Jan. 14, 2000 GAINESVILLE, Fla.---Mothers have long suspected what medical science in recent years has largely confirmed: Breast-feeding offers infection protection for newborns. But exactly which ingredient in human milk provides the benefit is not entirely understood.
Finding the answer could be key to improving the quality of formulas for infants whose mothers can't nurse, such as those who are HIV positive or undergoing chemotherapy, say University of Florida researchers, who are publishing findings from their studies of a powerful immune system protein in this month's journal Pediatrics. Formulas currently lack additives designed to specifically protect against infection.
The protein, known as granulocyte colony-stimulating factor, or G-CSF, is the body's primary stimulator of white blood cell production. White blood cells are the front line of defense in the body's war against infection.
In an effort to understand whether G-CSF might play a role in breast milk's ability to ward off disease, scientists from UF's College of Medicine examined milk samples from 126 women who recently gave birth. Of these women, 59 delivered at term and 67 delivered prematurely. Twelve women had an infection of the placental membranes.
In the study, supported through grants from the National Institutes of Health, researchers measured the G-CSF levels in the milk, comparing samples from mothers who delivered pre-term and at term as well as samples from those with and without infection.
"We found that G-CSF is measurable in human breast milk, including in moms who deliver early and even six weeks after they have delivered," said principal investigator Dr. Darlene Calhoun, an assistant professor in the department of pediatrics' division of neonatology.
Researchers also found that G-CSF concentrations were nearly double in healthy mothers who delivered at term compared with healthy mothers delivering pre-term, possibly indicating that the concentration increases throughout pregnancy. Further results showed that mothers with infections of the placental membranes had significantly higher concentrations of the protein, whether they delivered prematurely or at term.
"If a mom delivers at 24 weeks when she has an infection in her placental membranes, the concentration of G-CSF in her milk is as high as in the milk of the mom who delivers at term with an infection," Calhoun said. "Infection is the equalizer, making the concentration go up."
Study results also indicated that G-CSF levels were much higher in the first 48 hours following delivery than in subsequent days.
"Even if you can only breast-feed for awhile, breast-feed while your baby is in the hospital," Calhoun advised.
The fact that the protein's concentration levels vary - appearing to increase throughout pregnancy and to elevate with the presence of infection - indicates that G-CSF may well be a leading factor in breast milk's protective powers, but further research is ongoing to establish the protein's exact function, researchers said.
The UF research builds on findings from a 1998 study by researchers at Georgetown and Johns Hopkins universities that showed premature babies who were exclusively fed human milk had a 57 percent lower incidence of infection.
Breast-feeding is very important for premature babies because even if a mom delivers early, breast milk still contains many antibodies, proteins, cells and fats, each of which is important to overall nutrition, Calhoun added.
Calhoun also recently analyzed whether G-CSF is broken down during digestion. Interestingly, the protein in human milk withstood digestion, but it did not hold up when it was added to formula, UF researchers reported in the December issue of the journal Pediatric Research. More than 85 percent of breast milk G-CSF remained after digestion, compared with only 5 percent when it was added to formula.
UF researchers are currently working to identify exactly which properties in human milk protect G-CSF during digestion, and whether babies actually absorb the protein. The team has detected specialized sites in the intestines, known as receptors, where G-CSF acts. The discovery is the first step toward defining whether the protein functions locally in the intestines or elsewhere in the body if it is absorbed.
"This study definitively demonstrates that G-CSF is present in breast milk at biologically relevant levels and shows that the G-CSF receptor is expressed in the intestines," said Dr. Daniel Link, an assistant professor of medicine and pathology at Washington University School of Medicine. "These important observations suggest that G-CSF in breast milk may affect immune responses and provide a potential mechanism for the protective effect of breast milk against bacterial infections. More importantly, this study suggests that G-CSF supplementation of formula may provide a simple, non-toxic and inexpensive way to reduce the incidence and/or severity of infections in newborns."
Calhoun said the research team also will continue to address related issues in future studies. In particular, scientists would like to know where the G-CSF in milk comes from and how babies are affected if they suddenly no longer receive G-CSF from their mother.
"Babies swallow amniotic fluid before they are born and that fluid contains a significant amount of G-CSF," Calhoun said. "What happens if the baby is delivered at 24 weeks gestation and the supply of G-CSF is stopped? If babies are not breast-fed, what effect does interrupting the natural supply of G-CSF have on the infant? We know that unless babies are sick, they do not make much G-CSF on their own, so how does interrupting the normal sources of G-CSF affect the baby's ability to respond to infection?"
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