In a 2019 survey sample of women in a UK, only ~20% were aware of the increased requirements for iodine for perinatal nutrition, despite clear evidence on iodine requirements during pregnancy.
The recommended daily intake for the general adult population, including women, is 150mcg per day.
However, for pregnant and breastfeeding women this recommendation increases to 200-250mcg/d iodine, to cover the increased maternal iodine requirements.
The disconnect between the increased pregnancy/lactation requirements for iodine, and knowledge of those requirements, is worrying.
A 2007 World Health Organisation report declared that:
“On a worldwide basis, iodine deficiency is the single most preventable cause of brain damage.”
While overt iodine deficiency may not be a concern in developed countries, there may still be risks related to inadequate intakes during pregnancy, particularly when iodine requirements during pregnancy are not met early in gestation.
Why Do Iodine Requirements Increase for Pregnancy?
Iodine Deficiency Disorders (IDD) represents a spectrum of disorders, including goitre, low IQ, and congenital hypothyroidism.
The spectrum represents a range of severity in potential adverse effects of insufficiency to deficiency.
Iodine is a crucial trace mineral, required for the synthesis of the thyroid hormones thyroxine [T4] and triiodothyronine [T3], and the majority of iodine is stored in the thyroid gland.
Iodine requirements are significantly increased during pregnancy and lactation, for three primary reasons.
Iodine requirements during pregnancy and lactation are significantly increased for three primary reasons.
The first is that iodine is crucial for neural growth and development because during gestation and into infancy, thyroid hormones are required for neuronal growth
However, a developing foetus cannot produce its own thyroid hormones until after the first trimester.
Thus, the development of a foetal brain is dependant on maternal iodine status and maternal T4 production for the first 10-12 weeks gestation, a period during which iodine requirements in the first trimester are critical.
The second is that, after the onset of foetal thyroid hormone production, the foetus requires its own iodine for production of T4.
And the third is that during pregnancy, alterations in kidney function increase the clearance of iodine from the body.
Collectively this increases the general adult recommended intake from 150mcg/d to 250mcg for pregnancy and lactation.
Iodine and Baby’s Brain
With increased iodine requirements in this lifestage, there is a higher risk of mild-to-moderate iodine deficiency, particularly when iodine requirements during pregnancy are not met in early gestation.
During pregnancy, mild-to-moderate iodine deficiency is considered the most common cause of maternal hypothyroid and low T4 levels.
What of the consequences for neural development in offspring?
A 2019 paper from Berbel et al. found that low maternal T4 measured at 14-weeks gestation was associated with cognitive deficits in children, while children of mothers with normal T4 at 14-weeks displayed no cognitive deficits.
An early 1999 paper from Pop et al. also showed that low maternal T4 levels measured in early pregnancy were associated with cognitive deficits in the infants.
Interestingly, children born to mothers with normal T4 at 12-weeks, whose T4 levels had declined at 24-weeks or 32-weeks gestation, showed no signs of delayed cognitive development.
The specific timing of the associations in these studies is crucial.
Recall that mechanistically, we know that it is for the first trimester during which the infant is reliant on maternal iodine status and adequate T4 production.
Some research has also specifically investigated associations between maternal iodine status and childhood IQ.
In 2019, Levie et al. published an pooled analysis of data from three birth cohorts in the Netherlands, Spain, and the UK.
The data included 6,180 mother-child pairs with a measure of maternal iodine concentrations during pregnancy, and an IQ score available from the child.
During the first 12-weeks of pregnancy, higher iodine status correlated with a ~5-point higher verbal IQ.
When iodine was measured between weeks 12-14 of pregnancy, higher iodine status correlated with a ~3-point higher verbal IQ.
This relationship was no longer evident after week 14 of pregnancy.
Temporal Importance for Iodine
The available evidence indicates the importance of examining the effects of gestational age on the relationship between iodine status and child cognitive capacity.
Taken together, the evidence suggests that the primary benefit of normalising iodine intakes is derived primarily in the first trimester, when iodine requirements in early pregnancy are highest, and caps at ~14-weeks of the pregnancy.
There is consistency in the association with delayed or impaired child cognitive outcomes being observed primarily in the first trimester.
This is evident in studies measuring T4 levels or iodine status, when either are measured within the first trimester.
Importantly, this may explain why some interventions targeting iodine supplementation for childhood cognition have produce null findings; they may be supplementing too late in a pregnancy to observe a benefit.
Let’s Not Forget Lactation
A paper published this year from Næss et al. conducted an analysis in a Norwegian cohort of the associations between maternal iodine status, feeding method, and thyroid hormone status in offspring.
For context, the WHO threshold for urinary iodine sufficiency in infants is 100mcg/L, and for breastmilk iodine concentration ≥92mcg/L is required to meet infant requirements.
Infants were defined as either exclusively breast-fed [no formula], formula-fed [no breastfeeding], or mixed-fed.
113 infants were followed-up over the 3, 6, and 11-month postpartum visits.
Overall, 61% of infants were under the WHO threshold of 100mcg/L at 3-months, which declined to 41% and 37% at 6 and 11-months, respectively.
Infant urinary iodine concentrations positively correlated with maternal breast milk iodine content.
At 3-months postpartum the average infant urinary iodine concentration was 76mcg/L in breast-fed infants compared to 190mcg/L in formula-fed infants.
Thus, the exclusively breastfed infants exhibited insufficient iodine status, which directly reflected inadequate maternal iodine intakes.
Less than half of the women in the present study began supplementing iodine during pregnancy.
Maternal iodine was inadequate based on both average urinary iodine excretion in the mothers [~100mcg/L] and average breastmilk iodine concentrations [~77mcg/L].
For exclusively breast-fed infants, maternal iodine intake is the primary factor influencing infant iodine status, highlighting the importance of maintaining iodine requirements during lactation.
Final Thoughts
Iodine sufficiency in the population appears to relate directly to whether public health policies of iodising salt are in place.
For example, in the Americas ~87% of households use iodised salt and this region exhibits the lowest levels of deficiency.
In contrast, Europe exhibits the highest levels of iodine deficiency and has the lowest coverage of iodises salt.
We must also consider changes in diet in the population. Due to cow’s milk providing a substantial contribution to population iodine intakes, vegans are at a higher risk of iodine insufficiency.
Cow’s milk may contain up to 430mcg/L iodine, while in the UK only 3 of 47 commercially available plant “milk” alternatives were fortified with iodine.
The average iodine concentration in plant “milk” alternatives was 1.7% of the value for cow’s milk.
Until such time as fortification is more widespread, for individuals’ following a vegan diet, it may be prudent to look for iodine-fortified plant “milk” alternatives.
It is also important to note that infant formulas do contain adequate iodine levels. For exclusively breast-fed infants, maternal iodine intake is the primary factor influencing infant iodine status.
An important consideration may be timing, specifically to first trimester insufficiency/deficiency.
Achieving adequate maternal iodine intakes pre-conception appears to be the goal.
For breastfeeding mothers, maintaining the recommendations for ~200-250mcg/d total intake through lactation may also be important to meet ongoing iodine requirements during pregnancy and lactation.
Yours in Science,
Alan
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