title: Iodine supplementation for women during the preconception, pregnancy and postpartum period.
abstract: Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences.
  
  
  
  To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes.
  
  
  
  We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers.
  
  
  
  Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration.
  
  
  
  Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results.
  
  
  
  We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period.
  
  
  
  There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.
authors.affiliation: Research and Evaluation, Micronutrient Initiative, 180 Elgin Street, Suite 1000, Ottawa, ON, Canada, K2P 2K3.
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Harding
authors.affiliation: Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, Geneva, GE, Switzerland, 1211.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Peña-Rosas
authors.affiliation: Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, Sydney, NSW, Australia, 2006.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Webster
authors.affiliation: Department of Diabetes and Endocrinology, Westmead Hospital, Corner Hawkesbury and Darcy Roads, Westmead, NSW, Australia, 2145.
authors.forename: Constance My
authors.initials: CM
authors.lastname: Yap
authors.affiliation: National Nutrition Center, Ministry of Health Barbados, St Michael, Barbados.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Payne
authors.affiliation: Global Health Nursing, St. Luke's International University, Graduate School of Nursing Sciences, 10-1 Akashi-cho, Chuo-Ku, Tokyo, Japan, 104-0044.
authors.forename: Erika
authors.initials: E
authors.lastname: Ota
authors.affiliation: Research and Evaluation, Micronutrient Initiative, 180 Elgin Street, Suite 1000, Ottawa, ON, Canada, K2P 2K3.
authors.forename: Luz Maria
authors.initials: LM
authors.lastname: De-Regil
mesh_terms: D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000453:epidemiology; D007037:Hypothyroidism / Q000453:epidemiology; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology; D007455:Iodine / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency; D054238:Perinatal Mortality; D049590:Postpartum Period; D016742:Preconception Care / Q000379:methods*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D047928:Premature Birth / Q000453:epidemiology; D011295:Prenatal Care / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D013972:Thyrotropin; D007455:Iodine