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

Although iodine deficiency affects over 2 billion people worldwide and is re-emerging in formerly iodine-replete industrialised countries, pregnant women, lactating mothers and their offspring are more susceptible to the adverse effects of iodine deficiency [1]. These include stillbirths, miscarriages, intrauterine growth restriction, postpartum thyroiditis, subclinical and overt hypothyroidism, dyslipidemia, neuro-cognitive and psychomotor deficits [2‐4].

In endemic areas, chronic iodine deficiency among women in reproductive age will be exacerbated by the increased renal clearance and loss in urine which will predispose the foetus to defective neuronal migration, myelination and glial differentiation which are key features of brain central nervous system development [4, 5]. This is the underlying cause of cretinism in severe cases and neurocognitive and psychomotor deficits. Hence, whole generations will be at risk of chronic thyroid, metabolic and mental diseases, leading to low socio-economic productivity in areas without sustained adequate nutrition [2].

There is a trend towards the re-emergence of iodine deficiency in iodine-replete countries such as the USA, the UK, New Zealand and Australia [6‐9]. This has partially been attributed to inadequate use of iodized salt and voluntary instead of universal iodisation of salt used in commercial and household food production. As a result, the median urine iodine concentration (UIC) in the USA declined from 320 μg/l to 144 μg/l between 1971 and 2010 while pregnancy median UIC fell from 153 μg/l between 2001 and 2006 to insufficient levels <150 μg/l between 2007 and 2010 [6‐8]. Data from a survey of 21 European countries in 2014 revealed that despite the iodine status of some countries being adequate across all age groups, 13/21 countries had inadequate iodine intake during pregnancy due to poor access to iodized foodstuffs and inadequate of monitoring of iodine nutrition status [9].

Iodine deficiency is widespread in Africa such that without iodine supplementation, almost 90% of the population will be at risk of iodine deficiency [10‐12]. This is mainly due to iodine-deficient soils and goitrogens of which the most significant being poorly detoxified cassava which is rich in thiocyanate [13].

By early 1996, iodine deficiency disorder control programmes using iodised salt as the long-term strategy had been initiated in almost all of the 50 countries in Africa where WHO estimated that iodine deficiency disorder was of public health significance. As a result, more than 50% of the salt consumed in Africa was iodised [14]. Although universal iodisation of salt is the main source of dietary iodine in most African countries, other major sources of dietary iodine in some African countries include groundwater in Somalia and Djibouti and bouillon cubes and canned and processed foods such as in Senegal and Ghana [1, 15‐18].

By 2017, 85% of the African countries had achieved sufficient iodine nutrition in the general population [19]. However, only four of the eleven African countries that had median pregnancy UIC survey data (South Africa, Tanzania, Sierra Leone and Ghana) had adequate iodine intake during pregnancy; five (Burkina Faso, Egypt, Niger, Morocco, and Senegal) had insufficient intake during pregnancy, while Djibouti and Liberia had more than enough iodine intake during pregnancy.

Since about 90% of dietary iodine intake is excreted in the urine, the World Health Organization (WHO) recommended that urinary iodine concentration (UIC) is a good marker of recent iodine intake. Hence, median UIC has been used to map out populations at increased risk of thyroid disorders due to iodine deficiency [20]. The median school-age children (SAC) UIC is commonly used to estimate the iodine nutrition status of the most population, but this may underestimate the degree of iodine deficiency in pregnancy due to differing dietary habits of SAC and pregnant women, in addition to specific physiological changes of pregnancy [9, 21, 22].

During pregnancy, the urinary iodine excretion increases by about 30–50% secondary to the increased blood volume, hyperdynamic state and the increased renal blood flow and glomerular filtration [23, 24]. Furthermore, serum iodide concentration is progressively reduced in the second and third trimesters by increased trans-placental transfer to the growing foetus which begins production of thyroid hormones from about 20 weeks’ gestation [25]. In addition, there is extra iodine demand due to the physiological increase in maternal thyroid hormone output. This is as a result of the oestrogen mediated increase in thyroid-binding globulin that progressively decreases the free T4 in the serum, transfer of iodine to the foetus and increased renal iodine clearance [26]. Therefore, women with mild-to-moderate iodine deficiency may develop severe iodine deficiency in pregnancy with resultant subclinical hypothyroidism (SCH), overt hypothyroidism (OH) or isolated T4 deficiency with resultant maternal and offspring short term and long-term complications [25‐27].

Hence, the WHO recommends that the average iodine intake to maintain normal thyroid clearance and cater for renal losses in pregnancy should be at least 200 μg daily for pregnant women compared to 100–150 μg per day for non-pregnant women [1]. Among pregnant women, a median UIC < 150, 150–249, 250–499 and > 500 μg is considered an estimate of, respectively, insufficient, adequate, more than adequate and excessive iodine nutritional status [28].

However, there is a paucity of data on the magnitude of iodine deficiency among pregnant women on the continent of Africa [29] and around the globe [19]. We intend to conduct a systematic review and meta-analysis of observational studies carried out to establish the trend in the state of iodine nutrition among pregnant women in Africa following the implementation of national iodization programmes.

Although much gain in access to iodised salt has been achieved in most African countries since the early 1990s, of recent, the implementation of universal salt iodization, the major method of iodine supplementation, seems to be slowing down [7]. Due to challenges with monitoring [30], it is not clear if iodine deficiency may be re-emerging in African countries as in industrialised nations. Like elsewhere around the globe, women in reproductive age, pregnant women and their children will be the most affected, yet the degree of iodine deficiency in pregnancy in Africa is not well documented.

Although the most recent Iodine Global Network (IGN) data suggests that 85% of the African countries have sufficient iodine nutrition in the general population [19], further evaluation of these statistics using the method described by De Benoist et al [30] reveals that 30% of these countries have more than > 50% of the general population with a median UIC < 100 μg/L. This implies a high risk of insufficient iodine intake at the inception of pregnancy among women in reproductive age given that adequate iodine nutrition status in pregnancy is defined by median UIC of 150–249 μg/L [1]. It is recommended that pregnant and lactating women, who make up the most vulnerable portion of the general population, should be considered for supplementation with iodine until the population-based iodization programme is scaled up. Not only is it necessary to achieve sufficient iodine nutrition status, but it is also equally important to sustain adequate iodine nutrition status of the entire population especially the most vulnerable portions. Hence, the impact of iodization should be monitored at a regional or national level at least every 5 years.

The aim of this systematic review and meta-analysis is to ascertain the trend in the prevalence of insufficient iodine nutrition status (median UIC < 150 μg/L) among pregnant women in Africa following the implementation of national iodization programmes and to establish if this has had a sustainable positive impact on the iodine nutrition status of pregnant women in Africa.

The purpose of this review is to address the following questions:

The degree of iodine nutrition during pregnancy all over the African continent following the implementation of USI and other methods of iodization is not known with certainty. It is not certain whether the trend towards the re-emergence of iodine deficiency among pregnant women in several developed countries around the world is also affecting pregnant women in Africa. A high prevalence of iodine deficiency among pregnant women in Africa would imply an enormous but probably unrecognised predisposition to iodine deficiency disorders affecting not only pregnant women but also lactating mothers and their offspring. The association of iodine deficiency in pregnancy with various adverse pregnancy outcomes and chronic neurocognitive, psychomotor thyroid and cardiovascular diseases among mothers and their offspring requires concerted attention. This review seeks to address the knowledge gap on the magnitude of insufficient iodine intake among pregnant women on the African continent. The data will help shed light on the magnitude of iodine deficiency in pregnancy in Africa which can help inform policy makers on the degree and desirable methods for intervention and the appropriate frequency of monitoring of iodine nutrition status in pregnancy.

Possible limitations of this study would include a predominance of poor quality studies and significant heterogeneity of studies precluding further analysis.