Iodine and Reproduction

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

The first objective of this study was to look at fecundability prospectively in women planning to become pregnant. The LIFE Study, a population-based prospective cohort study, enrolled 501 women who had discontinued contraception within 2 months to become pregnant between 2005 and 2009. Women reported on risk factors for infertility by interview then kept daily journals of relevant information. Women used fertility monitors to time intercourse relative to ovulation then used home digital pregnancy tests to identify pregnancies on the day of expected menstruation. Urine samples for iodine analysis were collected on enrollment. samples were in the deficiency range in 44.3% of participants. The group whose iodine-creatinine ratios were below 50 g/g (moderate to severe deficiency) had a 46% reduction in fecundity (P = 0.028) compared with the group whose iodine-creatinine ratios were in the adequate range: adjusted fecundability odds ratio of becoming pregnant per cycle, 0.54 (95% confidence interval 0.31-0.94). Significant delays in becoming pregnant occur at iodine concentrations that are common in women in the USA and parts of Europe. Replicating these findings will be important to determine whether improving iodine status could be beneficial in improving fecundability. Our next investigation was to determine whether there was an increased risk of pregnancy loss in those women who achieved a pregnancy. The LIFE study provided an excellent opportunity to examine the relationship between iodine status and pregnancy loss because women were monitored prospectively to ensure excellent ascertainment of conceptions. The LIFE study, a population-based prospective cohort study, monitored 501 women who had discontinued contraception within two months to become pregnant; 329 became pregnant, had urinary iodine concentrations measured on samples collected at enrollment, and were followed up to determine pregnancy outcomes. Of the 329, 196 had live births (59.5%), 92 (28.0%) had losses, and 41 (12.5%) withdrew or were lost to follow up. Urinary iodine concentrations were in the deficiency range in 59.6% of the participants. The risk of loss, however, was not elevated in the mildly deficient group (hazard ratio 0.69, 95% confidence interval 0.34, 1.38), the moderately deficient group (hazard ratio 0.81, 95% confidence interval 0.43, 1.51), or the severely deficient group (hazard ratio 0.69, 95% confidence interval 0.32, 1.50). Iodine deficiency, even when moderate to severe, was not associated with increased rates of pregnancy loss. This study provides some reassurance that iodine deficiency at levels seen in many developed countries does not increase the risk of pregnancy loss. We then examined the relationship between iodine and thyroid function on gestational diabetes risk in the Finnish pregnant population. Iodine is essential for thyroid function, and iodine deficiency during pregnancy is common in Europe. However, no published studies have examined the role of iodine deficiency in the relation between thyroid function and gestational diabetes mellitus (GDM). We conducted a population-based, nested case-control study within the Finnish Maternity Cohort using pregnancy and perinatal outcome data from the Finnish Maternal Birth Register. We randomly selected 224 GDM cases with singleton pregnancies and 224 controls without GDM from all singleton births occurring in Finland during 2012-2013. Blood was drawn at 10-14 weeks' gestation and analyzed for serum iodide, thyroglobulin, and thyroid-stimulating hormone (TSH) concentrations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of GDM. Very high thyroglobulin concentration (>95% percentile; >83 g/L) was not associated with significantly altered odds of GDM compared to those with normal levels (OR 0.41; 95% CI: 0.12, 1.38). High concentrations of TSH were also not associated with increased odds of GDM compared to normal levels of TSH (OR 0.45; 95% CI: 0.06, 3.18). Women in the lowest 5th percentile (<1.58 ng/mL) of iodine did not have increased odds of GDM compared to those with iodide in the highest quartile (OR 0.39; 95% CI: 0.11, 1.35). Low levels of iodide and thyroid function in early pregnancy are not associated with increased risk of GDM in this mildly iodine-deficient population.