Can a Simple Mineral Help Babies Survive Serious Infections? A Major New Trial Investigates Zinc

What a large study of adjunct zinc for very young babies with severe infection in India and Nepal found — and what it means for families

A large, carefully run study in India and Nepal tested whether giving babies a cheap, widely available mineral — zinc — on top of their usual antibiotics would help them survive a serious infection. Among more than 3,000 infants, slightly fewer of those given zinc died in hospital, but the difference was small enough that it could easily have been down to chance, and by three months there was no difference at all. Zinc was safe, causing only a little extra vomiting. The researchers concluded that zinc should not yet be added to routine treatment, and that more research is needed before it could be recommended.

Why researchers asked this question

For a newborn or a baby just a few weeks old, a serious infection is a frightening and dangerous event. Around the world, infections are among the biggest reasons very young babies are admitted to hospital, and they cause a large share of deaths in the first weeks of life — a burden felt most heavily in parts of South Asia and sub-Saharan Africa [1][2]. Antibiotics are the mainstay of treatment, but they are not a perfect shield. In many places the affordable, commonly available antibiotics are gradually becoming less effective as bacteria develop resistance, and the newer medicines that still work can be hard to get or too expensive [3]. That gap has pushed doctors and scientists to look for something extra — ideally something cheap, easy to give by mouth, and able to help a baby's own body fight the infection.

Zinc is exactly the kind of thing they hoped might work. It is a mineral our bodies need for a healthy immune system; without enough of it, the cells that fight infection do not work as well [4]. Doctors already use zinc successfully to treat another common childhood illness — diarrhoea — where it shortens how long the illness lasts [5]. So it was reasonable to wonder whether zinc could also help babies battling infections in the blood or body, known as sepsis.

The problem families and doctors faced before this study

For years, the evidence on zinc for infant infections was hopeful but unsettled — the kind of situation that leaves both parents and clinicians unsure. The most encouraging piece came from a 2012 study in India, which found that babies given zinc alongside antibiotics were noticeably less likely to have their treatment fail, and possibly less likely to die [6]. When researchers later pooled several such studies together, the overall picture still leaned in zinc's favour, especially at doses of at least 10 mg a day [7]. A few smaller studies agreed [8]. But these earlier studies were limited: many were done at a single hospital, enrolled only certain ages, or required a blood-test result before a baby could join. That made it hard to know whether zinc would truly help the wide range of sick babies who actually arrive at a hospital — babies who are identified mostly by warning signs a nurse can see, not by laboratory tests [9]. Families were left in an uncomfortable middle ground: a promising, harmless-seeming treatment existed, but no one could say for sure whether it worked. To answer that properly, scientists needed a much bigger and more realistic study [1].

What the researchers did

The new study, led by Dr. Nitya Wadhwa and a large team, was designed to be that bigger and fairer test [1]. Between 2017 and 2022, doctors at seven hospitals — five in India and two in Nepal — enrolled 3,153 babies between 3 and 59 days old who came in with at least one warning sign of severe infection. Those signs, drawn from World Health Organization guidelines, included having stopped feeding well, labored breathing, a temperature that was too high or too low, or being so drowsy that the baby moved only when prodded. Importantly, babies could join based on these signs alone, without needing a particular blood-test result — which is how real hospitals identify sick infants.

Every baby received the standard antibiotics and supportive care. On top of that, they were randomly sorted — like a coin toss — into two groups. Half received 10 mg of zinc by mouth each day for two weeks; the other half received a dummy tablet that looked and tasted identical. This is called a placebo-controlled, double-blind trial: neither the families nor the hospital staff knew which baby was getting zinc, so hopes and expectations could not tilt the results. Almost every family completed the full two weeks of treatment, and very few dropped out, which makes the findings trustworthy [1].

What they found

The researchers focused on two main questions: did zinc reduce the chance of a baby dying in hospital, and did it reduce the chance of dying within the next three months? For deaths in hospital, 4.1% of the zinc babies died compared with 4.9% of the placebo babies [1]. That is a small difference in zinc's favour, but it was well within the range that chance alone could produce, so it cannot be counted as a real effect. By three months, even that small gap had disappeared — about 9% of babies in each group had died. To put the size of the study in perspective, the researchers had hoped to enrol more than 4,000 babies and expected roughly one in ten to die, which would have made even a modest benefit easy to detect; in the end, both the number of babies and the number of deaths were lower than planned, which makes it harder to be certain a small effect was not missed. Zinc also made no clear difference to how quickly babies recovered or to whether their treatment needed to be changed. It was safe: the only difference was a little more vomiting in the zinc group, and nothing serious was linked to the treatment [1].

There was one intriguing hint. When the researchers looked at the babies who were most clearly and severely infected — those with abnormal blood markers, for instance — zinc seemed to do a little better. But these were small slices of the study, the numbers were uncertain, and the pattern did not hold up for the three-month results, so the team was careful to call it only a possibility worth exploring, not a finding to act on [1][7].

What this means for families

If your baby is being treated for a serious infection, the practical message is simple: based on this large study, zinc is not a standard add-on to antibiotics, and its absence from your baby's treatment is not something to worry about [1]. The things that genuinely save babies remain the same — spotting the warning signs early, starting effective antibiotics quickly, and providing good supportive care such as fluids, warmth, and oxygen when needed [3][9]. Zinc is not harmful, so if a baby is receiving it for another reason, such as diarrhoea, there is no need to stop [5]. But for infection specifically, this study did not find the benefit that earlier, smaller studies had suggested.

It also helps to understand why a "negative" result like this is valuable rather than disappointing. A treatment that seems promising can turn out to make little difference once it is tested fairly and at scale — and knowing that spares families and health systems from spending effort and hope on something that does not deliver [6]. One reason the study could not detect a small benefit is that fewer babies died than expected, partly because the careful monitoring in the trial itself helped keep babies safe, and the COVID-19 pandemic interrupted enrolment, so the study ended up smaller than planned [1]. That means a modest benefit of zinc has not been completely ruled out — it simply has not been proven.

What researchers are working on next

The scientists behind this study are not giving up on zinc; they are asking a sharper question [1]. Because the faint signal of benefit appeared mostly in the most clearly infected babies, future studies may focus on that group specifically, while still measuring survival and enrolling enough babies to give a clear answer [7]. Other work may look at whether a different dose gets more zinc into a baby's system where it can help [4]. Combining this study with earlier ones may also help researchers see patterns that a single trial cannot [8]. For now, the honest and careful conclusion — the one the researchers themselves reached, and reported to the highest modern standards [10][11] — is that zinc should be studied further before it becomes part of routine treatment for infant infections. That kind of patience is how medicine makes sure that what we give the smallest, most vulnerable patients truly helps them.

References

  1. Wadhwa N, Sinha A, Basnet S, Arya S, Singh R, Jajoo M, et al; Zinc Sepsis Study Group. Zinc as adjunct treatment for clinical severe infection in young infants: A randomized double-blind placebo-controlled trial in India and Nepal. PLoS Med. 2025;22(10):e1004759. doi:10.1371/journal.pmed.1004759 ↩
  2. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200–11. doi:10.1016/S0140-6736(19)32989-732989-7) ↩
  3. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629–55. doi:10.1016/S0140-6736(21)02724-002724-0) ↩
  4. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S–463S. doi:10.1093/ajcn/68.2.447S ↩
  5. Bhatnagar S, Bahl R, Sharma PK, Kumar GT, Saxena SK, Bhan MK. Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial. J Pediatr Gastroenterol Nutr. 2004;38(1):34–40. doi:10.1097/00005176-200401000-00010 ↩
  6. Bhatnagar S, Wadhwa N, Aneja S, Lodha R, Kabra SK, Natchu UCM, et al. Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial. Lancet. 2012;379(9831):2072–8. doi:10.1016/S0140-6736(12)60477-260477-2) ↩
  7. Irfan O, Black RE, Lassi ZS, Bhutta ZA. Zinc supplementation and the prevention and treatment of sepsis in young infants: a systematic review and meta-analysis. Neonatology. 2022;119(2):164–75. doi:10.1159/000521275 ↩
  8. Banupriya N, Bhat BV, Benet BD, Catherine C, Sridhar MG, Parija SC. Short term oral zinc supplementation among babies with neonatal sepsis for reducing mortality and improving outcome — a double-blind randomized controlled trial. Indian J Pediatr. 2018;85(1):5–9. doi:10.1007/s12098-017-2444-8 ↩
  9. African Neonatal Sepsis Trial (AFRINEST) Group; Tshefu A, Lokangaka A, Ngaima S, Engmann C, Esamai F, et al. Simplified antibiotic regimens compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with clinical signs of possible serious bacterial infection when referral is not possible: a randomised, open-label, equivalence trial. Lancet. 2015;385(9979):1767–76. doi:10.1016/S0140-6736(14)62284-462284-4) ↩
  10. Wadhwa N, Basnet S, Natchu UCM, Shrestha LP, Bhatnagar S, Sommerfelt H, et al. Zinc as an adjunct treatment for reducing case fatality due to clinical severe infection in young infants: study protocol for a randomized controlled trial. BMC Pharmacol Toxicol. 2017;18(1):56. doi:10.1186/s40360-017-0162-5 ↩
  11. Hopewell S, Chan A-W, Collins GS, Hróbjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. PLoS Med. 2025;22(4):e1004587. doi:10.1371/journal.pmed.1004587 ↩