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The Reduced Thyroid Function of the Premature Newborn: Relation With Molecular Changes in the Placenta and Maternal Thyroid Hormone Status and Neurodevelopmental Implications

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by Universitaire Ziekenhuizen Leuven
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier:
NCT01466023
First received: November 2, 2011
Last updated: April 26, 2012
Last verified: July 2011
  Purpose

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 Unpublished data of our center showed also the presence of THOP, although less frequent, in the group of late preterm infants.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.


Condition
Thyroid Metabolism

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: The Reduced Thyroid Function of the Premature Newborn: Relation With Molecular Changes in the Placenta and Maternal Thyroid Hormone Status and Neurodevelopmental Implications

Resource links provided by NLM:


Further study details as provided by Universitaire Ziekenhuizen Leuven:

Biospecimen Retention:   Samples With DNA

Placenta and blood samples


Estimated Enrollment: 300
Study Start Date: October 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Pregnant women in a tertiairy hospital

Criteria

Inclusion Criteria:

  • pregnant
  • at risk of preterm delivery

Exclusion Criteria:

  • known congenital abnormality
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466023

Contacts
Contact: An Eerdekens, MD 003216343211 an.eerdekens@uzleuven.be
Contact: Chris Vanhole, PhD 003216342111 christine.vanhole@uzleuven.be

Locations
Belgium
University Hospitals Leuven Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: An Eerdekens, MD    003216343211    an.eerdekens@uzleuven.be   
Contact: Chris Vanhole, PhD    003216343211    christine.vanhole@uzleuven.be   
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
  More Information

No publications provided

Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT01466023     History of Changes
Other Study ID Numbers: S53423
Study First Received: November 2, 2011
Last Updated: April 26, 2012
Health Authority: Belgium: Ethics Committee

Keywords provided by Universitaire Ziekenhuizen Leuven:
thyroid metabolism during pregnancy
impact on neonate

Additional relevant MeSH terms:
Premature Birth
Thyroid Diseases
Endocrine System Diseases
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications

ClinicalTrials.gov processed this record on November 25, 2014