The Reduced Thyroid Function of the Premature Newborn: Relation With Molecular Changes in the Placenta and Maternal Thyroid Hormone Status and Neurodevelopmental Implications
Condition: Thyroid Metabolism
MeSH terms: Premature Birth; Thyroid Diseases
Study type: Observational

Summary: 
      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 Unpublished data of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 complications like hypertension, preterm birth, low birth weight, placental abruption,
      and fetal death. One can wonder if there are compensating mechanisms in the placenta,
      providing the fetus with sufficient thyroid hormone in cases of compromised thyroid supply.
      One study showed that total placenta deiodinase type 3 (D3) activity in pregnancies with
      severely hypothyroid fetuses was not significantly lower than in euthyroid controls. Two
      studies showed increased monocarboxylate transporter 8 (MCT8) and decreased MCT10 expression
      within placentae of pregnancies complicated by IUGR. As far as we know, nothing is known
      about possible compensating effects in placentae of mothers with subclinical hypothyroidism
      and the possible influence on the development of THOP.

      Maternal subclinical hypothyroidism during pregnancy is a predisposition for the development
      of overt hypothyroidism. The influence of maternal thyroid antibodies during pregnancy
      towards thyroid hormone function of the fetus and consequently neurodevelopmental outcome is
      still not clear. One single study of Negro et al. showed that euthyroid pregnant women who
      are positive for thyroid peroxidase antibodies (TPOAb) develop impaired thyroid function,
      which is associated with an increased risk of miscarriage and premature deliveries. They also
      showed that substitutive treatment with levothyroxine (LT4) is able to lower the chance of
      miscarriage and premature delivery.A study of Pop et al. concluded that children of pregnant
      women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired
      development.Nothing is known about the possible influence of maternal thyroid antibodies
      towards the development of THOP, although a theoretical link is possible.

      The investigators want to investigate whether there are compensatory mechanisms in placentas
      of premature born infants and whether the maternal thyroid hormone condition is a prediction
      of the development of THOP in the premature infant. The investigators want to investigate the
      differences between several groups of preterm infants: 24-28 weeks, 28-32 weeks and 32-36
      weeks. The further aim of this study is to investigate the impact of maternal thyroid hormone
      condition during pregnancy on neurodevelopmental outcome of the neonate.

      In Belgium, 8% of the newborns are born preterm. There are about 2000 deliveries each year in
      the University Hospitals Leuven. Between 2 and 5% of all pregnant women are considered to
      have subclinical hypothyroidism and preterm birth is almost 2-fold higher in women with
      subclinical hypothyroidism.The incidence of THOP is 30 %. We performed a statistical power
      calculation with a confidence level of 95%. Given the above data and with the assumption that
      50% of the premature babies born to a hypothyroid mothers will develop THOP, we need to
      include 320 patients who give premature birth to obtain a statistical power of 80%.
      Therefore, the inclusion time will be 2 years.
    


Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women in a tertiairy hospital
      
Biospecimen description: 
      Placenta and blood samples
    
Keywords: thyroid metabolism during pregnancy; impact on neonate