Trial Outcomes & Findings for Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy (NCT NCT00388297)
NCT ID: NCT00388297
Last Updated: 2019-02-21
Results Overview
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+
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1203 participants
Primary outcome timeframe
60 months of age
Results posted on
2019-02-21
Participant Flow
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.
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.
Participant milestones
| Measure |
Levothyroxine for 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 - Subclinical Hypothyroidism
Placebo for Levothyroxine for the Subclinical Hypothyroidism group
|
Levothyroxine for Hypothyroxinemia
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 Hypothyroxinemia
Placebo for Levothyroxine for the Hypothyroxinemia group
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
339
|
338
|
265
|
261
|
|
Overall Study
COMPLETED
|
323
|
326
|
254
|
253
|
|
Overall Study
NOT COMPLETED
|
16
|
12
|
11
|
8
|
Reasons for withdrawal
| Measure |
Levothyroxine for 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 - Subclinical Hypothyroidism
Placebo for Levothyroxine for the Subclinical Hypothyroidism group
|
Levothyroxine for Hypothyroxinemia
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 Hypothyroxinemia
Placebo for Levothyroxine for the Hypothyroxinemia group
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
16
|
12
|
11
|
8
|
Baseline Characteristics
Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy
Baseline characteristics by cohort
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=265 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
Total
n=1203 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
27.7 years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
27.3 years
STANDARD_DEVIATION 5.7 • n=7 Participants
|
27.8 years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
28.0 years
STANDARD_DEVIATION 5.8 • n=4 Participants
|
27.7 years
STANDARD_DEVIATION 5.7 • n=21 Participants
|
|
Sex: Female, Male
Female
|
339 Participants
n=5 Participants
|
338 Participants
n=7 Participants
|
265 Participants
n=5 Participants
|
261 Participants
n=4 Participants
|
1203 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
27 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
178 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
195 Participants
n=5 Participants
|
185 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
125 Participants
n=4 Participants
|
636 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
109 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
364 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
339 Participants
n=5 Participants
|
338 Participants
n=7 Participants
|
265 Participants
n=5 Participants
|
261 Participants
n=4 Participants
|
1203 Participants
n=21 Participants
|
|
Body-mass index
|
28.1 kg/m^2
STANDARD_DEVIATION 6.4 • n=5 Participants
|
28.2 kg/m^2
STANDARD_DEVIATION 6.4 • n=7 Participants
|
30.3 kg/m^2
STANDARD_DEVIATION 6.4 • n=5 Participants
|
30.2 kg/m^2
STANDARD_DEVIATION 7.1 • n=4 Participants
|
29.0 kg/m^2
STANDARD_DEVIATION 6.6 • n=21 Participants
|
|
Nulliparous
|
124 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
64 Participants
n=4 Participants
|
391 Participants
n=21 Participants
|
|
Baseline thyrotropin (mU/liter) Median
|
4.5 mU/liter
n=5 Participants
|
4.3 mU/liter
n=7 Participants
|
1.5 mU/liter
n=5 Participants
|
1.4 mU/liter
n=4 Participants
|
3.4 mU/liter
n=21 Participants
|
|
Baseline free thyroxine (ng/dl Median
|
1.01 ng/dl
n=5 Participants
|
1.02 ng/dl
n=7 Participants
|
0.83 ng/dl
n=5 Participants
|
0.83 ng/dl
n=4 Participants
|
0.90 ng/dl
n=21 Participants
|
|
Urinary iodine (µg/liter) Median
|
199 µg/liter
n=5 Participants
|
196 µg/liter
n=7 Participants
|
185 µg/liter
n=5 Participants
|
191 µg/liter
n=4 Participants
|
194 µg/liter
n=21 Participants
|
|
Weeks Gestation at Randomization
|
16.6 Weeks
STANDARD_DEVIATION 3.0 • n=5 Participants
|
16.7 Weeks
STANDARD_DEVIATION 3.0 • n=7 Participants
|
18.0 Weeks
STANDARD_DEVIATION 2.8 • n=5 Participants
|
17.7 Weeks
STANDARD_DEVIATION 2.9 • n=4 Participants
|
17.2 Weeks
STANDARD_DEVIATION 3.0 • n=21 Participants
|
PRIMARY outcome
Timeframe: 60 months of ageThe 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+
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=323 Participants
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 - Subclinical Hypothyroidism
n=326 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=254 Participants
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 - Hypothyroxinemia
n=253 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
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.
|
97 score on a scale
Interval 94.0 to 99.0
|
94 score on a scale
Interval 92.0 to 96.0
|
94 score on a scale
Interval 91.0 to 95.0
|
91 score on a scale
Interval 89.0 to 93.0
|
SECONDARY outcome
Timeframe: DeliveryGestational age at delivery and preterm birth \< 37 weeks' gestation or \< 34 weeks' gestation
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Week of Gestation at Delivery
|
39.1 weeks
Standard Deviation 2.5
|
38.9 weeks
Standard Deviation 3.1
|
39.0 weeks
Standard Deviation 2.4
|
38.8 weeks
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: DeliveryPreterm delivery at less than 37 weeks or less than 34 weeks gestation
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Participants With Preterm Delivery
Preterm birth < 34 wk
|
9 Participants
|
10 Participants
|
10 Participants
|
7 Participants
|
|
Number of Participants With Preterm Delivery
Preterm birth < 37 wk
|
31 Participants
|
37 Participants
|
31 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: 60 monthsStandardized 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.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=311 Participants
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 - Subclinical Hypothyroidism
n=314 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=243 Participants
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 - Hypothyroxinemia
n=243 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)
|
97 score on a scale
Interval 95.0 to 99.0
|
95 score on a scale
Interval 93.0 to 97.0
|
94 score on a scale
Interval 91.0 to 95.0
|
92 score on a scale
Interval 90.0 to 95.0
|
SECONDARY outcome
Timeframe: 36 monthsOverall 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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=304 Participants
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 - Subclinical Hypothyroidism
n=308 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=244 Participants
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 - Hypothyroxinemia
n=235 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
|
90 score on a scale
Interval 88.0 to 93.0
|
90 score on a scale
Interval 87.0 to 93.0
|
90 score on a scale
Interval 87.0 to 92.0
|
89 score on a scale
Interval 87.0 to 91.0
|
SECONDARY outcome
Timeframe: 48 months of agePopulation: 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.
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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=335 Participants
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 - Subclinical Hypothyroidism
n=329 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=260 Participants
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 - Hypothyroxinemia
n=255 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
Median Recall of Digits Forward Score
|
84 score on a scale
Interval 76.0 to 91.0
|
84 score on a scale
Interval 76.0 to 91.0
|
91 score on a scale
Interval 84.0 to 99.0
|
74 score on a scale
Interval 74.0 to 80.0
|
|
Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
Median Recognition of Pictures Score
|
74 score on a scale
Interval 74.0 to 80.0
|
74 score on a scale
Interval 74.0 to 80.0
|
84 score on a scale
Interval 84.0 to 91.0
|
74 score on a scale
Interval 74.0 to 80.0
|
SECONDARY outcome
Timeframe: 12 and 24 months of agePopulation: 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.
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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=323 Participants
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 - Subclinical Hypothyroidism
n=326 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=254 Participants
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 - Hypothyroxinemia
n=253 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 12 mo cognitive score
|
100 score on a scale
Interval 95.0 to 100.0
|
100 score on a scale
Interval 95.0 to 100.0
|
100 score on a scale
Interval 100.0 to 100.0
|
100 score on a scale
Interval 100.0 to 100.0
|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 12 mo motor score
|
97 score on a scale
Interval 97.0 to 97.0
|
97 score on a scale
Interval 97.0 to 97.0
|
97 score on a scale
Interval 94.0 to 97.0
|
97 score on a scale
Interval 94.0 to 97.0
|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 12 mo language score
|
94 score on a scale
Interval 94.0 to 97.0
|
94 score on a scale
Interval 94.0 to 97.0
|
94 score on a scale
Interval 91.0 to 94.0
|
94 score on a scale
Interval 91.0 to 94.0
|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 24 mo cognitive score
|
90 score on a scale
Interval 90.0 to 90.0
|
90 score on a scale
Interval 90.0 to 90.0
|
90 score on a scale
Interval 85.0 to 90.0
|
90 score on a scale
Interval 85.0 to 90.0
|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 24 mo motor score
|
97 score on a scale
Interval 97.0 to 97.0
|
97 score on a scale
Interval 97.0 to 100.0
|
97 score on a scale
Interval 94.0 to 100.0
|
97 score on a scale
Interval 94.0 to 97.0
|
|
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Median 24 mo language score
|
89 score on a scale
Interval 89.0 to 91.0
|
91 score on a scale
Interval 89.0 to 94.0
|
89 score on a scale
Interval 89.0 to 94.0
|
89 score on a scale
Interval 89.0 to 94.0
|
SECONDARY outcome
Timeframe: 36 and 60 months of agePopulation: 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.
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.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=335 Participants
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 - Subclinical Hypothyroidism
n=314 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=260 Participants
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 - Hypothyroxinemia
n=255 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)
CBCL T score at 36 mo
|
46 T-score
Interval 45.0 to 48.0
|
46 T-score
Interval 45.0 to 48.0
|
48 T-score
Interval 46.0 to 50.0
|
48 T-score
Interval 45.0 to 49.0
|
|
Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)
CBCL T score at 60 mo
|
44 T-score
Interval 43.0 to 46.0
|
44 T-score
Interval 42.0 to 46.0
|
45 T-score
Interval 43.0 to 46.0
|
43 T-score
Interval 42.0 to 45.0
|
SECONDARY outcome
Timeframe: 48 months of ageThe 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.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=302 Participants
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 - Subclinical Hypothyroidism
n=303 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=238 Participants
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 - Hypothyroxinemia
n=228 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised
|
48 T-score
Interval 47.0 to 49.0
|
49 T-score
Interval 47.0 to 51.0
|
50 T-score
Interval 49.0 to 51.0
|
49 T-score
Interval 48.0 to 51.0
|
SECONDARY outcome
Timeframe: Duration of pregnancy, deliveryClinically significant placental abruption will be determined by centralized (blinded) chart review
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Participants With Placental Abruption
|
1 Participants
|
5 Participants
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: During pregnancy and until deliveryGestational hypertension defined as patient having a diastolic ≥ 90 during pregnancy without proteinuria
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Participants With Gestational Hypertension
|
33 Participants
|
36 Participants
|
20 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Duration of pregnancy, DeliveryPreeclampsia defined as patient having a diastolic ≥ 90 during pregnancy with at least 1 + proteinuria. Preeclampsia will also include HELLP syndrome or eclampsia.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Participants With Preeclampsia
|
22 Participants
|
20 Participants
|
9 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: During pregnancy until deliveryA patient is considered to have gestational diabetes if clinically diagnosed with class A1 or A2
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Gestational Diabetes Mellitus
|
25 Participants
|
22 Participants
|
21 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Within 72 hours of delivery.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.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Participants With Composite Neonatal Outcome
|
7 Participants
|
12 Participants
|
5 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: DeliveryStillbirth or miscarriage.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Participants Who Experienced a Stillbirth or Miscarriage
|
4 Participants
|
7 Participants
|
2 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Through 72 hours post deliveryFetal and neonatal death
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Neonatal Deaths
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 minute and 5 minutes post deliveryApgar score \< 4 at 1 minute and \< 7 at 5 minutes
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes
Apgar < 4 at 1 minute
|
6 Participants
|
7 Participants
|
6 Participants
|
7 Participants
|
|
Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes
Apgar < 7 at 5 minutes
|
2 Participants
|
3 Participants
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: DeliveryAdmission to NICU
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants Admitted to NICU
|
29 Participants
|
21 Participants
|
31 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: DeliveryBirth weight \< 10th percentile (gestational age z score)
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Infants With Birth Weight < 10th Percentile (Gestational Age z Score)
|
33 Participants
|
27 Participants
|
23 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Within 24 hours of birthNeonatal 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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Neonatal Head Circumference (Centimeters)
|
33.9 centimeters
Standard Deviation 1.8
|
33.9 centimeters
Standard Deviation 1.7
|
33.9 centimeters
Standard Deviation 1.8
|
34.2 centimeters
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Delivery and greater than or equal to 24 hoursRespiratory 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.
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Respiratory Distress Syndrome
|
9 Participants
|
6 Participants
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Through 72 hours of birthThis 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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Retinopathy or Prematurity
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Delivery within 2 weeks of birthNecrotizing 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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Necrotizing Enterocolitis
|
1 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Through 72 hours post deliveryBronchopulmonary 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
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Bronchopulmonary Dysplasia
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 72 hours post deliveryoxygen therapy (FiO2 ≥ 0.40) for greater than or equal to 24 hours
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day
|
11 Participants
|
11 Participants
|
13 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Through hospital dischargeMedian number of days in the hospital nursery
Outcome measures
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=339 Participants
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 - Subclinical Hypothyroidism
n=338 Participants
Placebo for Levothyroxine for the Subclinical Hypothyroidism
|
Levothyroxine for Hypothyroxinemia
n=263 Participants
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 - Hypothyroxinemia
n=261 Participants
Placebo for Levothyroxine for the Hypothyroxinemia
|
|---|---|---|---|---|
|
Number of Days in the Hospital Nursery
|
2 days
Interval 2.0 to 2.0
|
2 days
Interval 2.0 to 2.0
|
2 days
Interval 2.0 to 2.0
|
2 days
Interval 2.0 to 2.0
|
Adverse Events
Levothyroxine for Subclinical Hypothyroidism
Serious events: 4 serious events
Other events: 51 other events
Deaths: 0 deaths
Placebo for Levothyroxine - Subclinincal Hypothyroidism
Serious events: 2 serious events
Other events: 41 other events
Deaths: 0 deaths
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia
Serious events: 3 serious events
Other events: 25 other events
Deaths: 0 deaths
Placebo for Levothyroxine
Serious events: 2 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=338 participants at risk；n=339 participants at risk
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 - Subclinincal Hypothyroidism
n=336 participants at risk；n=338 participants at risk
Placebo for Levothyroxine for participants with subclinical hypothyroidism
Placebo for Levothyroxine
|
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia
n=261 participants at risk；n=265 participants at risk
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
n=259 participants at risk；n=261 participants at risk
Placebo for Levothyroxine for participants with hypothyroxinemia
Placebo for Levothyroxine
|
|---|---|---|---|---|
|
Cardiac disorders
Maternal atrial fibrillation
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.38%
1/265 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Endocrine disorders
Hashimoto's thryoiditis
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.30%
1/338 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Pregnancy, puerperium and perinatal conditions
Chest/abdominal pain
|
0.29%
1/339 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
General disorders
Maternal death
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.38%
1/265 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Pregnancy, puerperium and perinatal conditions
Irregular fetal heart rate
|
0.29%
1/339 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Pregnancy, puerperium and perinatal conditions
IUGR, non-reassuring
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.30%
1/338 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Pregnancy, puerperium and perinatal conditions
Abnormal Doppler
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.38%
1/265 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Pregnancy, puerperium and perinatal conditions
Neonatal Hypoxic-Ischemic Encephalopathy
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.38%
1/261 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Psychiatric disorders
Autism Spectrum Disorder
|
0.29%
1/339 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/339 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.38%
1/261 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Ear and labyrinth disorders
Neonatal Severe Hearing Loss
|
0.29%
1/339 • Number of events 1 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/265 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.00%
0/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
Other adverse events
| Measure |
Levothyroxine for Subclinical Hypothyroidism
n=338 participants at risk；n=339 participants at risk
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 - Subclinincal Hypothyroidism
n=336 participants at risk；n=338 participants at risk
Placebo for Levothyroxine for participants with subclinical hypothyroidism
Placebo for Levothyroxine
|
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia
n=261 participants at risk；n=265 participants at risk
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
n=259 participants at risk；n=261 participants at risk
Placebo for Levothyroxine for participants with hypothyroxinemia
Placebo for Levothyroxine
|
|---|---|---|---|---|
|
General disorders
Nervousness
|
1.2%
4/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.89%
3/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.77%
2/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.77%
2/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
General disorders
Fatigue
|
1.2%
4/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.2%
4/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.5%
4/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.9%
5/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
General disorders
Headaches
|
3.0%
10/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
2.4%
8/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.1%
3/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.5%
4/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
General disorders
Other side effects
|
5.3%
18/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
3.9%
13/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.5%
4/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
3.9%
10/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Gastrointestinal disorders
Vomiting/Nausea
|
5.3%
18/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
2.4%
8/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
3.8%
10/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
5.8%
15/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
|
Respiratory, thoracic and mediastinal disorders
shortness of breath
|
0.89%
3/338 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
1.5%
5/336 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.77%
2/261 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
0.77%
2/259 • Data on adverse events was collected for each participant beginning with enrollment through the final 5-year follow-up with the mother and child.
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.
|
Additional Information
Elizabeth Thom, Ph.D.
The George Washington University Biostatistics Center
Phone: 301-881-9260
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place