Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy (TSH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00388297
Recruitment Status : Completed
First Posted : October 16, 2006
Results First Posted : January 30, 2019
Last Update Posted : February 21, 2019
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Subclinical Hypothyroidism
Hypothyroxinemia
Pregnancy
Interventions Drug: Levothyroxine
Drug: Placebo for Levothyroxine
Enrollment 1203
Recruitment Details This study enrolled women with a singleton pregnancy before 20 weeks gestation who met the criteria for either subclinical hypothyroidism or hypothyroxinemia based on serum thyrotropin and free T4 values. The study was conducted as two multicenter, randomized, placebo-controlled trials at 15 NICHD MFMU network centers.
Pre-assignment Details 97,228 patients were screened during the recruitment period October 2006 to October 2009, Of the 800 eligible based on subclinical hypothyroidism, 677 completed the 7-day placebo adherence run-in and were randomized. Of the 632 eligible based on hypothyroxinemia, 526 completed the run-in phase and were randomized.
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine for Hypothyroxinemia
Hide Arm/Group Description

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism group

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia group
Period Title: Overall Study
Started 339 338 265 261
Completed 323 326 254 253
Not Completed 16 12 11 8
Reason Not Completed
Lost to Follow-up             16             12             11             8
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia Total
Hide Arm/Group Description

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia Total of all reporting groups
Overall Number of Baseline Participants 339 338 265 261 1203
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
27.7  (5.7) 27.3  (5.7) 27.8  (5.7) 28.0  (5.8) 27.7  (5.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
Female
339
 100.0%
338
 100.0%
265
 100.0%
261
 100.0%
1203
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
Black
27
   8.0%
25
   7.4%
61
  23.0%
65
  24.9%
178
  14.8%
Hispanic
195
  57.5%
185
  54.7%
131
  49.4%
125
  47.9%
636
  52.9%
White
109
  32.2%
117
  34.6%
69
  26.0%
69
  26.4%
364
  30.3%
Other
8
   2.4%
11
   3.3%
4
   1.5%
2
   0.8%
25
   2.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
339
 100.0%
338
 100.0%
265
 100.0%
261
 100.0%
1203
 100.0%
Body-mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
28.1  (6.4) 28.2  (6.4) 30.3  (6.4) 30.2  (7.1) 29.0  (6.6)
Nulliparous  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
124
  36.6%
134
  39.6%
69
  26.0%
64
  24.5%
391
  32.5%
Baseline thyrotropin (mU/liter) Median  
Median (Inter-Quartile Range)
Unit of measure:  mU/liter
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
4.5
(4.0 to 5.5)
4.3
(4.0 to 5.3)
1.5
(1.1 to 2.1)
1.4
(1.0 to 2.1)
3.4
(1.6 to 4.6)
Baseline free thyroxine (ng/dl Median  
Median (Inter-Quartile Range)
Unit of measure:  Ng/dl
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
1.01
(.94 to 1.09)
1.02
(0.96 to 1.11)
0.83
(0.81 to 0.84)
0.83
(0.81 to 0.84)
0.90
(0.83 to 1.03)
Urinary iodine (µg/liter) Median  
Median (Inter-Quartile Range)
Unit of measure:  µg/liter
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
199
(106 to 340)
196
(114 to 331)
185
(108 to 341)
191
(118 to 325)
194
(111 to 334)
Weeks Gestation at Randomization  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 339 participants 338 participants 265 participants 261 participants 1203 participants
16.6  (3.0) 16.7  (3.0) 18.0  (2.8) 17.7  (2.9) 17.2  (3.0)
1.Primary Outcome
Title Intellectual Function of Children at 5 Years of Age in Women Diagnosed With a) Subclinical Hypothyroidism or b) Hypothyroxinemia During the First Half of Pregnancy, or Death.
Hide Description

The primary outcome was death or IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing). The full-scale IQ was assessed with the use of the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years of age or the overall (general conceptual ability) score from the Differential Ability Scales-II at 3 years of age if the WPPSI-III score was not available. Results are expressed as an age-standardized score, with an expected population mean of 100 and a standard deviation of 15. Death before 3 years of age was assigned a score of 0 (lowest possible rank) and was included in the estimation of the median.

For Quotient and Composite score:

below 70 is Extremely Low, 70-79 is Borderline, 80-89 is Low Average, 90-109 is Average, 110-119 is High Average, 120-129 is Superior, 130+

Time Frame 60 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 323 326 254 253
Median (95% Confidence Interval)
Unit of Measure: score on a scale
97
(94 to 99)
94
(92 to 96)
94
(91 to 95)
91
(89 to 93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann estimate
Estimated Value -1
Confidence Interval (2-Sided) 95%
-4 to 1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Week of Gestation at Delivery
Hide Description Gestational age at delivery and preterm birth < 37 weeks' gestation or < 34 weeks' gestation
Time Frame Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Mean (Standard Deviation)
Unit of Measure: weeks
39.1  (2.5) 38.9  (3.1) 39.0  (2.4) 38.8  (3.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Preterm Delivery
Hide Description Preterm delivery at less than 37 weeks or less than 34 weeks gestation
Time Frame Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
Preterm birth < 34 wk
9
   2.7%
10
   3.0%
10
   3.8%
7
   2.7%
Preterm birth < 37 wk
31
   9.1%
37
  10.9%
31
  11.8%
20
   7.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Analysis for < 34 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Analysis for <34 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Analysis for <37 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Analysis for < 37 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley-III Motor (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley-II Language (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-III Cognitive (12 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-III Motor (12 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-III Language (12 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-III Cognitive (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-III Motor (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Bayley-II Language (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)
Hide Description

Standardized full-scale IQ scores from the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years of age. Quotient and Composite scores have a mean of 100 and a standard deviation of 15. Subtest scaled scores have a mean of 10 and a standard deviation of 3.

For Quotient and Composite score:

below 70 is Extremely Low, 70-79 is Borderline, 80-89 is Low Average, 90-109 is Average, 110-119 is High Average, 120-129 is Superior, 130+ is Very Superior.

Time Frame 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 311 314 243 243
Median (95% Confidence Interval)
Unit of Measure: score on a scale
97
(95 to 99)
95
(93 to 97)
94
(91 to 95)
92
(90 to 95)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value -1
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
Hide Description

Overall general conceptual ability score as measured by the DAS-II at 36 months of age.

GCA General Conceptual Ability Classification ≥ 130 Very high 120-129 High 110-119 Above average 90-109 Average 80-89 Below average 70-79 Low

≤ 69 Very low

Time Frame 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 304 308 244 235
Median (95% Confidence Interval)
Unit of Measure: score on a scale
90
(88 to 93)
90
(87 to 93)
90
(87 to 92)
89
(87 to 91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-2 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value -1
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
Hide Description

Cognitive and achievement levels from two DAS-II subtests (Recall of Digits Forward and Recognition of Pictures)

GCA General Conceptual Ability Classification ≥ 130 Very high 120-129 High 110-119 Above average 90-109 Average 80-89 Below average 70-79 Low

≤ 69 Very low

Time Frame 48 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
For all outcomes except the primary outcome, the potential follow-up cohort consisted of 335 children in the levothyroxine group and 329 in the placebo group for the mothers with subclinical hypothyroidism and for the hypothyroxinemia group - 260 children in the levothyroxine group and 255 children in the placebo group.
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 335 329 260 255
Median (95% Confidence Interval)
Unit of Measure: score on a scale
Median Recall of Digits Forward Score Number Analyzed 298 participants 299 participants 236 participants 224 participants
84
(76 to 91)
84
(76 to 91)
91
(84 to 99)
74
(74 to 80)
Median Recognition of Pictures Score Number Analyzed 298 participants 302 participants 234 participants 226 participants
74
(74 to 80)
74
(74 to 80)
84
(84 to 91)
74
(74 to 80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Analysis for recall of digits forward
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-5 to 7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Analysis for recall of digits forward
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-8 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Analysis for Recognition of Pictures
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-6 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Analysis for Recognition of Pictures
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-4 to 0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Hide Description Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Results can also be expressed as percentile ranks relative to the standardization sample, with a mean and median of 50 and range from 1 to 99
Time Frame 12 and 24 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
For all outcomes except the primary outcome the potential follow-up cohort in the subclinical hypothyroidism groups consisted of 335 children in the levothyroxine group and 329 in the placebo group, and for the hypothyroxinema groups: 254 children in the levothryoxine group and 253 children in the placebo group.
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 323 326 254 253
Median (95% Confidence Interval)
Unit of Measure: score on a scale
Median 12 mo cognitive score Number Analyzed 311 participants 315 participants 247 participants 238 participants
100
(95 to 100)
100
(95 to 100)
100
(100 to 100)
100
(100 to 100)
Median 12 mo motor score Number Analyzed 312 participants 314 participants 246 participants 236 participants
97
(97 to 97)
97
(97 to 97)
97
(94 to 97)
97
(94 to 97)
Median 12 mo language score Number Analyzed 309 participants 312 participants 246 participants 237 participants
94
(94 to 97)
94
(94 to 97)
94
(91 to 94)
94
(91 to 94)
Median 24 mo cognitive score Number Analyzed 308 participants 302 participants 235 participants 235 participants
90
(90 to 90)
90
(90 to 90)
90
(85 to 90)
90
(85 to 90)
Median 24 mo motor score Number Analyzed 304 participants 300 participants 233 participants 232 participants
97
(97 to 97)
97
(97 to 100)
97
(94 to 100)
97
(94 to 97)
Median 24 mo language score Number Analyzed 300 participants 296 participants 232 participants 229 participants
89
(89 to 91)
91
(89 to 94)
89
(89 to 94)
89
(89 to 94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley II Cognitive (12 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley II Motor (12 mo)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.83
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley-III Language (12 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 3
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Bayley-III Cognitive (24 months)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)
Hide Description Behavioral problems and social competencies at 36 and 60 months of age, as measured by the Child Behavior Checklist (CBCL). The CBCL is filled out by the caregiver. Each of the 100 questions indicates a behavior for which the caregiver scores as Not True (0), Sometimes True (1), or Often True (2). The scores for all the questions are then summed and evaluated against the normative data/T-scores. A Tscore of less than 60 is considered to be in the normal range. A T score of 60-63 is a borderline, and a T score of more than 63 is in the clinical range. Lower scores represent better outcomes.
Time Frame 36 and 60 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
The potential follow-up cohort consisted of 335 children in the levothyroxine group and 329 in the placebo group for subclinical hypothyroidism and for hypothyroxinemia - 260 children in the levothyroxine group and 255 in the placebo group. A Child Behavior Checklist T score of less than 60 is considered to be in the normal range.
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 335 314 260 255
Median (95% Confidence Interval)
Unit of Measure: T-score
CBCL T score at 36 mo Number Analyzed 306 participants 309 participants 244 participants 237 participants
46
(45 to 48)
46
(45 to 48)
48
(46 to 50)
48
(45 to 49)
CBCL T score at 60 mo Number Analyzed 314 participants 313 participants 244 participants 243 participants
44
(43 to 46)
44
(42 to 46)
45
(43 to 46)
43
(42 to 45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments CBCL at 36 months
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-2 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments CBCL at 60 months
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-2 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments CBCL at 36 months
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-2 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments CBCL at 60 months
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value -1
Confidence Interval (2-Sided) 95%
-3 to 1
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised
Hide Description The Conners' Rating Scales-Revised were used to assess attention deficit-hyperactivity disorder (ADHD). A T score of 45 to 55 is considered to be typical or average; a T score of 44 or less is not a concern, a T score of 56 to 60 is considered to be a borderline score, and a T score of 61 or higher indicates a possible or clinically significant problem.
Time Frame 48 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 302 303 238 228
Median (95% Confidence Interval)
Unit of Measure: T-score
48
(47 to 49)
49
(47 to 51)
50
(49 to 51)
49
(48 to 51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-1 to 2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann
Estimated Value 0
Confidence Interval (2-Sided) 95%
-2 to 2
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Participants With Placental Abruption
Hide Description Clinically significant placental abruption will be determined by centralized (blinded) chart review
Time Frame Duration of pregnancy, delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.3%
5
   1.5%
3
   1.1%
2
   0.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Participants With Gestational Hypertension
Hide Description Gestational hypertension defined as patient having a diastolic ≥ 90 during pregnancy without proteinuria
Time Frame During pregnancy and until delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
33
   9.7%
36
  10.7%
20
   7.6%
24
   9.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
12.Secondary Outcome
Title Participants With Preeclampsia
Hide Description Preeclampsia defined as patient having a diastolic ≥ 90 during pregnancy with at least 1 + proteinuria. Preeclampsia will also include HELLP syndrome or eclampsia.
Time Frame Duration of pregnancy, Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
22
   6.5%
20
   5.9%
9
   3.4%
11
   4.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
13.Secondary Outcome
Title Gestational Diabetes Mellitus
Hide Description A patient is considered to have gestational diabetes if clinically diagnosed with class A1 or A2
Time Frame During pregnancy until delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
25
   7.4%
22
   6.5%
21
   8.0%
24
   9.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
14.Secondary Outcome
Title Participants With Composite Neonatal Outcome
Hide Description The composite neonatal outcome was defined as periventricular leukomalacia, intraventricular hemorrhage of grade III or IV, necrotizing enterocolitis (stage ≥II), severe retinopathy of prematurity (stage ≥III), the severe respiratory distress syndrome, bronchopulmonary dysplasia, neonatal death, stillbirth, or serious infectious complication.
Time Frame Within 72 hours of delivery.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
7
   2.1%
12
   3.6%
5
   1.9%
7
   2.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
15.Secondary Outcome
Title Participants Who Experienced a Stillbirth or Miscarriage
Hide Description Stillbirth or miscarriage.
Time Frame Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
4
   1.2%
7
   2.1%
2
   0.8%
5
   1.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
16.Secondary Outcome
Title Number of Neonatal Deaths
Hide Description Fetal and neonatal death
Time Frame Through 72 hours post delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   0.3%
1
   0.4%
1
   0.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
17.Secondary Outcome
Title Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes
Hide Description Apgar score < 4 at 1 minute and < 7 at 5 minutes
Time Frame 1 minute and 5 minutes post delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
Apgar < 4 at 1 minute
6
   1.8%
7
   2.1%
6
   2.3%
7
   2.7%
Apgar < 7 at 5 minutes
2
   0.6%
3
   0.9%
2
   0.8%
4
   1.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Apgar at 1 min < 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Apgar > 4 at 1 minute
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments Apgar < 7 at 5 minutes
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments Apgar < 7 at 5 minutes
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
18.Secondary Outcome
Title Number of Infants Admitted to NICU
Hide Description Admission to NICU
Time Frame Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
29
   8.6%
21
   6.2%
31
  11.8%
31
  11.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
19.Secondary Outcome
Title Infants With Birth Weight < 10th Percentile (Gestational Age z Score)
Hide Description Birth weight < 10th percentile (gestational age z score)
Time Frame Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
33
   9.7%
27
   8.0%
23
   8.7%
20
   7.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
20.Secondary Outcome
Title Neonatal Head Circumference (Centimeters)
Hide Description Neonatal head circumference measured within 24 hours of birth. This measurement is included based on a report showing that maternal treatment with thyroxine for overt hypothyroidism was associated with reduced head circumference in the newborn infant
Time Frame Within 24 hours of birth
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Mean (Standard Deviation)
Unit of Measure: centimeters
33.9  (1.8) 33.9  (1.7) 33.9  (1.8) 34.2  (1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
21.Secondary Outcome
Title Number of Infants With Respiratory Distress Syndrome
Hide Description Respiratory distress syndrome (RDS) will be defined based on a clinical diagnosis of RDS Type I and oxygen therapy (FiO2 ≥ 0.40) for greater than or equal to 24 hours. For infants dying before 24 hours of age, a clinical diagnosis of RDS Type I and oxygen therapy (FiO2 ≥ 0.40) are sufficient.
Time Frame Delivery and greater than or equal to 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
9
   2.7%
6
   1.8%
4
   1.5%
5
   1.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
22.Secondary Outcome
Title Number of Infants With Retinopathy or Prematurity
Hide Description This diagnosis will be reached when an ophthalmologic examination of the retina has been performed and ROP is diagnosed at Stage I (demarcation line in the retina) or greater
Time Frame Through 72 hours of birth
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
23.Secondary Outcome
Title Number of Infants With Necrotizing Enterocolitis
Hide Description Necrotizing enterocolitis (NEC) is defined by the following: the unequivocal presence of intramural air on abdominal x-ray, perforation seen on abdominal x-ray, clinical evidence as suggested by erythema and induration of the abdominal wall, or intra-abdominal abscess formation, or stricture formation observed at surgery or autopsy following an episode of suspected NEC. The condition is classified based on the Bell staging system
Time Frame Delivery within 2 weeks of birth
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.3%
1
   0.3%
2
   0.8%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
24.Secondary Outcome
Title Number of Infants With Bronchopulmonary Dysplasia
Hide Description Bronchopulmonary dysplasia (BPD) is defined as the need for supplemental oxygen at 36 weeks corrected age, for babies born <34 weeks by project gestational age only
Time Frame Through 72 hours post delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   0.3%
0
   0.0%
1
   0.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
25.Secondary Outcome
Title Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day
Hide Description oxygen therapy (FiO2 ≥ 0.40) for greater than or equal to 24 hours
Time Frame 72 hours post delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Measure Type: Count of Participants
Unit of Measure: Participants
11
   3.2%
11
   3.3%
13
   4.9%
12
   4.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
26.Secondary Outcome
Title Number of Days in the Hospital Nursery
Hide Description Median number of days in the hospital nursery
Time Frame Through hospital discharge
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinical Hypothyroidism Levothyroxine for Hypothyroxinemia Placebo for Levothyroxine - Hypothyroxinemia
Hide Arm/Group Description:

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Subclinical Hypothyroidism

Levothyroxine

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for the Hypothyroxinemia
Overall Number of Participants Analyzed 339 338 263 261
Median (95% Confidence Interval)
Unit of Measure: days
2
(2 to 2)
2
(2 to 2)
2
(2 to 2)
2
(2 to 2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Subclinical Hypothyroidism, Placebo for Levothyroxine - Subclinical Hypothyroidism
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levothyroxine for Hypothyroxinemia, Placebo for Levothyroxine - Hypothyroxinemia
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
Adverse Event Reporting Description The at-risk population for non-serious adverse events (side effects) was based on patients who had been seen for a least one study visit where side effect information was assessed, so the at-risk population for side effects varies from the total number of patients randomized and assessed for serious adverse events.
 
Arm/Group Title Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinincal Hypothyroidism Levothyroxine for Hypothyroxinemia - Hypothyroxinemia Placebo for Levothyroxine
Hide Arm/Group Description

100 µg of Levothryoxine for participants with subclinical hypothyroidism

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for participants with subclinical hypothyroidism

Placebo for Levothyroxine

50 µg of Levothyroxine for participants with hypothyroxinemia

Levothyroxine: Coded study drug is thyroxine encapsulated in a gel capsule; matching placebo contains only cellulose. Color of capsule corresponds to mcg dose level (100mcg or 25 mcg). Subjects in subclinical hypothyroidism stratum are started on 1 capsule of 100 mcg per day; subjects in hypothyroxinemia stratum are started on 2 capsules of 25 mcg per day. Thyroxine dosing adjustments for both strata are determined centrally, using an algorithm, based on results of monthly TSH or free-T4 assays. Subjects take study medication until delivery.

Placebo for Levothyroxine for participants with hypothyroxinemia

Placebo for Levothyroxine

All-Cause Mortality
Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinincal Hypothyroidism Levothyroxine for Hypothyroxinemia - Hypothyroxinemia Placebo for Levothyroxine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinincal Hypothyroidism Levothyroxine for Hypothyroxinemia - Hypothyroxinemia Placebo for Levothyroxine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/339 (1.18%)      2/338 (0.59%)      3/265 (1.13%)      2/261 (0.77%)    
Blood and lymphatic system disorders         
Thrombocytopenia *  0/339 (0.00%)  0 0/338 (0.00%)  0 0/265 (0.00%)  0 1/261 (0.38%)  1
Cardiac disorders         
Maternal atrial fibrillation *  0/339 (0.00%)  0 0/338 (0.00%)  0 1/265 (0.38%)  1 0/261 (0.00%)  0
Ear and labyrinth disorders         
Neonatal Severe Hearing Loss *  1/339 (0.29%)  1 0/338 (0.00%)  0 0/265 (0.00%)  0 0/261 (0.00%)  0
Endocrine disorders         
Hashimoto's thryoiditis *  0/339 (0.00%)  0 1/338 (0.30%)  1 0/265 (0.00%)  0 0/261 (0.00%)  0
General disorders         
Maternal death * [1]  0/339 (0.00%)  0 0/338 (0.00%)  0 1/265 (0.38%)  1 0/261 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Chest/abdominal pain *  1/339 (0.29%)  1 0/338 (0.00%)  0 0/265 (0.00%)  0 0/261 (0.00%)  0
Irregular fetal heart rate *  1/339 (0.29%)  1 0/338 (0.00%)  0 0/265 (0.00%)  0 0/261 (0.00%)  0
IUGR, non-reassuring * [2]  0/339 (0.00%)  0 1/338 (0.30%)  1 0/265 (0.00%)  0 0/261 (0.00%)  0
Abnormal Doppler *  0/339 (0.00%)  0 0/338 (0.00%)  0 1/265 (0.38%)  1 0/261 (0.00%)  0
Neonatal Hypoxic-Ischemic Encephalopathy * [3]  0/339 (0.00%)  0 0/338 (0.00%)  0 0/265 (0.00%)  0 1/261 (0.38%)  1
Psychiatric disorders         
Autism Spectrum Disorder *  1/339 (0.29%)  1 0/338 (0.00%)  0 0/265 (0.00%)  0 0/261 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Maternal death at 2 years postpartum
[2]
Non-reassuring Intrauterine Growth Restriction
[3]
Hypoxic-Ischemic Encephalopathy
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Levothyroxine for Subclinical Hypothyroidism Placebo for Levothyroxine - Subclinincal Hypothyroidism Levothyroxine for Hypothyroxinemia - Hypothyroxinemia Placebo for Levothyroxine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/338 (15.09%)      41/336 (12.20%)      25/261 (9.58%)      34/259 (13.13%)    
Gastrointestinal disorders         
Vomiting/Nausea * [1]  18/338 (5.33%)  8/336 (2.38%)  10/261 (3.83%)  15/259 (5.79%) 
General disorders         
Nervousness * [1]  4/338 (1.18%)  3/336 (0.89%)  2/261 (0.77%)  2/259 (0.77%) 
Fatigue * [1]  4/338 (1.18%)  4/336 (1.19%)  4/261 (1.53%)  5/259 (1.93%) 
Headaches * [1]  10/338 (2.96%)  8/336 (2.38%)  3/261 (1.15%)  4/259 (1.54%) 
Other side effects * [2]  18/338 (5.33%)  13/336 (3.87%)  4/261 (1.53%)  10/259 (3.86%) 
Respiratory, thoracic and mediastinal disorders         
shortness of breath * [1]  3/338 (0.89%)  5/336 (1.49%)  2/261 (0.77%)  2/259 (0.77%) 
*
Indicates events were collected by non-systematic assessment
[1]
Participant reported side effect
[2]
Participant reported side effects including allergic reaction.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Elizabeth Thom, Ph.D.
Organization: The George Washington University Biostatistics Center
Phone: 301-881-9260
EMail: e_thom@bsc.gwu.edu
Layout table for additonal information
Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT00388297    
Other Study ID Numbers: HD36801-TSH
U10HD021410 ( U.S. NIH Grant/Contract )
U10HD027869 ( U.S. NIH Grant/Contract )
U10HD027917 ( U.S. NIH Grant/Contract )
U10HD027860 ( U.S. NIH Grant/Contract )
U10HD027915 ( U.S. NIH Grant/Contract )
U10HD034116 ( U.S. NIH Grant/Contract )
U10HD034208 ( U.S. NIH Grant/Contract )
U10HD034136 ( U.S. NIH Grant/Contract )
U10HD040500 ( U.S. NIH Grant/Contract )
U10HD040485 ( U.S. NIH Grant/Contract )
U10HD040544 ( U.S. NIH Grant/Contract )
U10HD040545 ( U.S. NIH Grant/Contract )
U10HD040560 ( U.S. NIH Grant/Contract )
U10HD040512 ( U.S. NIH Grant/Contract )
U10HD036801 ( U.S. NIH Grant/Contract )
U10HD053118 ( U.S. NIH Grant/Contract )
First Submitted: October 12, 2006
First Posted: October 16, 2006
Results First Submitted: October 24, 2018
Results First Posted: January 30, 2019
Last Update Posted: February 21, 2019