Insufficient iodine nutrition status and the risk of pre-eclampsia: a protocol for systematic review and meta-analysis

IntroductionPre-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 analysisA 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 disseminationSince 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 numberCRD42018099427.

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Iodine nutrition status in Africa: potentially high prevalence of iodine deficiency in pregnancy even in countries classified as iodine sufficient

Public Health Nutrition ◽

10.1017/s1368980020002384 ◽

2020 ◽

pp. 1-6

Author(s):

Charles Bitamazire Businge ◽

Benjamin Longo-Mbenza ◽

Andre Pascal Kengne

Keyword(s):

Iodine Deficiency ◽

Iodine Intake ◽

Nutrition Status ◽

Urinary Iodine Concentration ◽

School Age ◽

African Countries ◽

Iodine Nutrition ◽

High Prevalence ◽

Iodine Deficiency In Pregnancy ◽

In Pregnancy

Abstract Objective: To assess the burden of iodine deficiency in pregnancy in Africa using estimated pregnancy median urinary iodine concentration (pMUIC). Design: pMUIC for each African country was estimated using a regression equation derived by correlating the school-age children (SAC) median UIC (mUIC) and pMUIC from countries around the globe, and the SAC mUIC data for African countries obtained from the Iodine Global Network (IGN) 2017 and 2019 Score cards. Setting: Iodine deficiency was endemic in many African countries before the introduction of iodine fortification, mainly through universal salt iodisation programmes about 25 years ago. There is a scarcity of data on the level of iodine nutrition in pregnancy in Africa. Women living in settings with pMUIC below 150 µg/l are at risk of iodine deficiency-related pregnancy complications. Participants: Fifty of the fifty-five African countries that had data on iodine nutrition status. Results: A cut-off school age mUIC ≤ 175 µg/l is correlated with insufficient iodine intake in pregnancy (pregnancy mUIC ≤ 150 μg/l). Twenty-two African countries had SAC mUIC < 175 μg/l, which correlated with insufficient iodine intake during pregnancy (pMUIC < 150 μg/l). However, nine of these twenty-two countries had adequate iodine intake based on SAC mUIC. Conclusions: There is likely a high prevalence of insufficient iodine intake in pregnancy, including in some African countries classified as having adequate iodine intake in the general population. A SAC mUIC ≤ 175 µg/l predicts insufficient iodine intake among pregnant women in these settings.

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The Prevalence of Insufficient Iodine Intake in Pregnancy in Africa: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-291707/v1 ◽

2021 ◽

Author(s):

Charles Bitamazire Businge ◽

Hannibal Tafadzwa Musarurwa ◽

Benjamin Longo-Mbenza ◽

Andre Pascal Kengne

Keyword(s):

Iodine Deficiency ◽

Meta Analysis ◽

Grey Literature ◽

Population Based ◽

Iodine Intake ◽

Nutrition Status ◽

African Countries ◽

Iodine Nutrition ◽

Before And After ◽

In Pregnancy

Abstract BackgroundFortification of foodstuffs with iodine, mainly through iodisation of salt, which commenced in several African countries after 1995 is the main method for mitigating iodine deficiency in Africa. We assessed the degree of iodine nutrition in pregnancy across Africa before and after the implementation of national iodine fortification programs (CRD42018099434).MethodsElectronic databases and grey literature were searched for baseline data before implementation of population-based iodine supplementation and for follow-up data up to September 2020. R-metamedian and metamean packages were used to pool country-specific median UIC estimates and derived mean UIC from studies with similar features. ResultsOf 54 African countries, 23 had data on iodine nutrition in pregnancy mostly from subnational samples. Data before 1995 showed that severe iodine deficiency was prevalent in pregnancy with a pooled pregnancy median UIC of 28.6 µg/L (95% CI 7.6 – 49.5). By 2005, five studies revealed a trend towards improvement in iodine nutrition state in pregnancy with a pooled pregnancy median UIC of 174.1 µg/L (95% CI 90.4 – 257.7). Between 2005 and 2020 increased numbers of national and subnational studies revealed that few African countries had sufficient, while most had mildly inadequate, and some severely inadequate iodine nutrition in pregnancy. The pooled pregnancy median UIC was 145 μg/L (95% CI 126 – 172). Conclusion Improvement in iodine nutrition status in pregnancy following the introduction of fortification of foodstuffs with iodine in Africa is sub-optimal, exposing a large proportion of pregnant women to the risk of iodine deficiency and associated disorders.

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Iodine in pregnancy and breastfeeding

10.1093/med/9780198722700.003.0019 ◽

2015 ◽

Author(s):

Sir Peter Gluckman ◽

Mark Hanson ◽

Chong Yap Seng ◽

Anne Bardsley

Keyword(s):

Thyroid Gland ◽

Thyroid Hormones ◽

Iodine Deficiency ◽

Attention Deficit Disorder ◽

Fetal Brain ◽

Iodine Intake ◽

Food Sources ◽

Increased Risk ◽

Iodine Deficiency In Pregnancy ◽

In Pregnancy

Iodine is a key component of thyroid hormones. Development of the fetal brain and nervous system are dependent on thyroid hormones supplied by the mother via the placenta, increasing the maternal demand for iodine throughout pregnancy. Women with adequate iodine intake before conception (~150 #amp;#x03BC;g/day) can adapt to the increased demand for thyroid hormones during pregnancy, because the thyroid gland adjusts its hormonal output; but this depends on sufficient availability of dietary iodine and the integrity of the thyroid gland. Iodine deficiency causes congenital hypothyroidism, and in severe form, the irreversible brain damage associated with cretinism. Moderate iodine deficiency in pregnancy is associated with lower learning capacity, reduced IQ, hearing impairment, and increased risk of attention deficit disorder. Pregnant women should take a daily multivitamin that contains 150 #amp;#x00B5;g of iodine, unless they regularly consume concentrated food sources of iodine.

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Mild-to-moderate iodine deficiency is associated with lower birthweight and increased risk of preterm delivery in a large Norwegian pregnancy cohort

Proceedings of The Nutrition Society ◽

10.1017/s0029665120003572 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Marianne H. Abel ◽

Ida H. Caspersen ◽

Verena Sengpiel ◽

Bo Jacobsson ◽

Per M. Magnus ◽

...

Keyword(s):

Preterm Delivery ◽

Iodine Deficiency ◽

Iodine Intake ◽

Z Score ◽

Gestational Length ◽

Foetal Growth ◽

Increased Risk ◽

Gestational Week ◽

Iodine Deficiency In Pregnancy ◽

In Pregnancy

AbstractIodine is essential in foetal development through being an integral part of the thyroid hormones. Severe iodine deficiency is associated with foetal growth restriction and preterm delivery. Less is known about the potential impact of mild-to-moderate iodine deficiency on these outcomes.The aim of this study was to investigate whether maternal iodine intake in pregnancy was associated with birth weight (BW) z-score (i.e. BW adjusted for gestational length and sex) and preterm delivery (before week 37).The study population included 77,995 singleton pregnancies from The Norwegian Mother and Child Cohort Study recruited in gestational week 15 in the period 2002–2008. Habitual iodine intake was calculated from a validated food frequency questionnaire covering the first half of pregnancy. Use of supplements was reported in questionnaires. Urinary iodine concentration (UIC) was measured in gestational week 18 in a subsample of n = 2795 women. Median iodine intake from food was 121 μg/day and median UIC was 69 μg/L. Median UIC < 150 μg/L is considered insufficient in pregnant women. Median birthweight was 3610 g and 5.0% were born before gestational week 37. Associations were modelled flexibly by use of restricted cubic splines, and adjusted for age, parity, pre-pregnancy BMI, education, smoking in pregnancy, energy intake, and fibre intake.In non-users of iodine-containing supplements (n = 48,958), a low habitual iodine intake from food (lower than about 150 μg/day) was associated with a lower mean BW z-score (p < 0.001). Compared to an intake of 150 μg/day (reference), mean z-score was 0.04 SD lower at 100 μg/day and 0.12 SD lower at 75 μg/day. Results were similar when using UIC as the exposure (n = 2795, p = 0.017). Any use of iodine containing supplements in pregnancy was associated with 0.03 (95% CI: 0.01, 0.04) SD increase in BW z-score compared to no use (n = 77,949, p < 0.001).A low habitual iodine intake from food (lower than about 100 μg/day) was associated with increased risk of preterm delivery (p = 0.003). Compared to an intake of 100 μg/day (reference), 75 μg/day was associated with 10% increased risk, and 50 μg/day with 28% increased risk. Use of an iodine-containing supplement was not associated with the risk of preterm delivery (OR: 0.97 (95%CI: 0.91, 1.04, p = 0.42)).Inadequate iodine intake is prevalent in women of childbearing age in otherwise well-nourished populations. Our results indicate that mild-to-moderate iodine deficiency in pregnancy is associated with restricted foetal growth and increased risk of preterm delivery.

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Assessment of iodine intake in mildly iodine-deficient pregnant women by a new automated kinetic urinary iodine determination method

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.047 ◽

2005 ◽

Vol 43 (3) ◽

Cited By ~ 8

Author(s):

Mustafa Gültepe ◽

Ömer Özcan ◽

Osman Metin İpçioglu

Keyword(s):

Pregnant Women ◽

Iodine Deficiency ◽

Urinary Iodine ◽

Iodine Intake ◽

Second Trimester ◽

Third Trimester ◽

Iodine Excretion ◽

Iodine Deficiency In Pregnancy ◽

Iodine Determination ◽

In Pregnancy

AbstractMaternal iodine deficiency can compromise the thyroid status of the mother, fetus and newborn child. Therefore, it is important to assess the iodine excretion level of groups of pregnant women. In this study we aimed to determine iodine intake in pregnancy using a recently reported automated kinetic method for urinary iodine determination. Urinary iodine measurements of 123 pregnant women (18 first, 28 second and 77 third trimester) were carried out using a new automated kinetic assay based on the Sandell-Kolthoff reaction at 37°C and its kinetic measurement at 340nm in a random-access automated analyzer after ammonium persulfate digestion at 95°C in a water bath with ±0.1°C precision. Statistical analyses were carried out using SPSS software. Whole group, first trimester, second trimester and third trimester urinary iodine concentrations (mean±SD) in pregnant women were 1.13±0.81, 1.08±0.71, 0.86±0.58 and 1.27±0.87μmol/L, respectively. The urinary iodine concentration significantly increased with gestational age (p<0.05). We found that our study group was mildly iodine-deficient according to WHO criteria. Furthermore, the pregnant women were found to be mildly iodine-deficient in the first and third trimesters and moderately so in the second trimester. The only statistical difference was between second and third trimester values (p<0.05). Even though the increased iodine deficiency in the second trimester is not useful for early detection of iodine deficiency in pregnancy, the severity of this deficiency in the second trimester may lead to important effects on thyroid metabolism for both mother and fetus. Our study suggests that the iodine excretion of pregnant women living in iodine-deficient areas could be assessed using this fast and automated method.

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Insufficient iodine nutrition status and the risk of pre-eclampsia: a systemic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-043505 ◽

2021 ◽

Vol 11 (2) ◽

pp. e043505

Author(s):

Charles Bitamazire Businge ◽

Anthony Usenbo ◽

Benjamin Longo-Mbenza ◽

AP Kengne

Keyword(s):

Pregnant Women ◽

Iodine Deficiency ◽

Meta Analysis ◽

Random Effect Model ◽

Urinary Iodine ◽

Systemic Review ◽

Nutrition Status ◽

Urinary Iodine Concentration ◽

Iodine Nutrition ◽

Significant Difference

BackgroundAlthough subclinical hypothyroidism 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. We conducted a systematic review to determine the iodine nutrition status of pregnant women with and without pre-eclampsia and the risk of pre-eclampsia due to iodine deficiency.MethodsMEDLINE, EMBASE, Google Scholar, Scopus and Africa-Wide Information were searched up to 30th June 2020. Random-effect model meta-analysis was used to pool mean difference in urinary iodine concentration (UIC) between pre-eclamptic and normotensive controls and pool ORs and incidence rates of pre-eclampsia among women with UIC <150 µg/L.ResultsFive eligible studies were included in the meta-analysis. There was a significant difference in the pooled mean UIC of 254 pre-eclamptic women and 210 normotensive controls enrolled in three eligible case–control studies (mean UIC 164.4 µg/L (95% CI 45.1 to 283.6, p<0.01, I2 >50)). The overall proportions of pre-eclampsia among women with UIC <150 µg/L and UIC >150 µg/L in two cross-sectional studies were 203/214 and 67/247, respectively, with a pooled OR of 0.01 (95% CI 0 to 4.23, p=0.14, I2 >50) for pre-eclampsia among women with UIC >150 µg/L. The overall incidence of pre-eclampsia among women with UIC <150 µg/L and UIC >150 µg/L in two cohort studies was 6/1411 and 3/2478, respectively, with a pooled risk ratio of 2.85 (95% CI 0.42 to 20.05, p=0.09, I2 <25).ConclusionAlthough pre-eclamptic women seem to have lower UIC than normotensive pregnant women, the available data are insufficient to provide a conclusive answer on association of iodine deficiency with pre-eclampsia risk.PROSPERO registration numberCRD42018099427.

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Mild to moderate iodine deficiency in pregnancy: A matter of debate

Archive of Food and Nutritional Science ◽

10.29328/journal.afns.1001028 ◽

2021 ◽

Vol 5 (1) ◽

pp. 018-026

Author(s):

Delshad Hossein ◽

Azizi Fereidoun

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

Iodine Deficiency ◽

Urinary Iodine ◽

Iodine Concentration ◽

Urinary Iodine Concentration ◽

Iodine Nutrition ◽

Iodine Supplementation ◽

Iodine Deficiency In Pregnancy ◽

In Pregnancy

During the last few decades painstaking efforts have been made to eliminate iodine deficiency through the world. Nowadays in regions where dietary iodine intake is adequate or borderline, the main focus is increasing dietary iodine supply in the target population during pregnancy and the first years of life. Severe iodine deficiency during pregnancy increases the risk of irreversible brain damage, intellectual disability, neurologic abnormalities, stunted growth, increased pregnancy loss, infant mortality, impairments in child development and cretinism. The potential effects of mild-to-moderate iodine deficiency are debated. Results from animal studies and observational human studies indicate that maternal mild-to-moderate iodine deficiency disturbs thyroid function in pregnancy and it also may affects fetal neurodevelopment. The effect of supplementation of iodine on thyroid function of pregnant women and their newborn, neurodevelopment of infants and cognitive performance of children have been investigated using iodine nutrition in pregnancy, based on median urinary iodine concentration. However they have found conflicting results regarding the benefits or harms of iodine supplementation in pregnancy. Although many epidemiological, interventional and clinical studies have supported the association between thyroid function in pregnant women and later psychomotor and mental development of their children, the effect of iodine supplementation in pregnant women on neurodevelopment of children is inconclusive. Even in areas with well-established universal salt iodization program, pregnancy could be at risk of having iodine deficiency and despite WHO/ICCIDD/UNICEF recommendation which believe that dietary iodine fortification during pregnancy depends primarily on the extent of pre-existing iodine deprivation, systematic dietary fortification needs to be implemented in this vulnerable group. However, iodine supplementation of mildly iodine deficient pregnant women may not have beneficial effects in their thyroid function or neurodevelopment of their children.

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Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10040667 ◽

2021 ◽

Vol 10 (4) ◽

pp. 667

Author(s):

Kjerstine Breintoft ◽

Regitze Pinnerup ◽

Tine Brink Henriksen ◽

Dorte Rytter ◽

Niels Uldbjerg ◽

...

Keyword(s):

Preterm Birth ◽

Cesarean Section ◽

Placental Abruption ◽

Gestational Hypertension ◽

Adverse Pregnancy Outcome ◽

Placenta Previa ◽

Meta Analysis ◽

Increased Risk ◽

Spontaneous Hemoperitoneum ◽

In Pregnancy

Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy. Methods: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle–Ottawa Scale, to assess the risk of bias and confounding. Results: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria. Conclusions: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth.

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