A comprehensive clinical trial, published in the New England Journal of Medicine, challenges three decades worth of observational studies by conclusively demonstrating that treatment between eight and 20 weeks of gestation does not have an impact on adverse outcomes in children through five years of age.
Jennifer Rumbach, Center for Women’s Health Research at UNC
Screening expectant mothers for thyroid dysfunction, and then providing thyroxine treatment as needed during pregnancy, has become a routine procedure in pre-natal care.
Scientists have believed that management provides a boost in the cognitive development of infants that might otherwise have experienced lower-than-average IQ. A comprehensive clinical trial, published in the New England Journal of Medicine, challenges three decades worth of observational studies by conclusively demonstrating that treatment between eight and 20 weeks of gestation does not have an impact on adverse outcomes in children through five years of age.
“Proper thyroid function is critical in normal fetal brain development,” says John Thorp, Jr, professor and maternal-fetal medicine division director at the UNC department of obstetrics and gynecology. “Up until about midway, if not closer to the end of pregnancy, a baby’s thyroid function is minimal and [the infant] is dependent on mom’s thyroid hormone.”
Thyroxine is the hormone produced by the thyroid. When a mother’s thyroid does not produce appropriate levels of thyroxine, the fetus, who is dependent on her thyroxine, may not experience typical brain development.
Routine testing within the first half of pregnancy includes a thyroid-stimulating hormone (TSH) blood test. During the test, the hypothalamus releases a thyrotropin-releasing hormone that triggers the pituitary gland to release TSH. This then causes the thyroid to make two hormones known as triiodothyronine (T3) and thyroxine (T4) which affect metabolism. Within the first three years of life, T3 and T4 are vital to healthy brain development. For this study, expectant mothers with elevated TSH (>= 4.0 mU/L) and normal free-T4 (0.86-1.9 ng/dL) were diagnosed with subclinical hypothyroidism. Hypothyroxinemia was defined as a normal TSH (0.08 – 3.99 mU/L) and low free-T4 (< 0.86 ng/dl). Doctors traditionally treat both conditions with the thyroid medication Levothyroxine.
“The prevailing question that had never been definitively answered,” Thorp, who led the UNC portion of the study, said, “was could treating women with subclinical hypothyroidism or hypothyroxinemia improve baby IQ?”
Thorp noted that the team expected to see a mean improvement in IQ scores comparable to the IQ impact Head Start, a school-readiness program for low-income families, has on childhood neuropsychological development.
“The study concluded there was no evidence that this massive effort made during pregnancy has any difference in helping to make baby’s brain better,” Thorp added.
The study assessed 97,228 for eligibility. Following an analysis of excluding criteria, including those with normal thyroid function, overt thyroid disease, etc., the study enrolled 1,432 women with 526 undergoing randomization in the hypothyroxinemia trial, and 677 undergoing randomization in the subclinical hypothyroidism trial. Approximately half the patients in each leg of the study received levothyroxine, while the other half received a placebo. A total of 649 patients completed the subclinical hypothyroidism trial, while 507 completed the hypothyroxinemia trial.
Maternal thyroid testing continued one and five years following delivery. Infants and children received developmental testing every year until age five. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 in the levothyroxine group and 94 in the placebo group. In the hypothyroxinemia trial, the median IQ score was 94 in the levothyroxine group and 91 in the placebo group.
“The retention rate exceeded 90% at five-years,” Thorp said. “That is a great feat that I think is a tribute to our patients, and motherhood in general. Their commitment to this study was outstanding.”
Thorp also praised the unique talents of the study’s research nurses and research assistants for their ability to maintain engagement with the study participants.
This trial was a collaboration of the entire Maternal-Fetal Medicine Unit Network (MFMU), which currently spans 12 institutions across the United States. Thorp feels that the real strength of the network is in its ability to coordinate large studies while maintaining consistency in data collection and retention. MFMU recruitment in North Carolina was a collaborative effort between UNC Healthcare, UNC Rex Healthcare, and WakeMed Health & Hospitals.
“Our partnership with [these hospitals] is crucial to the study’s success,” Thorp said. “I truly want to express my gratitude to them.”
Funding for this study came from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. The Maternal-Fetal Medicine Units Network’s UNC site has received on-going funding since 2000 and with administrative support from the Center for Women’s Health Research at UNC.
ClinicalTrials.gov number, NCT00388297