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.
REFERENCES
1. Al-Attas OS, Al-Daghri NM, Alkharfy KM, Alokail MS, Al-Johani NJ, Abd-Alrahman SH, et al. Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc 2012;120:618–22.
2. Yang S, Shi F-T, Leung PCK, Huang H-F, Fan J. Low thyroid hormone in early pregnancy is associated with an increased risk of gestational diabetes mellitus. J Clin Endocrinol Metab 2016;101:4237–43.
3. Neven K, Cox B, Cosemans C, Gyselaers W, Penders J, Plusquin M, et al. Lower iodine storage in the placenta is associated with gestational diabetes mellitus. BMC Med 2021;19:47.
4. Sonowal T, Sarmah J, Sarma PK, Deka M. Iodine status, thyroid disorder and feto-maternal outcome among the tribal pregnant women of Eastern Himalayas. Indian J Endocr Metab 2023;27:66–72.
5. Bell GA, Männistö T, Liu A, Kannan K, Yeung EH, Kim U-J, et al. The joint role of thyroid function and iodine concentration on gestational diabetes risk in a population-based study. Acta Obstet Gynecol Scand 2019;98:500–6.
6. Silva de Morais N, Ayres Saraiva D, Corcino C, Berbara T, Schtscherbyna A, Moreira K, et al. Consequences of iodine deficiency and excess in pregnancy and neonatal outcomes:A prospective cohort study in Rio de Janeiro, Brazil. Thyroid Off J Am Thyroid Assoc 2020;30:1792–801.
7. Businge CB, Longo-Mbenza B, Kengne AP. Iodine deficiency in pregnancy along a concentration gradient is associated with increased severity of preeclampsia in rural Eastern Cape, South Africa. BMC Pregnancy Childbirth 2022;22:98.
8. Abel MH, Caspersen IH, Sengpiel V, Jacobsson B, Meltzer HM, Magnus P, et al. Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian mother, father and child cohort study. BMC Med 2020;18:211.
9. Businge CB, Usenbo A, Longo-Mbenza B, Kengne AP. Insufficient iodine nutrition status and the risk of pre-eclampsia:A systemic review and meta-analysis. BMJ Open 2021;11:e043505.
10. Reische EC, Männistö T, Purdue-Smithe A, Kannan K, Kim U-J, Suvanto E, et al. The joint role of iodine status and thyroid function on risk for preeclampsia in Finnish women:A population-based nested case-control study. Biol Trace Elem Res 2021;199:2131–7.
11. Cui X, Yu H, Wang Z, Wang H, Shi Z, Jin W, et al. No association was found between mild iodine deficiency during pregnancy and pregnancy outcomes:A follow-up study based on a birth registry. Biol Trace Elem Res 2022;200:4267–77.
12. Torlinska B, Bath SC, Janjua A, Boelaert K, Chan S-Y. Iodine status during pregnancy in a region of mild-to-moderate iodine deficiency is not associated with adverse obstetric outcomes;results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Nutrients 2018;10:291.
13. Pathak P, Kapil U, Kapoor SK, Saxena R, Kumar A, Gupta N, et al. Prevalence of multiple micronutrient deficiencies amongst pregnant women in a rural area of Haryana. Indian J Pediatr 2004;71 doi:10.1007/BF02828117.
14. Allen L. Multiple micronutrients in pregnancy and lactation:An overview. Am J Clin Nutr 2005;81 doi:10.1093/ajcn/81.5.1206.
15. Mills JL, Ali M, Buck Louis GM, Kannan K, Weck J, Wan Y, et al. Pregnancy loss and iodine status:The LIFE prospective cohort study. Nutrients 2019;11:534.
16. Nazarpour S, Ramezani Tehrani F, Behboudi-Gandevani S, Bidhendi Yarandi R, Azizi F. Maternal urinary iodine concentration and pregnancy outcomes in euthyroid pregnant women:A systematic review and meta-analysis. Biol Trace Elem Res 2020;197:411–20.
17. Greenwood DC, Webster J, Keeble C, Taylor E, Hardie LJ. Maternal iodine status and birth outcomes:A systematic literature review and meta-analysis. Nutrients 2023;15:387.
18. Zha H, Yu L, Tang Y, Sun L, Yuan Q. Effect of iodine nutrition status on thyroid function and pregnancy outcomes. Biol Trace Elem Res 2023 doi:10.1007/s12011-023-03600-8.
19. Snart CJP, Threapleton DE, Keeble C, Taylor E, Waiblinger D, Reid S, et al. Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort. BMC Med 2020;18:132.
20. Harding KB, Peña-Rosas JP, Webster AC, Yap CM, Payne BA, Ota E, et al. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev 2017;3:CD011761.
