TOPIC: Potential role of iron deficiency adversely affecting maternal thyroid function.
Title: Iron deficiency predicts poor maternal thyroid status during pregnancy.
Authors: Zimmerman MB, Burgi H, & Hurrell RF.
Reference: Journal of Clinical Endocrinology & Metabolism 92: 3436-3440, 2007
Pregnant women are often iron deficient during the 2 nd and 3 rd trimesters of pregnancy. Iron deficiency has adverse effects on thyroid metabolism, for example it decreases circulating thyroid hormone concentrations and blunts the efficacy of iodine prophylaxis. As impaired thyroid function in pregnancy (increase in TSH and/or low T4) has been shown to be associated with impaired childhood neurodevelopment, iron deficiency may be a determinant of TSH and/or TT4 in pregnancy.
Objective: To investigate whether maternal iron status is a determinant of TSH and/or TT4 concentrations during pregnancy.
Blood and urine samples were obtained from a representative national sample of Swiss pregnant women (N = 365) in the 2 nd and 3 rd trimesters. Maternal characteristics and supplement use were noted. TSH, TT4, Hb, MCV, ferritin, transferrin, transferrin receptor and urinary iodine were measured. Body iron stores were calculated and stepwise regression performed to look for associations.
Median urinary iodine was 139 -g/L (borderline iodine deficient in pregnancy). Women with negative body iron stores (40%) had a higher TSH and lower TT4 (R.R.: 7.8 for TT4 <100 nmol/L). Ferritin, transferrin receptor and body iron stores were highly significant predictors of serum TSH.
Poor maternal iron status predicts higher TSH and lower TT4 concentrations during pregnancy in an area of mild iodine deficiency.
There are now substantial data to show that a high serum TSH and/or a low total T4/free T4 in pregnancy are associated with a risk for a reduced neurodevelopment of the offspring. The etiology of the impaired thyroid function in many – but certainly not all – cases is autoimmune thyroid disease. Iodine deficiency also plays an important role. The present study emphasises another factor, namely iron deficiency, possibly contributing to the impairment of thyroid function during gestation, at least in an area of borderline iodine deficiency. This cross-sectional study does not establish causation between iron status and thyroid function, but it is known that iron deficiency blunts the TSH response to TRH, thereby decreasing serum T4 and T3 in rats. Animal studies have shown that the heme dependent enzyme, TPO, is also adversely affected by iron deficiency, resulting in lower circulating TT3 and TT4.
There may be other explanations for the findings reported in present study. Iron status may be an indicator of an unmeasured confounder; vitamin status was not specifically measured, nor were there any specific measures of overall nutrition, both of which may also influence thyroid status. Another possibility is that impairment of thyroid function could lower iron status. This is less likely to have occurred in the present study, as only 6% of the women were anaemic and the data did not suggest anemia due to hypothyroidism. Furthermore, the fact that iron status was determined both by measurements of transferrin and transferrin receptor strengthens the observed association between iron status and thyroid function. The exact relation of iron status to iodine status in this study is not clear and requires further evaluation.
Do these data have relevance to fetal and child neurodevelopment? Unfortunately, no measurements were performed during the first trimester when the influence of reduced maternal T4 is paramount. In addition, there were no estimates of maternal thyroid antibodies (TPO), which have also been noted to influence neurodevelopment even when the mothers remained euthyroid. Nevertheless, this well conducted study does suggest that iron status deserves further investigation as a contributory factor to low circulating maternal thyroid hormone concentrations in pregnancy, at least in mildly iodine deficient areas. The etiology of impaired gestational thyroid function is slowly being unravelled. Summary and commentary prepared by John Lazarus Related to Chapters 14 & 20 of TDM