Congenital Hypothyroidism in Preterm Newborns - The Challenges of Diagnostics and Treatment: A Review

Abstract

Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate thyroid hormones secretion as well as the impaired regulation of hypothalamus-pituitary-thyroid axis may lead to hypothyroxinemia. Two first weeks after birth are pivotal for brain neurons development, synaptogenesis and gliogenesis. The decreased level of thyroxine regardless of cause may lead to delayed mental development. Congenital hypothyroidism (CH) is a disorder highly prevalent in premature neonates and it originates from maternal factors, perinatal and labor complications, genetic abnormalities, thyroid malformations as well as side effects of medications and therapeutic actions. Because of that, the prevention is not fully attainable. CH manifests clinically in a few distinctive forms: primary, permanent or transient, and secondary. Their etiologies and implications bear little resemblance. Therefore, the exact diagnosis and differentiation between the subtypes of CH are crucial in order to plan an effective treatment. Hypothyroxinemia of prematurity indicates dynamic changes in thyroid hormone levels dependent on neonatal postmenstrual age, which directly affects patient's maintenance and wellbeing. The basis of a successful treatment relies on an early and accurate diagnosis. Neonatal screening is a recommended method of detecting CH in preterm newborns. The preferred approach involves testing serum TSH and fT4 concentrations and assessing their levels according to the cut-off values. The possible benefits also include the evaluation of CH subtype. Nevertheless, the reference range of thyroid hormones varies all around the world and impedes the introduction of universal testing recommendations. Unification of the methodology in neonatal screening would be advantageous for prevention and management of CH. Current guidelines recommend levothyroxine treatment of CH in preterm infants only when the diagnose is confirmed. Moreover, they underline the importance of the re-evaluation among preterm born infants due to the frequency of transient forms of hypothyroidism. However, results from multiple clinical trials are mixed and depend on the newborn's gestational age at birth. Some benefits of treatment are seen especially in the preterm infants born <29 weeks' gestation. The discrepancies among trials and guidelines create an urgent need to conduct more large sample size studies that could provide further analyses and consensus. This review summarizes the current state of knowledge on congenital hypothyroidism in preterm infants. We discuss screening and treatment options and demonstrate present challenges and controversies.

Keywords: congenital hypothyroidism; hypothyroxinemia; neonatal screening; preterm newborns; thyroid hormones.

Figure 1

Fetal thyroid gland maturation. The fetus is dependent on maternal thyroid hormones supplementation until the end of the first trimester. The hypothalamus-pituitary-thyroid axis is not sufficiently developed until the end of pregnancy, thus preterm-born children present a disorder called hypothyroxinemia of prematurity, which results in numerous consequences. Created with BioRender.com.

Figure 2

The role of thyroid hormones in fetal and infant development. Thyroid hormones are essential for the general accretion of fetal mass and to provoke developmental events in the fetal brain and somatic tissues from early in gestation. Moreover, they affect the production of other hormones and regulate tissue accretion near term. Furthermore, TH ensure activation of physiological processes as thermogenesis, gluconeogenesis, pulmonary gas exchange and cardiac adaptations at birth (49). Created with BioRender.com.