Early iron supplementation in exclusively breastfed Gambian infants: a randomized controlled trial.

Objective: To investigate the effect of daily iron supplementation for 14 weeks on the serum iron concentration and other markers of iron status in exclusively breastfed infants in Gambia. Methods: A placebo-controlled, randomized, double-blind trial was performed in rural Gambia between 3 August 2021 and 9 March 2022. Overall, 101 healthy, exclusively breastfed infants aged 6 to 10 weeks were recruited at vaccination clinics and through community health workers. Infants were randomized to receive iron supplementation (7.5 mg/day as ferrous sulfate in sorbitol solution) or placebo for 98 days. Venous blood samples were collected at baseline and on day 99 to assess the serum iron concentration and other markers of iron and haematological status. Findings: At day 99, the serum iron concentration was significantly higher in the iron supplementation group than the placebo group (crude difference in means: 2.5 µmol/L; 95% confidence interval: 0.6 to 4.3) and there were significant improvements in other iron and haematological markers. There were 10 serious adverse events (five in each group), 106 non-serious adverse events (54 with iron supplementation; 52 with placebo) and no deaths. There was no marked difference between the groups in maternally reported episodes of diarrhoea, fever, cough, skin infection, eye infection or nasal discharge. Conclusion: In exclusively breastfed Gambian infants, iron supplementation from 6 weeks of age was associated with a significant improvement in markers of iron status at around 6 months of age. There was no indication of adverse effects on growth or infections.

Caregiver perceptions of nutrition interventions in infants and children under 24 months of age: a systematic review.

OBJECTIVE: Efficacy studies show early nutrition interventions improving infant nutrition status, but understanding caregiver acceptability is required for implementation of such interventions. This systematic review examines caregivers' perceptions of nutrition interventions in young children. DESIGN: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL and PsychINFO from date of online journal inception through December 2020. Interventions included oral (powder/liquid/tablet) and/or intravenous supplementation, food fortification and nutrition counselling. Inclusion criteria included primary research, data presented on caregiver perception and studies published in English. Quality assessment was performed using the Critical Appraisal Skills Programme tool. Studies underwent narrative synthesis using inductive thematic analysis. SETTING: No restriction. PARTICIPANTS: Caregivers of children under 24 months of age. RESULTS: Of 11 798 records identified, thirty-seven publications were included. Interventions included oral supplementation, food fortification and nutrition counselling. Caregivers included mothers (83 %), fathers, grandparents and aunts. Perceptions were gathered through individual interviews, focus group discussions, questionnaires, surveys and ratings. Totally, 89 % of studies noted high acceptability (n 33 most notably increased appetite (n 17). In total, 57 % of studies (n 21) cited low acceptability, commonly from side effects (n 13) such as gastrointestinal issues, appetite loss and stained teeth. CONCLUSIONS: Positive perceptions and enthusiasm for interventions were frequently reported. Key to implementation was the increased appetite noted by caregivers. A substantial proportion of studies reported negative perceptions, mainly due to side effects. In future interventions, mitigation and education around common side effects are crucial for acceptability. Understanding both positive and negative caregiver perceptions is important for informing future nutrition interventions and strengthening sustainability and implementation.

Iron supplementation of breastfed Gambian infants from 6 weeks to 6 months of age: protocol for a randomised controlled trial.

Background: A recent analysis showed that plasma iron concentrations decline rapidly from birth in Gambian infants, irrespective of sex or birthweight, to concentrations well below normal expected values for iron-replete children older than two months of age (typically >10 µmol/L). The development and function of neural and immune cells may thus be compromised before the minimum age at which children should receive iron supplementation as per World Health Organisation recommendations. Methods: This study is a two-arm, double-blind, placebo-controlled, randomised superiority trial. Infants will be randomised to receive iron drops (7.5mg/day of iron as ferrous sulphate) or placebo daily for 98 days, to test the impact on serum iron concentrations in healthy, breastfed infants (n = 100) aged 6-10 weeks at enrolment. Participants will be visited daily and supplemented by the field team. Daily health and weekly breastfeeding questionnaires will be administered. Anthropometry, and venous blood and faecal samples will be collected at enrolment and after 98 days of supplementation with serum iron as the primary endpoint. Low birthweight (less than 2.5kg at birth) and infants born prematurely (< 37 weeks) will not be excluded. Formula-fed and infants with any illness will be excluded. An additional study exploring maternal stakeholder perspectives of the intervention will be conducted by means of maternal interviews and four focus group discussions with local stakeholders. Discussion: Most breast-fed Gambian infants have very low circulating iron levels by five months of age. This study will introduce iron supplements much earlier in infancy than has previously been attempted in a low-income setting with the primary aim of increasing serum iron concentration. Trial registration: Clincaltrials.gov ( NCT04751994); 12 th February 2021.

The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers, Facilitators, and Benefits.

INTRODUCTION: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. METHODS: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. RESULTS: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. CONCLUSIONS: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.

Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age.

Background: Micronutrient deficiencies remain common worldwide, but the consequences to growth and development in early infancy (under six months of age) are not fully understood. We present a systematic review of micronutrient interventions in term infants under six months of age, with a specific focus on iron supplementation. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) from January 1980 through December 2019. Interventions included iron or multiple micronutrients (MMNs). Results: Of 11,109 records identified, 33 publications from 24 trials were included (19 iron and five MMN supplementation trials). All but one trial (evaluating only morbidity and mortality) evaluated the effect of supplementation on biochemical outcomes, ten reported on growth, 15 on morbidity and/or mortality and six on neuro-behavioural development. Low- and middle- income countries made up 88% (22/25) of the total trial locations. Meta-analysis was not possible due to extensive heterogeneity in both exposure and outcome measures.  However, these trials indicated that infants less than six months of age benefit biochemically from early supplementation with iron, but the effect of additional nutrients or MMNs, along with the impacts on growth, morbidity and/or mortality, and neuro-behavioural outcomes remain unclear. Conclusions: Infants less than six months of age appear to benefit biochemically from micronutrient supplementation. However, well-powered randomised controlled trials are required to determine whether routine supplementation with iron or MMNs containing iron should commence before six months of life in exclusively breast-fed infants in low-resource settings.

Iron deficiency anaemia: experiences and challenges.

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes.