Effectiveness of Iron Therapy During Pregnancy and Early Childhood on Infant Developmental Outcomes

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Iron deficiency anaemia (IDA) is the most common nutrition deficiency worldwide and the leading cause of morbidity globally from a micronutrient deficiency. Women of reproductive age are more susceptible to iron deficiency due to blood loss and increased iron requirements in pregnancy, while about 43% of infants between six and 59 months of age are reported to be anaemic. Additionally, iron deficiency (ID) is five times more common in low- and middle- income countries (LMICs) and is the leading cause of years lived with disability in these contexts. ID is multifactorial, can be impacted by infection and inflammation, and is more commonly seen in infants in children in LMICs where iron rich foods are less frequently consumed.

Healthy, full-term infants should be born with an iron endowment acting as a buffer for growth and development in the first six months of life, but recent evidence suggests that in areas with high rates of ID this may not be sufficient during the period of exclusive breastfeeding (EBF). While maternal supplementation with iron during pregnancy is recommended by the World Health Organization (WHO), infants may be at risk during the first six months of life when the only practices recommended to prevent anaemia are EBF and delayed cord clamping.

This Thesis explores the gap of iron interventions in early infancy, specifically around impacts to feeding and growth, as well as exploring caregiver acceptability of nutrition interventions in young infants.

This Thesis starts with a systematic review of iron and/or multiple micronutrient (MMN) supplements in infants under six months of age. The objective was to systematically review iron and/or MMN supplementation in healthy, term, normal birthweight infants under six months of age to summarise the evidence and identify any gaps in the literature. Twenty- four trials across 25 locations were included (19 iron and five MMN supplementation trials). Biochemical, growth, morbidity and/or mortality, and neurobehavioral development outcomes were reviewed. LMICs made up 88% (22/25) of the total trial locations. This review found 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 neurobehavioral outcomes remain unclear.

Next, a second systematic review exploring the evidence of caregiver perceptions of nutrition interventions in infants and young children under 24 months of age, as well as any side effects and impacts on infant feeding, was undertaken. The objective was to systematically review caregiver acceptability of nutrition interventions in their infants and children (under 24 months of age) to inform the feasibility of future proposed nutrition interventions in infants. While efficacy studies in infants have shown that early nutrition interventions improve infant nutrition status, to examine whether such interventions can be effectively taken to scale, a better understanding of caregiver acceptability is required. Thirty-seven publications were included with interventions including oral supplementation, food fortification, and nutrition counselling. Caregivers included mothers (83%), fathers, grandparents, and aunts. Eighty-nine percent of studies noted high acceptability (N=33), most notably increased appetite (N=17). Fifty seven percent of studies (N=21) cited low acceptability, commonly from side effects (N=13) such as gastrointestinal, appetite loss and stained teeth. This review supports the need for implementation focused interventions to improve the nutritional status of infants and young children to strengthen sustainability and acceptability, especially in settings with high rates of deficiencies.

A pilot trial conducted among breastfed, young infants (N=101) in rural Gambia (The “Iron Babies” trial) found that being supplemented daily with iron from six to ten weeks of age for 98 days showed improvements in biomarkers, with no difference in adverse events and no reported deaths versus placebo. Work presented in this Thesis went on to explore the relationship between infant feeding and growth within the Iron Babies trial. The objective was to analyse the impacts on nutrition specific outcomes from Iron Babies such as the link between supplementation, breastfeeding rates, and anthropometry. Thirty-three percent of infants (N=31) were exclusively breastfed throughout the study. The mean age of cessation of EBF in the iron group was not different to the placebo group and supplementation with iron versus placebo had no impact on whether infants were exclusively breastfed throughout the study duration. There was no difference in mean infant weight or length at endline, weight or length gains over the study duration, or in the proportion of infants who were underweight, stunted, or wasted between trial arms. There were no negative impacts of early iron intervention on mode of feeding or growth parameters.

To support the quantitative data from the Iron Babies trial, an adjunct qualitative study was conducted to explore acceptability of early iron interventions to infants. The objective was to assess the acceptability of early administration of iron, through qualitative research with local stakeholders and mothers from Iron Babies, to inform future scale up and implementation of nutrition interventions in young infants. Generally, caregivers and stakeholders understood the benefits of the early iron intervention and were supportive. However, some concerns were raised around confusion around nutritional messaging and practicalities of taking such an intervention to scale.

The overall aim of this Thesis was to examine if iron supplementation before six months of age in healthy, term, normal birthweight infants, with a focus on low- and middle- income countries, improved infant outcomes, specifically the health impacts for the infant (breastfeeding and growth) as well as the barriers and associated practicalities of implementing an early intervention.

The research presented in this Thesis highlights the importance of iron interventions in young infants, during a critical period of growth and development, when foetal endowments and nutrition provided through EBF may not be sufficient in areas with high rates of maternal nutritional deficiencies. Additionally, implementation factors, such as maternal acceptability are key for consideration for sustainability and effectiveness of interventions. These findings are a particularly valuable contribution to the literature of iron supplementation in infants under six months of age living in West Africa, where data in this field is scarce.
Date of Award1 May 2024
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorSophie Moore (Supervisor) & Karen Edmond (Supervisor)

Cite this

'