Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy | NCT00388297

ID	Type	Link
U10HD021410	U.S. NIH Grant/Contract	View source
U10HD027869	U.S. NIH Grant/Contract	View source
U10HD027917	U.S. NIH Grant/Contract	View source
U10HD027860	U.S. NIH Grant/Contract	View source
U10HD027915	U.S. NIH Grant/Contract	View source
U10HD034116	U.S. NIH Grant/Contract	View source
U10HD034208	U.S. NIH Grant/Contract	View source
U10HD034136	U.S. NIH Grant/Contract	View source
U10HD040500	U.S. NIH Grant/Contract	View source
U10HD040485	U.S. NIH Grant/Contract	View source
U10HD040544	U.S. NIH Grant/Contract	View source
U10HD040545	U.S. NIH Grant/Contract	View source
U10HD040560	U.S. NIH Grant/Contract	View source
U10HD040512	U.S. NIH Grant/Contract	View source
U10HD036801	U.S. NIH Grant/Contract	View source
U10HD053118	U.S. NIH Grant/Contract	View source

Name	Class
National Institute of Neurological Disorders and Stroke (NINDS)	NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	NIH

Label	Type	Description	Intervention Names
Levothyroxine for Subclinical Hypothyroidism	Experimental	100 µg of Levothryoxine for participants with subclinical hypothyroidism	Drug: Levothyroxine
Placebo for Levothyroxine - Subclinincal Hypothyroidism	Placebo Comparator	Placebo for Levothyroxine for participants with subclinical hypothyroidism	Drug: Placebo for Levothyroxine
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia	Experimental	50 µg of Levothyroxine for participants with hypothyroxinemia	Drug: Levothyroxine
Placebo for Levothyroxine	Placebo Comparator	Placebo for Levothyroxine for participants with hypothyroxinemia	Drug: Placebo for Levothyroxine

Name	Type	Description	Arm Group Labels	Other Names
Levothyroxine	Drug	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.

Measure	Description	Time Frame
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.	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+	60 months of age

Measure	Description	Time Frame
Week of Gestation at Delivery	Gestational age at delivery and preterm birth < 37 weeks' gestation or < 34 weeks' gestation	Delivery
Number of Participants With Preterm Delivery	Preterm delivery at less than 37 weeks or less than 34 weeks gestation

Name	Affiliation	Role
Brian Casey, MD	University of Texas Southwestern Medical Center	Study Chair
Menachem Miodovnik, MD	NICHD Project Scientist	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama - Birmingham		Birmingham	Alabama	35249	United States
Northwestern University

PubMed Identifier	Type	Citation	Retractions
34856574	Derived	Smid MC, Metz TD, McMillin GA, Mele L, Casey BM, Reddy UM, Wapner RJ, Thorp JM, Saade GR, Tita ATN, Miller ES, Rouse DJ, Sibai B, Costantine MM, Mercer BM, Caritis SN; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes. Obstet Gynecol. 2022 Jan 1;139(1):21-30. doi: 10.1097/AOG.0000000000004632.
28249134

Label	URL
Click here for more information about this study	View source

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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+

Posted

Median

95% Confidence Interval

score on a scale

60 months of age

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.
OG003	Placebo for Levothyroxine - Hypothyroxinemia	Placebo for Levothyroxine for the Hypothyroxinemia

Units	Counts
Participants	OG000323 OG001326 OG002254 OG003

Title

Denominators

Categories

Title	Measurements
	OG00097(94 to 99) OG00194(92 to 96) OG00294(91 to 95) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.71		Hodges-Lehmann estimate	0			2-Sided	95	-3	2					Superiority or Other
OG002 OG003		Wilcoxon (Mann-Whitney)		0.30

Secondary

Week of Gestation at Delivery

Gestational age at delivery and preterm birth < 37 weeks' gestation or < 34 weeks' gestation

Posted

Mean

Standard Deviation

weeks

Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Participants With Preterm Delivery

Preterm delivery at less than 37 weeks or less than 34 weeks gestation

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)

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

For Quotient and Composite score:

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

Posted

Median

95% Confidence Interval

score on a scale

60 months

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism

Secondary

Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)

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

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

≤ 69 Very low

Posted

Median

95% Confidence Interval

score on a scale

36 months

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)

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

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.

Posted

Median

95% Confidence Interval

score on a scale

48 months of age

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism

Secondary

Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition

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

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.

Posted

Median

95% Confidence Interval

score on a scale

12 and 24 months of age

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism

Secondary

Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)

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.

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.

Posted

Median

95% Confidence Interval

T-score

36 and 60 months of age

ID	Title	Description
OG000	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.

Secondary

Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised

The Conners' Rating Scales-Revised were used to assess attention deficit-hyperactivity disorder (ADHD). A T score of 45 to 55 is considered to be typical or average; a T score of 44 or less is not a concern, a T score of 56 to 60 is considered to be a borderline score, and a T score of 61 or higher indicates a possible or clinically significant problem.

Posted

Median

95% Confidence Interval

T-score

48 months of age

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	Levothyroxine for Hypothyroxinemia

Secondary

Participants With Placental Abruption

Clinically significant placental abruption will be determined by centralized (blinded) chart review

Posted

Count of Participants

Participants

Duration of pregnancy, delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Participants With Gestational Hypertension

Gestational hypertension defined as patient having a diastolic ≥ 90 during pregnancy without proteinuria

Posted

Count of Participants

Participants

During pregnancy and until delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Participants With Preeclampsia

Preeclampsia defined as patient having a diastolic ≥ 90 during pregnancy with at least 1 + proteinuria. Preeclampsia will also include HELLP syndrome or eclampsia.

Posted

Count of Participants

Participants

Duration of pregnancy, Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Gestational Diabetes Mellitus

A patient is considered to have gestational diabetes if clinically diagnosed with class A1 or A2

Posted

Count of Participants

Participants

During pregnancy until delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Participants With Composite Neonatal Outcome

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.

Posted

Count of Participants

Participants

Within 72 hours of delivery.

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	Levothyroxine for Hypothyroxinemia

Secondary

Participants Who Experienced a Stillbirth or Miscarriage

Stillbirth or miscarriage.

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Neonatal Deaths

Fetal and neonatal death

Posted

Count of Participants

Participants

Through 72 hours post delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes

Apgar score < 4 at 1 minute and < 7 at 5 minutes

Posted

Count of Participants

Participants

1 minute and 5 minutes post delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants Admitted to NICU

Admission to NICU

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Infants With Birth Weight < 10th Percentile (Gestational Age z Score)

Birth weight < 10th percentile (gestational age z score)

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Neonatal Head Circumference (Centimeters)

Neonatal head circumference measured within 24 hours of birth. This measurement is included based on a report showing that maternal treatment with thyroxine for overt hypothyroidism was associated with reduced head circumference in the newborn infant

Posted

Mean

Standard Deviation

centimeters

Within 24 hours of birth

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants With Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) will be defined based on a clinical diagnosis of RDS Type I and oxygen therapy (FiO2 ≥ 0.40) for greater than or equal to 24 hours. For infants dying before 24 hours of age, a clinical diagnosis of RDS Type I and oxygen therapy (FiO2 ≥ 0.40) are sufficient.

Posted

Count of Participants

Participants

Delivery and greater than or equal to 24 hours

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants With Retinopathy or Prematurity

This diagnosis will be reached when an ophthalmologic examination of the retina has been performed and ROP is diagnosed at Stage I (demarcation line in the retina) or greater

Posted

Count of Participants

Participants

Through 72 hours of birth

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants With Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is defined by the following: the unequivocal presence of intramural air on abdominal x-ray, perforation seen on abdominal x-ray, clinical evidence as suggested by erythema and induration of the abdominal wall, or intra-abdominal abscess formation, or stricture formation observed at surgery or autopsy following an episode of suspected NEC. The condition is classified based on the Bell staging system

Posted

Count of Participants

Participants

Delivery within 2 weeks of birth

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	Levothyroxine for Hypothyroxinemia

Secondary

Number of Infants With Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is defined as the need for supplemental oxygen at 36 weeks corrected age, for babies born <34 weeks by project gestational age only

Posted

Count of Participants

Participants

Through 72 hours post delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day

oxygen therapy (FiO2 ≥ 0.40) for greater than or equal to 24 hours

Posted

Count of Participants

Participants

72 hours post delivery

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

Secondary

Number of Days in the Hospital Nursery

Median number of days in the hospital nursery

Posted

Median

95% Confidence Interval

days

Through hospital discharge

ID	Title	Description
OG000	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.
OG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
OG002	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.

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Levothyroxine for Subclinical Hypothyroidism	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.	4	339	51	338
EG001	Placebo for Levothyroxine - Subclinincal Hypothyroidism	Placebo for Levothyroxine for participants with subclinical hypothyroidism Placebo for Levothyroxine	2	338	41	336
EG002	Levothyroxine for Hypothyroxinemia - Hypothyroxinemia	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.	3	265	25	261
EG003	Placebo for Levothyroxine	Placebo for Levothyroxine for participants with hypothyroxinemia Placebo for Levothyroxine	2	261	34	259

Term	Organ System	Assessment Type	Notes	Statistical Information
Maternal atrial fibrillation	Cardiac disorders	Non-systematic Assessment		EG0000 events0 affected339 at risk EG0010 events0 affected338 at risk EG0021 events1 affected265 at risk EG0030 events0 affected261 at risk
Hashimoto's thryoiditis	Endocrine disorders	Non-systematic Assessment		EG0000 events0 affected339 at risk EG0011 events1 affected338 at risk EG0020 events0 affected265 at risk EG003
Chest/abdominal pain	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment		EG0001 events1 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003
Maternal death	General disorders	Non-systematic Assessment	Maternal death at 2 years postpartum	EG0000 events0 affected339 at risk EG0010 events0 affected338 at risk EG0021 events1 affected265 at risk EG003
Irregular fetal heart rate	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment		EG0001 events1 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003
IUGR, non-reassuring	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Non-reassuring Intrauterine Growth Restriction	EG0000 events0 affected339 at risk EG0011 events1 affected338 at risk EG0020 events0 affected265 at risk EG003
Abnormal Doppler	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment		EG0000 events0 affected339 at risk EG0010 events0 affected338 at risk EG0021 events1 affected265 at risk EG003
Neonatal Hypoxic-Ischemic Encephalopathy	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Hypoxic-Ischemic Encephalopathy	EG0000 events0 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003
Autism Spectrum Disorder	Psychiatric disorders	Non-systematic Assessment		EG0001 events1 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment		EG0000 events0 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003
Neonatal Severe Hearing Loss	Ear and labyrinth disorders	Non-systematic Assessment		EG0001 events1 affected339 at risk EG0010 events0 affected338 at risk EG0020 events0 affected265 at risk EG003

Term	Organ System	Assessment Type	Notes	Statistical Information
Vomiting/Nausea	Gastrointestinal disorders	Non-systematic Assessment	Participant reported side effect	EG00018 affected338 at risk EG0018 affected336 at risk EG00210 affected261 at risk EG00315 affected259 at risk
shortness of breath	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	Participant reported side effect	EG0003 affected338 at risk EG0015 affected336 at risk EG0022 affected261 at risk EG003
Nervousness	General disorders	Non-systematic Assessment	Participant reported side effect	EG0004 affected338 at risk EG0013 affected336 at risk EG0022 affected261 at risk EG003
Fatigue	General disorders	Non-systematic Assessment	Participant reported side effect	EG0004 affected338 at risk EG0014 affected336 at risk EG0024 affected261 at risk EG003
Headaches	General disorders	Non-systematic Assessment	Participant reported side effect	EG00010 affected338 at risk EG0018 affected336 at risk EG0023 affected261 at risk EG003
Other side effects	General disorders	Non-systematic Assessment	Participant reported side effects including allergic reaction.	EG00018 affected338 at risk EG00113 affected336 at risk EG0024 affected261 at risk EG003

ID	Term
D013963	Thyroid Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	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.
BG001	Placebo for Levothyroxine - Subclinical Hypothyroidism	Placebo for Levothyroxine for the Subclinical Hypothyroidism
BG002	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.
BG003	Placebo for Levothyroxine - Hypothyroxinemia	Placebo for Levothyroxine for the Hypothyroxinemia
BG004	Total	Total of all reporting groups