The 'PANDA' research programme: Primary prevention of maternal ANaemia to avoid preterm Delivery and other Adverse outcomes

Research Question Does universal primary prevention of anaemia during pregnancy with oral-iron supplementation have an incremental benefit on reducing adverse maternal and infant outcomes? Background Around a third of UK-women develop anaemia during pregnancy, which is associated with adverse outcomes including maternal and neonatal mortality, haemorrhage, prematurity, and stillbirth. Preventing antenatal anaemia using oral-iron supplementation is a significant opportunity for improving maternal and infant outcomes. There is a need for a pragmatic randomised trial of preventative oral-iron supplementation powered on clinical outcomes. Aims and Objectives This programme aims to improve maternal and infant outcomes by evaluating prevention of anaemia during pregnancy with oral-iron supplementation. The specific objectives are to: 1) identify the barriers and facilitators to the initial decision to take, and ongoing adherence to oral-iron, as a basis for designing a behavioural intervention to improve recruitment and adherence during the definitive trial; 2) identify the optimal preventative oral-iron dose, pilot behavioural intervention, and finalise definitive trial protocol; 3) establish clinical and cost-effectiveness in a definitive trial of oral-iron supplementation with a behavioural intervention; 4) evaluate intervention fidelity and enactment; and 5) explore the impact of anaemia prevention on long-term neurodevelopment and maternal outcomes. Methods Five interlinked workstreams (WS) will be conducted. WS1 includes theory-based semi-structured interviews to understand factors influencing preventative oral-iron use during pregnancy. We will develop a behavioural intervention to target the barriers/enablers to initiating taking oral-iron supplements and ongoing adherence. WS2 will select an optimal dose schedule for oral-iron supplementation and pilot the behavioural intervention, to inform the main trial protocol. 240 women will be randomised to one of three oral-iron schedules: single-daily dose; alternate-daily; and three-times/week, taken up to 28-weeks gestation. Outcomes for WS2 will include intervention acceptability, feasibility, adherence, tolerability and changes in haemoglobin concentration. WS3 is a pragmatic, two-arm, multicentre trial of oral-iron supplementation versus placebo, using the preventative dosage regimen defined in WS2. The behavioural intervention will be delivered to all participating women in both trial arms, to optimise recruitment and oral-iron adherence. A sample of 11020 pregnant women will be enrolled across 20 maternity units. The primary outcome is a composite of pre-term birth, stillbirth, neonatal death and small-for-gestational age. Analysis will apply mixed logistic regression alongside an economic evaluation. A mixed-methods parallel process evaluation (WS4) using observations, interviews and surveys will assess fidelity of intervention delivery, adherence and acceptability. WS5 includes seeking consent from women (participating in WS3) to support future data collection from national databases to evaluate long-term maternal and infant neurodevelopment outcomes. Timelines for delivery The research is planned over 61 months. WS1 and WS2 will be completed by month 27 as the definitive trial starts. Anticipated Impact and Dissemination The findings will address the clinical/cost-effectiveness of a primary prevention strategy of anaemia. If effective, understanding barriers/enablers to adherence will inform subsequent wider-scale implementation, as well as having broader implications for other areas of prevention medicine. Dissemination of findings will target key stakeholders including media, online forums, patient and public involvement and health care professional events, and publications.