Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

NEONATAL NUTRITIONAL INTERVENTION

March 2008

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Health care providers have long been proponents of breast-feeding, encouraging new mothers to give their baby a head start by breast-feeding them exclusively for the first six months of life. Organizations including the Canadian Paediatric Society (CPS), the American Academy of Pediatrics and the World Health Organization support this recommendation and mothers are encouraged to continue to breast-feed for up to two years and beyond after nutrient-rich, solid foods are introduced at six months.

The benefits of exclusive breast-feeding are well documented. According to the American Academy of Pediatrics (Pediatrics 2005;115:496-506), mother’s milk decreases the incidence or severity of many infectious diseases including gastrointestinal (GI) infections, respiratory tract infections and otitis media.

For mothers, breast-feeding prolongs lactational amenorrhea and promotes postpartum weight loss (Paediatr Child Health 2005;103(3):148). Prolonged amenorrhea in turn increases birth spacing and reduces blood loss, resulting in reduced iron requirements for lactating mothers. Over the long term, breast-feeding also reduces the risk of ovarian and breast cancer and it may also decrease the risk of developing osteoporosis and hip fractures when a woman reaches the menopause.

Despite the undeniably salutary benefits of exclusive breast-feeding, a certain percentage of women either cannot breast-feed exclusively or need supplemental nutrition to meet their infant’s needs. At this point, mothers may ask their health care provider: are there any meaningful differences between infant formulas in terms of the quality or quantity of their ingredients and can these differences influence healthy growth and development of their infant? This question has been addressed by many researchers, among them, Dr. Winston Koo, Professor of Pediatrics, Division of Neonatal-Perinatal Medicine, Wayne State University, Detroit, Michigan.

Formula Contents

As he writes (Pediatrics 2003;111:1017-23), most infant formulas contain palm and palm olein (PO) oils as their main source of fat. Manufacturers add these oils to their formulas in an attempt to better match the composition of human milk, specifically, its high palmitic acid content—by weight, about 20% of total fatty acids. Over the past few years, some researchers have come to appreciate that the structure of palmitic acid in human milk is different from that of a vegetable source and formulas containing PO have been found to have unanticipated consequences.

In one study comparing formulas with different amounts of palmitic acid, Lucas et al. (Arch Dis Child Fetal Neonatal Ed 1997;77:F178-F184) found that infants fed a formula that had high amounts of palmitic acid that behaved in the same way as palmitic acid does in breast milk absorbed more fat from the formula than infants fed formulas containing less fat in the “right” configuration. Another study comparing the effect of a PO formula vs. another formula with a very similar fat makeup but which contained no PO also found that infants fed the PO formula absorbed significantly less fat than they did when fed the PO-free formula (JACN 1998;17(4):327-32). In the same study, investigators also observed infants fed the PO formula excreted more calcium in their stools than when fed the PO-free formula, a signal that infants absorb less calcium when fed a PO formula.

Infant Bone Mineral and Calcium

These findings have been replicated by other researchers but do these differences in fat and calcium absorption make any meaningful difference in the infant’s development? The answer is quite possibly affirmative. In Dr. Koo’s own study, infants were fed one of two commercially available infant formulas, starting two weeks after birth until the age of six months. The main difference between the formulas tested was that one contained PO and the other did not. Investigators then measured the degree of bone mineralization both at the time the study started and then again at three and six months of age.

Out of approximately 100 infants who finished the study, Dr. Koo found that infants fed the formula containing PO had significantly lower bone mineral content (BMC) than those who received the PO-free formula. The difference in BMC seen in this study between the two formula groups meant that if infants are fed a formula containing PO, they would need to receive an additional 200 mL of formula a day to achieve the same gain in bone mass as infants fed a formula without PO.

More importantly, as Dr. Koo indicated, skeletal growth is extremely rapid during infancy. Thus, strategies that bolster calcium absorption and increase bone mass would seem to make sense as an important nutritional goal for all infants, as he suggested. Infants who excrete more calcium as a result of being fed formulas that do not exactly mimic the way fats work in breast milk also excrete harder stools. In another comparison of a standard formula vs. a formula containing high amounts of palmitate similar to that in breast milk, infants receiving the more breast milk-like formula again had higher BMC than those on standard formula. They also had softer stools because they excreted less calcium than infants fed a standard formula.

Gastrointestinal Effects

The real goal in the development of infant formulas is to make one that is as well tolerated as breast milk. In an effort to demonstrate that some formulas are better tolerated than others, Gil-Alberdi and colleagues evaluated the gastrointestinal (GI) tolerance of Similac, a non-PO-containing formula with total potentially available nucleosides (TPAN), maternal milk or other formulas on the market at the time (Nutr Hosp 2000;15(1):21-31). Results showed that GI intolerance was reduced by more than half when infants were fed the TPAN formula compared with other formulas. Indeed, rates of GI intolerance were low and virtually identical between infants receiving the TPAN formula and those receiving maternal milk.

Not all types of supplementation used in infant formulas have unintended effects. Indeed, there is ample evidence that dietary nucleotides affect the maturation of an infant’s immune system, thereby potentially affording earlier benefit against various illnesses. Nucleotides are also felt to mitigate against suppression of the immune system associated with malnutrition and increase resistance to some bacterial and fungal pathogens. Perhaps the most important action of dietary nucleotides rests in their ability to reduce the risk of diarrhea. As reported by Yau et al. (J Pediatr Gastroenterol Nutr 2003;36(1):37-43), infants between the ages of one and seven days were randomized to receive an infant formula fortified with nucleotides or to a control formula. Infants remained exclusively on either formula until 12 weeks of age, and then received solid food in addition to the assigned formula. The formula fortified with nucleotides contained 72 mg/L of nucleotides, similar to that of human milk.

Between the ages of eight and 48 weeks, there was a trend towards less diarrhea in infants fed the nucleotide-supplemented formula vs. those fed the control formula.When the analysis was confined to infants between eight and 28 weeks of age, however, nucleotide-supplemented infants had a significantly lower risk of diarrhea (25.4%) than control infants. Significantly higher serum immunoglobulin A (IgA)—a component of humoral immunity—was also seen among the nucleotide- supplemented infants throughout the 48-week study. Although some researchers have reported that higher IgA levels translated into improved immune responses in vaccinated infants, no difference in antibody responses in the current study was seen between the two treatment groups.

Another study also compared infant formulas that differed in composition by two factors: formula A had additional nucleotides but not PO, while formula B had additional PO but no nucleotides (Pediatrics 1999; 103(1):E7). In the first part of the study, babies who had been breast-fed were assigned to either formula A or formula B for a period of two weeks. Another group of infants who were formula-fed at the time of enrolment were also assigned to receive formula A or B for two weeks.

Parents measured GI tolerance by such indicators as the rate of “spit-ups” or vomiting and the colour and consistency of the infants’ stools. After two weeks, infants who had been weaned from breast milk to exclusive formula had fewer and firmer stools as they were introduced to either formula but infants weaned to formula B that contained PO had less frequent stools, fewer brown stools and more yellow stools than infants fed PO-free formula A.

In both parts of the study, infants fed formula B both had significantly firmer stools than those fed formula A. As researchers explained, unabsorbed palmitic acid in the formula reacts with calcium to form insoluble calcium soaps and these soaps are related to stool hardness.

Results from another large study carried out in 17 countries confirm these findings (Nutrition 2002; 18(6):484-9). Again, infants were either maintained on their current feeding (which could be human milk) or introduced to either a new infant formula (Similac Advance) or to other infant formulas. Out of almost 7000 infants involved in the study, investigators again found that infants fed human milk had softer and more frequent stools than the other groups but infants fed the new formula had softer and more frequent stools than those fed other formulas. Regurgitation and colic were also reportedly less frequent among infants fed the new formula, although both feeding regimens were well tolerated.

Results from a nation-wide study involving 5009 infants reported by Italian investigators (Minerva Pediatr 1998;50(7-8):347-58) again found that after two weeks, parents reported a lower incidence of hard stools when infants were fed a new formula enriched with nucleotides (Similac FormulaPlus) compared with infants fed other milk formulas. Rates of regurgitation were also about half at approximately 10% in infants fed the nucleotide-enriched formula vs. about 18% for those fed other formulas. Infants on the new enriched formula also had less flatulence.

Summary

Most mothers want to make the right choice when it comes to caring for a new infant and most choose to breast-feed exclusively for the first six months of life, as recommended by many organizations. For those mothers who cannot breast-feed exclusively, selection of an infant formula becomes an important choice and formulas that best approximate the benefits of breast milk would seem to be an obvious one. Research shows that there are differences in the way certain constituents within formulas are absorbed and these differences may have some bearing on the optimal growth and development of an infant. Health care providers who care for new mothers and their infants are thus ideally suited to address mothers’ concerns about infant formulas and help them make an informed choice when selecting the best substitute for mother’s milk.

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