Michael B. Zimmermann
Laboratory for Human Nutrition, Institute of Food,Nutrition and Health,Swiss Federal Institute ofTechnology (ETH), Zürich, Switzerland
Iodine requirements are increased 50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In moderate-to-severely iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birthweight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10–20%. Mild maternal iodine deficiency can cause thyroid dysfunction but whether it impairs cognitive and/or neurologic function in the offspring remains uncertain. Two meta-analyses have estimated that iodine-deficient populations experience a mean reduction in IQ of 12–13.5 points. In nearly all regions affected by iodine deficiency, salt iodisation is the most cost-effective way of delivering iodine and improving maternal and infant health.
Iodine (atomic weight 126.9) is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. In the early 1920s, Switzerland was the first country to fortify household salt with iodine to control endemic goiter and cretinism. In the 1970s and 1980s, controlled studies showed that iodine supplementation before and during pregnancy not only eliminated new cases of cretinism but also improved cognitive function in the rest of the population.
From 1990 to 2007, global population coverage with iodised salt increased from about 20% to 70%.2
But the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) estimates that nearly two billion individuals in 2011 continue to have insufficient iodine intake worldwide, including 1/3 of all school-age children, and iodine deficiency remains a public health problem in 32 countries. There are insufficient data from nearly all countries to estimate the prevalence of iodine deficiency in pregnant women.
In healthy adults, the absorption of iodide is >90%.1 The body of a healthy adult contains 15–20 mg of iodine, of which 70–80% is in the thyroid. In chronic iodine deficiency, the iodine content of the thyroid may fall to <20 mg. Iodine is cleared from the circulation mainly by the thyroid and kidney, and while renal iodine clearance is fairly constant, thyroid clearance varies with iodine intake. In conditions of adequate iodine supply, 20% of absorbed iodine is taken up by the thyroid. In chronic iodine deficiency, this fraction can exceed 80%. Despite high fractional clearance of iodine by the thyroid, in chronic severe iodine deficiency, thyroid hormone synthesis falls, leading to hypothyroidism and its sequelae.
The iodine requirement during pregnancy is sharply increased because of: (1) an increase in maternal thyroxine (T4) production to maintain maternal euthyroidism and transfer thyroid hormone to the fetus early in the first trimester, before the fetal thyroid is functioning; (2) iodine transfer to the fetus, particularly in later gestation; and (3) an increase in renal iodine clearance.4 Iodine requirements from the US Institute of Medicine (IOM)5 and WHO2 for pregnancy, lactation and infancy are shown in Table 1. The recommended method to assess iodine nutrition in pregnant women is the urinary iodine concentration (UIC).2 Because >90% of dietary iodine eventually appears in the urine, UIC is an excellent indicator of recent iodine intake.1 UIC is usually measured in spot urine specimens from a representative sample of women, and expressed as the median, in mg/L.2 Recommendations for using the median UIC to classify iodine status of pregnant and lactating women, and infants, are shown in Table 2.2
In nearly all regions affected by iodine deficiency, salt iodisation is the most cost-effective way of delivering iodine and of improving cognition.1,2 Worldwide, the annual costs of salt iodisation are estimated at US$0.02–0.05 per child covered, and the costs per child death averted are US$1000 and per Disabilityadjusted life year (DALY) gained are US$34–36.6
However, in some regions, iodisation of salt may not be practical for control of iodine deficiency, at least in the short term. In these areas, iodised oil supplementation can be used. Iodised oil can be given orally or by intramuscular injection. Usual doses are 200– 400 mg iodine/year1 and it is often targeted to women of childbearing age and pregnant women. Iodine can also be given as KI or KIO3 as drops or tablets. In order to ensure adequate iodine supply during pregnancy, women should ideally be provided with ample iodine intake (at least 250 mg/day) for a long period before conception to ensure plentiful intrathyroidal iodine stores.
A systematic literature search in PubMed, Current Contents Connect® and ISI Web of Science® for articles in English, French, German, Spanish (search terms included: iodine, urinary iodine, iodine deficiency, iodine status, pregnancy, infancy, children, cretinism, cognition, school performance, mental development, intelligence, growth, perinatal mortality, infant mortality, maternal mortality, preterm birth, prematurity, abortion, stillbirth, miscarriage, birthweight, meta-analysis) was conducted. Study reports were also obtained from book chapters and through correspondence with iodine experts around the world. Approximately 3300 abstracts were reviewed.
Of these, approximately 450 full-length papers were reviewed. Of these, 27 original studies and two metaanalyses were included in this review. It was decided not to attempt to perform a meta-analysis of the pregnancy studies because: (i) the number of randomised controlled intervention trials of iodine in pregnancy and/or infancy is small; (ii) in many, blinding is uncertain, drop-outs were high and follow-up was inconsistent; and (iii) the studies vary widely in their designs (oral vs. intramuscular delivery of high doses of iodised oil; daily low dose potassium iodide; iodisation of irrigation water; timing of intervention).