Variability of iodine concentrations in the human placenta

Abstract

Iodine is an essential trace element, necessary for the production of thyroid hormones, which play a key role in optimal foetal growth and (neuro-) development. To date, iodine deficiency remains a health burden in many countries. We investigated the variability of placental iodine concentrations within and between individuals. We used 20 mother-neonate pairs from the ENVIRONAGe birth cohort, took samples at three standardized locations of the placentas, pooled and digested them, and determined the iodine concentrations using an ICP-MS method as an alternative for the Sandell-Kolthoff method. the variability between and within the three sample regions was calculated using the intra-class correlation coefficient (ICC) from the variance components of mixed models. With the Friedman test, the differences between placental biopsies were assessed. The ICC showed a higher between-placenta (68.6%) than within-placenta (31.4%) variability. Subsequently, we used our optimized method to determine iodine concentrations in 498 mother-neonate pairs, which averaged 26.1 μg/kg. For 96 mothers, the urinary iodine concentrations were also determined, which showed no correlation with the placental iodine storage, as was expected. Future studies are necessary to explore the effects of these placental iodine concentrations in relation to health outcomes of mother and child at birth and later in life. During gestation, the placenta acts as an important gatekeeper between the foetal and the maternal environment. This crucial organ is able to prevent harmful substances from reaching the foetus and allows nutrients, like iodine, to be transported from mother to child. This trace element plays a vital role in the production and regulation of thyroid stimulating hormone (TSH) and the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4), which are essential for optimal foetal growth and (neuro)development 1. These thyroid hormones are produced by the maternal thyroid gland, bind to plasma proteins for transportation throughout the body, cross the placenta and subsequently reach the foetus 2. Both hormones play an essential role in the foetal neurogenesis, as well as normal development and differentiation of numerous cell types throughout the body 3. Both inadequate or excess amounts of iodine can lead to a decrease in the thyroid hormone levels in both mother and foetus, which could impair the neurocognitive development 4. In the first trimester of pregnancy, the foetus is unable to produce these hormones itself, and relies entirely on the maternal thyroid hormone stores 5,6. In the later stages of pregnancy, the role of the mother is to maintain an adequate iodine supply to the foetal thyroid gland 7. The diet is the most important source of iodine for humans. According to the World Health Organization (WHO), the recommended daily iodine intake for the pregnant and lactating population should range between 150 to 249 μg per day to ensure iodine sufficiency 8. While numerous iodine supplementation programmes have been implemented over the last decade, an estimated 2.2 billion individuals (i.e. 38% of the world's population) are affected by iodine deficiency 9 , and it still remains as the leading cause of preventable mental retardation around the world 8. It has been proposed that the placenta plays a role in the uptake and reserve-storage of iodine 10 , which may represent an adaptive mechanism protecting the foetus from inadequacies in maternal iodine intake. The primary elimination route for iodine in humans is the renal clearance, and the urinary iodine concentration (UIC) reflects very recent dietary iodine intake 11. Several studies have used spot urine samples or 24-h UIC to assess the maternal iodine status during pregnancy 12-15. However, for such purpose, this approach is not without limitations. For example, the UIC does not reflect long-term iodine deficiency, as it varies from day to day and even within a given day, depending on the iodine content of recently consumed food. This often results