Clinical trial NCT01528904: Maternal Autoimmune Thyroid Disease and Fetal Thyroxin
Official title: Fetal Thyroid Hormones Concentration In Hyperthyroid or Hypothyroid Pregnant Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy Complicated by Hyperthyroidism
Hypothyroidism in Pregnancy
Keywords: pregnancy
autoimmune thyroid disease
fetal thyroid hormones
antithyroid antibodies
ultrasound parameters
Lead sponsor: University of Belgrade
Sponsor class: OTHER
First posted: 2012-02-08
Enrollment: 83
Sex: FEMALE
Minimum age (years): 23
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Groups are selected from State tertiary referral centre for Gynecology and Obstetrics

Brief summary: The purpose of this trial is to correlate fetal thyroid hormones from fetal cord blood with clinical (maternal antithyroid drug dose and antithyroid antibodies) and ultrasound (US) parameters of fetal thyroid function from pregnant mothers with autoimmune thyroid disease (AITD).

Detailed description: Maternal hyperthyroidism in pregnancy is complicated with hypertension, preeclampsia, heart failure, thyroid storm, preterm labor and stillbirth, while the fetus suffers from intrauterine growth retardation (IUGR), goiter; neonatal prematurity and low birth weight.

Maternal hypothyroidism is seen in 2 % of pregnancies. Risks are higher for preeclampsia, postpartum hemorrhage, miscarriage, stillbirth, preterm birth and lower IQ score.

Thyroid stimulating hormone (TSH) receptor antibodies, antithyroid drugs and iodine pass to the fetus. So the fetus may also become a patient. Monitoring fetal growth, fetal heart rate (tachycardia is a late sign of fetal hyperthyroidism), bone maturation and the size of the fetal thyroid by ultrasound are important parameters for the assessment of transfer of hyperthyroidism from mother to the fetus

Patients follow up:

After inclusion into the study, thyroid function tests (fT4, TSH), and auto-antibodies assessment (anti TPO, TRAK) were performed once every two months in mothers with AITD, and from the 24th week of gestation monthly. Treatment was adjusted accordingly. Ultrasound for fetal size, morphology and fetal heart rate (FHR) was performed once in two months, and from the 24th week of gestation, monthly. The fetal biophysical profile score was determined weekly from the 30th week of gestation. The single centre design was chosen: all fetal sonograms were performed by the same gynecologist. Cardiotocography was performed once weekly from the 30th week of gestation.

Study design:

Fetal and maternal free thyroxin (fT4) and TSH, thyroid antibodies in mothers and fetal ultrasound (fetal size, morphology and fetal heart rate) were determined at the same time, once, from 22nd to 33rd weeks of gestation.

Procedure: Cordocentesis (Cordocentesis is a highly specialized prenatal test in which a fetal blood sample is removed from the umbilical cord and tested for genetic problems, hormones or infections. Cordocentesis can be done at 18 weeks of pregnancy or later). Fetal fT4 and TSH were measured from cord blood samples. Healthy pregnant subjects were directed for cordocentesis for karyotype analysis due to age (missed previous procedures for karyotyping).

The diagnosis of fetal hypo or hyperthyroidism was established taking into account fT4 concentrations according to the nomograms Thorpee-Beeston et al., 1996, 1991.

When fetal hyperthyroidism is diagnosed, antithyroid drugs given to the mother are administered or adjusted. When fetal hypothyroidism is diagnosed, then the possibility of intraamniotic thyroxin application is discussed with the mother.

Eligibility criteria: Inclusion Criteria:

* Autoimmune hyper or hypothyroidism, diagnosed by an endocrinologist, treated, based on clinical and laboratory tests and ultrasound thyroid examination.
* Patients were included if they were seen by gynecologist at Clinic for Gynecology up until 20th week of gestation and not later.
* 20 healthy pregnant women in control group were directed for cordocentesis due to age.

Exclusion Criteria:

* Any other chronic diseases.

Primary outcomes:
measure: Fetal free thyroxin
timeFrame: 24th to 32nd week of gestation
Secondary outcomes:
measure: fetal ultrasound parameters
timeFrame: 24th to 32nd week of gestation
measure: maternal antithyroid antibodies
timeFrame: 24th to 32nd week of gestation
measure: dose of maternal antithyroid medication (ATD)
timeFrame: 24th to 32nd week of gestation
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Clinic for Gynecology and Obstetrics
Study officials:
affiliation: Medical School of the University of Belgrade
name: Svetlana Spremovic-Radjenovic, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007 Aug;92(8 Suppl):S1-47. doi: 10.1210/jc.2007-0141.