The Reduced Thyroid Function of the Premature Newborn: Relation With Molecular Changes in the Placenta and Maternal Thyroid Hormone Status and Neurodevelopmental Implications
Information source: Universitaire Ziekenhuizen Leuven
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Thyroid Metabolism
Phase: N/A
Status: Recruiting
Sponsored by: Universitaire Ziekenhuizen Leuven Overall contact:
An Eerdekens, MD, Phone: 003216343211, Email: an.eerdekens@uzleuven.be
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Unpublished data of our center showed also the presence of THOP, although less frequent, in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.
Clinical Details
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
Study design: Observational Model: Case Control, Time Perspective: Prospective
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- pregnant
- at risk of preterm delivery
Exclusion Criteria:
- known congenital abnormality
Locations and Contacts
An Eerdekens, MD, Phone: 003216343211, Email: an.eerdekens@uzleuven.be
University Hospitals Leuven, Leuven, Vlaams-Brabant 3000, Belgium; Recruiting
An Eerdekens, MD, Phone: 003216343211, Email: an.eerdekens@uzleuven.be
Chris Vanhole, PhD, Phone: 003216343211, Email: christine.vanhole@uzleuven.be
Additional Information
Starting date: October 2011
Last updated: April 26, 2012
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