Establishing the Iodine Requirement in Infancy

Iodine is an essential trace element for human health and an integral component of the
thyroid hormones. Thyroid hormones regulate normal growth and development, particularly of
the brain. Iodine deficiency results in low levels of thyroid hormones that can impair brain
development and lower intelligence. Infants have only small iodine stores at birth and are
entirely dependent on iodine provided by breast milk or infant formula. However, the exact
amount of daily iodine that infants need for healthy development is poorly understood and
there is insufficient data to define an Estimated Average Requirement (EAR) for this age
group.

The current recommendation for dietary iodine intake for 0-6 month (mo) old infants of 110
µg/day is only an adequate intake (AI), in the absence of an EAR. This AI is based on the
iodine intake in breast fed infants from breast milk iodine concentration (BMIC) measured in
U.S. women during a period when overall iodine intakes in the U.S. population were
excessive. The AI sharply disagrees with the current WHO recommendation for assessment of
infant iodine nutrition based on excretion of iodine in the urine. The discrepancy makes
assessment and monitoring of iodine status at this age problematic and has led to major
confusion on how to interpret adequate iodine intake and optimal iodine status.

The objective of this study is to measure the daily iodine retention from dietary iodine and
define the physiological iodine requirement (the EAR) during the first six months of life.
The study hypothesis is that the AI is set too high and its use in assessing iodine intake
and status overestimates the prevalence of iodine deficiency in infants.

The study will be a metabolic balance study of breast milk consumption and three
dose-response cross-over arms of iodine enriched infant formula milk in 60 healthy 2-3 mo
old infants (30 breast fed and 30 formula fed). Breast fed infants will be exclusively and
unrestrictedly breast fed by the mother and the breast milk consumption will be monitored
for 4 days by weighing the infants before and after each feeding session. Formula fed
infants will be randomly allocated to three 11 days cross-over periods of exclusive
consumption of infant formula milks (IFM) providing 60 µg I/day, 110 µg I/day and 220 µg
I/day. The iodine intake will be monitored by recording the amount of infant formula milk
fed to the infants. The iodine excretion will be measured from complete collections of urine
and feces for a 4-day period for each arm. The iodine retention will be calculated from the
difference between measured iodine intake and excretion. Analytical determination of the
iodine content in biological samples will be done by mass spectrometry after digestion and
iodine extraction. The sample size is based on an estimated dose-response of the different
levels of dietary iodine on iodine excretion.

Inclusion Criteria:

- Healthy mother/infant pairs (considering the following criteria: normal thyroid
function, adequate iron status, no apparent infection)

- Full term birth (in week 38 to 42), birth weight >2 500 g, singleton birth

- No known family history of thyroid disease

- Infant does not have persistent stomach and/or intestine symptoms

- Mother did not use: a) X-ray or CT contrast agent (both may contain iodine); b)
iodine containing medication within the last year

- Formula fed infants study arm: Infant is fully formula fed and was already formula
fed prior to the study

- Formula fed infants study arm: Infant was fed with formula based on cow's milk
protein prior to the study

- Formula fed infants study arm: Infant shows no signs of cow's milk allergy

- Breast fed infants study arm: Infant is fully breast fed and was fully breast fed
prior to the study