Preconceptional Thyroid Screening and Childhood Nerocognitive Function

To assess the effect of universal preconception hypothyroidism for maternal pregnancy outcome, and 0-3yrs offspring neurocognitive ability and IQ score.

Study Overview

• Status: Unknown
• Conditions: Hypothyroidism
• Intervention / Treatment: Procedure: levothyroxine

Detailed Description

Epidemic evidence and animal studies suggested that hypothyroidism is related with maternal pregnancy outcome, offspring cognitive ability. Negro's study found improved maternal health in those screened in early trimester; while Lazarus et al. reported no significant offspring IQ score at 3yrs in universal screening in early trimester. Currently, it lacks evidence of universal pre-conception screening for maternal pregnancy outcome and offspring cognitive development, motivation ability, attention. China Governmental Health Department has included thyroid function screening into preconception in 2011. The investigators hypothesize that pre-conception effective treatment may be helpful for decrease possible negative effects on maternal and offspring health, instead of early trimester.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaotian Li, MD, PhD; Phone Number: 862163455050; Email: xiaotianli555@163.com
• Study Contact Backup: Name: Qiongjie Zhou, MD; Phone Number: 862163455050; Email: qj_zhou@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Obstetrics and Gynecology Hospital, Fudan University
      • Contact: Xiaotian Li, MD, PhD; Phone Number: 862163455050; Email: xiaotianli555@163.com
      • Contact: Qiongjie Zhou, MD; Phone Number: 862163455050; Email: qj_zhou@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Preconceptional group：TSH ≥ 97.5%th and/or FT4 ≤ 2.5%th
2. age: 18-55
3. those who can obey the rules of this study and assign the consent

Exclusion Criteria:

1. age: less than 18 or more than 55
2. multiple pregnancy
3. thyroid tumor disease history
4. those who cannot obey the rules of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: preconception; Participants will be included according to their first outpatient visiting time. Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks. Medical records include: a)maternal thyroid function at enrollment; b) Levothyroxine: length, dose, drug adverse effects; c)Early trimester of pregnancy: Down's screening; d)2nd trimester of pregnancy: fetal echocardiography; e)Whole course of pregnancy: maternal complications, maternal blood pressure at each visit, fetal growth; f)Pregnancy outcome: type of delivery, length of labor, type and timing of analgesia/anesthesia, Apgar scores, postpartum hemorrhage, fetal complications; g)Offspring cognitive assessment at 0-3 years old	Procedure: levothyroxine; Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks.
Active Comparator: early conception; Participants will be included according to their first outpatient visiting time before 15+6 gestational week. Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks. Medical records include: a)maternal thyroid function at enrollment; b) Levothyroxine: length, dose, drug adverse effects; c)Early trimester of pregnancy: Down's screening; d)2nd trimester of pregnancy: fetal echocardiography; e)Whole course of pregnancy: maternal complications, maternal blood pressure at each visit, fetal growth; f)Pregnancy outcome: type of delivery, length of labor, type and timing of analgesia/anesthesia, Apgar scores, postpartum hemorrhage, fetal complications; g)Offspring cognitive assessment at 0-3 years old	Procedure: levothyroxine; Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks.
Placebo Comparator: late conception; Participants will be included according to their first outpatient visiting time after 16 gestational week. Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks. Medical records include: a)maternal thyroid function at enrollment; b) Levothyroxine: length, dose, drug adverse effects; c)Early trimester of pregnancy: Down's screening; d)2nd trimester of pregnancy: fetal echocardiography; e)Whole course of pregnancy: maternal complications, maternal blood pressure at each visit, fetal growth; f)Pregnancy outcome: type of delivery, length of labor, type and timing of analgesia/anesthesia, Apgar scores, postpartum hemorrhage, fetal complications; g)Offspring cognitive assessment at 0-3 years old	Procedure: levothyroxine; Women with TSH≥97.5%th and/or FT4≤2.5%th will accept levothyroxine 150ug daily and follow-up every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Offspring neurocognitive assessment at 0-3 yrs	Peabody scale, Griffith scale	3 months, 6 months, 1 year, 2 years, 3 years
Offspring IQ assessment at 0-3 yrs	Wechsler Preschool Intelligence Scale at 1, 2, 3-year-old	3 months, 6 months, 1 year, 2 years, 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of neonatal hypothyroid and complications	neonatal hypothyroid function, NICU rate, neonatal death rate	up to 28 days of birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of maternal complications	preeclampsia, GDM, maternal death rate, maternal hemorrhage rate	up to 42 days postpartumn

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Shanghai Municipal Science and Technology Commission; Shanghai Municipal Health Bureau
• Investigators: Principal Investigator: Xiaotian Li, MD, PhD, Obstetrics and Gynecology Hospital, Fudan University

Publications and helpful links

General Publications

• Zhou Q, Wang C, Xu H, Li X. Impact of Preconception Treatment Initiation for Hypothyroidism on Neurocognitive Function in Children. J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa565. doi: 10.1210/clinem/dgaa565.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: October 20, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (Estimate): December 7, 2012

Study Record Updates

• Last Update Posted (Estimate): December 11, 2012
• Last Update Submitted That Met QC Criteria: December 7, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: hypothyroidism; neurocognitive development; preconception
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: 12XD1401300