Limits to commercially iodized salt to address dietary iodine deficiency in rural Papua New Guinea.

BACKGROUND AND OBJECTIVES: Fortifying commercial table salt with iodine is the principal strategy used globally to prevent dietary iodine deficiency. However, the costs of providing fortified salt to remote communities may result in it not being locally available or too expensive for many households. This study shows that barriers to consuming adequately iodized salt remain significant for remote rural households in Papua New Guinea (PNG). METHODS AND STUDY DESIGN: Using data from a rural household survey conducted in four areas of PNG in 2018, two issues are examined. First, we contrast the characteristics of households that reported consuming or not consuming iodized table salt, respectively. Second, the adequacy of the iodine content of samples of table salt consumed was assessed in the laboratory. RESULTS: Nine percent of the 1,026 survey households reported not consuming iodized table salt. These households tend to live in remote communities, are among the poorest households, have received no formal education, and have experienced recent food insecurity. Second, 17 percent of the 778 salt samples tested had inadequate iodine. The brand of salt most commonly consumed had the highest share of samples with inadequate iodine levels. CONCLUSIONS: Particularly in remote communities, ensuring that individuals consume sufficient iodine will require going beyond salt iodization to use other approaches to iodine supplementation. To ensure that the iodine intake of those using commercial table salt is adequate, closer monitoring of the iodine content in table salt produced or imported into PNG and enforcement of salt iodization regulations is required.

Universal Salt Iodisation: Lessons learned from Cambodia for ensuring programme sustainability.

Iodine deficiency is the leading cause of preventable intellectual disability in the world, but it has been successfully prevented in most countries through universal salt iodization (USI). In 2011, Cambodia appeared to be an example of this success story, but today, Cambodian women and children are once again iodine deficient. In 2011, Cambodia demonstrated high-household coverage of adequately iodized salt and had achieved virtual elimination of iodine deficiency in school-age children. However, this achievement was not sustained because the USI programme was dependent on external funding, and the national government and salt industries had not institutionalized their implementation responsibilities. Recent programmatic efforts, in particular the establishment of a regulatory monitoring and enforcement system, are turning the situation around. Although Cambodia has not yet fully regained the achievements of 2011 (only 55% of tested salt was adequately iodized in 2017 compared with 67% in 2011), the recent steps taken by the government and the salt industry point to greater sustainability of the USI programme and the long-term prevention of iodine deficiency in children, women, and the general population.

The legislative framework for salt iodization in Asia and the Pacific and its impact on programme implementation.

OBJECTIVE: Fortification of food-grade (edible) salt with iodine is recommended as a safe, cost-effective and sustainable strategy for the prevention of iodine-deficiency disorders. The present paper examines the legislative framework for salt iodization in Asian countries. DESIGN: We reviewed salt iodization legislation in thirty-six countries in Asia and the Pacific. We obtained copies of existing and draft legislation for salt iodization from UNICEF country offices and the WHO's Global Database of Implementation of Nutrition Actions. We compiled legislation details by country and report on commonalities and gaps using a standardized form. The association between type of legislation and availability of iodized salt in households was assessed. RESULTS: We identified twenty-one countries with existing salt iodization legislation, of which eighteen were mandatory. A further nine countries have draft legislation. The majority of countries with draft and existing legislation used a mandatory standard or technical regulation for iodized salt under their Food Act/Law. The remainder have developed a 'stand-alone' Law/Act. Available national surveys indicate that the proportion of households consuming adequately iodized salt was lowest in countries with no, draft or voluntary legislation, and highest in those where the legislation was based on mandatory regulations under Food Acts/Laws. CONCLUSIONS: Legislation for salt iodization, particularly mandatory legislation under the national food law, facilitates universal salt iodization. However, additional important factors for implementation of salt iodization and maintenance of achievements include the salt industry's structure and capacity to adequately fortify, and official commitment and capacity to enforce national legislation.

Performance of rapid test kits to assess household coverage of iodized salt.

OBJECTIVE: The main indicator adopted to track universal salt iodization has been the coverage of adequately iodized salt in households. Rapid test kits (RTK) have been included in household surveys to test the iodine content in salt. However, laboratory studies of their performance have concluded that RTK are reliable only to distinguish between the presence and absence of iodine in salt, but not to determine whether salt is adequately iodized. The aim of the current paper was to examine the performance of RTK under field conditions and to recommend their most appropriate use in household surveys. DESIGN: Standard performance characteristics of the ability of RTK to detect the iodine content in salt at 0 mg/kg (salt with no iodine), 5 mg/kg (salt with any added iodine) and 15 mg/kg ('adequately' iodized salt) were calculated. Our analysis employed the agreement rate (AR) as a preferred metric of RTK performance. Setting/Subjects Twenty-five data sets from eighteen population surveys which assessed household iodized salt by both the RTK and a quantitative method (i.e. titration or WYD Checker) were obtained from Asian (nineteen data sets), African (five) and European (one) countries. RESULTS: In detecting iodine in salt at 0 mg/kg, the RTK had an AR>90 % in eight of twenty-three surveys, while eight surveys had an AR90 %. CONCLUSIONS: The RTK is not suited for assessment of adequately iodized salt coverage. Quantitative assessment, such as by titration or WYD Checker, is necessary for estimates of adequately iodized salt coverage.

The Rise and Fall of Universal Salt Iodization in Vietnam: Lessons Learned for Designing Sustainable Food Fortification Programs With a Public Health Impact.

BACKGROUND: In 2005, more than 90% of Vietnamese households were using adequately iodized salt, and urinary iodine concentration among women of reproductive age was in the optimal range. However, household coverage declined thereafter to 45% in 2011, and urinary iodine concentration levels indicated inadequate iodine intake. OBJECTIVE: To review the strengths and weaknesses of the Vietnamese universal salt iodization program from its inception to the current day and to discuss why achievements made by 2005 were not sustained. METHODS: Qualitative review of program documents and semistructured interviews with national stakeholders. RESULTS: National legislation for mandatory salt iodization was revoked in 2005, and the political importance of the program was downgraded with consequential effects on budget, staff, and authority. CONCLUSIONS: The Vietnamese salt iodization program, as it was initially designed and implemented, was unsustainable, as salt iodization was not practiced as an industry norm but as a government-funded activity. An effective and sustainable salt iodization program needs to be reestablished for the long-term elimination of iodine deficiency, building upon lessons learned from the past and programs in neighboring countries. The new program will need to include mandatory legislation, including salt for food processing; industry responsibility for the cost of fortificant; government commitment for enforcement through routine food control systems and monitoring of iodine status through existing health/nutrition assessments; and intersectoral collaboration and management of the program. Many of the lessons would apply equally to universal salt iodization programs in other countries and indeed to food fortification programs in general.

Regulatory monitoring systems of fortified salt and wheat flour in selected ASEAN countries.

BACKGROUND: Considerable efforts have been made over the past decade to address vitamin and mineral deficiencies. An increasing number of countries in the Association of Southeast Asian Nations (ASEAN) are adopting mandatory food fortification as one of the primary strategies to overcome these deficiencies. Experience shows that fortified foods can reach large parts of the population, including the poor, if the fortification is done on a mandatory rather than a voluntary basis and if the food vehicle is widely consumed. OBJECTIVE: To review the importance of regulatory monitoring as an essential component of food fortification efforts in selected ASEAN countries, with special focus on the available information on regulatory monitoring systems for iodized salt and fortified wheat flour. METHODS: The role of regulatory monitoring in strengthening food fortification programs was discussed during a joint regional meeting of the World Health Organization, UNICEF, the Flour Fortification Initiative, the Global Alliance for Improved Nutrition, the Micronutrient Initiative, and the World Bank on regulatory monitoring of salt and wheat flour fortification programs in Asia, which took place in Manila, Philippines, on 27-29 September 2011. This paper reviews the regulatory monitoring systems of selected ASEAN countries that participated in this meeting. RESULTS: Problems and challenges in regulatory monitoring systems for iodized salt and fortified wheat flour in selected ASEAN countries are identified, and a description of the role of regulatory monitoring in strengthening food fortification initiatives, particularly of salt and flour, and highlights of areas for improvement are presented. CONCLUSIONS: Regulatory monitoring consists of monitoring activities conducted at the production level, at customs warehouses, and at retail stores by concerned regulatory authorities, and at the production level by producers themselves, as part of quality control and assurance efforts. Unless there are appropriate enforcement and quality assurance mechanisms in place to stimulate compliance by food producers, i.e., regulatory monitoring, having national legislation will not necessarily lead to increased coverage of fortified products and associated outcomes.

Introduction to the programme guidance for the use of iodised salt in processed foods and its pilot implementation, strengthening strategies to improve iodine status.

Efforts to achieve optimal iodine intake through salt iodisation have focussed primarily on iodisation of household salt. However, there is strong evidence that in most regions of the world, industrially processed foods and condiments are an increasingly important source of dietary salt. In this context The Iodine Global Network (IGN) and partners developed programme guidance to help national programme managers assess the potential contribution of widely consumed industrially processed foods and condiments to iodine intake. The programme guidance additionally aimed to facilitate better understanding of iodised salt use by the processed food industry, review existing salt iodisation legislation for inclusion of food industry salt, and investigate how regulatory monitoring of food industry practices could be strengthened if needed. To evaluate the utility of the guidance in practice and identify areas where it could be improved, the IGN requested expressions of interest to pilot test implementation. Five pilots were implemented in Kenya, North Macedonia, The Republic of Moldova, Sri Lanka and Thailand, with remote technical support from IGN. The pilots demonstrated how evidence from implementation could be used to strengthen existing salt iodisation initiatives. In particular, how modelling existing processed food intake data enhanced understanding of potential or actual iodised salt intake and provided an evidence base for strategic change, as well as encouraging alignment with salt reduction programmes. In summary, the guidance provided a useful framework for national teams to conduct a relatively rapid assessment of the existing programme for achieving optimal iodine nutrition and opportunities to strengthen it. National teams involved with the pilot implementation were highly engaged and motivated by the outcomes. The pilot implementation process resulted in the development of strategic recommendations nationally and provided invaluable feedback to IGN on the utility of the guidance, facilitating development of an improved version.

Comparison of Salt Iodization Requirements in National Standards with Global Guidelines.

Background: Food fortification is the addition of 1 or more micronutrients to commonly consumed foods and is utilized by many countries as a public health intervention to prevent and control micronutrient deficiencies. As iodine deficiency was a major public health issue globally, the WHO developed evidence-based guidelines for the fortification of salt with iodine. The implementation of salt iodization has been highly successful in reducing iodine deficiency disorders worldwide and is recommended as the main strategy to prevent iodine deficiency. Objectives: This analysis compared salt iodization requirements specified in countries' salt standards with WHO 2014 Guidelines on salt fortification. Methods: For countries with mandatory salt iodization legislation, data from the Global Fortification Data Exchange regarding iodine amounts and iodine compounds, to be added to salt per the country standard and corresponding national salt intake quantities, were compared with 2014 WHO Guidelines. Results: As of 4 September 2021, 110 countries with mandatory salt iodization legislation had national salt standards that specified iodine amounts and compounds and salt intake data. All but 1 specified at least 1 recommended iodine compound, but the majority specified higher iodine amounts in salt standards than indicated in the guidelines, taking salt consumption levels into account. Our analysis did not find excess iodine intake as a result; however, we did not have data on the extent of compliance with national salt standards. Conclusions: Existing iodization requirements in salt standards appear to be appropriate for most countries. Countries in which iodine amounts in salt standards are significantly higher than those recommended in the 2014 Guidelines, in particular those with low compliance with national standards or excess iodine intake, may wish to review program process and output indicators and assess whether current iodine amounts in standards would result in excessive intake if implementation was improved.

Modelling the contribution of iodised salt in industrially processed foods to iodine intake in Macedonia.

Evidence from the 1950s showed that Macedonia was iodine deficient. After the introduction of mandatory universal salt iodisation, the country saw a steady increase in iodine intake and decline in goitre prevalence, earning iodine-deficiency free status in 2003. Iodine status assessments in 2007 and 2016 showed adequate iodine intake among school age children (median urinary iodine concentration of 241 µg/L and 236 µg/L respectively). Macedonia participated in piloting the Iodine Global Network Programme Guidance on the use of iodised salt in industrially processed foods to better understand potential iodised salt intake from processed foods. One objective of implementation was to identify the need, opportunities, and required actions to strengthen the processed food component of the national salt iodisation policy. Data from the 2017 Household Consumption and Expenditure Survey (HCES) was used to determine household salt consumption, to identify widely-consumed, salt-containing industrially processed foods, and estimate typical daily intake of these foods. Their estimated contribution to iodine intake was estimated based on their salt content and the percentage of food industry salt that is iodised. Although the study has limitations, including a relatively small selection of foods, the results indicate potential iodine intake from iodised household salt and iodised salt in the selected foods of nearly 300% of the Estimated Average Requirement and over 220% of the Recommended Nutrient Intake for adults. This was approximately 50% of the tolerable safe Upper Level for iodine intake. The study confirmed high daily salt intake (11.2 grams from household salt only). Successful salt reduction would be expected to reduce iodine intake, however, modelling with 10% and 30% reduction implied this is unlikely to put any population group at risk of deficiency. It is recommended that implementation of salt iodisation and salt reduction policies are harmonized, alongside continued regular iodine status monitoring for different population groups.

Estimated contribution of most commonly consumed industrialized processed foods to salt intake and iodine intakes in Sri Lanka.

In Sri Lanka dietary patterns are shifting towards increased consumption of industrially processed foods (IPF). This study aimed to estimate the contribution of IPF to salt and iodine intake and assess the possible impact of salt reduction on iodized salt intake. The assessment was conducted using guidance published by the Iodine Global Network. National nutrition and household income expenditure surveys were used to estimate adult per capita consumption of household salt and commonly consumed salt-containing IPF. Industry and laboratory data were used to quantify salt content of IPF. Modelling estimated the potential and current iodine intake from consumption of household salt and using iodized salt in the identified IPF. Estimates were adjusted to investigate the likely impact on iodine intake of achieving 30% salt reduction. IPF included were bread, dried fish and biscuits, with daily per capita consumption of 32g, 10g and 7g respectively. Daily intake of household salt was estimated to be 8.5g. Potential average national daily iodine intake if all salt in these products was iodized was 166µg. Estimated current daily iodine intake, based on iodization of 78% of household salt and dried fish being made with non-iodized salt, was 111µg nationally, ranging from 90 to 145µg provincially. Estimated potential and current iodine intakes were above the estimated average requirement of 95µg iodine for adults, however, current intake was below the recommended nutrient intake of 150µg. If the 30% salt reduction target is achieved, estimated current iodine intake from household salt, bread and biscuits could decrease to 78µg. The assessment together with data for iodine status suggest that current iodine intake of adults in Sri Lanka is adequate. Recommendations to sustain with reduced salt intake are to strengthen monitoring of population iodine status and of food industry use of iodized salt, and to adjust the salt iodine levels if needed.

The Potential Contribution of Fortified Maize Flour, Oil, Rice, Salt, and Wheat Flour to Estimated Average Requirements and Tolerable Upper Intake Levels for 15 Nutrients in 153 Countries.

Food fortification is designed to improve the nutritional profile of diets. The purpose of this research was to estimate the potential nutrient contribution of fortified maize flour, oil, rice, salt, and wheat flour in 153 countries, using the national intake (or availability) of the food and the nutrient levels required for fortification. This was done under two scenarios-maximum, where 100% of the food is assumed to be industrially processed and fortified, and realistic, where the maximum value is adjusted based on the percent of the food that is industrially processed and fortified. Under the maximum scenario, the median Estimated Average Requirements (EARs) met ranged from 22-75% for 14 nutrients (vitamins A, B1, B2, B3, B6, B12, D, E, folic acid and calcium, fluoride, iron, selenium and zinc), and 338% for iodine. In the realistic scenario, the median EARs met were 181% for iodine and <35% for the other nutrients. In both scenarios, the median Tolerable Upper Intake Levels (ULs) met were <55% for all nutrients. Under the realistic scenario, no country exceeded 100% of the UL for any nutrient. Current fortification practices of the five foods of interest have the global potential to contribute up to 15 nutrients to the diets of people, with minimal risk of exceeding ULs.

Iodine status of non-pregnant women and availability of food vehicles for fortification with iodine in a remote community in Gulf province, Papua New Guinea.

Adequate iodine status of women of childbearing age is essential for optimal growth and development of their offspring. The objectives of the current study were to assess the iodine status of non-pregnant women, availability and use of commercial salt, extent to which it is iodised, and availability of other industrially processed foods suitable for fortification with iodine. This prospective cross-sectional study was carried out in 2018 in a remote area in Gulf province, Papua New Guinea. Multistage cluster sampling was used to randomly select 300 women visiting local markets. Of these, 284 met study criteria of being non-pregnant and non-lactating. Single urine samples were collected from each of them. Discretionary salt intake was assessed; salt samples were collected from a sub-sample of randomly selected households. A semi-structured, pre-tested questionnaire to assess use and availability of commercial salt and other processed foods was modified and used. Salt was available on the interview day in 51.6% of households. Mean iodine content in household salt samples was 37.8 ± 11.8 ppm. Iodine content was below 30.0 ppm in 13.1% and below 15.0 ppm in 3.3% of salt samples. Mean iodine content of salt available at markets was 39.6 ± 0.52 ppm. Mean discretionary intake of salt per capita per day was 3.9 ± 1.21 g. Median UIC was 34.0 µg/L (95% CI, 30.0-38.0 ppm), indicating moderate iodine deficiency. For women with salt in the household, median UIC was 39.5 µg/L (95% CI, 32.0-47.0 µg/L), compared to median UIC of 29.0 µg/L (95% CI, 28.0-32.0 µg/L) for those without salt. This community has low consumption of iodised salt, likely due to limited access. Investigation of other industrially processed foods indicated salt is the most widely consumed processed food in this remote community, although 39.8% of households did use salty flavourings.

Potential Dietary Contributions From Rice and Wheat Flour Fortification in the Solomon Islands: Results From the 2012-2013 Household Income and Expenditure Survey.

BACKGROUND: Solomon Islands (SI) mandated wheat flour fortification in 2010. Rice is a key staple food in SI, and its fortification may provide an opportunity to deliver additional micronutrients to the population. OBJECTIVE: To determine whether fortified rice (proposed) and fortified wheat flour potentially benefit women of reproductive age (WRA). METHODS: We analyzed data from the 2012-2013 Household Income and Expenditure Survey to quantify food purchases, which served as a proxy for food consumption. We accounted for varied household composition by using adult male equivalent (AME) adjustments. RESULTS: Among 4478 households, 95.6% purchased rice and 86.6% purchased at least 1 food containing fortified wheat flour in the previous 14 days. Median apparent intake of rice among WRA was 205 g/d/AME. If fortified according to proposed standards, this apparent intake could result in the consumption of 12.3 mg iron/d, fulfilling 44% of the estimated average requirement (EAR), and 226 µg folic acid/d, satisfying 57% of World Health Organization's recommended intake of 400 µg/d. Overall, apparent rice consumption could fulfill 113%, 114%, and 131% of the EAR for WRA for zinc, thiamin, and niacin, respectively. Fortified wheat flour was consumed in much lower quantities, with an estimated apparent median intake of 22 g/d/AME among WRA and 78 g/d/AME among women in urban populations. CONCLUSIONS: The potential benefit of fortified wheat flour in SI is likely limited to urban populations. Apparent consumption of fortified rice in SI could contribute considerably to daily intake of iron, B vitamins including folic acid, and zinc among WRA.

Iodine status of children and knowledge, attitude, practice of iodised salt use in a remote community in Kerema district, Gulf province, Papua New Guinea.

Iodine deficiency is the single most common cause of preventable mental impairment in communities with suboptimal iodine intake. Objective of the present study was to assess in more detail the iodine status and knowledge, attitudes and practice (KAP) relating to use of iodised salt in a remote community in Kotidanga area, Kerema district, Gulf province, Papua New Guinea. This prospective school and community based cross-sectional study was carried out in 2017. Simple random sampling was used to select schools. Multistage sampling was used to randomly select 300 children aged 6 to 12 years, of which 289 consented to participate in the study. A single urine sample was collected from each of the consenting children, as well as a salt sample from their households. Discretionary salt intake was assessed in a sub-sample of the children's households. Salt iodine content and urinary iodine concentration (UIC) were analysed. A semi-structured modified Food and Agriculture Organisation questionnaire was used to assess KAP of three different community groups. Only 64% of households had salt on the day of data collection. Mean iodine content in household salt samples was 29.0 ± 19.1 ppm. Iodine content was below 30.0 ppm in 54.8% and below 15.0 ppm in 31.2% of salt samples. Mean per capita discretionary intake of household salt was 2.9 ± 1.8 g/day. Median UIC was 25.5 µg/L and Interquartile Range was 15.0 to 47.5 µg/L, indicating moderate status iodine nutrition. Median UIC was 34.3 µg/L for children in households with salt, compared to 15.5 µg/L for children in households without salt, indicating severe iodine deficiency in the latter group. The three community groups had limited knowledge about importance of using iodised salt and consequences of iodine deficiency on health outcomes. This remote community has limited access to adequately iodised household salt due to high cost, inappropriate packaging, storage and food preparation, resulting in iodine deficiency. Strategies to increase iodine intake are needed.

Instant noodles made with fortified wheat flour to improve micronutrient intake in Asia: a review of simulation, nutrient retention and sensory studies.

BACKGROUND AND OBJECTIVES: Consumption of foods made with wheat flour, particularly instant noodles, is increasing in Asia. Given this trend, fortifying wheat flour with vitamins and minerals may improve micronutrient intake in the region. The objective of this review was to understand what is known about fortifying wheat flour used to make instant noodles. METHODS AND STUDY DESIGN: A literature review of seven databases was performed using the search terms "noodle" and ("Asian" or "instant"). Grey literature was requested through a food fortification listserv. Articles were title screened first for relevance and duplicity, with exclusion criteria applied during the second round of abstract-level screening. This review considered studies examining simulation, retention, sensory, bioavailability, efficacy, and effectiveness of instant noodles made with fortified wheat flour. RESULTS: Fourteen relevant documents were reviewed for simulation (n=1), retention (n=11), and sensory studies (n=3). The documents revealed that instant noodles produced from fortified wheat flour have potential to improve nutrient intakes, have high retention of most nutrients, and provoke no or minimal changes in sensory characteristics. CONCLUSIONS: The available literature indicates that using fortified wheat flour for instant noodle production results in retention of the added nutrients, except thiamin, with no significant sensory change to the final product. Given the rising consumption of instant noodles, production of this item with fortified wheat flour has potential to improve nutrient intakes in Asia. This review provides a resource for the design of a wheat flour fortification program in countries where a large proportion of wheat flour is consumed as instant noodles.

Eliminating Iodine Deficiency in China: Achievements, Challenges and Global Implications.

The prevention of iodine deficiency through salt iodization has been recognized as a global success story, and China stands at the forefront of this achievement with one of the most successful programs in the world. High level political commitment, national mandatory legislation, a state-managed edible salt industry and a complex and highly sophisticated surveillance system have facilitated the success of the program. Challenges have arisen however, including: (i) concern that adequate iodine status in pregnant women cannot be achieved without causing above adequate iodine intakes in children; (ii) declining iodine intake as a result of reductions in salt consumption and increased consumption of processed foods, which may not be made with iodized salt; (iii) the existence of areas with high iodine content in the water; and (iv) declines in household use of iodized salt due to concerns about excess iodine intake and thyroid disease. This article reviews the achievements and challenges of the Chinese Iodine Deficiency Disorders (IDD) Elimination Program and reflects on lessons learned and implications for other national salt iodization programs.

Anaemia prevalence over time in Indonesia: estimates from the 1997, 2000, and 2008 Indonesia Family Life Surveys.

OBJECTIVE: To summarize anaemia prevalence data for children, women, and men using data from the second, third and fourth waves of the Indonesia Family Life Surveys (IFLS), which were conducted in 1997/8, 2000, and 2007/8, respectively. METHODS: Anaemia prevalence was determined for children 0 to 5 years, 5 to 12 years, 12 to 15 years, non-pregnant women at least 15 years, pregnant women at least 15 years, and men at least 15 years, based on haemoglobin adjusted for altitude and smoking status. RESULTS: Compared with 1997/8 estimates, anaemia prevalence estimates were lower in 2007/8 for all groups, with the greatest relative decline occurring in children 5 to 12 years (25.4%). Trend analysis found anaemia significantly declined over the survey years for all groups (χ² p=0.005 for pregnant women, χ² p<0.001 for all other groups). CONCLUSIONS: IFLS anaemia estimates for different population groups decreased between 1997/8 and 2007/8 and were consistent with estimates from Southeast Asia, and with other studies conducted in Indonesia. While the prevalence of anaemia consistently decreased in all groups, anaemia remains a moderate public health problem for children 0 to 5 years, children 5 to 12 years, and non-pregnant and pregnant women.