Pregnancy Outcomes, Pregnant Woman, Thyroid Abnormalities
Conditions
Keywords
TSH, TPOAb, pregnant women, levothyroxine, outcome
Brief summary
The goal of this clinical trial is to learn if levothyroxine (L-T4) works to treat pregnant women with TSH 2.5 mIU/L-the upper limit of reference range (ULRR) of pregnancy and TPOAb-negative. It will also learn about the safety of L-T4. The main quesitons the investigator want to answer are: * Will L-T4 reduce miscarriage rates and have an impact on pregnancy complications in pregnant participants? * What medical issues do participants have when taking L-T4 during pregnancy? -Investigators will compare L-T4 with placebo (a substance with a similar appearance without medication) to see if L-T4 could reduce miscarriage rates Participants should: * Take L-T4 or placebo during the whole pregnancy. * Visit the hospital once every 6-8 weeks during pregnancy for checkups and tests * Keep a diary of their pregncny complications and daily record of L-T4 or placebo intake. * Visit the hospital for examination 42 days postpartum for checkups and follow up by phone at 6 and 12 months postpartum.
Interventions
Participants in our study will determine the dosage of L-T4 based on their weight (BW): 1. BW ≥50kg: Starting with a daily dose of 1 tablet; 2. BW \< 50kg: Starting with a daily dose of half a tablet. At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH: 1. When TSH \> ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up; 2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion; 3. When TSH at LLRR -2.5mIU/L, maintain the original dose; 4. When TSH \<LLRR, reduce 1/4 tablets of medictaion. 5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.
DRUGPlacebo
Participants in our study will determine the dosage of placebo based on their weight (BW): 1. BW ≥50kg: Starting with a daily dose of 1 tablet; 2. BW \< 50kg: Starting with a daily dose of half a tablet. At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH: 1. When TSH \> ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up; 2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion; 3. When TSH at LLRR -2.5mIU/L, maintain the original dose; 4. When TSH \<LLRR, reduce 1/4 tablets of medictaion. 5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.
Sponsors
National Research Institute for Family Planning, China
The Fourth Hospital of Shijiazhuang
Yang ZHANG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Women of childbearing age（18-45 years old）, natural pregnancy, singleton pregnancy. 2. Measure thyroid related indexes within 8 weeks of pregnancy: TSH 2.5mIU/L-ULRR, FT4 is normal and TPOAb negativity. 3. Willing to sign an informed consent form.
Exclusion criteria
1. History of recurrent miscarriage (≥3 times). 2. Assisted reproduction (artificial insemination, in vitro fertilization and embryo transfer); 3. Suffer from diseases that seriously affect pregnancy outcome, including hypertension, diabetes, heart disease, liver and kidney dysfunction, etc. 4. Failure of vital organs. 5. Except autoimmune thyroid disease，suffer from other autoimmune diseases. 6. Thyroid diseases (including hyperthyroidism, thyroid cancer, thyroid amyloidosis and other extensive intrathyroidal diseases, current subacute thyroiditis, iodine-deficiency endemic goiter, thyroidectomy or 131I treatment, previous thyroid Ultrasound prompts diffuse thyroid disease, etc.). 7. Use of thyroid-related drugs (lithium carbonate, thioureas, sulfonamides, sodium para-amino salicylate, potassium perchlorate, phenylbutazone, sulfate, tyrosine kinase inhibitor, etc.) during screening and affect thyroid Functional testing drugs. (Including glucocorticoids, metoclopramide, propranolol, amiodarone, sodium valproate, etc.) 8. Secondary hypothyroidism or central hypothyroidism. (Including pituitary tumors, surgery, radiotherapy, lymphocytic hypophysitis, etc.) 9. L-T4 allergy. 10. Unwilling to sign an informed consent. 11. Other clinicians judged that they are not suitable to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of fetal loss | From enrollment to the end of treatment at 40 weeks | * Abortion: Ultrasound examination shows no embryo sac or only empty sac, no fetal heart or bud development. * Intrauterine fetal death: Fetal death in utero at 20 weeks or more of pregnancy. * Stillbirth: Death at birth over 28 weeks of pregnancy. * Neonatal death: Newborns die within 7 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of gestational diabetes | From enrollment to the end of treatment at 40 weeks | GDM: 1. FPG≥5.1mmol/L,\<7.0mmol/L during the first prenatal examination 2. During weeks 24-28, if blood glucose was elevated in a 75 g oral glucose tolerance test according to the criteria of International Association of the Diabetes and Pregnancy Study Groups; 0 hour ≥5.1 mmol/L, 1 hour ≥10.0 mmol/L, 2 hours ≥8.5 mmol/L Satisfy any of the above criteria to diagnose GDM |
| Rate of macrosomia | From enrollment to the end of newborn delivery date. | Macrosomia: the newborn's birth weight \>=4000 g |
| Rate of low birth weight | From enrollment to the end of newborn delivery date. | Low birth weight: the newborn's birth weight \<2500 g |
| Incidence of composite adverse outcomes | From enrollment to the end of treatment at 40 weeks | The occurrence of one or more of these above events (maternal and fetal) was defined as the occurrence of prenatal composite adverse outcomes. |
| Fetal loss rates and reasons within 12 weeks of pregnancy. | From enrollment to the end of treatment at 12 weeks | — |
| Fetal loss rates and reasons within 24 weeks of pregnancy. | From enrollment to the end of treatment at 24 weeks | — |
| Fetal loss rates and reasons within 28 weeks of pregnancy. | From enrollment to the end of treatment at 28 weeks | — |
| Fetal loss rates and reasons within 34 weeks of pregnancy. | From enrollment to the end of treatment at 34 weeks | — |
| Rate of cesarean section | From enrollment to the end of treatment at 40 weeks | — |
| Gestational week of delivery | From enrollment to the end of treatment at 40 weeks | — |
| Number of Participants requiring treatments for preventing miscarriage | From enrollment to the end of treatment at 40 weeks | Drugs, cervical cerclage, etc. |
| Rate of hyperemesis gravidarum | From enrollment to the end of treatment at 40 weeks | — |
| Rate of hypertensive disorders of pregnancy | From enrollment to the end of treatment at 40 weeks | Hypertensive disorders of pregnancy include: hypertension during pregnancy, preeclampsia and eclampsia |
| Rate of early preterm delivery | From enrollment to the end of treatment at 34 weeks | 28 weeks ≤ gestational week of delivery \<34 weeks; |
| Rate of late preterm delivery | From enrollment to the end of treatment at 37 weeks | 34 weeks ≤ delivery gestational week \<37 weeks |
| Rate of intrauterine growth restriction | From enrollment to the end of treatment at 40 weeks | — |
| Rate of abruption of placenta | From enrollment to the end of treatment at 40 weeks | — |
| Rate of dystocia | From enrollment to the end of treatment at 40 weeks | Dystocia: fetus delivery is difficult, requiring assisted delivery or cesarean section |
Other
| Measure | Time frame | Description |
|---|---|---|
| Thyrotoxicosis | From enrollment to the end of treatment at 40 weeks | Defined as serum TSH less than the lower limit of the pregnancy-specific reference range (or 0.1 mU/L). |
| Adverse events (AEs) | From enrollment to the end of treatment at 40 weeks | Any unexpected medical occurrence in a subjects administered a pharmaceutical product and which may have no causal relationship with the treatment. An AE can be the aggravation of original symptoms, signs, laboratory abnormalities or newly diagnosed diseases, unfavorable and unintended symptoms, signs, clinically significant laboratory abnormalities, etc. The following situations should not be recorded as AEs: * Existing conditions found during first visiting * Planned hospitalization/surgery * Invasive medical and surgical examinations, however, diseases that require these examinations may be adverse events * Expected progression of thyroid disease. * Existing accompanying diseases or existing symptoms and signs exhibited the expected periodic fluctuations at the time of screening, but did not worsen |
| Serious adverse events (SAEs) | From enrollment to the end of treatment at 40 weeks | Defined as any untoward medical position that meets one or more of the following criteria: 1. Death 2. Life-threatening 3. Requires hospitalisation or prolong existing hospitalisation 4. Results in disability/incapacity 5. Results in a birth defect. |
Countries
China
Contacts
Primary ContactYang Zhang, Doctor
Outcome results
None listed