Introduction
Thyroid hormones have a crucial role in body metabolism and maintenance. In infants, thyroid hormones are necessary for the development of the brain, especially in the fetal stage. For a fetus, a full-term birth ensures the proper development of bodily functions. In earlier times in premature babies, there was an increased risk of thyroid system immaturity, but advances in medicine have helped to increase the survival of premature infants.
What Is Transient Hypothyroxinemia?
Transient hypothyroxinemia is the reduction in the total and free levels of thyroxine and low or normal levels of stimulating thyroid hormone, found in infants born prematurely due to the thyroid system being immature. This is related to poor neurodevelopmental outcomes; however, the studies vary in the opinion regarding the benefits of treating thyroid hormones in cases of transient hypothyroxinemia of prematurity (THOP).
What Is the Mechanism of Thyroid Hormone?
T4 and T3 hormones are collectively known as thyroid hormones. These hormones are responsible for metabolism in adults and brain development in children. These hormones are produced based on a feedback mechanism involving multiple organs such as the hypothalamus, pituitary gland, and thyroid gland. The cycle is started by the hypothalamus, which, based on the body's metabolism, stimulates the pituitary gland by producing thyroid-releasing hormone (TRH). This TRH stimulates the pituitary gland to produce TSH or thyroid-stimulating hormone, which in turn activates the thyroid gland to produce thyroid hormones (T4 and T3). When there are sufficient levels of thyroid hormone in the serum, TRH production is stopped, thereby the production of T3 and T4. The cycle is restarted only when the level of thyroid hormones reduces.
What Is Hypothyroxinemia?
-
Hypothyroxinemia is the normal concentration of stimulating thyroid hormone with no thyroid autoantibodies and low maternal free thyroxine (FT4) concentration. This results in various problems while pregnant (perinatally) and maternally.
-
Maternal outcomes include gestational diabetes mellitus and hypertension, membranes rupture before labor, placental abruption, placenta previa, and premature delivery.
-
Perinatal outcomes include fetal distress, low birth weight, intrauterine fetal death, fetal growth restriction, and malformation.
-
For the normal growth of a fetus, thyroid hormone is necessary. In the first trimester, the fetus gets this hormone from the mother through the placenta. As it reaches the second trimester, the fetus produces some amount of thyroid hormone but mainly receives it from the mother. And for this reason, hypothyroidism in pregnancy can significantly affect fetal growth. Hypothyroidism during pregnancy can be due to different conditions, such as clinical hypothyroidism, hypothyroxinemia, and subclinical hypothyroidism.
What Causes Transient Hypothyroxinemia?
The etiology for transient hypothyroxinemia of prematurity (THOP) are several, which include:
-
Losing placental transfer of the T4 hormone mainly occurs in premature birth.
-
The limited capacity of the thyroid to increase the synthesis of hormones.
-
Immature hypothalamus-pituitary-thyroid axis.
-
Drugs that affect thyroid functions.
It has also been seen as associated with the following:
-
Increased length of mechanical ventilation.
-
Damage of cerebral white matter.
How Does Transient Hypothyroxinemia Progress?
1. The risk of hypothyroxinemia increases as the gestational age decreases and therefore is seen in 50 percent of premature newborns.
2. Serum T4 and free T4 generally decline between the tenth and fourteenth days after birth. These levels vary in premature infants, especially severe in children with low birth weight and low gestational age.
3. In full-term infants, the T4 levels in serum increase in the first week of life; however, in premature infants, the levels decrease for a transient period of time, resulting in hyperthyroxinaemia. This is especially true in the cases of infants below 30 weeks of gestation. During the postpartum period, TSH level is seen to increase in term newborns. But this TSH increase is late, and T4 and free T4 levels remain low in preterm infants. This can be due to the following:
-
Blunted physiological hyperthyroidism.
-
Deficiencies in the metabolism of iodine.
-
The thyroid gland does not respond to TRH.
-
Faulty hypothalamic-pituitary-thyroid axis.
-
Increased thyroid demand to meet bodily needs such as skeletal muscle, cardiac function, and thermogenesis.
-
Additionally, thyroid metabolism may be disturbed due to medications used to treat premature infants for diseases such as necrotizing enterocolitis, respiratory distress syndrome, malnutrition, patent ductus arteriosus, iron deficiency, or chorioamnionitis. Necrotizing enterocolitis is considered to be a serious gastrointestinal disorder that is predominant in premature babies. Patent ductus arteriosus refers to the existing opening called the ductus arteriosus, which fails to close after birth. It is present between two main blood vessels of the heart, and normally it closes two to three days after birth. Chorioamnionitis is an infection during pregnancy, and it can occur before birth or during labor.
How to Diagnose Transient Hypothyroxinemia?
The go-to evaluation test for identifying the condition is stimulating thyroid hormone (TSH) screening. But in some cases, there is a delayed elevation of TSH, and in such circumstances, the diagnosis may be incorrect. Therefore it has been recommended to perform rescreening for all preterm babies as a standard procedure.
Transient Hypthyroxinemia In Infants Born to Mothers with Grave's Disease:
Grave's disease is an autoimmune disorder that leads to the overproduction of thyroid hormones or hyperthyroidism. Infants born to mothers who suffer from this condition have been noted to have transient central hypothyroidism. The mothers often suffered from thyrotoxicosis during the last trimester or had uncontrolled thyroid levels during pregnancy. Thyrotoxicosis is extremely high levels of thyroid hormones.
THOP and CHD:
Transient hypothyroidism of prematurity and congenital heart diseases are frequently seen to be associated with most preterm infants.
How to Treat Transient Hypothyroxinemia?
The need and mode of treatment are still debatable in the case of hypothyroxinemia. It is recommended to administer treatment for infants born at less than 28 weeks of gestational age. One study demonstrated that babies who were given treatment showed better brain development and showed better results in tests performed at 42 weeks in regard to language, motor, and cognitive abilities.
Conclusion
Transient hypothyroxinemia is the reduction in thyroid hormone production in prematurely born infants. It affects the brain development and normal growth of the child. It can be due to various different factors. Although the treatment for this condition is still not universally accepted, it has been shown in some studies that the administration of thyroid hormones has helped improve the development of the infant when compared to newborns who were untreated.
