A Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,203
- 试验地点
- 14
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Levothyroxine for Subclinical Hypothyroidism
100 µg of Levothryoxine for participants with subclinical hypothyroidism
干预措施: Levothyroxine (Drug)
Placebo for Levothyroxine - Subclinincal Hypothyroidism
Placebo for Levothyroxine for participants with subclinical hypothyroidism
干预措施: Placebo for Levothyroxine (Drug)
Levothyroxine for Hypothyroxinemia - Hypothyroxinemia
50 µg of Levothyroxine for participants with hypothyroxinemia
干预措施: Levothyroxine (Drug)
Placebo for Levothyroxine
Placebo for Levothyroxine for participants with hypothyroxinemia
干预措施: Placebo for Levothyroxine (Drug)
结局指标
主要结局
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.
时间窗: 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+
次要结局
- Number of Infants Admitted to NICU(Delivery)
- Number of Days in the Hospital Nursery(Through hospital discharge)
- Week of Gestation at Delivery(Delivery)
- Number of Participants With Preterm Delivery(Delivery)
- Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)(60 months)
- Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)(36 months)
- Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)(48 months of age)
- Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition(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)(36 and 60 months of age)
- Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised(48 months of age)
- Participants With Placental Abruption(Duration of pregnancy, delivery)
- Participants With Gestational Hypertension(During pregnancy and until delivery)
- Gestational Diabetes Mellitus(During pregnancy until delivery)
- Participants Who Experienced a Stillbirth or Miscarriage(Delivery)
- Number of Neonatal Deaths(Through 72 hours post delivery)
- Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes(1 minute and 5 minutes post delivery)
- Infants With Birth Weight < 10th Percentile (Gestational Age z Score)(Delivery)
- Number of Infants With Respiratory Distress Syndrome(Delivery and greater than or equal to 24 hours)
- Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day(72 hours post delivery)
- Participants With Preeclampsia(Duration of pregnancy, Delivery)
- Participants With Composite Neonatal Outcome(Within 72 hours of delivery.)
- Number of Infants With Retinopathy or Prematurity(Through 72 hours of birth)
- Number of Infants With Necrotizing Enterocolitis(Delivery within 2 weeks of birth)
- Number of Infants With Bronchopulmonary Dysplasia(Through 72 hours post delivery)
- Neonatal Head Circumference (Centimeters)(Within 24 hours of birth)