Thyroxine Supplementation in Small for Gestational Age (SGA) Infants With Birth Weight <1500g and TSH 6-20 mIU/ml

Growth and Neurodevelopmental Outcomes at Two Years of Age After Postnatal Thyroid Hormone Supplementation in SGA Infants With Birth Weight <1500g and TSH 6-20 mIU/ml

The primary objective of this clinical trail is to evaluate whether early supplementation of levothyroxine (L-T4) at a dosage of 8 ug/kg/d, initiated in the second week of life, improves physical growth and neurodevelopmental outcomes at 2 years of corrected age in Small for Gestational Age (SGA) infants with birth weights < 1500g and TSH levels between 6 and 20 mIU/ml. Preterm infants in the intervention group will receive 8 ug/kg/d of L-T4, while the control group will receive no supplementation. Physical growth will be assessed through height, weight, and head circumference, while neurodevelopmental status will be evaluated using the Bayley-IV scales and cranial MRI imaging findings.

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm; Thyroid Function; SGA and Growth; Neurodevelopment Outcome
• Intervention / Treatment: Drug: Levothyroxine Sodium (LT4) Tablets

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yonghui Yu; Phone Number: +8615168887236; Email: alice20402@126.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital Affiliated to Shandong First Medical University
      • Contact: Yonghui Yu; Phone Number: +8615168887236; Email: alice20402@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Preterm infants born Small for Gestational Age (SGA) with a birth weight < 1500g；
• Admitted to a participating Neonatal Intensive Care Unit (NICU) within 7 days of birth；
• Serum concentrations of TSH, FT4, and FT3 are measured weekly during the first and second weeks of life，any single TSH measurement during this period is between 6 and 20 mIU/mL；
• Written informed consent obtained from the parents.

Exclusion Criteria:

• Diagnosis of Congenital Hypothyroidism (CH) with serum TSH > 20 mIU/mL within the first 2 weeks of life and receiving L-T4 treatment;
• Persistent serum TSH < 6 mIU/mL throughout the first 2 weeks;
• Elevated thyroid hormone levels(T3, T4, FT3, or FT4) above the reference range within the first 2 weeks;
• Diagnosis of Grade III or IV Intraventricular Hemorrhage (IVH) within the first 2 weeks of life;
• Presence of major congenital malformations of vital organs or known chromosomal/genetic disorders;
• History of maternal thyroid disease or maternal use of thyroid-related medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group
Experimental: intervention group	Drug: Levothyroxine Sodium (LT4) Tablets; The intervention group will receive oral levothyroxine (L-T4) initiated on postnatal day 14 at a starting dose of 8 ug/kg/day. Thyroid function will be monitored every 2-4 weeks until 36 weeks postmenstrual age or hospital discharge, with subsequent follow-up at corrected ages of 40 weeks, 3, 6, 12, 18, and 24 months. The L-T4 dosage will be dynamically titrated to achieve therapeutic targets of TSH < 5 mIU/L and FT3/FT4 levels within the upper 50% of the age-specific reference range. Treatment will be discontinued if therapeutic targets are sustained at a dosage below 2 ug/kg/day or if FT3/FT4 levels exceed the upper limit of normal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cognitive function evaluated by Bayley-IV	At 24 months corrected age
Motor function evaluated by Bayley-IV	At 24 months corrected age
Language function evaluated by Bayley-IV	At 24 months corrected age
Social-Emotional evaluated by Bayley-IV	At 24 months corrected age
Adaptive behavior evaluated by Bayley-IV	At 24 months corrected age
Body length（cm）assessed by the WHO 0-5 years Child Growth Standards.	At 24 months corrected age
Head circumference（cm）assessed by the WHO 0-5 years Child Growth Standards.	At 24 months corrected age
Weight（kg）assessed by the WHO 0-5 years Child Growth Standards.	At 24 months corrected age

Secondary Outcome Measures

Outcome Measure	Time Frame
the incidence of neonatal morbidities （EUGR、PNAC、MBDP、Moderate to severe BPD、Stage III or higher ROP）during the initial hospitalization	at 36 weeks of postmenstrual age
All-cause Mortality	At 24 months corrected age

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): June 20, 2029

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Pharmaceutical Preparations; Dosage Forms; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Thyroid Hormones; Tablets; Thyroxine
• Other Study ID Numbers: SWYX：NO.2025-1019-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No