Lactoferrin lost to plain iron for anaemia in pregnancy

Researchers in Australia and Pakistan randomly assigned 919 pregnant women with iron deficiency or iron-deficiency anaemia to one of two daily capsules: bovine lactoferrin, an iron-binding protein from cow's milk, or ferrous sulphate, the standard iron tablet. The capsules looked identical, and neither the women nor their doctors knew which one they were taking. The LEAP1 trial is published in the November 2026 issue of The Lancet Obstetrics, Gynaecology, & Women's Health.

Why a milk protein was tested against iron tablets

Ferrous sulphate is the standard first-line oral treatment for iron-deficiency anaemia in pregnancy, but, as the authors note, nausea, abdominal pain and constipation often make it hard to keep taking. Earlier studies and a 2024 meta-analysis of seven trials in 1,397 pregnant women suggested that lactoferrin worked at least as well, with fewer stomach problems. The authors point out the weak spots of that evidence: most trials were small and single-centre, five were at high risk of bias, and one trial of 200 patients was later retracted because of concerns about data integrity.

Who did better by the end of pregnancy

The women were recruited between 2015 and 2021 at 12 to 29 weeks of pregnancy, in 14 hospitals across five Australian states and one hospital in Pakistan. The trial had two coprimary outcomes, one for the baby and one for the mother.

Birthweight, adjusted for gestational age and sex, did not differ between the groups. The maternal outcome did. Between 34 weeks and delivery, 57% of women on lactoferrin (254 of 442) either needed intravenous iron or were still anaemic, compared with 39% on ferrous sulphate (172 of 443), a difference of 18.6 percentage points. Intravenous iron during pregnancy was given to 17% and 9% respectively.

The milder stomach effects reported in earlier studies did not show up either. Side-effects that affected the ability to take the capsules were reported by 8% of women on lactoferrin and 6% on ferrous sulphate, and fewer women on lactoferrin stayed on treatment until delivery: 63% against 71%.

A safety finding that needs a careful reading

Up to six months after birth there were eight deaths of children, including stillbirths, in the lactoferrin group and two in the ferrous sulphate group (log-rank p=0.057). The difference is at the edge of statistical significance, and the confidence interval is wide. Most of these deaths followed preterm birth and occurred mainly in Pakistan; the independent safety committee saw no signal when half of the women had been recruited. The authors do not state that lactoferrin caused these deaths. They read the finding together with the lack of any benefit for mother or baby.

What the trial does not settle

One specific lactoferrin product was tested, and the authors write that products may differ in their biological activity. They leave room for lactoferrin in particular situations, for example when standard oral iron cannot be used, but say that role has to be shown in new, rigorous trials. The standard treatment is not a complete answer either: 39% of women on ferrous sulphate were still anaemic late in pregnancy or needed intravenous iron. Multivitamins, many containing iron, were allowed in both groups. The trial was funded by Australia's National Health and Medical Research Council, which had no role in its design, analysis or writing.

What to bring to the next antenatal visit

For anyone choosing between iron tablets and a lactoferrin supplement during pregnancy, this is the largest blinded comparison so far, and it favoured the ordinary iron tablet. The authors conclude that ferrous sulphate should be prioritised in pregnancy and lactoferrin reserved for research settings. If iron tablets are hard to tolerate, or a blood test late in pregnancy still shows anaemia, discuss the options, including intravenous iron, with your doctor.

This article is for information only and does not replace a consultation with a doctor.

Sources

• Said JM, O'Connell RL, Reynolds RM, et al. Effects of oral bovine lactoferrin versus oral iron sulphate in iron-deficiency anaemia in pregnancy (LEAP1): a multicentre, double-blind, randomised, phase 3 trial. Lancet Obstet Gynaecol Womens Health, 2026;2(11):e959–e972; registration ACTRN12614000988651. doi:10.1016/S3050-5038(26)00262-1