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Insufficient iodine nutrition status and the risk of pre-eclampsia: a protocol for systematic review and meta-analysis
  1. Charles Bitamazire Businge1,2,
  2. Namhla Madini3,
  3. Benjamin Longo-Mbenza4,5,
  4. A P Kengne6,7
  1. 1 Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
  2. 2 Department of Obstetrics and Gynaecology, Walter Sisulu University Faculty of Health Sciences, Mthatha, Eastern Cape, South Africa
  3. 3 Health Sciences Library, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa
  4. 4 Universite de Kinshasa Faculte de Medecine, Kinshasa, The Democratic Republic of the Congo
  5. 5 LOMO Medical Centre, Kinshasa, The Democratic Republic of the Congo
  6. 6 Non-Communicable Disease Research Unit, South African Medical Research Council, Tygerberg, South Africa
  7. 7 Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa
  1. Correspondence to Dr Charles Bitamazire Businge; cbusingae{at}


Introduction Pre-eclampsia is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Although subclinical hypothyroidism (SCH) in pregnancy is one of the established risk factors for pre-eclampsia, the link between iodine deficiency, the main cause of hypothyroidism and pre-eclampsia remains uncertain. About two billion people live in areas with iodine insufficiency. The increased renal blood flow during pregnancy leading to increased renal iodine clearance together with the increased placental transfer of iodine to the fetus leads to further iodine deficiency in pregnancy. Iodine is one of the most potent exogenous antioxidants whose deficiency is associated with oxidant imbalance and endothelial dysfunction, one of the mechanisms associated with increased risk of pre-eclampsia.

Methods and analysis A systematic search of published literature will be conducted for case–control studies that directly determined the iodine nutrition status of women with pre-eclampsia and appropriate normotensive controls. A similar search will be conducted for cohort studies in which the incidence of pre-eclampsia among pregnant women with adequate and inadequate iodine nutrition status was reported. Databases including MEDLINE, EMBASE, Google Scholar, SCOPUS and Africa Wide Information will be searched up to 31 December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias of the included studies will be assessed using a Newcastle-Ottawa Scale. Appropriate meta-analytic techniques will be used to pool prevalence and incidence rates, odds and relative risk of pre-eclampsia from studies with similar features, overall and by geographical regions. Heterogeneity of the estimates across studies will be assessed and quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines.

Ethics and dissemination Since the proposed study will use published data, there is no requirement for ethical approval. This review seeks to identify the risk of pre-eclampsia associated with insufficient iodine nutrition in pregnancy. This will help to ascertain whether insufficient iodine intake may be an independent risk factor for pre-eclampsia. This will advise policy makers on the possibility of maximising iodine nutrition in pregnancy and reproductive age as one of the remedies for prevention of pre-eclampsia among populations at risk of inadequate iodine intake. This review is part of the thesis that will be submitted for the award of a PhD in Medicine to the Faculty of Health Sciences of the University of Cape Town. In addition the results will be published in a peer-reviewed journal.

PROSPERO registration number CRD42018099427.

  • iodine
  • deficiency
  • pregnancy
  • preeclampsia

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  • Contributors CBB and APK conceived and designed the protocol. CBB was responsible for manuscript drafting. APK, NM and BL-M took part in critical revision for methodological and intellectual content. CBB is the guarantor of this review. All the authors read and approved the final version of the manuscript.

  • Funding This study is part of a research project supported by Discovery Foundation Rural Fellowship Grant number 038372. APK is employed by the South African Medical Research Council.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

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