Effect of iodine supplementation in Indian pregnant women on maternal and newborn thyroid function and cognitive development

ABSTRACT

Background: Iodine is a key nutrient in neurodevelopment, and the fetus is entirely dependent on the iodine intake of the mother to fulfill this important requirement for proper brain function. While this is clearly known, it is uncertain if maternal iodine nutrition should be monitored separately against what is in current practice in public health programs to control iodine deficiency. Also, it is unclear whether it is beneficial to supplement pregnant women with iodine in mild-to moderately iodine deficient and also iodine sufficient areas. Finally, the role of thyroid dysfunction in depression during pregnancy is uncertain.

Objectives: 1) to determine whether iodine supplementation to pregnant women improves maternal and newborn thyroid function, pregnancy outcome, birth weight, infant growth and cognitive performance; 2) to assess iodine intake and potential determinants of intake, in pregnant women and their children who were sharing all meals; 3) to measure thyroid status during pregnancy and assess potential determinants of maternal thyroid function including iodine status, thyroid autoimmunity, body weight and anemia; 4) to assess the association of maternal depression, and thyroid function during pregnancy.

Methods: 1) In a randomized placebo controlled trial (RCT), the MITCH (Maternal Iodine Supplementation and its Effects on Thyroid function and CHild Development) study, pregnant women, gestational age ≤14 weeks, in Bangalore, India, were randomized to receive either a daily supplement of 200 µg oral iodine or placebo from enrolment until delivery. Women were followed through delivery, and then with postnatal follow-up of their infants at 6 weeks, 1 and 2 year. Early neonatal development was assessed using the Neonatal Behavioral Assessment Scale (NBAS) at 6 weeks of age; neurocognitive assessment was done using the Bayley Scales of Infant Development (BSID III) at 1 and 2 years, and BRIEF-P (Behavior Rating Inventory of Executive Function) at 2 years; 2) A cross-sectional study comparing iodine status of pregnant women and their children, who were sharing all meals in Bangalore, India; 3) A cross-sectional study among 334 pregnant women ≤14 weeks of gestation, in Bangalore, India, who were screened for the RCT; 4) Secondary analysis of the longitudinal data on 318 pregnant women in the RCT.

Results: 1) In the RCT, there were no significant differences between groups in maternal thyroid function tests or thyroid volume during gestation. The prevalence of thyroid dysfunction or anti-TPO antibodies did not differ significantly during gestation and postpartum. Postpartum, there were no significant differences between the maternal and infant groups in thyroid function, birth outcomes or UIC. Neonates whose mothers received iodine supplementation during pregnancy had better orientation scores at 6 weeks of age and lower scores of inhibition suggesting better executive function at 2 years of age although neurocognitive development on the BSID III were not significantly different between groups; 2) In the pilot study, a) median UIC in pregnant women was 172 µg/L, b) the median UIC was >150 µg/L in all trimesters and c) thyroid size was not significantly different across trimesters;  the median UIC in children was 220µg/L, indicating ‘more than adequate’ iodine intake at this age. Median UIC was significantly higher in children than in their mothers (p=0.008). 3) In the cross-sectional study, 21% women were vegetarian, 19% were anemic and 23% were overweight or obese. Iodized salt was used by 98% of women and they were iodine sufficient, median UIC was 184.2 µg/L and all had normal thyroid volume. However, 18% of women had thyroid insufficiency: 3.7% had overt hypothyroidism (83% with positive TPO-Ab), 9.2% had subclinical hypothyroidism and 5.2% had hypothyroxinemia. Women consuming vegetarian diets did not have significantly lower iodine intakes or higher risk of hypothyroidism than those consuming mixed diets, but overweight/obesity and anemia predicted thyroid insufficiency; 4) In the longitudinal study, there was no significant difference in depressive symptoms between the iodine intervention and placebo groups. Women with depressive symptoms had significantly lower serum TSH compared to women without depressive symptoms in the first trimester. Pregnant women with prenatal depressive symptoms had a significantly higher number of medical symptoms.

Conclusion: 1) Iodine supplementation in mildly iodine deficient and in iodine sufficient pregnant women was well-accepted and safe and did not increase the risk of excess iodine intake, hyper- or hypothyroidism, or thyroid autoimmunity. Though there were no significant effects of iodine supplementation on neonatal and maternal thyroid function and birth outcomes, there were modest effects on neurocognitive development of children as assessed by executive function of children at 2 years. Thus, additional follow-up of these children for neurocognitive testing at a later age when development and cognitive testing is more reliable would provide valuable add on information; 2) The iodized salt program in Bangalore, India was providing adequate iodine to women throughout pregnancy, at the expense of higher iodine intake in their children, suggesting that the current WHO/UNICEF/ICCIDD cut-off for median UIC in children indicating more-than-adequate intake may need to be reconsidered; 3) Despite iodine sufficiency, many pregnant women had thyroid insufficiency predicted by low hemoglobin and higher BMI. The prevalence of overt hypothyroidism was >5-fold higher than reported in other iodine-sufficient populations of pregnant women, thus, screening of maternal thyroid function should be considered in antenatal care at hospitals in Bangalore, India; 4) Although iodine supplementation did not affect maternal depression, we highlighted the need for systemic screening for prenatal depression during antenatal visits as it is an independent risk factor for later development of clinical depression