Primary prevention of maternal anaemia to prevent preterm delivery and other adverse outcomes (PANDA): a protocol for a double-blind placebo-controlled randomised trial of a daily iron supplement during pregnancy.

UNLABELLED: Iron deficiency anaemia (IDA) affects up to 30% of all pregnant women often causing symptoms including malaise and lethargy which can significantly impact daily life and well-being. Additionally, IDA is associated with serious complications, including an increased risk of bleeding, preterm birth, small for gestational age babies and rarely, but significantly, stillbirth. The most common current management approach reactively treats IDA once it is diagnosed, usually with an oral iron preparation such as ferrous sulphate or another ferrous salt. There have been calls to investigate a policy of prevention, to discover if outcomes can be improved. We therefore designed the primary prevention of maternal anaemia to prevent preterm delivery and other adverse outcomes trial, to assess whether the prevention of IDA during pregnancy, through routine iron supplementation from early pregnancy, will reduce the risks of significant adverse clinical outcomes for women and their babies.

DESIGN: Randomised, double-blind, placebo-controlled trial to evaluate the effectiveness of low-dose ferrous sulfate in the primary prevention of IDA, alongside an intervention to support medication adherence, with a parallel process evaluation to explore acceptability, fidelity and mechanisms of action.

PARTICIPANTS: 11 020 women in their first trimester of pregnancy, who are not anaemic and have no contraindication to oral iron, will be recruited from maternity units.

INTERVENTION: A tablet of ferrous sulfate 200 mg (65 mg of elemental iron) once daily compared with an identically matched placebo tablet, administered from recruitment in the first trimester (anytime ≤15 weeks+6 days gestation) through until 6 weeks post partum or when all of the tablets have been taken, whichever is sooner. Participants are supplied with a total of 240 tablets to cover the whole period of the study. An adherence intervention to support initiation and adherence to iron supplementation was also delivered.

OUTCOMES: The primary outcome is a composite of preterm birth, small for gestational age, stillbirth and neonatal death. Secondary outcomes include development of maternal anaemia, post-partum haemorrhage, postnatal depression, breast feeding rates, quality of life scores, and in the neonate admissions to a higher level of care and early-onset infection. Long-term offspring neurodevelopmental follow-up will continue beyond this period.This study will establish the clinical and cost-effectiveness of universal oral iron supplementation in pregnancy. (ISRCTN16425597).