Is Lactoferrin more effective than inorganic iron in treating iron def anaemia in non-pregnant and if effective in pregnant women? 2 randomised trials

Oral bovine lactoferrin is a novel, unconventional way to prevent low birthweight, preterm birth & neonatal deaths associated with maternal iron
deficiency in low income settings. Each year about 20 million low birthweight babies are born worldwide. Low birthweight is caused by either preterm delivery (babies born earlier than expected) or fetal growth retardation. In countries where perinatal health services are limited, low birthweight and preterm birth are a major cause of neonatal deaths. Low birthweight babies are 20 or more times likely to die than heavier babies, with much of this mortality burden due to preterm birth. The current paradigm of using iron supplements (and folic acid) targeted at pregnant women often fails, in part because of the side effects, which are a strong barrier to use of the supplements early in pregnancy, a period of vulnerability for iron deficient women and their fetus and future newborn. And also because maternal inflammation and micronutrient deficiencies block effective utilization of iron Our approach will provide a product that will efficiently deliver iron and that can be taken early in pregnancy during a critical intervention window, which offers the potential to prevent neonatal deaths.

There will be 2 phase in the study.

Phase 1: Phase 1 will aim to establish that Lactoferrin is safe and equally effective to iron (ferrous sulphate) in treating iron deficiency anaemia in non-pregnant women of reproductive age. The study will also assess different doses of Lactoferrin to establish the dose that most effectively corrects iron deficiency. Volunteer women of reproductive age will be screened to identify 75 women with low haemoglobin (Hb < 12 g/L), and 75 with very low haemoglobin (Hb < 10 g/L). In each of these groups we will randomly allocate the women to receive 60 days of either 100 mg of bovine Lactoferrin, or 200 mg of bovine Lactoferrin, or 60 mg of ferrous sulphate. Blood will be collected at the start, and after one month of treatment, and after 60 days of treatment, to measure haemoglobin & serum ferritin. If Lactoferrin compared to iron is equally or more efficacious in restoring iron status, and no adverse side effects are reported, we will proceed to the next step.

Phase 2: In the second phase we will conduct a hospital-based randomized controlled trial in pregnant women reporting to a local hospital for antenatal care with three treatment groups: Lactoferrin alone (dose based on results of first study); Lactoferrin; and 60 mg of ferrous sulphate. We will recruit 204 women in their first trimester for intensive follow up who will be randomly allocated to receive daily till the end of pregnancy, one of the two treatments above.

The secondary outcomes will be the duration of gestation and birthweight will be monitored together with reports of side effects, compliance, episodes of maternal infections, and adverse perinatal outcomes. The interventions will be assigned to eligible women at individual level at different phases using a fixed randomization scheme.

Iron-deficiency is the most common nutritional deficiency globally. It is highly prevalent and most severe in pregnant women and children, because of the additional requirements for child growth and pregnancy. Strong evidence about the importance of correcting iron deficiency in pregnancy comes from a recent community-based randomized controlled trial in China that reported a 54% reduction of early neonatal deaths amongst women who received iron supplements compared to those who received no iron (Zeng et al 2008). The iron supplements also reduced rates of low birthweight and early preterm delivery.This result combined indicate that iron supplements in iron deficient pregnant women can lead to decreased rates of low birthweight, preterm delivery & neonatal deaths.

The value of Lactoferrin, a natural safe product, to pregnant women will be its potential to rapidly restore iron status during pregnancy. Using lactoferrin to prevent iron deficiency anemia in pregnancy will make women feel better and less tired, and compliance will be higher because of the reduced side effects and the potential to reduce the frequency of supplementation. Improved iron status will reduce the rates of low birthweight and preterm delivery and improve the survival of the newborns, and issue of concern to women in low resource settings. The cost of this intervention for providers will be similar or less than standard iron because of the potential to reduce the frequency of supplements.