Square-root TSH (μIU/mL) Presence vs. Absence TPO Abᵈ Lead Exposure and Thyroid Autoantibodies in Pregnant Women LG Kahn, X Liu, JH Graziano, P Factor-Litvak Mailman School of Public Health, Columbia University, New York, NY Abstract Exposure to environmental lead (Pb) is associated with decreased thyroid function in highly exposed workers. No data are available to evaluate this association in pregnant women. The purpose of this analysis is to examine associations between Pb exposure during pregnancy and markers of maternal thyroid function. This study draws on a prospective cohort study in two towns in Kosovo, one with high and one with low levels of Pb exposure, which recruited women during the first half of their pregnancies. We measured blood Pb (BPb), free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibodies (TPO Ab), and obtained questionnaire data on demographic variables and lifestyle habits. Mean BPbs were 20.01 and 5.57 μg/dL in the exposed and unexposed towns, respectively. FT4 and TSH concentrations were in the normal range for pregnancy. The prevalence of elevated TPO antibodies was nearly five times greater among women in the exposed compared to the unexposed town (32.64% vs. 6.80%). After control for potential confounders, we found a significant association between ln(BPb) and FT4 (estimated β = -0.075; 95% confidence interval (CI) -0.10, -0.048). We also found an increased risk for testing positive to TPO Ab (estimated adjusted odds ratio 2.41; 95% CI 1.53, 3.82) per log unit increase in BPb. No relationship was found between BPb and TSH. We conclude that exposure to Pb during pregnancy may be associated with decrements in maternal thyroid function and risk for autoimmune thyroid disease, which may translate to adverse effects in their children. Objective The aim of this study is to examine the association between BPb and maternal thyroid function among participants in the Yugoslavia Prospective Study of Environmental Lead Exposure. Results After adjustment for potential confounders, we observed a strong negative association between BPb and FT4, and a strong positive association between BPb and TPO Ab, which we considered as both a continuous and dichotomous variable. We found no statistically significant association between BPb and TSH (see below). Regression coefficients and odds ratios for blood lead level vs. thyroid outcome measures, Pristina and Mitrovica combined. FT4 (mg/dL) Square-root TSH (μIU/mL) ln TPO Ab (IU/mL) Presence vs. Absence TPO Abᵈ n 279 277 278 276 291 Unadjusted β Adjusted βᵃ Adjusted βᵇ Adjusted βᶜ Unadjusted OR Adjusted ORᶜ ln(BPb) (μg/dL) -0.079** -0.075** 0.0018 0.024 0.34** 0.31** 2.51** 2.41* (-0.11, -0.052) (-0.10, -0.048) (-0.048, 0.051) (-0.028, 0.076) (0.20, 0.48) (0.17, 0.46) (1.62, 3.89) (1.53, 3.82) ᵃ Adjusted for height, ethnicity, BMI, adults per room, fetal gestational age, maternal education ᵇ Adjusted for iron-deficiency, ethnicity, fetal gestational age, maternal age, BMI ᶜ Adjusted for ethnicity, fetal gestational age, maternal age, adults per room ᵈ Cutoff ≥ 10 IU/mL * p-value < 0.0005 ** p-value < 0.0001 Compared to women from the unexposed town, women from the exposed town had lower mean FT4 (0.91 vs. 1.03 mg/dL) and higher mean TPO Ab (15.45 vs. 5.12 IU/mL). There was no statistically significant difference in TSH levels between the two groups of women (data not shown). Methods 291 pregnant women were included in this study (see above). Stored mid-pregnancy maternal serum samples were assayed for BPb, FT4, TSH, and TPO Ab. We examined associations between ln(BPb) and each thyroid outcome measure using multiple linear regression and, where appropriate, logistic regression, controlling for potential confounders. Data were analyzed using SAS 9.2. Conclusion Our finding of a strong positive association between BPb and TPO Ab among pregnant women in the absence of any relationship between BPb and TSH suggests that prolonged lead exposure contributes to maternal hypothyroidism by stimulating autoimmunity to the thyroid gland. Figure A Figure B Figure C 148.41 54.60 20.09 7.39 2.72 1.00 2.72 7.39 20.09 54.60 2.72 7.39 20.09 54.60 2.72 7.39 20.09 54.60 Scatterplots showing the unadjusted relationships between BPb and FT4 (figure A), TSH (figure B), and TPO Ab (figure C).