Subclinical HypothyroidismPhase 3TSHNCT00388297
Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy
A Phase 3 study testing Levothyroxine in people with Subclinical Hypothyroidism and Hypothyroxinemia, run by The George Washington University Biostatistics Center at 14 sites in United States.
Trial summary
The purpose of this study is to determine whether treating women, who are diagnosed with a mild imbalance of thyroid hormones during pregnancy, with thyroid hormone replacement affects their children's intellectual development at 5 years of age. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Subclinical Hypothyroidism, Hypothyroxinemia, Pregnancy
- What is being tested?
- Levothyroxine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,203 participants
- Where
- 14 sitesUnited States
- Study dates
- Oct 2006to Oct 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Subclinical Hypothyroidism as defined by an elevated TSH (≥ 3.00 mU/L) and a free-T4 in the normal range (i.e. 0.86 to 1.90 ng/dL) or Hypothyroxinemia as defined by a TSH in the normal range (0.08 to 2.99 micrometers (mU)/L) and a low free-T4 (<0.86 ng/dL)
- Singleton Pregnancy
- Gestational age at randomization between 8 weeks 0 days and 20 weeks 6 days
Who cannot join
- Major fetal anomaly or demise
- Planned termination of the pregnancy
- History of thyroid cancer or current thyroid disease requiring medication
- Diabetes, on medication (insulin, glyburide)
- Collagen vascular disease (autoimmune disease), such as lupus, scleroderma and polymyalgia rheumatica, on medication
- Receiving anticoagulant therapy
Show all 18Show fewer
- Depression, currently on treatment with tricyclics or selective serotonin reuptake inhibitors (SSRIs)
- Other known serious maternal medical complications including:
- Chronic hypertension requiring antihypertensive medication (including diuretics)
- Epilepsy or other seizure disorder, on medication
- Active or chronic liver disease (acute hepatitis, chronic active hepatitis) with persistently abnormal liver enzymes
- Cancer (including melanoma but excluding other skin cancers)
- Heart disease (tachyrhythmia, class II or greater heart disease or on heart medication). Mitral valve prolapse without arrhythmia is not an exclusion.
- Asthma, on oral corticosteroids
- Known illicit drug or alcohol abuse during current pregnancy
- Delivery at a non-network hospital
- Participation in another intervention study that influences maternal and fetal morbidity and mortality, or participation in this trial in a previous pregnancy
- Unwilling or unable to commit to 5 year follow-up of the infant
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Alabama - Birmingham
Birmingham, Alabama, 35249
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Case Western University
Cleveland, Ohio, 44109
Ohio State University
Columbus, Ohio, 43210
University of Texas - Southwest
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
University of Texas Medical Branch - Galveston
Galveston, Texas, 77555
University of Texas-Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
Oregon Health & Sciences University
Portland, Oregon, 97239
Brown University
Providence, Rhode Island, 02905
University of Utah Medical Center
Salt Lake City, Utah, 84132
About this study
Official title: A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy
The purpose of this study is to determine whether treating women, who are diagnosed with a mild imbalance of thyroid hormones during pregnancy, with thyroid hormone replacement affects their children's intellectual development at 5 years of age.
Read the detailed description
Published research reports have stimulated national and international controversy regarding the value of maternal thyroxine therapy given to improve neurodevelopment of the fetus in women with variously defined hypothyroidism. These reports have led to conflicting and confusing recommendations as to whether or not all pregnant women in the U.S. should be screened for subclinical hypothyroidism or hypothyroxinemia.
Pregnant women less than 20 weeks gestation will have a blood test to screen for subclinical hypothyroidism or hypothyroxinemia. If eligible for the trial, patients will receive levothyroxine or placebo until delivery. Blood draws will be done at monthly study visits and the dosage will be adjusted based on test results. The children of these patients will have developmental testing done annually until they are 5 years of age.
Comparison(s): thyroxine supplementation versus placebo given during pregnancy to determine whether therapy is effective in improving intellectual ability at 5 years of age.
- Conditions
- Subclinical Hypothyroidism, Hypothyroxinemia, Pregnancy
- Being tested
- Levothyroxine, Placebo for Levothyroxine
- Keywords
- Subclinical Hypothyroidism, Hypothyroxinemia, Thyroid, Pregnancy, Intellectual Development
- Medical subject headings
- Thyroid Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
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 LevothyroxineDrug
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine for Subclinical Hypothyroidism | Experimental | 100 µg of Levothryoxine for participants with subclinical hypothyroidism Receives: Drug: Levothyroxine |
| Placebo for Levothyroxine - Subclinincal Hypothyroidism | Placebo comparator | Placebo for Levothyroxine for participants with subclinical hypothyroidism Receives: Drug: Placebo for Levothyroxine |
| Levothyroxine for Hypothyroxinemia - Hypothyroxinemia | Experimental | 50 µg of Levothyroxine for participants with hypothyroxinemia Receives: Drug: Levothyroxine |
| Placebo for Levothyroxine | Placebo comparator | Placebo for Levothyroxine for participants with hypothyroxinemia Receives: Drug: Placebo for Levothyroxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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+
Measured: 60 months of age
Secondary outcomes (25)
Week of Gestation at Delivery
Gestational age at delivery and preterm birth < 37 weeks' gestation or < 34 weeks' gestation
Measured: Delivery
Number of Participants With Preterm Delivery
Preterm delivery at less than 37 weeks or less than 34 weeks gestation
Measured: Delivery
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.
Measured: 60 months
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
Measured: 36 months
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
Measured: 48 months of age
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
Measured: 12 and 24 months of age
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.
Measured: 36 and 60 months of age
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.
Measured: 48 months of age
Participants With Placental Abruption
Clinically significant placental abruption will be determined by centralized (blinded) chart review
Measured: Duration of pregnancy, delivery
Participants With Gestational Hypertension
Gestational hypertension defined as patient having a diastolic ≥ 90 during pregnancy without proteinuria
Measured: During pregnancy and until delivery
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.
Measured: Duration of pregnancy, Delivery
Gestational Diabetes Mellitus
A patient is considered to have gestational diabetes if clinically diagnosed with class A1 or A2
Measured: During pregnancy until delivery
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.
Measured: Within 72 hours of delivery.
Participants Who Experienced a Stillbirth or Miscarriage
Stillbirth or miscarriage.
Measured: Delivery
Number of Neonatal Deaths
Fetal and neonatal death
Measured: Through 72 hours post delivery
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
Measured: 1 minute and 5 minutes post delivery
Number of Infants Admitted to NICU
Admission to NICU
Measured: Delivery
Infants With Birth Weight < 10th Percentile (Gestational Age z Score)
Birth weight < 10th percentile (gestational age z score)
Measured: Delivery
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
Measured: Within 24 hours of birth
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.
Measured: Delivery and greater than or equal to 24 hours
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
Measured: Through 72 hours of birth
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
Measured: Delivery within 2 weeks of birth
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
Measured: Through 72 hours post delivery
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
Measured: 72 hours post delivery
Number of Days in the Hospital Nursery
Median number of days in the hospital nursery
Measured: Through hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionAug 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Subclinical HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,203 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Washington University Biostatistics Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Brian Casey, MD, Study chair, University of Texas Southwestern Medical CenterMenachem Miodovnik, MD, Study director, NICHD Project Scientist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00388297
- Sponsor's protocol ID
- HD36801-TSH
- Other IDs
- U10HD021410, U10HD027869, U10HD027917, U10HD027860, U10HD027915, U10HD034116, U10HD034208, U10HD034136
- Acronym
- TSH
- Status last verified
- Feb 2019
- First submitted
- 12 Oct 2006
- Last updated
- 21 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The data will be shared after the completion of the trial and publication of the main analyses per NIH policy. When made available, requests for the dataset(s) can be sent to mfmudatasets@bsc.gwu.edu.
Publications
Theilen LH, Mele L, Peaceman AM, Reddy UM, Varner MW, Thorp JM Jr, Saade GR, Tita ATN, Rouse DJ, Sibai BM, Costantine MM, Caritis SN, Casey BM; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Thyroid Function Throughout Pregnancy in Women With Subclinical Hypothyroidism or Hypothyroxinemia. Obstet Gynecol. 2026 Sep 1;148(3):383-390. doi: 10.1097/AOG.0000000000006373. Epub 2026 Jul 27.
PubMed 42492995Smid 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.
PubMed 34856574Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.
PubMed 28249134
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy
- ClinicalTrials.gov ID
- NCT00388297
- Acronym / sponsor ID
- TSH / HD36801-TSH
- Conditions
- Subclinical Hypothyroidism, Hypothyroxinemia, Pregnancy
- Keywords
- Subclinical Hypothyroidism, Hypothyroxinemia, Thyroid, Pregnancy, Intellectual Development
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,203 participants (actual)
- Lead sponsor
- The George Washington University Biostatistics CenterUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Oct 2006
- Primary completion
- Aug 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 16 Oct 2006 (estimated)
- Results
- Posted 30 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether treating women, who are diagnosed with a mild imbalance of thyroid hormones during pregnancy, with thyroid hormone replacement affects their children's intellectual development at 5 years of age.
Detailed description
Published research reports have stimulated national and international controversy regarding the value of maternal thyroxine therapy given to improve neurodevelopment of the fetus in women with variously defined hypothyroidism. These reports have led to conflicting and confusing recommendations as to whether or not all pregnant women in the U.S. should be screened for subclinical hypothyroidism or hypothyroxinemia.
Pregnant women less than 20 weeks gestation will have a blood test to screen for subclinical hypothyroidism or hypothyroxinemia. If eligible for the trial, patients will receive levothyroxine or placebo until delivery. Blood draws will be done at monthly study visits and the dosage will be adjusted based on test results. The children of these patients will have developmental testing done annually until they are 5 years of age.
Comparison(s): thyroxine supplementation versus placebo given during pregnancy to determine whether therapy is effective in improving intellectual ability at 5 years of age.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine for Subclinical Hypothyroidism | Experimental | Drug: Levothyroxine100 µg of Levothryoxine for participants with subclinical hypothyroidism |
| Placebo for Levothyroxine - Subclinincal Hypothyroidism | Placebo comparator | Drug: Placebo for LevothyroxinePlacebo for Levothyroxine for participants with subclinical hypothyroidism |
| Levothyroxine for Hypothyroxinemia - Hypothyroxinemia | Experimental | Drug: Levothyroxine50 µg of Levothyroxine for participants with hypothyroxinemia |
| Placebo for Levothyroxine | Placebo comparator | Drug: Placebo for LevothyroxinePlacebo for Levothyroxine for participants with hypothyroxinemia |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Subclinical Hypothyroidism as defined by an elevated TSH (≥ 3.00 mU/L) and a free-T4 in the normal range (i.e. 0.86 to 1.90 ng/dL) or Hypothyroxinemia as defined by a TSH in the normal range (0.08 to 2.99 micrometers (mU)/L) and a low free-T4 (<0.86 ng/dL)
- Singleton Pregnancy
- Gestational age at randomization between 8 weeks 0 days and 20 weeks 6 days
Key exclusion criteria (18 listed)
- Major fetal anomaly or demise
- Planned termination of the pregnancy
- History of thyroid cancer or current thyroid disease requiring medication
- Diabetes, on medication (insulin, glyburide)
- Collagen vascular disease (autoimmune disease), such as lupus, scleroderma and polymyalgia rheumatica, on medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineCoded 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. | Drug | Levothyroxine for Hypothyroxinemia - Hypothyroxinemia, Levothyroxine for Subclinical Hypothyroidism |
| Placebo for Levothyroxine | Drug | Placebo for Levothyroxine, Placebo for Levothyroxine - Subclinincal Hypothyroidism |
Primary outcome
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.
Time frame: 60 months of age
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+
25 secondary outcomes
Week of Gestation at Delivery
Time frame: Delivery
Number of Participants With Preterm Delivery
Time frame: Delivery
Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)
Time frame: 60 months
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
Time frame: 36 months
Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
Time frame: 48 months of age
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Time frame: 12 and 24 months of age
Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)
Time frame: 36 and 60 months of age
Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised
Time frame: 48 months of age
Participants With Placental Abruption
Time frame: Duration of pregnancy, delivery
Participants With Gestational Hypertension
Time frame: During pregnancy and until delivery
Participants With Preeclampsia
Time frame: Duration of pregnancy, Delivery
Gestational Diabetes Mellitus
Time frame: During pregnancy until delivery
Participants With Composite Neonatal Outcome
Time frame: Within 72 hours of delivery.
Participants Who Experienced a Stillbirth or Miscarriage
Time frame: Delivery
Number of Neonatal Deaths
Time frame: Through 72 hours post delivery
Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes
Time frame: 1 minute and 5 minutes post delivery
Number of Infants Admitted to NICU
Time frame: Delivery
Infants With Birth Weight < 10th Percentile (Gestational Age z Score)
Time frame: Delivery
Neonatal Head Circumference (Centimeters)
Time frame: Within 24 hours of birth
Number of Infants With Respiratory Distress Syndrome
Time frame: Delivery and greater than or equal to 24 hours
Number of Infants With Retinopathy or Prematurity
Time frame: Through 72 hours of birth
Number of Infants With Necrotizing Enterocolitis
Time frame: Delivery within 2 weeks of birth
Number of Infants With Bronchopulmonary Dysplasia
Time frame: Through 72 hours post delivery
Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day
Time frame: 72 hours post delivery
Number of Days in the Hospital Nursery
Time frame: Through hospital discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42492995Theilen LH, Mele L, Peaceman AM, Reddy UM, Varner MW, Thorp JM Jr, Saade GR, Tita ATN, Rouse DJ, Sibai BM, Costantine MM, Caritis SN, Casey BM; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Thyroid Function Throughout Pregnancy in Women With Subclinical Hypothyroidism or Hypothyroxinemia. Obstet Gynecol. 2026 Sep 1;148(3):383-390. doi: 10.1097/AOG.0000000000006373. Epub 2026 Jul 27.
- Derived from this study: PubMed 34856574Smid 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.
- Derived from this study: PubMed 28249134Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.
- Click here for more information about this studyLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The data will be shared after the completion of the trial and publication of the main analyses per NIH policy. When made available, requests for the dataset(s) can be sent to mfmudatasets@bsc.gwu.edu.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Casey, MD study chair
University of Texas Southwestern Medical Center
Menachem Miodovnik, MD study director
NICHD Project Scientist
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levothyroxine in people with Subclinical Hypothyroidism and Hypothyroxinemia, run by The George Washington University Biostatistics Center at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 60 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00388297, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.