In the present report, we studied the relationships between environmental perchlorate and thiocyanate exposures, maternal and breastfed infant iodine nutrition, and infant serum thyroid function. Despite recent concerns about the potentially adverse effects of environmental perchlorate exposure on thyroid function, we found no associations between perchlorate levels in breast milk, maternal urine, and infant urine and infant serum thyroid function tests. We believe that these data are reassuring and help clarify the current controversies surrounding the proposed regulation of the U.S. environmental perchlorate exposure.
The potential health risks of low-level environmental perchlorate and thiocyanate exposures are most relevant to women of childbearing age and their offspring, since insufficient maternal iodine during pregnancy and the immediate postpartum period results in various neurological and psychological deficits in children (12
). Iodine deficiency has been associated with an increased risk of developmental delays, a decreased intelligence quotient (IQ) (13
), and attention deficit and hyperactivity disorders (14
). Infants born to mothers who received iodine during pregnancy have improved psychological and neurocognitive outcomes compared to those born to nonsupplemented mothers (15
). However, a recent study has suggested that levo-T4 substitution in pregnant women with elevated serum TSH values did not affect cognitive function in their 3-year-old children, although the median gestational age of mothers was 12 weeks and 3 days, which may be too advanced during the gestational course to discern a measurable impact on neurocognitive outcomes (17
Thyroid hormone is an important factor for oligodendrocyte differentiation and myelin distribution (18
). Haddow et al.
reported that the 7–9-year-old children of pregnant women with untreated hypothyroidism have an average of 7 IQ points lower than those of matched euthyroid control mothers (19
). Low FT4 concentration in women during pregnancy is an independent predictor of impaired neurodevelopment in their children (20
Iodine deficiency affects over 2.2 billion individuals (38% of the world's population) (21
), and is the leading cause of preventable mental retardation worldwide (10
). Population iodine sufficiency is defined by median urinary iodine concentrations ≥100
μg/L in nonpregnant adults, lactating women, and children <2 years old (10
). According to NHANES data, although the median urinary iodine concentration of the general population remained adequate at ≥100
μg/L from the early 1970s to the early 1990s, there had been a decrease of >50% during this time period (22
). Particularly concerning was the almost fourfold increase in the prevalence of urinary iodine values <50
μg/L among women of childbearing age, from 4% to 15%, over the two decades. Although the median urinary iodine concentration in U.S. pregnant women is 125
μg/L according to the most recent (2005–2008) NHANES data, 35.3% have urinary iodine levels <100
). Thus, while the overall U.S. adult population remains iodine sufficient by WHO standards, a subset of pregnant and lactating women may have inadequate dietary iodine intake.
Sources of iodine in the U.S. diet have been difficult to identify due to its many potential sources, variation of iodine content in common foods, and lack of listed iodine amounts on food packaging. Also, urinary iodine concentration thresholds exist only for populations, but not for individuals, given significant day-to-day variation of iodine intake (24
). As such, a public health approach to iodine supplementation in the United States has been advocated. The American Thyroid Association recommends that women in North America receive dietary supplements containing 150
μg iodine daily during pregnancy and lactation and that all prenatal vitamins contain 150
μg of iodine (25
). Only 20.3% of pregnant and 14.5% of lactating women in the United States take a supplement containing iodine (26
). Currently, 114 of 223 (51%) brands of prescription and nonprescription prenatal multivitamins marketed in the United States list iodine as a constituent, and many of those that do contain iodine do not contain the labeled amount, especially when kelp is the iodine source (27
There has been a recent concern that low-level environmental perchlorate exposure has the potential to interfere with iodine utilization and thyroid function. Perchlorate appears to be ubiquitous and has been measured in the drinking water of communities around the United States, including Massachusetts (28
). The U.S. Environmental Protection Agency (EPA) had previously placed perchlorate on its Candidate Contaminant List (29
), and in February 2011, the EPA announced that the United States will proceed with regulating perchlorate in drinking water (30
). This anticipated monitoring has previously been estimated to cost up to $140 million per year if an upper limit of 4
pg/L is targeted (31
Perchlorate has been detected in foods such as lettuce, wheat, cows' milk (32
), and in prenatal multivitamins. Infants and children have the highest estimated intakes of perchlorate by body weight (33
), with urinary perchlorate levels <0.05–25.8
μg/L in 92 U.S. infants in a recent study (34
). In the NHANES data from 2001–2002, perchlorate was detected in all 2820 spot urine samples (median urine perchlorate concentration 3.6
) and was a significant negative predictor of total T4 and a positive predictor of TSH values in women, primarily those with urine iodine concentrations <100
). However, these relationships were not seen in men (35
), among pregnant women in 3 Chilean cities (36
), nor in a large European study assessing the serum thyroid function of iodine-deficient pregnant women (38
). Cao and colleagues reported that infant urinary perchlorate and thiocyanate exposures were associated with both increased infant urinary TSH and T4 levels (39
), an unanticipated finding, since increased TSH should be associated with lower T4. However, measurement of thyroid function in the urine is not standard, and the researchers found no significant associations between the two environmental agents and infant TSH and T4 levels when measured in serum (39
Data regarding breast milk iodine and perchlorate concentrations in U.S. women are limited. Recent studies, among which 57 women were the largest sample, report a range of median breast milk iodine levels from 35–155
). We reported that the median breast milk iodine concentration in 57 Boston-area women was 155
), similar to that of a 1984 study of 37 women (178
μg/L), but higher than those (33.5, 37.9, 43.0, 55.2, and 71.3
μg/L) reported recently in four studies (32
) and in the present report. Kirk et al.
reported that breast milk iodide and perchlorate levels were inversely correlated in six samples with perchlorate concentrations of ≥10
μg/L, although there were no correlations between breast milk iodide and perchlorate in the full data set (32
). We previously reported no correlation between breast milk and colostrum iodine and perchlorate concentrations, even in those breast milk samples with perchlorate concentrations ≥10
). As was observed in our prior study (8
), the present findings also demonstrate a significantly higher median perchlorate concentration in breast milk than in maternal urine, likely due to the ability of lactating breast cells to actively transport perchlorate into breast milk through the NIS (6
The present study is the only study which has examined the potential effects of environmental perchlorate exposure on serum thyroid function in breastfed infants. The recruited study population was underpowered to determine the statistical significance of perchlorate and thiocyanate exposures on serum infant thyroid function. However, perchlorate and thiocyanate levels in breast milk, maternal urine, and infant urine were associated with extremely small effect sizes on serum infant TSH and FT4 levels. Thus, we believe that environmental perchlorate and thiocyanate exposures are unlikely to be clinically relevant to the pituitary–thyroid axis, even in the subgroups of the general population who would be most vulnerable to their adverse effects.
We acknowledge some limitations to our study. The study sample, consisting of primarily Boston-area mothers and their infants of low socioeconomic status who were generally iodine sufficient, had overall adequate nutrition, and mostly nonsmokers, may not be representative of the general U.S. population. Our sample was also too small to obtain an estimate of the iodine sufficiency of the study population, which requires spot urinary iodine concentrations from a minimum for 125 individuals (44
). Also, the iodine concentrations and potential perchlorate and thiocyanate levels of supplemental infant formula, that a majority of the mothers used, were not measured and accounted for. The temporal relationship between the iodine content in breast milk and recent dietary iodine intake is unknown, and it is unclear if a random breast milk iodine concentration is an accurate indication of the dietary iodine available to breastfed infants. However, our findings do represent the largest sample size of breast milk iodine, perchlorate, and thiocyanate levels and infants' serum thyroid function in the United States and provide further understanding on the relationship of breast milk iodine content and infant urinary iodine concentrations.
We conclude that the mothers and their breastfed infants in our study sample were generally iodine-sufficient. Although environmental perchlorate and thiocyanate are ubiquitous, our results do not support the concern that maternal and infant perchlorate and thiocyanate exposures in low levels affect infant serum thyroid function.