L-Thyroxine Supplementation for Preterm Newborns Less Than 32 Weeks of Gestation With Hypothyroxinemia

Study Overview
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Brief Summary
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Transient hypothyroxinemia of prematurity (THOP) is associated with neurodevelopmental impairment in preterm newborns < 32 weeks of gestation (WG). It is not known whether L-Thyroxine supplementation for preterm newborns <32 WG with THOP is beneficial. The purpose of this study is to compare L-thyroxine treatment vs. placebo in newborn less than 32 WG with THOP. The primary endpoint is the neurodevelopmental outcome at two years of life, assessed by the Brunet-Lézine score. The secondary endpoints are: death, bronchopulmonary dysplasia (oxygen therapy at 28 days of life and at 36 weeks of postnatal age), patent ductus arteriosus, shock requiring fluid loading or vasoactive treatments, enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, deafness.

Detailed Description
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Preterm newborns <32 weeks of gestation (WG) are screened for THOP between day 5 and day 7 of life. THOP is defined by thyroid-stimulating hormone (TSH) < 20 mIU/L and FT4 < 0.80 ng/dL. After obtaining written consent from the parents, preterm newborns <32 WG with THOP will be included. Randomization is stratified by center and 2 age-groups (24-28 WG and 29-32 WG). One arm will receive L-thyroxine treatment and the other arm will receive placebo. Treatment will be started within one week after diagnosis and will last 6 weeks. TSH and FT4 will be assayed 2 weeks after stopping treatment. The primary endpoint is the neurodevelopmental outcome at two years of life, assessed by the Brunet-Lézine score.

Official Title
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L-Thyroxine Supplementation for Preterm Newborns Less Than 32 Weeks of Gestation With Transient Hypothyroxinemia of Prematurity: a Prospective Randomized Double-blind Trial

Conditions
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Hypothyroxinemia

Intervention / Treatment
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* Drug: L-Thyroxine
* Drug: water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age < 32 WG FT4 (5, 6 or 7 days of life) ≤ 0.8 ng/dL TSH (5, 6 or 7 days of life) < 20 mIU/L Written consent from the parents Exclusion Criteria: Maternal thyroid disease FT4 (5, 6 or 7 days of life) > 0.8 ng/dL TSH (5, 6 or 7 days of life) > 20 mIU/L Grade III or IV intracerebral hemorrhage

Ages Eligible for Study
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Minimum Age: 1 Week
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: water<br>Oral treatment with water for 6 weeks | Drug: water<br>* Oral treatment with water. Equal number of drop of water as compared with the treatment arm (according to the body weight of the newborn) in the morning, once a day.<br>|
| Experimental: L-Thyroxine<br>Oral treatment with L-Thyroxine for 6 weeks | Drug: L-Thyroxine<br>* Treatment with L-Thyroxine:7,5 µg/kg/day. Oral treatment (one drop =5µg) in the morning, once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopmental outcome | Brunet-Lézine score | 2 years old | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity associated with management of newborns < 32 WG with hypothyroxinemia | Death Bronchopulmonary dysplasia (oxygen therapy at 28 days of life and at 36 weeks of postnatal age) Patent ductus arteriosus, Shock requiring fluid loading or vasoactive treatments Enterocolitis Intraventricular hemorrhage Retinopathy of prematurity Deafness | discharge, 1 year, 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infant, newborn, Infant, preterm, Thyroid, Outcome, Newborns less than 32 weeks of gestation, TSH < 20 mIU/L and a FT4 < 0.80 ng/dL