Trial information

Inclusion criteria:

• Healthy non-anaemic pregnant women of all parities (haemoglobin concentration (Hb) ≥110 g/l measured by the first trimester blood profile) at booking or screening.
• A live fetus on a first trimester ultrasound scan carried out for viability or dating.
• 15 weeks + 6 days gestation or less.
• Age 18 and above.
• Able to give informed consent and willing to fulfil trial requirements.
  
  

Exclusion criteria:

• Known haemoglobinopathies (women with haemoglobinopathy trait are still eligible).
• Anaemia of any type, defined by BSH guidelines.
• Haematological conditions that require ongoing treatments with either regular oral or intravenous iron or transfusions, e.g. syndromes of bone marrow failure.
• Severe gastrointestinal disease, requiring on-going treatments, and potentially affecting tolerability of oral iron.
• Chronic renal failure (requiring replacement therapy).
• Allergies to iron.
• Multiple pregnancies, given the higher iron demands.
• Known haemochromatosis.
• Recent red cell transfusion, within 30 days.

Women who elect to take iron-containing (over the counter) supplements will not be excluded, but data on this form of supplement use will be collected.

The primary outcome is a composite outcome of the proportion of pregnancies with pre-term birth (<37 completed weeks gestation), stillbirth (at 24 weeks gestation or above), neonatal death (up to 28 days) and small for gestational age (SGA) (<10th centile sex-specific weight for age, defined by UK growth charts, for example Royal College Paediatrics and Child Health).

Secondary outcomes relating to the mother are as follows:

• Components of the composite primary outcome: pre-term birth (<37 completed weeks gestation), small for gestational age (<10th centile sex-specific weight for age), stillbirth (at 24 weeks gestation or above) and neonatal death (up to 28 days).
• Proportion of women developing anaemia during pregnancy.
• Transitions in haemoglobin from recruitment to 28 weeks and birth.
• Proportion of women with primary postpartum haemorrhage (PPH).
• Proportion of women requiring red cell transfusions prior to discharge but not more than 48 hours post birth.
• Proportion of women receiving an iron infusion prior to discharge and up to 6 weeks after birth.
• Proportion of women with an infection and/or sepsis before discharge and up to six weeks after birth.
• Proportion of women breastfeeding or providing breast milk for baby at discharge from maternity care and at 6 weeks.
• Proportion of women with postpartum depression assessed at 6 weeks post birth.
• Median adherence to medication at 28 weeks and at 6 weeks post birth, as measured using the MARS-5 score.
• Health-related quality of life (HRQoL) using EQ-5D-5L at baseline, 28 weeks and at 6 weeks post birth.
• Healthcare utilisation over trial period.

Secondary outcomes relating to the infant are as follows:

• Mean birthweight.
• Mean gestation at birth.
• Apgar score at 5 minutes.
• Proportion of infants treated for neonatal early onset infection, defined as culture-positive, occurring within 72 hours or prior to discharge home, whichever occurs first.
• Admission to neonatal unit.
• Healthcare utilisation including initial hospital stay, subsequent hospital readmissions, up to 6 weeks post birth.

Secondary outcomes relating to the process evaluation (WS4) are as follows:

• Intervention fidelity (i.e. whether intervention delivered and engaged with as planned).
• Intervention acceptability.
• Intervention feasibility.

Exploratory outcomes, relating to the infants, are as follows.

Proportion of infants with:

• Hypoxic ischaemic encephalopathy (HIE) (moderate or severe).
• Severe intraventricular haemorrhage (IVH), defined as grade III or IV.
• Necrotising enterocolitis (NEC).
• Late onset infection.
• Bronchopulmonary dysplasia
• Retinopathy of prematurity requiring treatment, e.g. laser, cryotherapy or intravitreal injection.

Exploratory outcomes, relating to the treatment of anaemia when this occurs in women recruited to PANDA (prevention), are as follows:

• Adherence to the clinical treatment algorithm based on national BSH guidelines, defined as correct primary treatment administered and haemoglobin taken 2-4 weeks after commencement.
• Response rate to initial course of oral iron at 2-4 weeks, assessed by change in: haemoglobin, reticulocytes (where collected routinely) and other markers of iron haemostasis (where collected routinely).
• Impact of treatment on HRQoL and other outcomes, including post-partum haemorrhage and mode of delivery.

• WHO guideline on haemoglobin cutoffs to define anaemia in individuals and populations 2024 (PDF 1.4MB)
• UK guidelines on the management of iron deficiency in pregnancy (PDF 148KB)

• Anaemia and pregnancy outcomes - a systematic review and meta analysis (PDF 899KB)
• Anaemic data for preventive screening and supplementation to address iron deficiency anaemia in pregnancy (PDF 230KB)
• BMC Gaps in the evidence for prevention and treatment of maternal anaemia: a review of systematic reviews (PDF 386KB)
• Cochrane review of daily oral iron supplementation during pregnancy (PDF 5MB)
• Cochrane review of intermittent oral iron supplementation during pregnancy (PDF 2MB)
• Iron deficiency and iron deficiency anemia during pregnancy - opportunities to optimize perinatal health and health equity (PDF 313KB)
• Screening for iron deficiency and iron deficiency anemia during pregnancy (PDF 357KB)
• Recommendation statement: screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy (PDF 582KB)
• Evidence report: screening and supplementation for iron deficiency and iron deficiency anaemia during pregnancy (PDF 669KB)