PhD defence Opeyemi Rebecca Akinajo

Supervisors

• Prof. Dr. Lenka Benova (ITM, Belgium)

• Prof. Dr. Kristi Sidney Annerstedt (Karolinska Institutet, Sweden)

• Prof. Dr. Bosede Afolabi (University of Lagos, Nigeria)

• Dr. Aduragbemi Banke-Thomas (London School of Hygiene and Tropical Medicine, UK) 

Summary

Introduction

Anaemia in pregnancy (AIP) is a major global health challenge, affecting 36% of women worldwide and up to 45% in Nigeria, leading to increased risk of developing complications such as postpartum haemorrhage, maternal death, preterm birth, low birth weight, and long-term neurodevelopmental problems. Beyond these health risks, AIP also causes fatigue and low productivity, adding financial strain on families, especially in contexts where healthcare expenses are largely out-of-pocket. 

Iron deficiency anaemia (IDA) is the leading cause, yet oral iron, the standard treatment, often fails due to poor adherence from the daily pill burden, forgetfulness and gastrointestinal side effects. Intravenous (IV) iron is a safe, rapid, and effective alternative, particularly for women who cannot tolerate or do not respond to oral iron. Despite its benefits, the use of IV iron remains limited in Nigeria, with little understanding of how to translate its evidence of effectiveness into practice. For widespread use, IV iron must be acceptable to users and providers, feasible to deliver safely with adherence to protocols, and offer better health outcomes at a good value, particularly in a health system dominated by out-of-pocket payments.

Aim

To increase the understanding of the implementation factors and how they influence key implementation outcomes related to the uptake of IV iron therapy for anaemia in pregnancy in Nigeria.

Methods

This doctoral research was embedded within the context of an open-label Intravenous versus Oral Iron for Iron Deficiency Anaemia in Pregnant Nigerian Women (IVON) trial, a hybrid type 1 effectiveness–implementation study conducted in Kano and Lagos States, Nigeria. The doctoral research, which focused on the implementation arm of the trial, was structured around four mixed-method studies. Study I was an exploratory qualitative study conducted in the pre-implementation phase to explore the acceptability of IV iron among diverse stakeholders. Among purposively selected and consenting participants, 12 focus group discussions (with 140 participants) and 29 key informant interviews
were conducted across 10 healthcare facilities. Transcribed data were analysed deductively using the Theoretical Framework of Acceptability. Studies II, III, and IV were conducted during the implementation phase of the IVON trial in 11 facilities. 

Study II was a repeated cross-sectional survey of trained healthcare providers (HCPs), with a longitudinal component for a subset, to assess how their perceptions of IV iron’s acceptability and feasibility varied by provider characteristics and change over time. The Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) survey tools were used at baseline (August 2021) and endline (May 2023) to collect data. Analysis was conducted using descriptive statistics, independent and paired t-tests, and ANOVA. In Study III, a sequential explanatory mixed-method design was employed to assess fidelity. Quantitatively, alternate IV iron administrations were directly observed using a checklist, with adherence compared across facilities and states. Qualitatively, 14 in-depth interviews (IDIs) were conducted with HCPs across nine facilities, with transcribed data analysed using deductive thematic analysis based on the Conceptual Framework of Implementation Fidelity. Qualitative  data were analysed in NVivo 12 Plus, while Stata version 17.0 was used for the quantitative studies. 

In Study IV, a decision tree model was used to assess the cost-effectiveness of IV iron (Ferric Carboxymaltose (FCM)) versus oral iron (Ferrous Sulphate (FS)). Costs, health outcomes, and disability-adjusted life years (DALYs) averted were estimated using the IVON Trial and secondary data sources from a limited societal perspective over a one-year horizon. Incremental cost-utility ratios (ICURs) were compared against an opportunity cost–based threshold, with sensitivity analyses conducted to assess parameter uncertainty. 

Results

In Study I, stakeholders highlighted some key factors that contributed to the acceptability of IV iron. The perception of IV iron benefits includes its single-dose administration, which promotes better adherence and rapid health improvements, as well as its potential to avert complications such as the need for blood transfusions. However, some factors hindered acceptance, including misconceptions surrounding IV iron, high out-of-pocket expenses, limited trained HCPs, space and irregular supply. These insights informed strategies to support the implementation of IV iron during the IVON trial. During the implementation phase in Study II, 53 and 39 trained HCPs were surveyed at baseline and endline, respectively, with 20 HCPs participating at both time points. Mean AIM scores differed by state at baseline (p = 0.001) but not at endline, and no differences were found by cadre or facility level. However, mean AIM scores increased significantly over time (p = 0.002). Mean FIM scores did not vary by time, cadre, state, or facility. In Study III, overall fidelity to the protocol was moderate (66%), with the highest rates observed in tertiary facilities (84%) and the lowest in primary facilities (36%). Factors such as working as a team and the readily available charts and protocols facilitated high fidelity. However, individual variations, institutional challenges like heavy workloads and logistical issues such as prolonged patient waiting times contributed to lower fidelity levels. In Study IV, FCM cost more per woman (US$135.50) than FS (US$104.28), but was also more effective, with lower DALYs incurred (0.0111) compared to that of FS (0.0372). The resulting ICUR was US$1,196.06 per DALY averted, which is below the threshold value, indicating that FCM was a cost-effective intervention.

Conclusion

The findings from this doctoral research increase the understanding of the factors influencing the implementation of IV iron therapy for anaemia in pregnancy in Nigeria. While the acceptability of IV iron was high and improved over time, its feasibility and fidelity were influenced by health system constraints. Although there are context-specific factors influencing its use, IV iron (FCM) has proven to be cost-effective and offers clear clinical benefits over oral iron. These findings highlight that with tailored strategies, including the integration of IV iron into health insurance schemes and national guidelines, there is a high potential for the wide uptake and utilisation of IV iron in Nigeria. Consequently, reducing the burden of AIP and improving outcomes for mothers and babies across Nigeria.