To the Editor: The family with resistance to thyroid hormone (RTH) described by Dr Anselmo and colleagues1 provides a unique opportunity to examine the effects of excess maternal thyroxine on the fetus. We believe that the conclusion that hormone overreplacement in hypothyroidism should be avoided in pregnant women is premature based on the data they provide.
First, in the obstetrics and gynecology literature, fetal loss is established only after confirmation of an intrauterine viable pregnancy. In this study, miscarriage could be defined by bleeding after a positive human chorionic gonadotropin test result. Data were not provided about other risk factors for miscarriage. It is therefore difficult to conclude that there was an increase in fetal loss primarily due to excess thyroid hormone.
Second, the statistically significant differences in birth weight may not be clinically relevant. Birth weights adjusted for gestational age are normal within 2 SDs. Only 3 of 8 unaffected infants born to affected mothers had low birth weight. Furthermore, low birth weight associated with maternal parity or body mass index does not increase perinatal morbidity or mortality,2 and the article did not give details about these factors or provide information about other causes for intrauterine growth retardation. Given the association of low maternal thyroxine levels with impaired neurocognitive development,3 - 4 this study’s outcomes of the unaffected infants of mothers affected by RTH would not favor underreplacement vs overreplacement of thyroid hormone.
Finally, RTH thyroxine levels are usually more than twice that of normal values.5 Overreplacement of the thyroid hormone to this degree should not occur when practicing with standard-of-care monitoring.
One of the more intriguing findings in this study is that high maternal thyroxine levels can suppress the fetal axis. It is believed that high placental levels of type 3 deiodinase protect the fetus from high levels of maternal thyroxine.6 Neonatal hyperthyroidism from mothers with Graves hyperthyroidism is thought to be rare for this reason. Since only 3 values were obtained from screening filter paper results, a prospective study measuring thyroid function tests at birth would help confirm these results.
We would be interested to learn more about the affected children of unaffected mothers. Given that a fetus is dependent on maternal thyroxine during the first trimester, we would expect impaired neurocognitive development in the affected children of unaffected mothers. If this has not been observed, the effect of T4 on fetal neurologic development may be independent of the TH receptor β gene.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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