Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00147433
Status:
UNKNOWN
Last Update Posted:
2006-03-31
First Post:
2005-09-02
Brief Title:
The Effect of Thyroid Hormone Levels in Pregnant Women on the Intelligence Quotient IQ of Their Children
Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD
Organization:
Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD
Study Overview
Official Title:
Are IQs Low in Offspring of Euthyroid Women With Low T4
Status:
UNKNOWN
Status Verified Date:
2005-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is designed to test the hypothesis that the level of the thyroid hormone thyroxine specifically free thyroxine FT4 circulating in the blood of pregnant women is the key thyroid-related factor to influence early fetal brain development The investigators will recruit 5000 pregnant women with clinically normal thyroid function normal thyroid stimulating hormone levels in the second trimester After the baby has been born the investigators will measure FT4 in the second trimester maternal blood sample to identify 100 cases very low FT4 levels and 100 matched controls normal FT4 levels The children of cases and controls will undergo neurodevelopmental testing at 2 years of age to determine whether IQ differs according to maternal FT4 levels during pregnancy The potential impact of the study is that if such an effect is found it might be possible to avoid these adverse developmental consequences in children by designing and testing strategies to identify and treat high risk women
Detailed Description:
Summary
The purpose of the proposed study is to test the hypothesis that the key thyroid-related factor in early fetal brain development is T4 derived from the maternal circulation According to this hypothesis low circulating maternal levels of free T4 may adversely influence fetal brain development even when the mother is clinically euthyroid ie has normal TSH levels
Specific Aims
The proposed project aims to determine whether free T4 levels at or below the 3rd centile in euthyroid women during early pregnancy are associated with reduced neuropsychological development in their offspring We will recruit a cohort of 5000 pregnant women whose serum samples have been submitted for routine prenatal screening for Down syndrome and neural tube defects in the early second trimester of pregnancy After the women provide consent thyroid-stimulating hormone TSH measurements will be performed The women defined as euthyroid by TSH measurement will comprise the study group Free T4 measurements will be performed on their stored sera after delivery Then a nested case-control study design will be used Inclusion criteria will include liveborn singleton infant delivered in Maine at 36 weeks or later weighing at least 2500 grams and with no reported congenital anomalies Multiple gestations will be excluded Eligible women with free T4 measurements below the 3rd percentile cases will each be matched with a womaninfant pair with normal free T4 measurements controls Overall 100 offspring in each category will undergo neurodevelopmental testing at age 2 years using a test battery that will focus on language development and attainment of milestones and motor development The study will have an 80 power to detect a 6 point difference in full scale IQ
Study Timeline
Phase 1 Preparation for Recruitment months 1-4
Validate reference ranges for TSH and Free T4 Assays Implement clinical reporting and management system for TSH measurements design and implement a Data Management System develop Provider and patient materials visit offices to introduce the project develop informed consent
Phase 2 Active Recruitment months 4-24
Recruit 5000 pregnant women classified as euthyroid based on second trimester TSH measurements measure free T4 measured in stored serum aliquots after the pregnancies have delivered
Phase 3 Identification of Study Subjects months 18-36
Identify 100 cases euthyroid women fulfilling all inclusion criteria and with free T4 measurements at or below the 3rd centile and 100 matched controls normal free T4 among the 5000 euthyroid recruits
Phase 4 LocateRecruit Cases and Controls months 20-38
Locate and re-recruit the womeninfant pairs identified in phase 3 obtain newborn hypothyroidism screening results
Phase 5 Neurodevelopmental Testing months 36-58
Perform neurodevelopmental testing and measure other thyroid analytes total T4 T3 and thyroid antibodies in the cases and controls
Phase 6 Data Analysis months 59-60
Compare demographic data along with pregnancy- and delivery-related information between case and control motherchild pairs to verify matching and to compare non-matched variables between the two groups Include covariates that differ significantly between cases and controls and that might be related to neurodevelopment in a more refined model to determine whether the unadjusted findings are robust
Significance
The knowledge gained from this study will expand our understanding of the role that thyroid hormone plays in normal pregnancy If the hypothesis under study in this proposal proves to be correct it will define a broader group of pregnancies in which fetal brain development might be suboptimal The primary benefit to documenting such a problem would be the opportunity to develop strategies for identifying and treating high risk women to avoid the adverse consequences in their children
The purpose of the proposed study is to test the hypothesis that the key thyroid-related factor in early fetal brain development is T4 derived from the maternal circulation According to this hypothesis low circulating maternal levels of free T4 may adversely influence fetal brain development even when the mother is clinically euthyroid ie has normal TSH levels
Specific Aims
The proposed project aims to determine whether free T4 levels at or below the 3rd centile in euthyroid women during early pregnancy are associated with reduced neuropsychological development in their offspring We will recruit a cohort of 5000 pregnant women whose serum samples have been submitted for routine prenatal screening for Down syndrome and neural tube defects in the early second trimester of pregnancy After the women provide consent thyroid-stimulating hormone TSH measurements will be performed The women defined as euthyroid by TSH measurement will comprise the study group Free T4 measurements will be performed on their stored sera after delivery Then a nested case-control study design will be used Inclusion criteria will include liveborn singleton infant delivered in Maine at 36 weeks or later weighing at least 2500 grams and with no reported congenital anomalies Multiple gestations will be excluded Eligible women with free T4 measurements below the 3rd percentile cases will each be matched with a womaninfant pair with normal free T4 measurements controls Overall 100 offspring in each category will undergo neurodevelopmental testing at age 2 years using a test battery that will focus on language development and attainment of milestones and motor development The study will have an 80 power to detect a 6 point difference in full scale IQ
Study Timeline
Phase 1 Preparation for Recruitment months 1-4
Validate reference ranges for TSH and Free T4 Assays Implement clinical reporting and management system for TSH measurements design and implement a Data Management System develop Provider and patient materials visit offices to introduce the project develop informed consent
Phase 2 Active Recruitment months 4-24
Recruit 5000 pregnant women classified as euthyroid based on second trimester TSH measurements measure free T4 measured in stored serum aliquots after the pregnancies have delivered
Phase 3 Identification of Study Subjects months 18-36
Identify 100 cases euthyroid women fulfilling all inclusion criteria and with free T4 measurements at or below the 3rd centile and 100 matched controls normal free T4 among the 5000 euthyroid recruits
Phase 4 LocateRecruit Cases and Controls months 20-38
Locate and re-recruit the womeninfant pairs identified in phase 3 obtain newborn hypothyroidism screening results
Phase 5 Neurodevelopmental Testing months 36-58
Perform neurodevelopmental testing and measure other thyroid analytes total T4 T3 and thyroid antibodies in the cases and controls
Phase 6 Data Analysis months 59-60
Compare demographic data along with pregnancy- and delivery-related information between case and control motherchild pairs to verify matching and to compare non-matched variables between the two groups Include covariates that differ significantly between cases and controls and that might be related to neurodevelopment in a more refined model to determine whether the unadjusted findings are robust
Significance
The knowledge gained from this study will expand our understanding of the role that thyroid hormone plays in normal pregnancy If the hypothesis under study in this proposal proves to be correct it will define a broader group of pregnancies in which fetal brain development might be suboptimal The primary benefit to documenting such a problem would be the opportunity to develop strategies for identifying and treating high risk women to avoid the adverse consequences in their children
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None