Neurodevelopmental Impact of Treatment in Hypothyroxinaemia of Prematurity. (NEO-TYR)

Nowadays, taking care of preterm birth is associated with an important increase in survival. This increased survival comes with impairment in neurodevelopmental outcomes in long term evaluation. Thyroid hormones are essentials for brain development, especially for neuronal differentiation. Transient hypothyroxinaemia of prematurity (THOP) is a frequent condition defined by decreased thyroid hormones without the expected rise in thyroid stimulating hormone. Various studies have showed various results regarding the consequences of THOP on neurodevelopment in premature neonates. However, the biggest and most powerful studies agree to say that THOP impair neurodevelopment. On the other hand, only a few studies evaluated the impact of treatment of THOP, and only two focused on treating exclusively the neonates with a biological diagnosis of THOP (Suzumura and co. in 2010 and Nomura and co. in 2014) and their results are inconsistent.

In this study, we aim to show that a treatment with L-thyroxine at a dose of 7.5 µg/kg/j for neonates diagnosed with THOP (defined as a level of l-T4 < 12 pmol/L and a level of TSH < 15 mUI/L before 15 days of life or < 85 mUI/L after 15 days of birth) is associated with an increased neurodevelopmental prognosis.

Study Overview

• Status: Completed
• Conditions: Transient Hypothyroxinemia of Prematurity
• Intervention / Treatment: Drug: L-thyroxine at a dose of 7.5 µg/kg/d for THOP; Other: THOP without treatment; Other: NoTHOP

• Study Type: Observational
• Enrollment (Actual): 373

Contacts and Locations

Study Locations

• France
  • Bron, France, 69300
    • HFME
  • Grenoble, France, 38100
    • CHU Grenoble
  • Saint-Étienne, France, 42000
    • CHU Saint EtienneHopital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Reanimation and intensive care units of neonatology in Auvergne-Rhone Alpes region (Lyon Croix Rousse hospital, Lyon Femme mère Enfant hospital, St Etienne Hopital Nord, Grenoble Hopital couple enfant).

Description

Inclusion Criteria:

• Premature infants born before or at 3032 weeks of gestation
• For whom blood sample for thyroid examination has been performed for routine care during his stay in neonatology unit.

Exclusion Criteria:

• Other type of thyroid dysfunction (including, but not exclusively: mother with Basedow disease, congenital hypothyroidism, hyperthyroidism)
• Associated polymalformative sindrome

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
THOP treated; Level of circulating T4 < 12 pmol/L at any time of life associated, on the same date, with a level of circulatingon thyro-stimulating hormone < 15 mUI/L if the sample was realiszed before or on the fifteenth day of life OR < 58 mUI/L if the sample was realiszed after the fifteenth day of life, and L-thyroxine treatment is recorded in the medical record (at any dose and with any duration)	Drug: L-thyroxine at a dose of 7.5 µg/kg/d for THOP; Subjects diagnosed with THOP (as previously defined) and treated with L-thyroxine at a dose of 7.5 µg/kg/d are less likely to have an impaired ASQ score at 4 years of corrected age.
THOP un-treated; Level of circulating T4 < 12 pmol/L at any time of life associated, on the same date, with a level of circulation thyro-stimulating hormone < 15 mUI/L if sample was realiszed before or on the fifteenth day of life OR < 5 mUI/L if sample was realiszed after the fifteenth day of life, and no L-thyroxine treatment recorded in the medical record.	Other: THOP without treatment; Subjects diagnosed with THOP (as previously defined) and who received no L-thyroxine treatment.
No-THOP; all level of circulating T4 > 12 pmol/L at any time in life	Other: NoTHOP; Subjects diagnosed no-THOP (as previously defined)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuro-development judged " abnormal " by the paediatrician during the two years of corrected age's consultation.	Neuro-development is evaluated routinely by paediatricians during consultation, and this evaluation is reported in medical files.	Evaluation at two years of corrected age.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: transient hypothyroxinaemia of prematurity, THOP, preterm, prematurity, neurodevelopment, L-thyroxine, ASQ score
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: 69HCL21_0843; 401 (Other Identifier: AGORA HCL)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No