The Race To Build A Better Baby Formula

Breast milk is a complex mixture. Some of its components are still a mystery, even to scientists who have spent their careers studying it. Apart from providing nutrition, breast milk offers babies protection against diarrhoea, allergies and asthma. And yet, two-thirds of new parents in the U.S. struggle to breastfeed as long as they’d like, according to a study by the Centers for Disease Control and Prevention, while some can’t breastfeed and others choose not to.

Baby-formula makers have long attempted to produce a product that confers as many of the benefits of breast milk as possible. “For babies who cannot be exclusively breastfed—what can we do to help those babies get at least one part of this important component?” said Ryan Carvalho, Chief Medical Officer at Nestlé SA. One answer may lie in a chemically complex type of sugar called human milk oligosaccharides (HMO), which make up about a third of the compounds in breast milk. Scientists think the sugars might be responsible for many of the infant health benefits of breast milk: They nourish and support healthy gut bacteria, block infectious bacteria, and support developing immune systems, according to laboratory research and clinical studies. Around 150 HMOs have been identified since the 1950s, but it took until 2010 for the Danish company Glycom to figure out how to mass-produce two of them, known as 2’FL and LNnT.

Mass production was a breakthrough for formula companies trying to better mimic breast milk, making it easier to do research on HMOs and providing a cost-effective way to add them to formula. Abbott Nutrition launched a formula with 2’FL in 2016, and Nestlé, which acquired a 35% stake in Glycom in 2011, released products containing 2’FL and LNnT in 2018. Now, researchers are working to identify and manufacture more HMOs in the hopes of further bolstering baby formulas, and bringing them closer to breast milk. “It’s an arms race to see how many compounds they can make and get into products,” said Steven Townsend, a chemist studying human milk at Vanderbilt University. Glycom, which is focusing on the HMOs found at higher concentrations in breast milk, has three HMOs awaiting safety recognition from the U.S. Food and Drug Administration. Others are in development in the lab. In the next five years, the company expects to mass-produce 15 to 25 different HMOs, covering around 90% to 95% of those in human milk, said Odd Hansen, chief executive officer of Glycom. Lars Bode, Endowed Chair of Collaborative Human Milk Research at the University of California, San Diego, has identified one HMO that appears to reduce the risk of an intestinal disease called necrotizing enterocolitis in preterm infants. “We know that breastfeeding is protective against it,” Dr Bode said, but the HMO is particularly difficult to mimic. “There’s a huge need to make it, but it’s not that easy to figure out,” he said.

Even as the introduction of HMOs into formulas speeds ahead, it’s not clear what the supplementation does for infant health. Research conducted by formula companies shows that, on some measures, HMO-supplemented formula affects babies similarly to breast milk. A 2016 Abbott trial of over 400 infants found that ones who were fed formula with 2’FL had lower levels of inflammatory proteins in their blood, similar to levels seen in breastfed infants. A 2017 Nestlé study of 175 infants found that those fed formulae with 2’FL and LNnT had lower rates of parent-reported bronchitis and medication use, including antibiotics than infants fed non-HMO formula. But data are limited, and long-term effects of individual HMOs at the concentrations currently found in the formula are unknown. Under FDA rules, HMOs are regulated like food ingredients, so companies do not have to prove that they provide health benefits—only that they’re safe. Formulas containing 2’FL and LNnT do not have to go through additional reviews before going to market, as long as they provide the same nutrition as formulas without them.

More research is needed to conclusively determine the clinical benefits of HMO formula, according to a 2018 review published in the journal Nutrients, co-authored by a researcher at the Nestlé Nutrition Institute. It’s still not clear, for example, how much of a benefit individual HMOs can offer or if their power comes through mixtures, Dr Townsend said. His research at the cellular level shows that, while the sugars show some activity in isolation, it’s nowhere near the level of the full, combined range found in breast milk. “We don’t know what the minimal mixture is,” he said.

Another issue is that breast milk is highly personalized. No two people have the same breakdown of HMOs. Around a quarter of women, for example, do not produce 2’FL. “Those moms don’t generate 2’FL, so their babies would never receive it. If we’re putting it in all formula, every baby will get it—and we don’t know if that’s good or bad,” said Meghan Azad, a research scientist at the Children’s Hospital Research Institute of Manitoba who studies the infant microbiome. Donated breast milk, which is pooled together before it’s given to infants, has the same issue: The entire supply will have 2’FL, meaning that some infants who were born to women who don’t secrete it will get it. Dr Azad is starting a clinical trial that will pool donated milk separately, with one batch containing 2’FL and one without, to determine if there are benefits or disadvantages.

Dr Townsend said that manufacturers integrating HMOs into formula should proceed cautiously and in step with the science. “I would love if they could take a step back, until we get a handle on what we’re working with, rather than going right into a formula,” he said. Mr Carvalho of Nestlé acknowledged that the science on HMOs is evolving and slow-moving. “That’s why we only have two right now,” he said. The formula might push closer, but it will likely never be able to mimic breast milk, he said. “I don’t think even if I was a visionary futurist we could even come close to the uniqueness of the composition of breast milk,” he said.

Credit: Nicole Wetsman for The Wall Street Journal, 31 October 2019.