Accelerating anaemia reduction: a comprehensive framework for action: web annex: WHO recommendations for the prevention, diagnosis and management of anaemia

Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Accelerating anaemia reduction A comprehensive framework for action

Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia A comprehensive framework for action Accelerating anaemia reduction Accelerating anaemia reduction: a comprehensive framework for action. Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia ISBN 978-92-4-007405-7 (electronic version) © World Health Organization 2023 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. 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It is being made publicly available for transparency purposes and information. iii Contents 1. Education 1 1.1 Social and behaviour change communication strategies 1 2. Food & Agriculture 2 2.1 Creation of a food environment that enables people to adopt and maintain healthy dietary practices, including dietary diversification 2 2.2 Fortification of staple foods with vitamins and minerals 4 3. Health & Nutrition 7 3.1 Nutrition counselling for pregnant women on healthy diet to reduce the risk of low birth weight 7 3.2 Uterotonic for the prevention of postpartum haemorrhage during the third stage of labour 8 3.3 Optimal timing of umbilical cord clamping 10 3.4 Provision of iron-containing micronutrient powders for point-of-use fortification of foods for infants and young children 6–23 months of age and children aged 2–12 years 11 3.5 Oral preventive iron supplementation in children 13 3.6 Oral preventive iron and folic acid supplementation in menstruating non-pregnant adolescent girls and women 16 3.7 Oral preventive iron and folic acid supplementation for pregnant women 19 3.8 Malaria: Indoor residual spraying (IRS) with a product prequalified by WHO 21 3.9 Malaria: Insecticide-treated nets 22 3.10 Malaria: Intermittent preventive treatment of malaria in pregnancy (IPTp) 24 3.11 Malaria: Perennial malaria chemoprevention (PMC) - formerly intermittent preventive treatment of malaria in infants (IPTi) 25 3.12 Soil-transmitted helminthiases: Preventive chemotherapy (deworming) 27 6Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia 11.1 Development and implementation of social and behaviour change communication strategies Applicable contexts/population groups: all settings Messages to raise awareness of appropriate practices and behaviors to prevent, diagnose and treat anaemia are essential to deliver with the key interventions. A full social and behaviour change communication strategy may be needed to accompany programmes, particularly where new intevetions are being implemented or where there has been low uptake of recommended behaviors and actions. Key actions for implementation: • Social and behaviour change communication strategies should be developed for a particular context, based on prior formative research or ethnographic work. • Multiple social and behaviour change communication approaches and channels (for example, interpersonal communication, media, community/social mobilization) are more effective than using one single approach. • Targeting multiple contacts in addition to the target group (for example, targeting husbands and mothers-in- law in addition to pregnant women or mothers) has a greater effect. WHO guidelines, recommendations and resources • World Health Organization. Sponsored symposium. Strategic behaviour change approaches to optimize the impact of micronutrient interventions. In collaboration with the Micronutrient Initiative, 2 June 2014, Addis Ababa, Ethiopi. • Accelerating nutrition improvements: best practices for scaling up. Examples from Ethiopia, Uganda and the United Republic of Tanzania. Geneva: World Health Organization; 2016 (WHO/NMH/ NHD/16.4; http://apps.who.int/iris/bitstream/10665/252535/1/WHO-NMH-NHD-16.4-eng. pdf). • Communication for development [website]. New York: UNICEF; 2023 (https://www.unicef.org/topics/ communication-development). • Lamstein S, Stillman T, Koniz-Booher P, Aakesson A, Collaiezzi B, Williams T et al. Evidence of effective approaches to social and behavior change communication for preventing and reducing stunting and anemia: report from a systematic literature review. Arlington (VA): USAID/Strengthening Partnerships, Results, and Innovations in Nutrition Globally (SPRING) Project; 2014 (https://www.spring-nutrition.org/ sites/default/files/publications/series/spring_sbcc_lit_review.pdf). 1. Education 2Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia 2.1 Creation of a food environment that enables people to adopt and maintain healthy dietary practices, including dietary diversification Applicable contexts/population groups: All countries, all settings; all population groups WHO recommendation: • Balance the production and consumption of iron-rich foods from animal sources (especially red meat, poultry and fish and plant sources (such as legumes). • Increase the production and consumption of foods that are rich in vitamin A/carotenoid, such as green leafy vegetables, orange-fleshed fruits and vegetables (for example, orange-fleshed sweet potatoes), dairy products, eggs, liver and fish oils. • Add fruits and vegetables that are rich in citric or ascorbic acid (for example, citrus fruits) to the diet, to increase the absorption of non-haem iron. Vitamin C degrades with cooking, so consumption of uncooked (or lightly cooked) fruits and vegetables with high vitamin C content should be encouraged (assuming considerations of food hygiene and food safety are addressed). • Identify and promote culturally appropriate and feasible methods of food processing and preparation, to improve bioavailability and absorption: » Iron: germination, fermentation and soaking may improve absorption. » Vitamin A: short cooking times and steaming rather than boiling will maintain pro-vitamin A activity. • Avoid combining known inhibitors of iron absorption with meals that are high in iron content; for example: » separate tea and coffee drinking from meal times; consumption 1–2 hours later will not inhibit iron absorption; » consume dairy products (milk, cheese and other foods made from milk) as a between-meal snack, not at meal time. 2. Food & Agriculture 3Key actions for implementation • Promote a healthy food environment, including food systems that promote a diversified, balanced and healthy diet. This requires the involvement of multiple sectors and stakeholders, including government and the public and private sectors. • Ensure coherence in national policies and investment plans – including policies on trade, food and agriculture through: » increasing incentives for producers and retailers to grow, use and sell fresh fruit and vegetables; » establishing standards to foster healthy dietary practices by, for example, ensuring the availability of healthy, nutritious, safe and affordable foods in preschools, schools, other public institutions and the workplace; » exploring regulatory instruments (for example, marketing restrictions, nutrition labelling policies, fiscal and pricing policies) to promote a healthy diet; » encouraging transnational, national and local food services and catering outlets to improve the nutritional quality of their foods, ensuring the availability and affordability of healthy choices, and to review portion sizes and pricing. • Encouraging consumer demand for healthy foods and meals through: » promoting consumer awareness of a healthy diet; » developing school policies and programmes that encourage children to adopt and maintain a healthy diet; » educating children, adolescents and adults about nutrition and healthy dietary practices; » encouraging culinary skills, including in children through schools; » supporting point-of-sale information, including through nutrition labelling that provides accurate, standardized and comprehensible information on nutrient contents in foods (in line with the Codex Alimentarius Commission guidelines), with the addition of front-of-pack labelling to facilitate consumer understanding; » providing nutrition and dietary counselling at primary health-care facilities. Considerations • The exact make-up of a diversified, balanced and healthy diet will vary, depending on individual characteristics (for example, age, sex, lifestyle and degree of physical activity), cultural context, locally available foods and dietary customs. However, the basic principles of what constitutes a healthy diet remain the same. 4Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia WHO guidelines, recommendations and resources • Healthy diet. Geneva: World Health Organization; 2018 (Fact sheet no. 394; https://www.who.int/ news-room/fact-sheets/detail/healthy-diet). • Vitamin and mineral requirements in human nutrition, 2nd ed. Report of a joint WHO/FAO expert consultation, Bangkok, Thailand, 21–30 September 1998. Geneva: World Health Organization and Food and Agriculture Organization of the United Nations; 2004 (https://apps.who.int/iris/bitstream/ handle/10665/42716/9241546123.pdf). • Diet, nutrition and the prevention of chronic diseases. Report of a joint WHO/FAO expert consultation. Geneva: World Health Organization; 2003 (WHO Technical Report Series No 916; https://apps.who. int/iris/bitstream/handle/10665/42665/WHO_TRS_916.pdf). • Promoting a healthy diet for the WHO Eastern Mediterranean Region: user-friendly guide. Cairo: WHO Regional Office for the Eastern Mediterranean; 2012 (https://apps.who.int/iris/ handle/10665/119951). • WHO, FAO. Sustainable healthy diets: guiding principles. Geneva: World Health Organization; 2019 (https://apps.who.int/iris/handle/10665/329409). License: CC BY-NC-SA 3.0 IGO. • Nutritional anaemias: tools for effective prevention and control. Geneva: World Health Organization; 2017. (https://apps.who.int/iris/handle/10665/259425). License: CC BY-NC-SA 3.0 IGO. • How together we can make the world’s most healthy and sustainable public food procurement. Copenhagen: WHO Regional Office for Europe; 2022 (https://apps.who.int/iris/ handle/10665/363337). License: CC BY-NC-SA 3.0 IGO. 2.2 Fortification of staple foods with vitamins and minerals Applicable contexts/population groups: Settings where the food vehicle to be fortified is commonly consumed; all population groups WHO recommendations: • Fortification of wheat flour with highly bioavailable iron is recommended as a public health strategy to improve haemoglobin concentrations and iron status, and to prevent anaemia and iron deficiency in populations, particularly for vulnerable groups such as children and women (strong recommendation, low certainty of evidence). • Fortification of wheat flour with folic acid is recommended as a public health strategy to improve folate status in populations (strong recommendation, low and very low certainty of evidence). • Fortification of maize flour and corn meal with iron is recommended to prevent iron deficiency in populations, particularly for vulnerable groups such and children and women. • Fortification of rice with iron is recommended as a public health strategy to improve the iron status of populations, in settings where rice is a staple food. • Fortification of rice with vitamin A may be used as a public health strategy to improve the iron status and vitamin A nutrition of populations. • Fortification of rice with folic acid may be used as a public health strategy to improve the folate nutritional status of populations. 5Summary of key evidence: • Evidence on fortification of maize flour with folic acid or iron shows a positive effect on health outcomes in the general population. Fortification of maize flour with iron, in combination with other micronutrients, reduced the risk of iron deficiency but had no effect on anaemia in children. • Addition of folic acid to wheat and maize flour in the USA and other countries had a significant impact on multiple measures, including folate intake and blood folate concentrations. • Provision of rice fortified with vitamins and minerals including iron, when compared with unfortified rice, probably improves iron status by reducing the risk of iron deficiency by 35% and increases the average concentration of haemoglobin by almost 2 g/L, but may not make a difference to the risk of anaemia in the general population of those aged over 2 years. • When the fortification of rice includes vitamin A, it may reduce both iron deficiency and vitamin A deficiency. • When fortification includes folic acid, fortified rice may slightly increase serum folate concentrations Key actions for implementation: • There is documented evidence from several countries that fortification of other staple foods with zinc, vitamin A, folic acid, vitamin D and calcium is associated with significant reductions in the incidence of deficiency-related outcomes, and improvements in the health status of populations. Countries can integrate fortification of staple foods as part of their national programmes for prevention and control of micronutrient deficiencies and insufficiencies. • The choice and concentration of nutrients should be adapted to the needs of the countrt, including consideration of the micronutrient needs and intake gaps of the target populations; the usual level of consumption of the food vechicle; the sensory and physical effects of the fortificant on the food vehichle; the fortification of other food vehicles; the population use of vitamin and mineral supplements; other ongoing nutrition interventions; costs; feasibility; and acceptability. » In countries with a high prevalence of vitamin B12 depletion and deficiency, the inclusion of vitamin B12 could be considered when staples are fortified with folic acid, to prevent unintended consequences of imbalances caused by the addition of folic acid alone. • The choice of iron compound is a compromise between cost, bioavailability, micronutrient interactions and the acceptance of texture, taste, smell and/or colour. » Nixtamalized flour (lime treated), commonly used in the Americas, is more reactive to ferrous compounds. The use of electrolytic iron does not appear to be effective in the fortification of nixtamalized maize flour. » Fortification of rice with iron has been a challenge, since most of the bioavailable iron powders used in food fortification are coloured, which produces changes in the aspect of fortified kernels compared to unfortified ones. • The addition of other vitamins and minerals in the fortification of staple foods is a common and optional practice. » Since some of the B-complex vitamins naturally present in the whole grains are removed during milling and/or degerming, the restoration of niacin, riboflavin and thiamine in the cereal flour should remain a regular practice in fortification. This strategy has contributed to the virtual elimination of beriberi and pellagra in many countries. » The addition of vitamin C and the removal of phytates in maize flour and corn meal could increase the bioavailability of iron. WHO guidelines, recommendations and resources • Healthy diet. Geneva: World Health Organization; 2018 (Fact sheet no. 394; https://www.who.int/ news-room/fact-sheets/detail/healthy-diet). • Vitamin and mineral requirements in human nutrition, 2nd ed. Report of a joint WHO/FAO expert consultation, Bangkok, Thailand, 21–30 September 1998. Geneva: World Health Organization and Food and Agriculture Organization of the United Nations; 2004 (https://apps.who.int/iris/bitstream/ handle/10665/42716/9241546123.pdf). • Diet, nutrition and the prevention of chronic diseases. Report of a joint WHO/FAO expert consultation. Geneva: World Health Organization; 2003 (WHO Technical Report Series No 916; https://apps.who. int/iris/bitstream/handle/10665/42665/WHO_TRS_916.pdf). • Promoting a healthy diet for the WHO Eastern Mediterranean Region: user-friendly guide. Cairo: WHO Regional Office for the Eastern Mediterranean; 2012 (https://apps.who.int/iris/ handle/10665/119951). • WHO, FAO. Sustainable healthy diets: guiding principles. Geneva: World Health Organization; 2019 (https://apps.who.int/iris/handle/10665/329409). License: CC BY-NC-SA 3.0 IGO. • Nutritional anaemias: tools for effective prevention and control. Geneva: World Health Organization; 2017. (https://apps.who.int/iris/handle/10665/259425). License: CC BY-NC-SA 3.0 IGO. • How together we can make the world’s most healthy and sustainable public food procurement. Copenhagen: WHO Regional Office for Europe; 2022 (https://apps.who.int/iris/ handle/10665/363337). License: CC BY-NC-SA 3.0 IGO. 2.2 Fortification of staple foods with vitamins and minerals Applicable contexts/population groups: Settings where the food vehicle to be fortified is commonly consumed; all population groups WHO recommendations: • Fortification of wheat flour with highly bioavailable iron is recommended as a public health strategy to improve haemoglobin concentrations and iron status, and to prevent anaemia and iron deficiency in populations, particularly for vulnerable groups such as children and women (strong recommendation, low certainty of evidence). • Fortification of wheat flour with folic acid is recommended as a public health strategy to improve folate status in populations (strong recommendation, low and very low certainty of evidence). • Fortification of maize flour and corn meal with iron is recommended to prevent iron deficiency in populations, particularly for vulnerable groups such and children and women. • Fortification of rice with iron is recommended as a public health strategy to improve the iron status of populations, in settings where rice is a staple food. • Fortification of rice with vitamin A may be used as a public health strategy to improve the iron status and vitamin A nutrition of populations. • Fortification of rice with folic acid may be used as a public health strategy to improve the folate nutritional status of populations. 6Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Considerations: • Food fortification should be guided by national standards, with quality assurance and quality control systems. Continuous programme monitoring should be in place as part of a process to ensure high- quality implementation. • Countries that fortify cereal grain products may also fortify other food items. A combined fortification strategy using multiple vehicles appears to be a suitably effective option for reaching all segments of the population. Fortification of cereal grain products should be integrated and monitored as part of the national programme for prevention and control of micronutrient deficiencies and insufficiencies. WHO guidelines, recommendations and resources: • Guidelines on food fortification with micronutrients. Geneva: World Health Organization; 2006 (https://apps.who.int/iris/handle/10665/43412). • Fortification of maize flour and corn meal with vitamins and minerals. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/251902). • Guideline: fortification of rice with vitamins and minerals as a public health strategy. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/272535). • Guideline: fortification of wheat flour with vitamins and minerals as a public health strategy. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/handle/10665/354783). 73.1 Nutrition counselling for pregnant women on healthy diet to reduce the risk of low birth weight Applicable contexts/population groups: Settings where 20% or more of women are underweight (low BMI); pregnant women WHO recommendation: • In undernourished populations (20% or more low BMI among women), nutrition education on increasing daily energy and protein intake is recommended for pregnant women to reduce the risk of low- birthweight neonates. Summary of key evidence: • Good nutrition and a healthy diet during pregnancy are critical for a mother’s health, as well as that of her child. A healthy diet contains adequate energy, protein, vitamins and minerals, obtained from a variety of foods, including green and orange vegetables, meat, fish, beans, nuts, whole grains and fruit. • Evidence suggests that nutrition education and counselling may support optimal gestational weight gain, reduce the risk of anaemia in late pregnancy, increase birth weight, and lower the risk of preterm delivery. This strategy aims to increase the diversity and amount of foods consumed; promote adequate weight gain through sufficient and balanced protein and energy intake; and promote consistent and continued use of micronutrient supplements, food supplements or fortified foods. • In undernourished populations, counselling may be more effective when women are also provided with nutrition support, such as food or micronutrient supplements where needed. Key actions for implementation: • Provide strong training to practitioners that includes standardized guidance on nutrition that is evidence informed, sustainable, reproducible, accessible and adaptable to different cultural settings. • Consider the delivery platform, provider and intervention style, to improve the engagement of pregnant women with antenatal care services. Women may be more receptive to advice and information provided in an unhurried, caring and supportive way. Stakeholders might wish to consider alternative delivery platforms (for example, peer counsellors, media reminders) and task-shifting for delivery of this intervention. • In areas that are also highly food insecure or those with little access to a variety of foods, providing additional complementary interventions, such as distribution of balanced protein and energy supplements, to improve the effectiveness of nutritional counselling, is recommended. Considerations: • Anthropometric characteristics of the general population are changing, and this needs to be taken into account by regularly reassessing the prevalence of undernutrition to ensure that the intervention remains relevant. Considerations: • Food fortification should be guided by national standards, with quality assurance and quality control systems. Continuous programme monitoring should be in place as part of a process to ensure high- quality implementation. • Countries that fortify cereal grain products may also fortify other food items. A combined fortification strategy using multiple vehicles appears to be a suitably effective option for reaching all segments of the population. Fortification of cereal grain products should be integrated and monitored as part of the national programme for prevention and control of micronutrient deficiencies and insufficiencies. WHO guidelines, recommendations and resources: • Guidelines on food fortification with micronutrients. Geneva: World Health Organization; 2006 (https://apps.who.int/iris/handle/10665/43412). • Fortification of maize flour and corn meal with vitamins and minerals. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/251902). • Guideline: fortification of rice with vitamins and minerals as a public health strategy. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/272535). • Guideline: fortification of wheat flour with vitamins and minerals as a public health strategy. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/handle/10665/354783). 3. Health & Nutrition 8Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia WHO guidelines, recommendations and resources: • WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/250796). • Healthy eating during pregnancy and breastfeeding: booklet for mothers. Copenhagen: World Health Organization. Regional Office for Europe; 2001 (https://apps.who.int/iris/ handle/10665/347891). 3.2 Uterotonic for the prevention of postpartum haemorrhage during the third stage of labour Applicable contexts/population groups: All countries, all settings; all births WHO recommendation: • The use of an effective uterotonic for the prevention of postpartum haemorrhage (PPH) during the third stage of labour is recommended for all births. To effectively prevent PPH, only one of the following uterotonics should be used: oxytocin, carbetocin, misoprostol, ergometrine/methylergometrine, oxytocin and ergometrine fixed-dose combination. • The use of oxytocin (10 international units [IU], intramuscular / intravenous) is recommended for the prevention of postpartum haemorrhage for all births. In situations where women giving birth vaginally already have intravenous access, the slow intravenous administration of 10 IU oxytocin is recommended in preference to intramuscular administration (context-specific recommendation). Summary of key evidence: • When used for PPH prevention, oxytocin, carbetocin, misoprostol, ergometrine/methylergometrine, and a fixed-dose combination of oxytocin and ergometrine demonstrated clinical benefits especially in terms of PPH reduction compared with no uterotonics. • The undesirable side effects do not outweigh the clinical benefits for any of these uterotonic options when considered in the context of not using any uterotonic. • Evidence suggests that there is probably no important variability in, or uncertainty about, how much women value the health outcomes associated with these uterotonics. • There is clear evidence in favour of intravenous oxytocin in terms of health outcomes. When compared to intramuscular oxytocin, intravenous oxytocin reduces the risk of postpartum haemorrhage, severe postpartum haemorrhage, blood transfusion and severe maternal morbidity, with no clear differences in undesirable effects. While it is uncertain whether intravenous administration is more cost-effective, routine intravenous oxytocin use for postpartum haemorrhage prevention imposes additional resource requirements, may negatively impact women’s comfort and can increase health inequities. The feasibility of intravenous administration may also vary in different settings. However, in situations where intravenous access is already in place at vaginal birth, the clinical benefits of intravenous administration outweigh these other considerations. 9Key actions for implementation: • The recommendations should be adapted into documents and tools that are appropriate for different locations and contexts, to meet the specific needs of each country and health service. • An enabling environment should be created for the implementation of these recommendations, including education to support behaviour change among skilled health personnel to facilitate the use of evidence- based practices. • National health systems need to ensure that supplies of good-quality uterotonics and the necessary equipment are available wherever maternity services are provided. This includes establishing robust and sustainable regulatory, procurement and logistics processes that can ensure good-quality medicines and equipment are obtained, transported and stored correctly. • Local professional societies and training institutions can play an important role in implementation, and an all-inclusive and participatory process should be encouraged. • Procurement agencies at all levels of supply chains should procure only quality-certified uterotonic medicines. • It is advised that programmes to implement uterotonics for PPH prevention ensure women are adequately informed in advance about the need to use a uterotonic to prevent PPH, the available uterotonic options, the possible side-effects of these options and their rights to choose what care they receive. Considerations: • This recommendation applies to women undergoing a vaginal birth or caesarean section. For injectable uterotonics, skilled health personnel who are trained to administer them are required. • To maximize efficacy, uterotonics are best given immediately (preferably within one minute) after the birth of the baby or babies. • Administration of a uterotonic for prevention of PPH need not impede the delaying of cord clamping, as recommended by WHO. • The guideline development group advised that all women are to be provided with information – ideally during antenatal care – on the need for an effective uterotonic to prevent PPH. WHO Essential Medicines List or Prequalified product: • oxytocin – Injection: 10 IU in 1 mL • carbetocin – Injection (heat stable): 100 micrograms/mL • misoprostol – Tablet: 200 micrograms • ergometrine/methylergometrine – Injection: 200 micrograms (hydrogen maleate) in 1 mL ampoule WHO guidelines, recommendations and resources • WHO recommendations: uterotonics for the prevention of postpartum haemorrhage. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/277276). • WHO recommendations for the prevention and treatment of postpartum haemorrhage. Geneva: World Health Organization; 2012 (https://apps.who.int/iris/handle/10665/75411). • World Health Organization model list of essential medicines: 22nd list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345533). • WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth. Geneva: World Health Organization; 2020 (https://apps.who.int/ iris/handle/10665/336308). License: CC BY-NC-SA 3.0 IG WHO guidelines, recommendations and resources: • WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/250796). • Healthy eating during pregnancy and breastfeeding: booklet for mothers. Copenhagen: World Health Organization. Regional Office for Europe; 2001 (https://apps.who.int/iris/ handle/10665/347891). 3.2 Uterotonic for the prevention of postpartum haemorrhage during the third stage of labour Applicable contexts/population groups: All countries, all settings; all births WHO recommendation: • The use of an effective uterotonic for the prevention of postpartum haemorrhage (PPH) during the third stage of labour is recommended for all births. To effectively prevent PPH, only one of the following uterotonics should be used: oxytocin, carbetocin, misoprostol, ergometrine/methylergometrine, oxytocin and ergometrine fixed-dose combination. • The use of oxytocin (10 international units [IU], intramuscular / intravenous) is recommended for the prevention of postpartum haemorrhage for all births. In situations where women giving birth vaginally already have intravenous access, the slow intravenous administration of 10 IU oxytocin is recommended in preference to intramuscular administration (context-specific recommendation). Summary of key evidence: • When used for PPH prevention, oxytocin, carbetocin, misoprostol, ergometrine/methylergometrine, and a fixed-dose combination of oxytocin and ergometrine demonstrated clinical benefits especially in terms of PPH reduction compared with no uterotonics. • The undesirable side effects do not outweigh the clinical benefits for any of these uterotonic options when considered in the context of not using any uterotonic. • Evidence suggests that there is probably no important variability in, or uncertainty about, how much women value the health outcomes associated with these uterotonics. • There is clear evidence in favour of intravenous oxytocin in terms of health outcomes. When compared to intramuscular oxytocin, intravenous oxytocin reduces the risk of postpartum haemorrhage, severe postpartum haemorrhage, blood transfusion and severe maternal morbidity, with no clear differences in undesirable effects. While it is uncertain whether intravenous administration is more cost-effective, routine intravenous oxytocin use for postpartum haemorrhage prevention imposes additional resource requirements, may negatively impact women’s comfort and can increase health inequities. The feasibility of intravenous administration may also vary in different settings. However, in situations where intravenous access is already in place at vaginal birth, the clinical benefits of intravenous administration outweigh these other considerations. 10 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia 3.3 Optimal timing of umbilical cord clamping Applicable contexts/population groups: All countries, all settings; all births WHO recommendation: Delayed umbilical cord clamping (not earlier than 1 minute after birth) is recommended for improved maternal and infant health and nutrition outcomes (Strong recommendation for, moderate certainty evidence) and should be performed during the provision of essential newborn care. Summary of key evidence: • Term infants receiving early cord clamping (less than 1 min after birth) are at significantly higher risk of developing iron deficiency at 3–6 months of age than infants receiving delayed cord clamping. • Early cord clamping in preterm infants increases the risk of necrotizing enterocolitis and intraventricular haemorrhage and the need for blood transfusions. • The primary intervention of active management of the third stage of labour for the prevention of postpartum hemorrhage is the use of a uterotonic drug. Early cord clamping is generally contraindicated as a component of active management. Key actions for implementation: • Revise and update policies (at regional, national and local levels), curricula/textbooks and clinical protocols to include delayed cord clamping as part of essential newborn care. In the past, protocols for neonatal resuscitation and active management of the third stage of labour have conflicted with the practice of delayed cord clamping. Policies need to be updated so that they reflect the most up-to-date evidence-based care, which includes delayed cord clamping. • Provide in-service training on the optimal timing of umbilical cord clamping and how it can be integrated with other care practices. • Address and adjust the organization of delivery care services (in terms of physical location of labour beds and resuscitation tables, responsibilities of delivery care providers, etc.), to allow implementation of delayed cord clamping along with other essential newborn care practices (for example, skin-to-skin contact, early initiation of breastfeeding), in a variety of settings and delivery modes (i.e. vaginal and caesarean). Considerations: • Early cord clamping (less than 1 min after birth) is not recommended unless the neonate is asphyxiated and needs to be moved immediately for resuscitation. • For newborn term or preterm babies who do not require positive-pressure ventilation, the cord should not be clamped earlier than 1 min after birth. • When newborn term or preterm babies require positive-pressure ventilation, the cord should be clamped and cut, to allow effective ventilation to be performed. » If there is experience in providing positive-pressure ventilation without cutting the umbilical cord, ventilation can be initiated before cutting the cord. • Newborn babies who do not breathe spontaneously after thorough drying should be stimulated by rubbing the back 2–3 times before clamping the cord and initiating positive-pressure ventilation. • Delayed cord clamping is also recommended among women living with HIV or women with unknown HIV status. WHO Essential Medicines List or Prequalified product: N/A 11 WHO guidelines, recommendations and resources • WHO recommendations: intrapartum care for a positive childbirth experience. Geneva: World Health Organziation; 2018 (https://apps.who.int/iris/handle/10665/260178). • Guideline: delayed umbilical cord clamping for improved maternal and infant health and nutrition outcomes. Geneva: World Health Organization; 2014 (https://apps.who.int/iris/ handle/10665/148793). • WHO recommendations for the prevention and treatment of postpartum haemorrhage. Geneva: World Health Organization; 2012 (https://apps.who.int/iris/handle/10665/75411). • Guidelines on basic newborn resuscitation. Geneva: World Health Organization; 2012 (https://apps. who.int/iris/handle/10665/75157). 3.4 Provision of iron-containing micronutrient powders for point-of-use fortification of foods for infants and young children 6–23 months of age and children aged 2–12 years Applicable contexts/population groups: Settings in which the prevalence of anaemia in children is 20% or more WHO recommendation: • In populations where anaemia is a public health problem, point-of-use fortification of complementary foods with iron-containing micronutrient powders (MNPs) is recommended, to improve iron status and reduce anaemia among infants and young children aged 6–23 months of age and children 2–12 years of age. • A suggested scheme for fortification and the composition of MNP sachets is provided in the table below. Suggested scheme for point-of-use fortification with iron-containing micronutrient powders of foods Composition per sacheta Iron: 10–12.5 mg of elemental iron for children 6 months–4 years of age and 12.5–30 mg of elemental iron for children 5–12 years of ageb Vitamin A: 300 µg of retinol Zinc: 5 mg of elemental zinc With or without other micronutrients to achieve 100% of the recommended nutrient intakec Regimen Programme target of 90 sachets/doses over a 6-month period a MNPs are generally packaged in small sachets that are temperature- and moisture-resistant, easy to transport and store, and have a long shelf-life b 12.5 mg of elemental iron equals 37.5 mg of ferrous fumarate or 62.5 mg of ferrous sulfate heptahydrate or equivalent amounts in other iron compounds. In children aged 6–12 months, sodium iron EDTA (NaFeEDTA) is generally not recommended. If NaFeEDTA is selected as a source of iron, the EDTA intake (including other dietary sources) should not exceed 1.9 mg EDTA/kg/day. c Recommended nutrient intake (RNI). Multiple micronutrient powders can be formulated with or without other vitamins and minerals in addition to iron, vitamin A and zinc, to achieve 100% of the recommended nutrient intake, and also taking into consideration the technical and sensory properties. 3.3 Optimal timing of umbilical cord clamping Applicable contexts/population groups: All countries, all settings; all births WHO recommendation: Delayed umbilical cord clamping (not earlier than 1 minute after birth) is recommended for improved maternal and infant health and nutrition outcomes (Strong recommendation for, moderate certainty evidence) and should be performed during the provision of essential newborn care. Summary of key evidence: • Term infants receiving early cord clamping (less than 1 min after birth) are at significantly higher risk of developing iron deficiency at 3–6 months of age than infants receiving delayed cord clamping. • Early cord clamping in preterm infants increases the risk of necrotizing enterocolitis and intraventricular haemorrhage and the need for blood transfusions. • The primary intervention of active management of the third stage of labour for the prevention of postpartum hemorrhage is the use of a uterotonic drug. Early cord clamping is generally contraindicated as a component of active management. Key actions for implementation: • Revise and update policies (at regional, national and local levels), curricula/textbooks and clinical protocols to include delayed cord clamping as part of essential newborn care. In the past, protocols for neonatal resuscitation and active management of the third stage of labour have conflicted with the practice of delayed cord clamping. Policies need to be updated so that they reflect the most up-to-date evidence-based care, which includes delayed cord clamping. • Provide in-service training on the optimal timing of umbilical cord clamping and how it can be integrated with other care practices. • Address and adjust the organization of delivery care services (in terms of physical location of labour beds and resuscitation tables, responsibilities of delivery care providers, etc.), to allow implementation of delayed cord clamping along with other essential newborn care practices (for example, skin-to-skin contact, early initiation of breastfeeding), in a variety of settings and delivery modes (i.e. vaginal and caesarean). Considerations: • Early cord clamping (less than 1 min after birth) is not recommended unless the neonate is asphyxiated and needs to be moved immediately for resuscitation. • For newborn term or preterm babies who do not require positive-pressure ventilation, the cord should not be clamped earlier than 1 min after birth. • When newborn term or preterm babies require positive-pressure ventilation, the cord should be clamped and cut, to allow effective ventilation to be performed. » If there is experience in providing positive-pressure ventilation without cutting the umbilical cord, ventilation can be initiated before cutting the cord. • Newborn babies who do not breathe spontaneously after thorough drying should be stimulated by rubbing the back 2–3 times before clamping the cord and initiating positive-pressure ventilation. • Delayed cord clamping is also recommended among women living with HIV or women with unknown HIV status. WHO Essential Medicines List or Prequalified product: N/A 12 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Summary of key evidence: • It can be challenging to meet the requirements for key nutrients like iron and vitamin A in young children through plant-based diets alone. In many settings, the cost of animal-source foods is prohibitive and mass- fortified products may not be available or may not meet nutrient needs. • MNPs that contain multiple micronutrients that can be mixed into complementary foods have been shown to reduce iron deficiency and anaemia and increase haemoglobin concentrations. • MNPs have several logistical advantages over supplements (for example, packaged in small sachets, making them easy to transport and store) as well as biological advantages (for example, reduced frequency and severity of side-effects, a more “physiological” provision of nutrients with food). Key actions for implementation: • The term “home fortification” has been substituted by the term “point-of-use fortification” because the process of fortification occurs not only at home but also at schools, nurseries, refugee camps or other places, where appropriate. • The use of multiple micronutrient powders is a preventive strategy for implementation at population level without screening for any condition or disease. Children diagnosed with anaemia should be treated appropriately, according to WHO and national guidelines. • Anaemia is frequently caused by iron deficiency, but other factors may contribute to anaemia,including other micronutrient deficiencies (for example, folic acid, zinc, vitamins A and B12), malaria, soil transmitted helminths, other infections, and blood disorders (for example, thalassaemias, sickle cell). The use of multiple micronutrient powders for the age groups indicated in the recommendations should be part of an integrated approach to address anaemia, which should explicitly address inequities in the causes of micronutrient deficiencies (such as some population groups are more affected by and/or vulnerable to micronutrient deficiencies than other groups. This may be determined by income level, place of residence or educational level, cultural practices, social norms around gender, or stigma. • Programmes of point-of-use fortification with micronutrient powders should include a behaviour change strategy that promotes awareness and correct use of this product, proper and hygienic preparation, feeding of complementary foods for children older than 6 months and a healthy diet for children older than 2 years. Recommended breastfeeding practices, hand-washing with soap, prompt attention to fever in malaria settings, and measures to manage diarrhoea should also be included. • Further, these programmes should include training for health-care workers or other types of workers to adequately provide nutrition counselling and demonstrate the correct use of multiple micronutrient powders. Considerations • In malaria-endemic areas, the provision of iron in any form, including micronutrient powders for point of-use fortification, should be implemented in conjunction with measures to prevent, diagnose and treat malaria. Provision of iron through these interventions should not be made to children who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated nets and vector control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • In settings where iron supplementation among the target population has been widely implemented and has proved to be effective, a cost-effectiveness analysis is recommended, to determine whether the current intervention should be replaced by provision of MNPs. WHO Essential Medicines List or Prequalified product Multiple micronutrient powder. Sachets containing: • iron (elemental) 12.5 mg (as coated ferrous fumarate) • zinc (elemental) 5 mg • vitamin A 300 micrograms • with or without other micronutrients at recommended daily values 13 WHO guidelines, recommendations and resources • WHO guideline: Use of multiple micronutrient powders for point-of-use fortification of foods consumed by infants and young children aged 6–23 months and children aged 2–12 years. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/252540). • World Health Organization model list of essential medicines for children: 8th list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345534). • eCatalogue of indicators for micronutrient programmes. (https://extranet.who.int/indcat/) 3.5 Oral preventive iron supplementation in children Applicable contexts/population groups: Settings in which the prevalence of anaemia is 20% or higher in infants and young children 6–23 months of age or children aged 2–12 years. WHO recommendation for. For the improvement of iron status and reducing the risk of anaemia: • Intermittent iron supplementation is recommended as a public health intervention for children 2–12 years of age, living in settings where the prevalence of anaemia is 20% or higher in this age group • Daily iron supplementation is recommended as a public health intervention for infants and young • children aged 6–23 months, and children aged 2–12 years, living in settings where the prevalence of anaemia is 40% or higher in these age groups. • A suggested scheme for supplementation is provided in the table below. Suggested scheme for preventive iron supplementation 6–23 months 24–59 months 24–59 months 5–12 years 5–12 years Dose 10–12.5 mg elemental irona 30 mg elemental irona 25 mg elemental irona 30–60 mg elemental irona 45 mg elemental irona Form Drops or syrups Drops, syrups, or tablets Drops, syrups Tablets or capsules Tablets or capsules Frequency Daily Daily One supplement per week Daily One supplement per week Duration 3 consecutive months per year 3 consecutive months per year 6 months per yearc 3 consecutive months per year 6 months per yearc Setting (population prevalence of anaemia) 40% or higherb 40% or higherb 20% or higherb 40% or higherb 20% or higherb Summary of key evidence: • It can be challenging to meet the requirements for key nutrients like iron and vitamin A in young children through plant-based diets alone. In many settings, the cost of animal-source foods is prohibitive and mass- fortified products may not be available or may not meet nutrient needs. • MNPs that contain multiple micronutrients that can be mixed into complementary foods have been shown to reduce iron deficiency and anaemia and increase haemoglobin concentrations. • MNPs have several logistical advantages over supplements (for example, packaged in small sachets, making them easy to transport and store) as well as biological advantages (for example, reduced frequency and severity of side-effects, a more “physiological” provision of nutrients with food). Key actions for implementation: • The term “home fortification” has been substituted by the term “point-of-use fortification” because the process of fortification occurs not only at home but also at schools, nurseries, refugee camps or other places, where appropriate. • The use of multiple micronutrient powders is a preventive strategy for implementation at population level without screening for any condition or disease. Children diagnosed with anaemia should be treated appropriately, according to WHO and national guidelines. • Anaemia is frequently caused by iron deficiency, but other factors may contribute to anaemia,including other micronutrient deficiencies (for example, folic acid, zinc, vitamins A and B12), malaria, soil transmitted helminths, other infections, and blood disorders (for example, thalassaemias, sickle cell). The use of multiple micronutrient powders for the age groups indicated in the recommendations should be part of an integrated approach to address anaemia, which should explicitly address inequities in the causes of micronutrient deficiencies (such as some population groups are more affected by and/or vulnerable to micronutrient deficiencies than other groups. This may be determined by income level, place of residence or educational level, cultural practices, social norms around gender, or stigma. • Programmes of point-of-use fortification with micronutrient powders should include a behaviour change strategy that promotes awareness and correct use of this product, proper and hygienic preparation, feeding of complementary foods for children older than 6 months and a healthy diet for children older than 2 years. Recommended breastfeeding practices, hand-washing with soap, prompt attention to fever in malaria settings, and measures to manage diarrhoea should also be included. • Further, these programmes should include training for health-care workers or other types of workers to adequately provide nutrition counselling and demonstrate the correct use of multiple micronutrient powders. Considerations • In malaria-endemic areas, the provision of iron in any form, including micronutrient powders for point of-use fortification, should be implemented in conjunction with measures to prevent, diagnose and treat malaria. Provision of iron through these interventions should not be made to children who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated nets and vector control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • In settings where iron supplementation among the target population has been widely implemented and has proved to be effective, a cost-effectiveness analysis is recommended, to determine whether the current intervention should be replaced by provision of MNPs. WHO Essential Medicines List or Prequalified product Multiple micronutrient powder. Sachets containing: • iron (elemental) 12.5 mg (as coated ferrous fumarate) • zinc (elemental) 5 mg • vitamin A 300 micrograms • with or without other micronutrients at recommended daily values 14 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia a 10 mg of elemental iron equals 50 mg of ferrous sulfate heptahydrate, 30 mg of ferrous fumarate or 83.3 mg of ferrous gluconate. b In the absence of prevalence data in this group, consider proxies for the risk of anaemia. For the most recent estimates, visit the WHO- hosted Vitamin and Mineral Nutrition Information System (VMNIS) (http://www.who.int/vmnis/en/). c Three months of supplementation followed by three months of no supplementation, after which the provision of supplements should restart. If feasible, intermittent supplements could be given throughout the school or calendar year. Summary of key evidence: • Iron deficiency is thought to be the primary nutritional cause of anaemia and is associated with impaired cognitive development and school performance in young children. • Children are particularly vulnerable to iron deficiency anaemia because of their increased iron requirements in the periods of rapid growth, especially in the first 5 years of life. • Supplementation with iron once, twice or three times per week on non-consecutive days has also been proposed as an effective and safe way to increase children’s iron intake. These intermittent regimens may lead to fewer side-effects than the daily regimen and increase adherence to supplementation. Key actions for implementation: • Prior to implementation, a public health programme that includes the provision of iron supplements to children should have well-defined objectives that take into account available resources, existing policies, suitable delivery platforms and suppliers, communication channels, and potential stakeholders. The selection of the most appropriate delivery platform should be context specific, with the aim of ensuring that the most vulnerable members of the populations are reached. • The provision of iron supplements may be integrated into school or community programmes to reach the target populations. The selection of the most appropriate delivery platform should be context specific, with the aim of ensuring that the most vulnerable members of the populations are reached. • Supplementation programmes should start with a pilot and be scaled up as experience and evidence grow and resources allow. • Ideally, an iron supplementation programme should be implemented as part of a multisectoral approach to control anaemia, through addressing other micronutrient deficiencies (vitamin A, folic acid, B vitamins, in addition to iron), and infectious disease (malaria, helminths/parasites). Though iron deficiency is frequently the primary factor contributing to anaemia, it is important to recognize that not all anaemia will be corrected with iron alone. • A plan for monitoring and evaluation with appropriate indicators is encouraged at all stages. As part of this, an ongoing assessment of the accessibility and acceptability of the intervention should be conducted, to inform programme design and development. • Proper training of health workers is necessary for delivery of the intervention and also for collection of the data needed for programme monitoring and surveillance, including information on factors related to health inequities. 15 Considerations: • The recommendations on oral iron supplementation are designed as a preventive strategy for implementation at the population level. If a child is diagnosed with anaemia, national guidelines for the treatment of anaemia should be followed. • If iron supplementation is integrated into existing school or community programmes, these programmes should ensure that the daily nutritional needs of children are met and not exceeded, through the evaluation of nutritional status and intake, as well as consideration of existing anaemia and micronutrient deficiency- control measures (such as provision of vitamin A supplements, fortified foods and anthelminthic therapy). • In malaria-endemic areas, iron supplementation does not increase the risk of clinical malaria or death when regular malaria-surveillance and treatment services are provided. Oral iron interventions should not be given to children who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria, and treatment with effective antimalarial drug therapy. • The risk of clinical malaria is not more likely among iron-replete children given iron supplementation in malaria-endemic areas. There is no need to screen for anaemia prior to iron supplementation in settings where anaemia is highly prevalent. • Since malaria infection can occur in early infancy and is especially dangerous at this age, in malaria- endemic areas, iron supplements should only be given to infants who sleep under insecticide-treated bednets, and where all episodes of malaria illness can be promptly treated with effective antimalarial drug therapy according to national guidelines. WHO Essential Medicines List or Prequalified product Ferrous salt • Oral liquid: equivalent to 25 mg iron (as sulfate)/mL. • Tablet: equivalent to 60 mg iron. WHO guidelines, recommendations and resources • Guideline: daily iron supplementation in infants and children. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/204712). • Guideline: Intermittent iron supplementation in preschool and school-age children. Geneva: World Health Organization; 2011 (https://apps.who.int/iris/handle/10665/44648). • World Health Organization model list of essential medicines for children: 8th list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345534). 16 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia 3.6 Oral preventive iron and folic acid supplementation in menstruating non-pregnant adolescent girls and women Applicable contexts/population groups: Settings in which the prevalence of anaemia is 20% or higher among non-pregnant women. WHO recommendation for. For the improvement of iron status and reducing the risk of anaemia: • Intermittent iron and folic acid supplementation is recommended as a public health intervention for menstruating non-pregnant adolescent girls and women living in settings where the prevalence of anaemia among non-pregnant women is 20% or higher. • Daily iron supplementation is recommended as a public health intervention for menstruating non-pregnant adolescent girls and women living in settings where the prevalence of anaemia among non-pregnant women is 40% or higher. • A suggested scheme for supplementation is provided in the table below. Suggested scheme for preventive and folic acid iron supplementation Daily Intermittent Composition Iron: 30–60 mg of elemental irona Iron: 60 mg of elemental irona Folic acid: 2800 μg (2.8 mg) Form Tablets Tablets Frequency Daily One supplement per week Duration 3 consecutive months per year 6 months per yearc Setting (population prevalence of anaemia) 40% or higherb 20% or higherb a 60 mg of elemental iron equals 300 mg of ferrous sulfate heptahydrate, 180 mg of ferrous fumarate or 500 mg of ferrous gluconate. b In the absence of prevalence data in this group, consider proxies for the risk of anaemia. For the most recent estimates, visit the WHO- hosted Vitamin and Mineral Nutrition Information System (VMNIS) (http://www.who.int/vmnis/en/). c Three months of supplementation followed by three months of no supplementation, after which the provision of supplements should restart. 17 Summary of key evidence: • About one third of non-pregnant women have anaemia and roughly half of these cases are estimated to be due to iron deficiency. Because of their iron losses due to menstruation and the typically low iron content of their diets, menstruating non-pregnant adolescent girls and women are at particular risk of iron deficiency and anaemia. • Adherence may be a concern if the intervention is perceived as non-essential. Barriers to adherence may need to be addressed (for instance, with behaviour change communication if the intervention is not perceived as necessary among the beneficiaries). • Intermittent supplementation with iron and folic acid (such as once, twice or three times a week) has been shown to be effective, safe and more acceptable than daily supplementation. Key actions for implementation: • Prior to implementation, a supplementation programme should have well-defined objectives that take into account available resources, existing policies, suitable delivery platforms and suppliers, communication channels and potential stakeholders. » Supplementation should be preceded by an evaluation of the nutritional status of menstruating non-pregnant adolescent girls and women, and of the existing measures to control anaemia and folate insufficiency, such as programmes for hookworm control, food fortification or adequate diet promotion, so as to not exceed recommended dosages of iron. » These interventions should ideally be integrated into national programmes for sexual and reproductive health. The selection of the most appropriate delivery platform should be context specific, with the aim of reaching the most vulnerable populations and ensuring a timely and continuous supply of supplements. • Supplementation programmes should start with a pilot and be scaled up as experience and evidence grow and resources allow. • Providing behaviour change communication on the benefits of the intervention and management of side- effects, along with provision of high-quality supplements with appropriate packaging, will improve the acceptability and adherence to supplementation. • A plan for monitoring and evaluation with appropriate indicators is encouraged at all stages. • All women, from the moment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement. Daily oral iron and folic acid supplementation should be part of routine antenatal care, started as early as possible and continued throughout the pregnancy. 3.6 Oral preventive iron and folic acid supplementation in menstruating non-pregnant adolescent girls and women Applicable contexts/population groups: Settings in which the prevalence of anaemia is 20% or higher among non-pregnant women. WHO recommendation for. For the improvement of iron status and reducing the risk of anaemia: • Intermittent iron and folic acid supplementation is recommended as a public health intervention for menstruating non-pregnant adolescent girls and women living in settings where the prevalence of anaemia among non-pregnant women is 20% or higher. • Daily iron supplementation is recommended as a public health intervention for menstruating non-pregnant adolescent girls and women living in settings where the prevalence of anaemia among non-pregnant women is 40% or higher. • A suggested scheme for supplementation is provided in the table below. Suggested scheme for preventive and folic acid iron supplementation Daily Intermittent Composition Iron: 30–60 mg of elemental irona Iron: 60 mg of elemental irona Folic acid: 2800 μg (2.8 mg) Form Tablets Tablets Frequency Daily One supplement per week Duration 3 consecutive months per year 6 months per yearc Setting (population prevalence of anaemia) 40% or higherb 20% or higherb a 60 mg of elemental iron equals 300 mg of ferrous sulfate heptahydrate, 180 mg of ferrous fumarate or 500 mg of ferrous gluconate. b In the absence of prevalence data in this group, consider proxies for the risk of anaemia. For the most recent estimates, visit the WHO- hosted Vitamin and Mineral Nutrition Information System (VMNIS) (http://www.who.int/vmnis/en/). c Three months of supplementation followed by three months of no supplementation, after which the provision of supplements should restart. 18 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Considerations: • These recommendations are designed as a preventive strategy for implementation at population level. If an individual is diagnosed as having anaemia in a clinical setting, she should be treated with daily supplementation of iron (120 mg of elemental iron) and folic acid (400 μg or 0.4 mg) supplementation until her haemoglobin concentration rises to normal. She can then switch to back to the preventive regimen to avoid recurrence of anaemia. • In malaria-endemic areas, the provision of iron and folic acid supplements should be implemented in conjunction with adequate measures to prevent, diagnose and treat malaria. • In malaria-endemic areas, iron supplementation does not increase the risk of clinical malaria or death when regular malaria-surveillance and treatment services are provided. Oral preventive iron interventions should not be given to those who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • The risk of clinical malaria is not more likely among iron-replete individuals given iron supplementation in malaria-endemic areas. There is no need to screen for anaemia prior to iron supplementation in settings where anaemia is highly prevalent. WHO Essential Medicines List or Prequalified product Ferrous salt • Oral liquid: equivalent to 25 mg iron (as sulfate)/mL. • Tablet: equivalent to 60 mg iron. Ferrous salt + folic acid • Tablet: equivalent to 60 mg iron + 400 µg folic acid WHO guidelines, recommendations and resources • Guideline: implementing effective actions for improving adolescent nutrition. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/260297). • Guideline. Daily iron supplementation in adult women and adolescent girls. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/204761). • Guideline: intermittent iron and folic acid supplementation in menstruating women. Geneva: World Health Organization; 2011 (https://apps.who.int/iris/handle/10665/44649). • World Health Organization model list of essential medicines: 22nd list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345533). 19 3.7 Oral preventive iron and folic acid supplementation for pregnant women Applicable contexts/population groups: All countries, all settings, routine antenatal care; pregnant women WHO recommendations: • Daily oral iron and folic acid supplementation is recommended for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight and preterm birth. • Intermittent iron and folic acid supplementation is recommended as a public health intervention for menstruating non-pregnant adolescent girls and women living in settings where the prevalence of anaemia among non-pregnant women is 20% or higher. • A suggested scheme for supplementation is provided in the table below. Suggested scheme for preventive and folic acid iron supplementation Daily Intermittent Composition Iron: 30–60 mg of elemental irona Iron: 60 mg of elemental irona Folic acid: 2800 μg (2.8 mg) Form Tablets Tablets Frequency Daily One supplement per week Duration 3 consecutive months per year 6 months per yearc Setting (population prevalence of anaemia) Allb 20% or higherb a 60 mg of elemental iron equals 300 mg of ferrous sulfate heptahydrate, 180 mg of ferrous fumarate or 500 mg of ferrous gluconate. b In the absence of prevalence data in this group, consider proxies for the risk of anaemia. For the most recent estimates, visit the WHO- hosted Vitamin and Mineral Nutrition Information System (VMNIS) (http://www.who.int/vmnis/en/). c Three months of supplementation followed by three months of no supplementation, after which the provision of supplements should restart. Summary of key evidence: • About one third of non-pregnant women have anaemia and roughly half of these cases are estimated to be due to iron deficiency. Because of their iron losses due to menstruation and often low iron content of their diets, menstruating non-pregnant adolescent girls and women are at particular risk of iron deficiency and anaemia. • Adherence may be a concern if the intervention is perceived as non-essential. Barriers to adherence may need to be addressed (for instance, with behaviour-change communication if the intervention is not perceived as necessary among the beneficiaries). • Intermittent supplementation with iron and folic acid (such as once, twice or three times a week) has been shown to be effective, safe and more acceptable than daily supplementation. Considerations: • These recommendations are designed as a preventive strategy for implementation at population level. If an individual is diagnosed as having anaemia in a clinical setting, she should be treated with daily supplementation of iron (120 mg of elemental iron) and folic acid (400 μg or 0.4 mg) supplementation until her haemoglobin concentration rises to normal. She can then switch to back to the preventive regimen to avoid recurrence of anaemia. • In malaria-endemic areas, the provision of iron and folic acid supplements should be implemented in conjunction with adequate measures to prevent, diagnose and treat malaria. • In malaria-endemic areas, iron supplementation does not increase the risk of clinical malaria or death when regular malaria-surveillance and treatment services are provided. Oral preventive iron interventions should not be given to those who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • The risk of clinical malaria is not more likely among iron-replete individuals given iron supplementation in malaria-endemic areas. There is no need to screen for anaemia prior to iron supplementation in settings where anaemia is highly prevalent. WHO Essential Medicines List or Prequalified product Ferrous salt • Oral liquid: equivalent to 25 mg iron (as sulfate)/mL. • Tablet: equivalent to 60 mg iron. Ferrous salt + folic acid • Tablet: equivalent to 60 mg iron + 400 µg folic acid WHO guidelines, recommendations and resources • Guideline: implementing effective actions for improving adolescent nutrition. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/260297). • Guideline. Daily iron supplementation in adult women and adolescent girls. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/204761). • Guideline: intermittent iron and folic acid supplementation in menstruating women. Geneva: World Health Organization; 2011 (https://apps.who.int/iris/handle/10665/44649). • World Health Organization model list of essential medicines: 22nd list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345533). 20 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Key actions for implementation: • Prior to implementation, a supplementation programme should have well-defined objectives that take into account available resources, existing policies, suitable delivery platforms and suppliers, communication channels and potential stakeholders. • Supplementation should be preceded by an evaluation of the nutritional status of menstruating non-pregnant adolescent girls and women, and of the existing measures to control anaemia and folate insufficiency, such as programmes for hookworm control, food fortification or adequate diet promotion, so as to not exceed recommended dosages of iron. • These interventions should ideally be integrated into national programmes for sexual and reproductive health and the selection of the most appropriate delivery platform should be context specific, with the aim of reaching the most vulnerable populations and ensuring a timely and continuous supply of supplements. • Supplementation programmes should start with a pilot and be scaled up as experience and evidence grow and resources allow. • Providing behaviour change communication on the benefits of the intervention and management of side- effects, along with provision of high-quality supplements with appropriate packaging, will improve the acceptability and adherence to supplementation. • A plan for monitoring and evaluation with appropriate indicators is encouraged at all stages. • All women, from the moment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement. Daily oral iron and folic acid supplementation should be part of routine antenatal care, started as early as possible and continued throughout pregnancy. Considerations: • These recommendations are designed as a preventive strategy for implementation at population level. If an individual is diagnosed as having anaemia in a clinical setting, she should be treated with daily iron (120 mg of elemental iron) and folic acid (400 μg or 0.4 mg) supplementation until her haemoglobin concentration rises to normal. She can then switch to back to the preventive regimen to avoid recurrence of anaemia. • In malaria-endemic areas, the provision of iron and folic acid supplements should be implemented in conjunction with adequate measures to prevent, diagnose and treat malaria. • In malaria-endemic areas, iron supplementation does not increase the risk of clinical malaria or death when regular malaria-surveillance and treatment services are provided. Oral preventive iron interventions should not be given to those who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • The risk of clinical malaria is not more likely among iron-replete than those given iron supplementation in malaria-endemic areas. There is no need to screen for anaemia prior to iron supplementation in settings where anaemia is highly prevalent. WHO Essential Medicines List or Prequalified product Ferrous salt • Oral liquid: equivalent to 25 mg iron (as sulfate)/mL. • Tablet: equivalent to 60 mg iron. Ferrous salt + folic acid • Tablet: equivalent to 60 mg iron + 400 µg folic acid 21 WHO guidelines, recommendations and resources • World Health Organization model list of essential medicines: 22nd list. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/345533). • WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/250796). • Guideline: Intermittent iron and folic acid supplementation in non-anaemic pregnant women. Geneva: World Health Organization; 2011 (https://apps.who.int/iris/handle/10665/75335). 3.8 Malaria: Indoor residual spraying (IRS) with a product prequalified by WHO Applicable contexts/population groups: Populations at risk of malaria WHO recommendation: IRS should be deployed for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission (Strong recommendation for, low certainty evidence) Summary of key evidence: • IRS may reduce P. falciparum incidence and parasite prevalence compared to no IRS in areas of intense malaria transmission and in areas of unstable malaria. • IRS may reduce P. falciparum incidence compared to no use of insecticide-treated nets (ITNs) in areas of intense malaria transmission but may increase incidence compared to ITNS in areas of unstable malaria. • IRS may result in little to no difference in parasite prevalence compared to ITNs in areas of intense malaria transmission and in areas of unstable malaria. Key actions for implementation: • WHO recommends that WHO-prequalified insecticidal products be selected for IRS use and that these be selected based on the insecticide susceptibility of the local malaria vector(s). Insecticide formulations currently used for IRS fall into five major insecticide classes with three modes of action, based on their primary target site in the vector. • IRS is considered an appropriate intervention where: » the majority of the vector population feeds and rests indoors; » people mainly sleep indoors at night; » the malaria transmission pattern is such that the population can be protected by one or two rounds of IRS per year; and » the majority of structures are suitable for spraying. Considerations: • The co-deployment of ITNs and IRS is not recommended for prevention and control of malaria in children and adults in areas with ongoing malaria transmission. Priority should be given to delivering either ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention. WHO Essential Medicines List or Prequalified product: WHO pre-qualified products have been assessed for their safety, quality and entomological efficacy, which includes evaluation of their mortality effect on mosquitoes when applied to a range of interior surfaces of dwellings found in malaria-endemic areas. Key actions for implementation: • Prior to implementation, a supplementation programme should have well-defined objectives that take into account available resources, existing policies, suitable delivery platforms and suppliers, communication channels and potential stakeholders. • Supplementation should be preceded by an evaluation of the nutritional status of menstruating non-pregnant adolescent girls and women, and of the existing measures to control anaemia and folate insufficiency, such as programmes for hookworm control, food fortification or adequate diet promotion, so as to not exceed recommended dosages of iron. • These interventions should ideally be integrated into national programmes for sexual and reproductive health and the selection of the most appropriate delivery platform should be context specific, with the aim of reaching the most vulnerable populations and ensuring a timely and continuous supply of supplements. • Supplementation programmes should start with a pilot and be scaled up as experience and evidence grow and resources allow. • Providing behaviour change communication on the benefits of the intervention and management of side- effects, along with provision of high-quality supplements with appropriate packaging, will improve the acceptability and adherence to supplementation. • A plan for monitoring and evaluation with appropriate indicators is encouraged at all stages. • All women, from the moment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement. Daily oral iron and folic acid supplementation should be part of routine antenatal care, started as early as possible and continued throughout pregnancy. Considerations: • These recommendations are designed as a preventive strategy for implementation at population level. If an individual is diagnosed as having anaemia in a clinical setting, she should be treated with daily iron (120 mg of elemental iron) and folic acid (400 μg or 0.4 mg) supplementation until her haemoglobin concentration rises to normal. She can then switch to back to the preventive regimen to avoid recurrence of anaemia. • In malaria-endemic areas, the provision of iron and folic acid supplements should be implemented in conjunction with adequate measures to prevent, diagnose and treat malaria. • In malaria-endemic areas, iron supplementation does not increase the risk of clinical malaria or death when regular malaria-surveillance and treatment services are provided. Oral preventive iron interventions should not be given to those who do not have access to malaria-prevention strategies (for example, provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy. • The risk of clinical malaria is not more likely among iron-replete than those given iron supplementation in malaria-endemic areas. There is no need to screen for anaemia prior to iron supplementation in settings where anaemia is highly prevalent. WHO Essential Medicines List or Prequalified product Ferrous salt • Oral liquid: equivalent to 25 mg iron (as sulfate)/mL. • Tablet: equivalent to 60 mg iron. Ferrous salt + folic acid • Tablet: equivalent to 60 mg iron + 400 µg folic acid 22 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7087). • WHO Prequalified Vector Control Products. https://extranet.who.int/pqweb/vector-control-products/ prequalified-product-list. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). Licence: CC BY-NC-SA 3.0 IGO. 3.9 Malaria: Insecticide-treated nets (ITNs) Applicable contexts/population groups: Populations at risk of malaria WHO recommendations: • Pyrethroid-only long-lasting insecticidal nets (LLINs) should be deployed for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission (Strong recommendation for, high certainty evidence). • Pyrethroid-PBO ITNs instead of pyrethroid-only LLINs can be deployed for the prevention and control of malaria in children and adults in areas with ongoing malaria transmission where the principal malaria vector(s) exhibit pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-chlorfenapyr ITNs should be deployed instead of pyrethroid-only LLINs for prevention of malaria in adults and children in areas with pyrethroid resistance (Strong recommendation for, moderate certainty evidence). • Pyrethroid-chlorfenapyr ITNs can be deployed instead of pyrethroid-PBO ITNs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-pyriproxyfen ITNs can be deployed instead of pyrethroid-only LLINs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-pyriproxyfen ITNs are not recommended for deployment over pyrethroid-PBO ITNs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation against, moderate certainty evidence). • The co-deployment of ITNs and IRS is not recommended for prevention and control of malaria in children and adults in areas with ongoing malaria transmission. Priority should be given to delivering either ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention (Conditional recommendation against, moderate certainty evidence). Summary of key evidence: • Pyrethroid-PBO ITNs currently have a higher cost compared to pyrethroid-only LLINs and therefore there was uncertainty of their cost-effectiveness. • PBO is less wash-resistant than pyrethroids, its bioavailability declines faster over the three-year estimated life of an ITN; therefore, the added impact of pyrethroid-PBO ITNs over that of pyrethroid-only LLINs may decline over time. • Available evidence indicates poor cost-effectiveness of pyrethroid-pyriproxyfen ITNs compared to pyrethroid-only LLINs and that the extra resources currently required to purchase these ITNs may negatively impact on coverage and equity. 23 Key actions for implementation: • WHO recommends ITNs that have been prequalified by WHO for deployment in protecting populations at risk of malaria. • ITNs are most effective where the principal malaria vector(s) bite predominantly at night after people have retired under their nets. • ITNs can be used both indoors and outdoors, wherever they can be suitably hung (though hanging nets in direct sunlight should be avoided, as sunlight can affect insecticidal activity). • In deciding whether pyrethroid-PBO ITNs may be appropriate in their context, malaria programmes should: » consider the deployment of pyrethroid-PBO ITNs in areas where resistance to pyrethroids in local vectors has been detected; and » determine whether resources are adequate to cover the extra cost of pyrethroid-PBO ITNs, while ensuring that coverage of populations at risk of malaria is not affected. • In deciding whether pyrethroid-pyriproxyfen ITNs should be deployed instead of pyrethroid-only LLINs, malaria programmes should: » determine whether resources are adequate to cover the extra cost compared to pyrethroid-only LLINs, while ensuring optimal coverage of populations at risk of malaria; and » generate additional information or conduct analyses with the aim of maximizing impact through targeted deployment (for example, stratification of malaria risk, assessment of the characteristics of local vectors, such as pyrethroid resistance mechanisms). Considerations: • To achieve and maintain optimal ITN coverage, countries should apply mass free net distribution through campaigns, combined with other locally appropriate delivery mechanisms such as continuous distribution using antenatal care (ANC) clinics and the Expanded Programme on Immunization (EPI). • Recipients of ITNs should be advised (through appropriate communication strategies) to continue using their nets beyond the three-year expected lifespan, irrespective of the condition and age of the net, until a replacement net is available. • Old ITNs should only be collected where there is assurance that: i) communities are not left without nets, i.e. new ITNs are distributed to replace old ones; and ii) there is a suitable and sustainable plan in place for safe disposal of the collected material. • If ITNs and their packaging (bags and baling materials) are collected, the best option for disposal is high-temperature incineration. They should not be burned in the open air. In the absence of appropriate facilities, they should be buried away from water sources and preferably in non-permeable soil. • Recipients of ITNs should be advised (through appropriate communication strategies) not to dispose of their nets in any water body, as the residual insecticide on the net can be toxic to aquatic organisms (especially fish). WHO Essential Medicines List or Prequalified product: WHO pre-qualified products have been assessed for their safety, quality and entomological efficacy, which includes evaluation of their mortality effect on mosquitoes when applied to a range of interior surfaces of dwellings found in malaria-endemic areas. https://extranet.who.int/pqweb/vector-control-products/prequalified-product-list. WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7087). • WHO Prequalified Vector Control Products. https://extranet.who.int/pqweb/vector-control-products/ prequalified-product-list. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). Licence: CC BY-NC-SA 3.0 IGO. 3.9 Malaria: Insecticide-treated nets (ITNs) Applicable contexts/population groups: Populations at risk of malaria WHO recommendations: • Pyrethroid-only long-lasting insecticidal nets (LLINs) should be deployed for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission (Strong recommendation for, high certainty evidence). • Pyrethroid-PBO ITNs instead of pyrethroid-only LLINs can be deployed for the prevention and control of malaria in children and adults in areas with ongoing malaria transmission where the principal malaria vector(s) exhibit pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-chlorfenapyr ITNs should be deployed instead of pyrethroid-only LLINs for prevention of malaria in adults and children in areas with pyrethroid resistance (Strong recommendation for, moderate certainty evidence). • Pyrethroid-chlorfenapyr ITNs can be deployed instead of pyrethroid-PBO ITNs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-pyriproxyfen ITNs can be deployed instead of pyrethroid-only LLINs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation for, moderate certainty evidence). • Pyrethroid-pyriproxyfen ITNs are not recommended for deployment over pyrethroid-PBO ITNs for prevention of malaria in adults and children in areas with pyrethroid resistance (Conditional recommendation against, moderate certainty evidence). • The co-deployment of ITNs and IRS is not recommended for prevention and control of malaria in children and adults in areas with ongoing malaria transmission. Priority should be given to delivering either ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention (Conditional recommendation against, moderate certainty evidence). Summary of key evidence: • Pyrethroid-PBO ITNs currently have a higher cost compared to pyrethroid-only LLINs and therefore there was uncertainty of their cost-effectiveness. • PBO is less wash-resistant than pyrethroids, its bioavailability declines faster over the three-year estimated life of an ITN; therefore, the added impact of pyrethroid-PBO ITNs over that of pyrethroid-only LLINs may decline over time. • Available evidence indicates poor cost-effectiveness of pyrethroid-pyriproxyfen ITNs compared to pyrethroid-only LLINs and that the extra resources currently required to purchase these ITNs may negatively impact on coverage and equity. 24 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7089). • WHO Prequalified Vector Control Products. https://extranet.who.int/pqweb/vector-control-products/ prequalified-product-list. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). License: CC BY-NC-SA 3.0 IGO. 3.10 Malaria: Intermittent preventive treatment of malaria in pregnancy (IPTp) Applicable contexts/population groups: Pregnant women living in malaria-endemic areas WHO recommendation: In malaria-endemic areas, pregnant women of all gravidities should be given antimalarial medicine at predetermined intervals to reduce disease burden in pregnancy and adverse pregnancy and birth outcomes. (Strong recommendation for, low certainty evidence). Summary of key evidence: • IPTp improves a wide range of outcomes in women in their first and second pregnancies, including maternal and placental infection, maternal anaemia and low birthweight. Administering IPTp to all pregnant women regardless of number of pregnancies facilitates ease of IPTp implementation for health workers. • A strong recommendation was made for IPTp based on its moderate beneficial effects, small undesirable effects, and moderate-certainty evidence. Key actions for implementation: • IPTp-sulfadoxing + pyrimethamine (SP) should start as early as possible in the second trimester and not before week 13 of pregnancy due to an increased risk of fetal malformation. • WHO recommends that the medicines used for IPTp be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention during pregnancy and has been shown to be efficacious, safe, well tolerated, available and inexpensive. A drug regimen that can be administered as a directly observed single dose, such as SP, is preferable to a multi-day regimen. • IPTp-SP should ideally be administered as directly observed therapy with three tablets of SP (each tablet containing 500 mg/25 mg SP), for the total required dosage of 1500 mg/75 mg SP. • Doses should be given at least one month apart, with the objective of ensuring that at least three doses are received. • Antenatal care (ANC) contacts remain an important platform for delivering IPTp. Where inequities in ANC service and reach exist, other delivery methods (such as the use of community health workers) may be explored, ensuring that ANC attendance is maintained and underlying inequities in ANC delivery are addressed. 25 Considerations: • Sulfadoxine-pyrimethamine (SP) has been widely used for malaria chemoprevention during pregnancy and remains effective in improving key pregnancy outcomes. • IPTp is generally highly cost-effective, widely accepted, feasible for delivery and justified by a large body of evidence generated over several decades. WHO Essential Medicines List or Prequalified product: Sulfadoxine (500 mg) + pyrimethamine tablet (25 mg) (only in combination with artesunate 50 mg). WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 202023 (https://app.magicapp. org/#/guideline/7089). • WHO Model List of Essential Medicines – 22nd List. Geneva: World Health Organization; 2021 (WHO/ MHP/HPS/EML/2021.02; https://apps.who.int/iris/handle/10665/345533). Licence: CC BY-NC- SA 3.0 IGO. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). Licence: CC BY-NC-SA 3.0 IGO 3.11 Malaria: Perennial malaria chemoprevention (PMC) - formerly intermittent preventive treatment of malaria in infants (IPTi) Applicable contexts/population groups: Infants living in malaria-endemic areas WHO recommendation: In areas of moderate to high perennial malaria transmission, children belonging to age groups at high risk of severe malaria can be given antimalarial medicines at predefined intervals to reduce disease burden. (Conditional recommendation for, moderate certainty evidence) Summary of key evidence: • PMC probably reduces the risk of clinical malaria, anaemia, and hospital admission compared to placebo or no PMC, although the effect size varied over time and between drugs such as sulfadoxine- pyrimethamine (SP), artesunate-amodiaquine (AS-AQ) or SP+AQ. WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7089). • WHO Prequalified Vector Control Products. https://extranet.who.int/pqweb/vector-control-products/ prequalified-product-list. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). License: CC BY-NC-SA 3.0 IGO. 3.10 Malaria: Intermittent preventive treatment of malaria in pregnancy (IPTp) Applicable contexts/population groups: Pregnant women living in malaria-endemic areas WHO recommendation: In malaria-endemic areas, pregnant women of all gravidities should be given antimalarial medicine at predetermined intervals to reduce disease burden in pregnancy and adverse pregnancy and birth outcomes. (Strong recommendation for, low certainty evidence). Summary of key evidence: • IPTp improves a wide range of outcomes in women in their first and second pregnancies, including maternal and placental infection, maternal anaemia and low birthweight. Administering IPTp to all pregnant women regardless of number of pregnancies facilitates ease of IPTp implementation for health workers. • A strong recommendation was made for IPTp based on its moderate beneficial effects, small undesirable effects, and moderate-certainty evidence. Key actions for implementation: • IPTp-sulfadoxing + pyrimethamine (SP) should start as early as possible in the second trimester and not before week 13 of pregnancy due to an increased risk of fetal malformation. • WHO recommends that the medicines used for IPTp be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention during pregnancy and has been shown to be efficacious, safe, well tolerated, available and inexpensive. A drug regimen that can be administered as a directly observed single dose, such as SP, is preferable to a multi-day regimen. • IPTp-SP should ideally be administered as directly observed therapy with three tablets of SP (each tablet containing 500 mg/25 mg SP), for the total required dosage of 1500 mg/75 mg SP. • Doses should be given at least one month apart, with the objective of ensuring that at least three doses are received. • Antenatal care (ANC) contacts remain an important platform for delivering IPTp. Where inequities in ANC service and reach exist, other delivery methods (such as the use of community health workers) may be explored, ensuring that ANC attendance is maintained and underlying inequities in ANC delivery are addressed. 26 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Key actions for implementation: • Perennial malaria chemoprevention (PMC) schedules should be informed by the age pattern of severe malaria admissions, the duration of protection of the selected drug, and the feasibility and affordability of delivering each additional PMC course. • Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa, including for PMC. Artemisinin-based combination therapies (ACTs) have been effective when used for PMC, but evidence is limited on their safety, efficacy, adherence to multi-day regimens, and cost-effectiveness in the context of PMC. • WHO recommends that medicines used for PMC be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention in Africa and has been shown to be efficacious, safe, well tolerated, available and inexpensive. • Previously, PMC was recommended in infants (<12 months of age) as intermittent preventive treatment in infants (IPTi). Since the initial recommendation, new data have documented the value of malaria chemoprevention in children aged 12 to 24 months. • The Expanded Programme on Immunization (EPI) platform remains important for delivering PMC. Other methods of delivery can be explored to optimize access to PMC and integration with other health interventions. • Moderate to high perennial malaria transmission settings are defined as areas with P. falciparum parasite prevalence greater than 10% or an annual parasite incidence greater than 250 per 1000. These thresholds are indicative and should not be regarded as absolutes for determining applicability of the PMC recommendation. Considerations: • Information about PMC should be fully accessible to caregivers and key stakeholders, such as government officials and religious leaders. As with all health interventions, consent should be obtained from the caregiver on behalf of the child prior to administration of PMC. • PMC is not recommended for individuals receiving other forms of malaria chemoprevention [for example, seasonal malaria chemoprevention (SMC) or mass drug administration (MDA)]. Although PMC and SMC could, in principle, be delivered to different age groups in the same geographical area, for example where there is perennial malaria transmission with seasonal peaks, there is no operational experience of the co-delivery of these strategies. There is currently no experience of co-administration of PMC with the RTS,S/AS01 malaria vaccine. • PMC is not recommended in children with severe acute illness or those who are unable to take oral medication, children who during the last 30 days received a dose of any of the drugs being used for PMC, or those allergic to any of the drugs being used for PMC. PMC with SP should not be given to individuals receiving a sulfa-based medication as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole). WHO Essential Medicines List or Prequalified product: Sulfadoxine (500 mg) + pyrimethamine tablet (25 mg) (only in combination with artesunate 50 mg). WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7089). • WHO Model List of Essential Medicines – 22nd List. Geneva: World Health Organization; 2021 (WHO/MHP/HPS/EML/2021.02; https://apps.who.int/iris/handle/10665/345533). Licence: CC BY-NC-SA 3.0 IGO. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). Licence: CC BY-NC-SA 3.0 IGO. 27 3.12 Soil-transmitted helminthiases: Preventive chemotherapy (deworming) Applicable contexts/population groups: pregnant women living in areas where the prevalence of hookworm and whipworm infection is 20% or higher and where anaemia is a severe public health problem (prevalence of 40% or higher); young children, preschool and school-age children living in areas where the baseline prevalence of any soil-transmitted infection is 20% or higher among children; adolescent girls and women 15–49 years of age living in areas where the baseline prevalence of any soil-transmitted helminth infection is 20% or higher. • Preventive chemotherapy (deworming), using single-dose albendazole (400 mg) or mebendazole (500 mg), is recommended as a public health intervention for pregnant women, after the first trimester, living in areas where both: (i) the baseline prevalence of hookworm and/or T. trichiura infection is 20% or higher among pregnant women, and (ii) anaemia is a severe public health problem, with a prevalence of 40% or higher among pregnant women, in order to reduce the worm burden of hookworm and T. trichiura infection (conditional recommendation, moderate-quality evidence). • Preventive chemotherapy (deworming), using annual or biannual single-dose albendazole (400 mg) or mebendazole (500 mg), is recommended as a public health intervention for all young children (13–23 months of age), preschool (24–59 months of age) and school-age children living in areas where the baseline prevalence of any soil-transmitted infection is 20% or higher among children, in order to reduce the worm burden of soil-transmitted helminth infections (strong recommendation, low-quality evidence). • Preventive chemotherapy (deworming), using annual or biannual single-dose albendazole (400 mg) or mebendazole (500 mg), is recommended as a public health intervention for all non-pregnant adolescent girls (13–19 years of age) and non-pregnant women of reproductive age (15–49 years of age) living in areas where the baseline prevalence of any soil-transmitted helminth infection is 20% or higher among non-pregnant adolescent girls and non-pregnant women of reproductive age, in order to reduce the worm burden of soil-transmitted helminth infection (strong recommendation, moderate-quality evidence). Summary of key evidence: • The morbidity caused by the different soil-transmitted helminth species in infected individuals is well documented and severe. Those infected with soil-transmitted helminths benefit significantly from anthelminthic treatment in terms of a reduction in worm burden. • Albendazole and mebendazole are well tolerated, with only minor and transient side-effects reported. Albendazole and mebendazole are effective against soil-transmitted helminthiases to significantly reduce the number of infecting worms and are considered safe for use among pregnant women after the first trimester of pregnancy. • With meta-analyses of randomized controlled trials, no average benefit of preventive chemotherapy was detected for outcomes related to anaemia, low birth weight or perinatal mortality probably due to dilution effect. • Preventive chemotherapy is intended to provide benefits only to infected individuals (uninfected individuals are treated only for logistical reasons). Measuring the benefit of preventive chemotherapy in the entire group treated (comprising infected and uninfected pregnant women) reduces the capacity to properly evaluate the benefits obtained by the infected individuals. • The most cost–effective approach to reach infected individuals is to treat the entire group at risk without individual diagnosis. Key actions for implementation: • Perennial malaria chemoprevention (PMC) schedules should be informed by the age pattern of severe malaria admissions, the duration of protection of the selected drug, and the feasibility and affordability of delivering each additional PMC course. • Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa, including for PMC. Artemisinin-based combination therapies (ACTs) have been effective when used for PMC, but evidence is limited on their safety, efficacy, adherence to multi-day regimens, and cost-effectiveness in the context of PMC. • WHO recommends that medicines used for PMC be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention in Africa and has been shown to be efficacious, safe, well tolerated, available and inexpensive. • Previously, PMC was recommended in infants (<12 months of age) as intermittent preventive treatment in infants (IPTi). Since the initial recommendation, new data have documented the value of malaria chemoprevention in children aged 12 to 24 months. • The Expanded Programme on Immunization (EPI) platform remains important for delivering PMC. Other methods of delivery can be explored to optimize access to PMC and integration with other health interventions. • Moderate to high perennial malaria transmission settings are defined as areas with P. falciparum parasite prevalence greater than 10% or an annual parasite incidence greater than 250 per 1000. These thresholds are indicative and should not be regarded as absolutes for determining applicability of the PMC recommendation. Considerations: • Information about PMC should be fully accessible to caregivers and key stakeholders, such as government officials and religious leaders. As with all health interventions, consent should be obtained from the caregiver on behalf of the child prior to administration of PMC. • PMC is not recommended for individuals receiving other forms of malaria chemoprevention [for example, seasonal malaria chemoprevention (SMC) or mass drug administration (MDA)]. Although PMC and SMC could, in principle, be delivered to different age groups in the same geographical area, for example where there is perennial malaria transmission with seasonal peaks, there is no operational experience of the co-delivery of these strategies. There is currently no experience of co-administration of PMC with the RTS,S/AS01 malaria vaccine. • PMC is not recommended in children with severe acute illness or those who are unable to take oral medication, children who during the last 30 days received a dose of any of the drugs being used for PMC, or those allergic to any of the drugs being used for PMC. PMC with SP should not be given to individuals receiving a sulfa-based medication as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole). WHO Essential Medicines List or Prequalified product: Sulfadoxine (500 mg) + pyrimethamine tablet (25 mg) (only in combination with artesunate 50 mg). WHO guidelines, recommendations and resources • WHO guidelines for malaria. Geneva: World Health Organization; 2023 (https://app.magicapp. org/#/guideline/7089). • WHO Model List of Essential Medicines – 22nd List. Geneva: World Health Organization; 2021 (WHO/MHP/HPS/EML/2021.02; https://apps.who.int/iris/handle/10665/345533). Licence: CC BY-NC-SA 3.0 IGO. • Global technical strategy for malaria 2016–2030, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/342995). Licence: CC BY-NC-SA 3.0 IGO. • World malaria report 2022. Geneva: World Health Organization; 2022 (https://apps.who.int/iris/ handle/10665/365169). Licence: CC BY-NC-SA 3.0 IGO. 28 Web Annex. WHO recommendations for the prevention, diagnosis and management of anaemia Key actions for implementation: • Member States adapt the recommendation according to their setting and its feasibility. • As the prevalence and intensity of soil-transmitted helminth infections are related, only light-intensity infection and low morbidity are expected where the prevalence of any soil-transmitted helminth infection at baseline is lower than 20%. Large-scale preventive chemotherapy programmes are, therefore, not required in these situations. • Delivering preventive chemotherapy to adolescent girls and women of reproductive age entails extra care and precaution in ensuring that women and girls receiving anthelminthic medicines are not pregnant. This is of particular concern in areas where rates of unplanned pregnancies are high and coverage of antenatal care is low. • Extra resources may be required for delivery of preventive chemotherapy to adolescent girls, who may not be easily reached within the existing infrastructure. • Anthelminthic medicines can be given to individuals coinfected with HIV, who are otherwise eligible for inclusion in large-scale preventive chemotherapy interventions. • Provision of adequate water, sanitation and hygiene services is fundamental to break the cycle of infection and reinfection and sustainably control soil-transmitted helminth infections. Collaboration between programmes for control of soil-transmitted helminth infections and water, sanitation and hygiene programmes is essential to ensure prioritization of water and sanitation services to areas that are endemic for soil-transmitted helminths. • Deworming should be delivered together with promotion of health and hygiene, to reduce transmission by encouraging healthy behaviours, such as hand washing, use of footwear and proper disposal of faeces. • Routine monitoring for effective coverage and evaluation of the impact of the intervention should be an integral part of preventive chemotherapy programmes to help inform the decision on continuation or cessation of the programme. Considerations: • Pregnant woman in the first trimester should be excluded from preventive chemotherapy interventions. If the pregnancy status or gestational age of women and girls is uncertain, preventive chemotherapy should be withheld. • Anthelminthic treatment must be considered a necessary but insufficient intervention that contributes to breaking the cycle between helminth infection, illness and chronic poverty, and should be complemented by an important and necessary improvement in delivery of services. • Large-scale preventive chemotherapy programmes may reduce health inequities if they involve an intervention that reduces disparities in levels of infection among population groups according to place of residence, income and other social stratifiers (for example, caste, social group). • The promotion of women’s health literacy and empowerment is essential and can increase the success of public health interventions, such as large-scale deworming. • Engaging with multiple stakeholders and partners will be critical in strengthening implementation and sustaining gains in controlling soil-transmitted helminth infections. 29 WHO Essential Medicines List or Prequalified product: In this context, albendazole chewable tablet (400 mg), mebendazole chewable tablet (130 mg) and mebendazole chewable tablet (500 mg) are listed in the sixth version of the Model List of Essential Medicines For Children. Albendazole is listed under intestinal anthelminthic and antifilarial therapeutic indication, and mebendazole as an intestinal anthelminthic medicine. Pharmacopoeial standards help ensure the quality and safety of essential medicines. The monographs for albendazole and mebendazole included in The International Pharmacopoeia provide publicly available quality standards, including a new test for the dissolution of the albendazole chewable tablets. WHO guidelines, recommendations and resources • Guideline: preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups. Geneva: World Health Organization; 2017 (https://apps.who.int/iris/ handle/10665/258983). Licence: CC BY-NC-SA 3.0 IGO • 2030 targets for soil-transmitted helminthiases control programmes. Geneva: World Health Organization; 2019 (https://apps.who.int/iris/handle/10665/330611). Licence: CC BY-NC-SA 3.0 IGO. • Report of the WHO Advisory Group on deworming in girls and women of reproductive age. Rockefeller Foundation Bellagio Center, Bellagio, Italy. 28–30 June 2017 (WHO/ CDS/NTD/PCT/2018.01). Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. • Schistosomiasis and soil-transmitted helminthiases: progress report, 2021. Wkly Epidemiol Rec. 2022;97:621–31. https://apps.who.int/iris/handle/10665/364998. World Health Organization 20 Avenue Appia 1211 Geneva 27 Switzerland www.who.int