Iron and Immune Response to Vaccine (IRONMUM)

This is a prospective interventional open label cohort study with an exploratory framework. After assessment of gestation by routine ultrasound, women will be invited to participate if they have a viable, singleton pregnancy with a gestation < 28 weeks. Consenting pregnant women will be enrolled at first antenatal clinic [7] visit and receive tetanus and diphtheria immunisation after confirmation of vaccination history, and SARS-CoV-2 immunisation (first dose if indicated). All women will be classified as non-anaemic or anaemic based on haematocrit (Haematocrit<33% in first trimester (defined <14 weeks) and Haematocrit <30% in 2nd trimester (defined 14 to <28 weeks)). Women will be assigned to groups and receive prophylactic (non-anaemic) or treatment (anaemic) doses of nutritional supplements, respectively, as per routine practice. These supplements will be provided daily for 3 months (12 weeks) and women will be followed up at day 7, 1 month (day 28), 2 and 3 months. There after they will follow routine antenatal care until birth when a cord blood sample will be taken. Mother and infant blood samples will be taken at the 2 months post-partum visit when the newborn attends for routine vaccinations of the expanded program of immunisation. Immunological and haematological responses will be measured by venous blood sampling and finger-prick sampling (routine at the clinics) at study visits; as will adverse events in relation to nutritional supplements by monthly questions using a checklist of common reactions to oral iron. The Adherence Starts with Knowledge (ASK-12) instrument has been modified and used in this population and will be compared to the Haematocrit levels, the pill count and adverse events, as a measure of adherence.

IRONMUM study is funded by Procter and Gamble. The grant reference number is Thailand-UK-IRONMUM-2021-01.

Inclusion criteria

• Viable singleton pregnancy<28 weeks confirmed by ultrasound
• 18 years and older
• Willingness and ability to comply with the study protocol for the duration of the study
• Can understand information about the study and provide consent

Exclusion criteria

• Any diphtheria-tetanus vaccine within the previous 2 years
• History of allergic reaction to diphtheria-tetanus or COVID-19 vaccine
• Haematocrit <21% or Haematocrit >50%
• Known severe haemoglobinopathy (HbE/beta-thalassaemia syndrome, beta-thalassaemia major or HbH syndrome)* or G6PD deficiency

• Iron supplementation is safe in pregnant women with haemoglobin E, alpha-thalassemia 1, or beta-thalassemia carriers.
• HIV-positive
• Slide confirmed presence of malaria
• Fever (defined at >37.5°C)
• Symptoms of COVID (these women will be PCR tested as routine in clinic)
• Known severe medical or obstetric complication e.g. valvular heart disease, placenta praevia
• Known or clinical vitB12 deficiency as indicated by megaloblastic anaemia (pernicious anaemia or clinical symptoms)