Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the risk-benefit profile of long-term treatment of two different initials treatment schemes with L-T4 on the neurodevelopmental and auxological outcomes in children with congenital hypothyroidism, diagnosed by neonatal screening in order to find the best dose of initial thyroid hormone replacement to assure the best long-term developmental outcome without any adverse effects on auxological, cardiovascular and skeletal outcomes. The secondary objective of the study is to evaluate the role of other factors that, in addition to the initial L-T4 therapy,can influence long-term neurodevelopmental and auxological outcomes as well as the cardiovascular system and bone metabolism outcomes.

Detailed Description
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Seventy-two neonates detected by the neonatal screening program for congenital hypothyroidism were randomly assigned to receive one of the two initial L-T4 replacement dose: Group A received an initial replacement dose of 10-12.5 mcg/kg/die and Group B received an initial replacement dose of 12.6-15 mcg/kg/die. The adequacy of treatment were monitored closely by clinical evaluation and regular measurement of FT4 and TSH. Cognitive development were evaluated through the Griffiths Mental Development Scales at the the age of 2 yeas. Cognitive and behavioural assessment at the age of 4 years were performed using the Wechsler Preschool and Primary scale of Intelligence. Growth were evaluate at the enrolment and at each visit. Skeletal maturation were evaluated at diagnosis and at the age of 1 and 4 years. At the age of 4 years a quantitative ultrasound measurements and cardiovascular evaluation were performed.

Official Title
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Evaluation of Long-term Benefit-risk Profile of Levothyroxine Treatment in Children With Congenital Hypothyroidism: Influence of Initial Levothyroxine Dose on Neurodevelopmental, Growth, Cardiovascular and Skeletal Outcomes

Conditions
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Congenital Hypothyroidism

Intervention / Treatment
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* Drug: Levothyroxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Congenital Hypothyroidism diagnosed by neonatal screening program Age less than 30 days at diagnosis TSH value at confirmatory diagnosis above 30 mU/l Caucasian ethnicity Exclusion Criteria: Prematurity Major congenital malformations Neonatal diseases Chromosomopathies Known maternal thyroid diseases

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 29 Days

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
Interventional Model Description: Children were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Group A) or 12.6-15 μg/kg/day (Group B). Randomization was designed according to a block scheme (8 blocks of 6 patients and 6 blocks of 4 patients which were randomly alternated) which guaranteed the frequency balance in the two groups during the enrolment without altering the causality of the assignment. Random allocation sequence was generated using the function sample in R statistical platform.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 10-12.5 μg/kg/day of L-T4<br>Children with congenital hypothyroidism who received an initial L-T4 dose of 10-12.5 μg/kg/day. | Drug: Levothyroxin<br>* Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.<br>* Other names: L-T4;|
| Active Comparator: 12.6-15 μg/kg/day of L-T4<br>Children with congenital hypothyroidism who received an initial L-T4 dose of 12.6-15 μg/kg/day. | Drug: Levothyroxin<br>* Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.<br>* Other names: L-T4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopmental outcomes | Cognitive and behavioral assessment was performed using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The WIPPSI-III evaluates the intelligence of children between 2.6 and 7.3 years and provides a Total Intelligence Quotient, a Verbal Intelligence Quotient, a Performance Intelligence Quotient and a Processing Speed Quotient. Quotients > 85 are considered normal. | At four years of age | 
| Linear Growth | Linear growth was evaluated periodically during the study through the measurement of length up to 3 years and height subsequently. Length and height were measured in centimeters and are expressed as standard deviation score. | 7-10 days after the start of treatment and at 1.5, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 months of life. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth, Neonatal screening, Levothyroxine treatment, Neurocognitive