Maternal Iodine Status and Pregnancy Outcomes: Looking Beyond Cretinism (original) (raw)

Iodine is a crucial micronutrient for production of thyroid hormones including triiodothyronine (T3) and thyroxine (T4). These hormones play a key role in regulating metabolism apart from being essential for growth and development during early years of life. Several areas of the world have suffered from iodine deficiency. India, in particular (barring a few coastal areas), has been an iodine-deficient country. However, the fortification of common salt with iodine has caused a significant improvement in iodine status.

Pregnancy is associated with increased iodine requirements. The reason for this is both increased renal excretion of iodine as well as increased synthesis of thyroid hormones.

Hence, pregnant females are at risk for iodine deficiency. The role of iodine and iodine deficiency in causing endemic cretinism and related thyroid disorders is well known.

While the spectre of severe iodine deficiency disorders including endemic cretinism has lifted, mild to moderate iodine deficiency still lurks in many parts of the country. An important area of research is regarding the effects of iodine deficiency on feto-maternal outcomes other than those directly attributable to thyroid dysfunction.

Gestational diabetes mellitus (GDM) and iodine deficiency are an interesting area of research. Iodine deficiency either directly or via causing hypothyroidism has been shown to be associated with both gestational diabetes as well as insulin resistance.[1,2] Further, a recent study by Neven et al. found that higher placental iodine concentrations were linked with a lower risk of developing GDM. Although the authors did not measure urinary iodine excretion, placental iodine levels were used as a surrogate marker for iodine status.[3] In this issue, Sarmah et al. reported higher GDM prevalence in the mild iodine deficiency group.[4] There were no cases of GDM in the moderate iodine deficiency probably due to small number of cases in this group. However, data from the Finnish Maternity Cohort showed no association between mild to moderate iodine deficiency and GDM.[5] Interestingly, high urinary iodine concentration (UIC) has also been associated with GDM in one study.[6] The data on GDM and iodine deficiency are contradictory and merit further study.

Preeclampsia is another common maternal complication of pregnancy with serious consequences. Sarmah et al. have found much greater preeclampsia prevalence in mild to moderate iodine deficiency as compared to iodine sufficient mothers.[4] A case-control study from rural South Africa also showed that patients with pre-eclampsia had significantly low UIC as compared to the controls.[7] The Norwegian Mother, Father, and Child Cohort Study (MoBa) reported a higher prevalence of pre-eclampsia in mild to moderate iodine deficiency.[8] Further, a recent meta-analysis also suggests that women with preeclampsia have a lower UIC compared with normotensive pregnant women.[9] However, there are several reports to the contrary also. A study from Finland however found no association between iodine status and preeclampsia.[10] A study from Shanghai reported that mild iodine deficiency did not increase adverse pregnancy outcomes including preeclampsia.[11] Similarly, a study from the United Kingdom, reported that mild to moderate iodine deficiency in pregnancy was not associated with an increase in preeclampsia.[12] Similar to GDM, this area requires further more studies to elucidate the relationship between iodine and preeclampsia. It will also be interesting to find out if the effects of iodine deficiency are amplified by co-existing micronutrient deficiencies.

Sarmah et al. found a high prevalence of anemia in the iodine deficient groups.[4] This observation reflects the co-existence of multiple micronutrient deficiencies in pregnancy.

Many publications have reported the presence of this co-existence both in India and abroad.[13,14]

The fetal outcomes in the face of iodine insufficiency have also been a subject of research.

A study from Shanghai reported that mild iodine deficiency did not increase adverse pregnancy outcomes.[11] Similarly, a study from the United Kingdom, reported that mild to moderate iodine deficiency in pregnancy was not associated with an increase in preterm births or low birth weight.[12] Data from the LIFE prospective cohort study, suggests that iodine deficiency irrespective of severity, does not increase the risk of pregnancy loss in developed countries.[15] Further, two recent meta analyses also reported that current data does not support any association between maternal iodine status and fetal outcomes including prematurity, low birth weight and stillbirths.[16,17] While Sarmah et al. did not find any association between iodine status and prematurity and still births, they did report significantly higher low birth weight in the iodine deficient mothers.[4] However, this observation is not unique. A recent study from China has also found an association between iodine deficiency and low birth weight.[18] Data from the Bradford birth cohort in the United Kingdom also reported an association between low birth weight or small for gestational-age babies and low maternal urinary iodine concentrations.[19] In a study from Brazil, low urinary iodine concentrations were associated with lower infant birth length.[6] Clearly, there is a need for more research to understand the role of iodine deficiency in determining fetal outcomes.

Sarmah et al. report a high prevalence of mild iodine deficiency in pregnant women in their study.[4] This is despite decades of iodization of common salt – indicating that more efforts are needed to improve the iodine status of the population. Whether specific efforts on improving the iodine status of pregnant women will improve feto-maternal outcomes is a question that has to be answered. A cochrane review of iodine supplementation in pregnancy reported that perinatal mortality was lowered in patients with severe iodine deficiency but other maternal and fetal outcomes were similar between the iodine supplemented and non-supplemented groups.[20] However, as evident from the data above, the relationship between iodine status and feto-maternal outcome is far from settled. While we can take pride in the near total elimination of severe iodine deficiency, more efforts are needed to get a clearer picture of how mild to moderate iodine insufficiency affects feto-maternal outcomes.

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