Thyroid peroxidase antibody titers, thyroid function, and iodine nutrition status of pregnant normotensive and preeclamptic women in Eastern Cape South Africa.

BACKGROUND: Autoimmune thyroid disease, one of the main risk factors for hypothyroidism, is associated with adverse pregnancy outcomes. The burden of autoimmune thyroid disease in pregnancy and its association with thyroid function among normotensive pregnant women and pregnant women with hypertension in South Africa are not known. OBJECTIVE: This study aimed to establish the magnitude of thyroid peroxidase autoantibodies in pregnancy in the Eastern Cape of South Africa and its relationship with iodine nutrition status and preeclampsia. STUDY DESIGN: Overall, 60 randomly selected normotensive pregnant controls at term and 120 pregnant participants with preeclampsia in the third trimester of pregnancy going to the Mthatha Regional Hospital and the Nelson Mandela Academic Hospital in the Eastern Cape Province who had complete data on thyroid peroxidase antibody titers, urinary iodine concentrations, serum thyroid-stimulating hormones, and free triiodothyronine, free thyroxine, and thyroglobulin levels were enrolled in this unmatched case-control study. RESULTS: The cases and controls had similar mean chronological age (23.8 vs 24.0 years), body mass index (29.4 vs 28.8 kg/m2), and median parity (both 1) (P>.05). The controls had a higher mean gestational age than participants with preeclampsia (38.5 vs 33.7 weeks, respectively; P<.001). Both participants with preeclampsia and normotensive participants had median thyroid peroxidase antibody levels consistent with a negative thyroid autoimmune status. Participants with preeclampsia had higher but nonstatistically significant median thyroid peroxidase antibody (2.14 vs 1.77 IU/L), thyroglobulin (25.9 vs 21.3 µg/L), and thyroid-stimulating hormone (2.4 vs 2.3 mIU/L) levels (P>.05) and significantly lower median urinary iodine concentration (123.4 vs 188.6 µg/L), free thyroxine (13.2 vs 14.1 pmol/L), and free triiodothyronine (4.3 vs 4.6 pmol/L) levels (P<.05) than normotensive controls. Thyroid peroxidase antibodies were positively correlated with thyroglobulin, urinary iodine concentration, and thyroid-stimulating hormone. CONCLUSION: In the rural Eastern Cape of South Africa, pregnant women in the third trimester of pregnancy have thyroid peroxidase antibody titers that show negative thyroid autoimmune status. Insufficient iodine intake, other than thyroid autoimmune disease, seems to be the underlying cause of the lower free triiodothyronine and free thyroxine levels observed among women with preeclampsia.

The prevalence of insufficient iodine intake in pregnancy in Africa: a systematic review and meta-analysis.

BACKGROUND: Fortification of foodstuffs with iodine, mainly through iodization 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). METHODS: Electronic databases and gray 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 urinary iodine concentration (UIC) estimates and derived mean UIC from studies with similar features. RESULTS: Of 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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099434.

Iodine deficiency in pregnancy along a concentration gradient is associated with increased severity of preeclampsia in rural Eastern Cape, South Africa.

BACKGROUND: Preeclampsia is a leading cause of maternal mortality and morbidity in South Africa. Iodine deficiency in pregnancy, which is amenable to correction through iodine supplementation, has been reported to increase the risk of preeclampsia. However, the association of iodine nutrition status with preeclampsia in South Africa has not been studied. METHODS: We enrolled 51 randomly selected normotensive pregnant controls at term together with 51 consecutively selected cases of preeclampsia and 51 cases of severe preeclampsia/eclampsia, all in the third trimester, from Mthatha Regional and Nelson Mandela Academic Hospital in the Eastern Cape Province. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH), triiodothyronine (FT3), thyroxine (FT4) and thyroglobulin (Tg) levels were compared between cases and controls. RESULTS: The respective chronological and gestational ages at enrolment for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were: age 23, 24 and 19 years (p = 0.001), and gestational age 38, 34, and 35 weeks (p < 0.001). The median gravidity was 1 for all three groups. The median UIC, FT4, FT3 revealed a decreasing and Tg a rising trend with the severity of preeclampsia (p < 0.05). TSH had a non-significant rising trend (p > 0.05). The respective median values for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were UIC 217.1, 127.7, and 98.8 µg/L; FT4 14.2, 13.7, and 12. pmol/L; FT3 4.8, 4.4, and 4.0 pmol//L; Tg 19.4, 21.4, and 32. Nine microgram per liter; TSH 2.3, 2.3, and 2.5 mIU/L. UIC < 100 µg/L, Tg > 16 µg/L and FT4 < 11.3 pmol/L were independent predictors of preeclampsia/eclampsia syndrome. CONCLUSION: Women with severe preeclampsia/eclampsia had significantly low UIC and high Tg, suggesting protracted inadequate iodine intake. Inadequate iodine intake during pregnancy severe enough to cause elevated Tg and FT4 deficiency was associated with an increased risk of severe preeclampsia/eclampsia.

Mildly elevated thyroid-stimulating hormone is associated with endothelial dysfunction and severe preeclampsia among pregnant women with insufficient iodine intake in Eastern Cape province, South Africa.

BACKGROUND: Preeclampsia and hypothyroidism are associated with endothelial dysfunction. Iodine deficiency is a risk factor for subclinical hypothyroidism in pregnancy. However, there is a paucity of data on the relationship between iodine nutrition state in pregnancy, the degree of endothelial dysfunction, and the risk of preeclampsia. METHODS: Ninety-five normotensive pregnant women, 50 women with preeclampsia with no severe features, and 50 women with severe preeclampsia were enrolled into the current study from the maternity units of Nelson Mandela Academic Hospital and Mthatha Regional Hospitals in Eastern Cape Province, South Africa. Urinary iodine concentration (UIC), serum markers of thyroid function, aortic augmentation index, and pulse wave velocity (PWV) were compared. RESULTS: Median UIC was 167.5, 127.7, and 88.5 µg/L, respectively for normotensive pregnant women, those with preeclampsia and severe preeclampsia (p = .150). Participants with severe preeclampsia had significantly higher median thyroid-stimulating hormone (TSH) and oxidized LDL than normotensive and preeclamptic women without severe features (respectively 3.0, 2.3, and 2.3 IU/L; 1.2, 1.0, and 1.0 IU/L, p < .05). The median Aortic augmentation index was 7.5, 19.0, and 21.0 (p < .001), and the pulse wave velocity 5.1, 5.7, and 6.3, respectively for normotensive, preeclampsia, and severe preeclampsia participants (both p < .001). In linear regressions, TSH, age, and hypertensive disease were independent predictors of elevated PWV. CONCLUSION: Upper normal-range TSH levels in women with severe preeclampsia were associated with markers of endothelial dysfunction. The low UIC and trend towards the elevation of thyroglobulin suggest that inadequate iodine intake may have increased TSH levels and indirectly caused endothelial dysfunction.

The barrier functions of crude cervical mucus plugs against HIV-1 infection in the context of cell-free and cell-to-cell transmission.

OBJECTIVE: The cervical mucus plugs are enriched with proteins of known immunological functions. We aimed to characterize the anti-HIV-1 activity of the cervical mucus plugs against a panel of different HIV-1 strains in the contexts of cell-free and cell-associated virus. DESIGN: A cohort of consenting HIV-1-negative and HIV-1-positive pregnant women in labour was recruited from Mthatha General Hospital in the Eastern Cape province of South Africa, from whom the cervical mucus plugs were collected in 6 M guanidinium chloride with protease inhibitors and transported to our laboratories at -80 °C. METHODS: Samples were centrifuged to remove insoluble material and dialysed before freeze--drying and subjecting them to the cell viability assays. The antiviral activities of the samples were studied using luminometric reporter assays and flow cytometry. Time-of-addition and BlaM-Vpr virus-cell fusion assays were used to pin-point the antiviral mechanisms of the cervical mucus plugs, before proteomic profiling using liquid chromatography-tandem mass spectrometry. RESULTS: The proteinaceous fraction of the cervical mucus plugs exhibited anti-HIV-1 activity with inter-individual variations and some degree of specificity among different HIV-1 strains. Cell-associated HIV-1 was less susceptible to inhibition by the potent samples whenever compared with the cell-free HIV-1. The samples with high antiviral potency exhibited a distinct proteomic profile when compared with the less potent samples. CONCLUSION: The crude cervical mucus plugs exhibit anti-HIV-1 activity, which is defined by a specific proteomic profile.

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

BACKGROUND: Although 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. METHODS: MEDLINE, 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. RESULTS: Five 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). CONCLUSION: Although 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 NUMBER: CRD42018099427.

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

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.

The prevalence of insufficient iodine intake in pregnancy in Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Insufficient iodine intake in pregnancy is associated with many adverse pregnancy outcomes. About 90% of African countries are at risk of iodine deficiency due to poor soils and dietary goitrogens. Pregnancy predisposes to insufficient iodine nutrition secondary to increased physiological demand and increased renal loss. Iodine deficiency is re-emerging in countries thought to be replete with pregnant women being the most affected. This review seeks to identify the degree of iodine nutrition in pregnancy on the entire African continent before and after the implementation of national iodization programmes. METHODS: A systematic search of published literature will be conducted for observational studies that directly determined the prevalence of insufficient iodine intake among pregnant women in Africa. Electronic databases and grey literature will be searched for baseline data before the implementation of population-based iodine supplementation and for follow-up data up to December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias and methodological quality of the included studies will be assessed using a risk of bias tool. Appropriate meta-analytic techniques will be used to pool prevalence estimates from studies with similar features, overall and by major characteristics including the region of the study, time period (before and after implementation of iodization programmes), sample size and age. Heterogeneity of the estimates across studies will be 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. DISCUSSION: This review will help ascertain the impact of national iodization programmes on the iodine nutrition status in pregnancy in Africa and advise policy on the necessity for monitoring and mitigating iodine deficiency in pregnancy in Africa. This review is part of a thesis that will be submitted to the Faculty of Health Sciences, University of Cape Town, for the award of a PhD in Medicine whose protocol has been granted ethics approval (UCT HREC 135/2018). In addition, the results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099434.

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

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.

Diagnostic performance of several biomarkers for identification of cases of non-communicable diseases among Central Africans.

BACKGROUND: This study determined the diagnostic performance of new biomarkers for a composite diagnosis of non-communicable diseases (NCDs) among Central Africans. METHODS: This case-control study was conducted at LOMO Medical Centre, Kinshasa, DR Congo (DRC) between January - December, 2008. The cases comprised 226 participants with concurrent presence of at least 2 or more of NCDs. Anthropometric parameters and blood pressure were measured while blood samples were assayed for biomarkers. The receiver operating characteristics curve and the logistic regression model were applied. RESULTS: Serum selenium (Se) had specificity and sensitivity of 72.4% and 91.1%, respectively with an area under the curve (AUC) of 0.802; Nitric oxide (NO) (specificity: 72.4%; sensitivity: 93.0%) (AUC = 0.800); Thyroid stimulating hormone (TSH) levels > 6 Mu/L (specificity: 75%; sensitivity: 65%) (AUC = 0.0.727); serum calcium levels of ≥ 110g/L (specificity: 76%; sensitivity: 75%) (AUC = 0.822); and daily salt intake of ≥10 g/day (specificity: 75%; sensitivity: 67%) (AUC = 0.653) in the diagnosis of all NCDs, which were all highly significant (<0.0001). CONCLUSION: Serum Se, NO, calcium, TSH and daily salt intake had high diagnostic performance as biomarkers for identification of patients with concurrent NCDs in the study population.

Risk factors for incident HIV infection among antenatal mothers in rural Eastern Cape, South Africa.

BACKGROUND: The prevalence of HIV among antenatal clients in South Africa has remained at a very high rate of about 29% despite substantial decline in several sub-Saharan countries. There is a paucity of data on risk factors for incident HIV infection among antenatal mothers and women within the reproductive age bracket in local settings in the Eastern Cape, South Africa. OBJECTIVE: To establish the risk factors for incident HIV infection among antenatal clients aged 18-49 years attending public antenatal clinics in rural Eastern Cape, South Africa. DESIGN: This was an unmatched case-control study carried out in public health antenatal clinics of King Sabata District Municipality between January and March 2014. The cases comprised 100 clients with recent HIV infection; the controls were 200 HIV-negative antenatal clients. Socio-demographic, sexual, and behavioral data were collected using interviewer-administered questionnaires adapted from the standard DHS5 women's questionnaire. Multivariate logistic regression models were used to identify the independent risk factors for HIV infection. A p<0.05 was considered statistically significant. RESULTS: The independent risk factors for incident HIV infection were economic dependence on the partner, having older male partners especially among women aged ≤20 years, and sex under the influence of alcohol. CONCLUSIONS: Therefore, effective prevention of HIV among antenatal mothers in KSDM must target the improvement of the economic status of women, thereby reducing economic dependence on their sexual partners; address the prevalent phenomenon of cross-generation sex among women aged <20 years; and regulate the brewing, marketing, and consumption of alcohol.