Should Formula Ever Be Used with Breastfeeding to Help Infants Thrive?

When babies fail to thrive, the outcomes can be tragic: Nearly half of the 4 million global infant deaths each year are due to malnutrition. All public health guidelines recommend breastfeeding for at least a year after birth — a crucial time for the developing brain and immune system — and exclusively breastfeeding for the first six months.  This guidance has led to large improvements in population health.

Even with exclusive breastfeeding, though, some babies are malnourished. This is particularly notable in low-income countries like Uganda in East Africa and Guinea-Bissau in West Africa, which is one of the 20 poorest countries in the world. Valerie Flaherman, MD, MPH, professor of pediatrics at UCSF Benioff Children’s Hospital, wondered if it were possible to maintain the health benefits of exclusive breastfeeding while preventing malnutrition for these infants through careful use of supplemental formula.

After conducting focus groups with community members in Guinea-Bissau and Uganda, Flaherman and two local physician-scientists designed a randomized controlled trial to examine the use of a small amount of premixed formula over the first 30 days of life. They carefully assessed the possibility of adverse outcomes, including fever, diarrhea, respiratory infection and changes to breastfeeding patterns.

Breastfeeding practices remained the same, and there were no differences in adverse outcomes between the group using the liquid formula and the group breastfeeding exclusively, but supplemental formula did not improve infant growth. Results were published Dec. 8, 2023, in Pediatrics.

“It was reassuring to see there were no differences in adverse outcomes between the group using the small amount of liquid formula and the group breastfeeding exclusively,” Flaherman said. “Naturally, since we had hoped we would see improvement, it also was disappointing that small amounts of supplemental formula didn’t change infant growth. This intervention was not effective, so other approaches are needed to help with this important public health problem.”

In-country conditions affect practices and solutions

Although supplementation isn’t usually needed or helpful for healthy newborns, hospitals in the U.S. sometimes use small amounts of premixed, liquid infant formula when breastfeeding isn’t sufficient, such as when a mother isn’t making enough milk. However, in low-income countries such as Guinea-Bissau and Uganda, premixed liquid formula is not available due to lack of access to refrigeration, and safe water sources for mixing powdered infant formula are rare.

In the U.S., donor breast milk can often be used for supplementation, and donor banks are spread out across the country to ensure access to milk that has been pasteurized and stored frozen to be safe. Few donor milk banks exist in low-income countries, and pasteurization and safe frozen storage is often difficult due to lack of reliable electrical sources.

Through Makerere University and the International Partnership for Human Development, Flaherman and physician scientists from Makerere University and the International Partnership for Human Development aimed to get a better picture of what happens with weight and health in the first weeks of life. The physicians weighed and measured newborns daily in Uganda and Guinea-Bissau, where one-quarter of children under age 5 have impaired growth. They found that robust growth in the first few days after birth helped to prevent failure to thrive at 30 days of age. Some early weight loss, they found, was normal, but a long period of weight loss or a pronounced drop in weight predicted bad outcomes.

To figure out how to prevent these bad outcomes, the trio conducted focus groups with mothers, fathers and community health workers. Community members spoke about their beliefs that breast milk should not be shared between mothers, and that donor breast milk would not be acceptable to many of the local parents because of religious and cultural beliefs.

Mothers and community members wondered whether there could be a safer way to supplement babies, so that they would grow well without getting sick from contaminated formula. A premixed liquid supplement might be helpful, they thought, but should be carefully studied before further use. This led to the Preventing Infant Malnutrition with Early Supplementation (PRIMES) study, funded by the Bill & Melinda Gates Foundation.

Mothers in both groups were counseled on how to breastfeed frequently on demand and at least eight times per day. Additionally, infants in the formula group had access to a single-use 59 mL bottle of formula daily for a month, and drank about 32 mL daily, on average. Their growth trajectory over six months remained the same as the babies who hadn’t received supplemental formula.

“The results may have been more favorable if, as in the U.S. research, there had been access to refrigeration so that a pre-mixed bottle of formula could be accessed in very small amounts several times a day,” Flaherman said. “Our team hopes that the results of this study can be useful to those looking for ways to ensure all infants develop and reach their full potential.”