm babies that do not experience a normal rise in T 3 (Eerdekens et al., 2019), as well as fetuses affected by thyroid disorders during pregnancy (Mallawa Kankanamalage et al., 2021; Maulik et al., 2022). The normal function of the fetal heart is also disrupted by experimental thyroidectomy, including impairing the normal age‐related decline in cardiac glycogen storage (Forhead et al., 2009).…”

Impact of iodine supplementation during preconception, pregnancy and lactation on maternal thyroid homeostasis and offspring psychomotor development: protocol of the IodineMinho prospective study

“…This instrument is one of the most reliable and widely used to evaluate children development at 1-42 months. Our group and others have previously used licensed Bayley Scales to address infants' psychomotor performance in the context of maternal hypothyroxinemia [6,20,21]. It includes three subscores: cognitive (information processing, information processing speed, problem-solving, play skills and numbers concepts); language communication (expressive, which is the ability to communicate, and receptive, which includes the abilities to hear, understand and respond) and motor development (fine and gross motor abilities, including movement quality, sensory and perceptual-motor integration and basic locomotion milestones).…”