OTC Review Infant Formula Products

Infant Formula Products Manufacturers have developed formulas that are similar to human milk. by Leisa L. Marshall

Introduction

content and types of formulas available, and describe appropriate preparation techniques. This information should preAn infant's primary food in the first months of life is pare the pharmacist to answer a parent's questions about human milk or a milk substitute. Human milk is considered the preferred milk source. In fact, the American Academy of infant formulas. Pediatrics eAAP) recommends that an infant less than 12 months old be fed breast milk. I The Academy believes that Human Milk mothers should be told, both before and after delivery of 2 Manufacturers have modified infant formulas over the their infants, to consider breast-feeding. years to increase the similarities between formula and human For various reasons, many American women decide to use milk. To understand the composition of infant formulas, one infant formula rather than breast-feed. Others routinely use infant formula to supplement breast-feeding. According to a recent Ross Laboratories survey of mothers, approximately half of American women never initiate breast-feeding but begin feeding their infant formula in the hospital. 3 Only 10% of full-time employed women and 24.3% of unemployed women report breastfeeding their infants at six months of age. 3 Since many American families feed their infants formula, pharmacists are often asked questions about formula products and infant nutrition. Most infants double their birth weight by five to six months and triple their birth weight by 12 months, thus the importance of an infant's nutrition is apparent. 4 AAP considers iron-fortified infant formulas to be the only acceptable alternative to human milk for the first 12 months of life. I Whole cow's milk should not be used until the infant is one year old. I Although solid foods are intro- Parents can select from a wide variety of high-quality, nutritious infant duced between four and six months of age, formulas to meet their infants' specific needs. human milk or infant formula remains the infant's primary food. This article will compare human milk with infant formulas, discuss the Vol. NS33, No. 10

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AMERICAN PHARMACY

Table 1

Composition of Human Milk and Infant Formulas for Full-Term Infants Fat

Protein Energy

Source

Human milk

21 Kcal!oz

Human milk

Infant formulas

20 Kcal!oz

Nonfat cow's milk with alterations or soy protein isolate

0/0

6 9- 12

Carbohydrate

Source

0/0

Source

0/0

Human milk

52

Lactose

42

Vegetable oil mixtures

35- 49

40- 43

Lactose, corn syrup sol ids, corn syrup, or sucrose

% = % of total calories. Source: References 5,6.

must ftrst look at the composition of human milk. Human milk is the milk produced for a full-term baby once a mother's milk supply is established. Table 1 gives an overview of the macronutrient composition of human milk and infant for-

mulas for full-term infants. Human milk is composed of protein, fat, carbohydrates, vitamins, and minerals. The protein in human milk is approximately 60-80% whey and 20-40% casein protein. The high percentage of whey protein in human milk produces small flocculent curds in the stomach that are easy to digest. The fat in human milk is a mixture of saturated and unsaturated fatty acids. Even though a high percentage of the fat is saturated, infants absorb it well. The carbohydrate source in human milk is lactose. The vitamin and mineral content of human milk meets the needs of most full-term infants. Human milk contains some nonnutritional ingredients that are not in infant formulas: white blood cells, antibodies, and hormonesJ The passive immunity transferred from the mother to the fetus in utero is continued by breast-feeding. For example, there is ample evidence that breast-feeding reduces the incidence of gastrointestinal illness in infants.8-l0 An array of host defense mechanisms acquired from the mother protect the breast-fed infant from common causes of infantile diarrhea, such as the rotavirus infection. 9 Whether breastfeeding reduces the incidence of nongastrointestinal infections remains controversial. 8 A review of the literature of the 1980's concluded that breast-feeding is associated with decreases in nongastrointestinal infections such as otitis media, pneumonia, bacteremia, and meningitis. 9 Other advantages of human milk use include its being readily available at the correct temperature, requiring no preparation, and containing no microbial contaminants. Breast-feeding may be contraindicated for mothers with certain diseases or conditions. Mothers with transmissible diseases need to discuss appropriate infant feeding with their physicians. Infectious transmissible diseases that preclude breast-feeding include hepatitis and sputum positive tuberculosis. 8 ,1l Debilitating illness such as rheumatoid arthritis AMERICANPHARMACY

could also contraindicate breast-feeding. Mothers who take prescription medications should discuss the appropriateness of breast-feeding with their physicians. In most cases the infant receives a smaller quantity of a drug taken by the mother through breast-feeding than the fetus does through the placenta. 12 Problems can develop because the dnlg may then accumulate in the infant's blood due to the infant's immature renal and hepatic function. 11 The physician must look at each mother and her medication use to determine whether breast-feeding is viable. For example, breast-feeding is usually contraindicated in women receiving antineoplastic agents.12 The box on p. 57 lists several good reference sources for the pharmacist asked about a specific medication and its transfer to human milk. The baby's pediatrician or the mother's obstetrician should have one of these references as well.

Infant Formulas-Composition Infant formulas provide a safe and nutritious alternative to human milk. 2 Manufacturers tailor these products to be as close to human milk as possible. The Food and Dnlg Administration (FDA) closely regulates the manufacture of infant formulas. The Infant Formula Act of 1980 broadened FDA's authority and regulations concerning the composition and quality of formulas. l l ,13 Published recommendations of the AAP's Committee on Nutrition are used as the basis for the nutrient composition of all infant formulas.11,1 3 Parents who use commercial infant formulas meeting the requirements of the AAP Committee on Nutrition and FDA regulations are assured high-quality, nutritious products for their infants. 2,1l Infant formulas, like human milk, are composed of protein, fat, carbohydrate, vitamins, and minerals. The traditional protein source for infant formulas is nonfat cow's milk. Nonfat cow's milk contains approximately 20% whey and 80% casein protein and is harder for the infant to digest than human milk protein. Many manufacturers add extra whey protein to their formulas to more closely approximate the October 1993

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percentage of whey protein found in human milk. Formulas are also heat treated to make the cow's milk easier to digest. Special formulas are available with hydrolyzed casein as the protein source for infants who cannot tolerate intact proteins,7,14 Soy-based infant formulas, which contain soy protein isolate with added methionine as the protein source, are also available. The fat source in cow's milk, butterfat, is inappropriate for infants because it is difficult to digest and absorb. 14 It is replaced in all formulas with mixtures of vegetable oils to ensure a fatty acid proftle close to that of human milk. 8 The exact mixture varies with each product, but some mixture of soy, com, coconut, oleo, and safflower oil is generally used. 15 Infants with digestive disorders such as short gut syndrome or cystic fibrosis will be placed on a formula that has a fat content tailored to their disorder, such as Pregestimil and Portagen. In such formulas, a large portion of the fat is made up of medium-chain triglycerides, which are easier to digest and absorb than long-chain triglycerides. 7,15 The carbohydrate source in formulas depends on the type of formula. Milk-based formulas contain lactose, as in human milk. Soy-based formulas contain corn synlp solids, corn syrup, sucrose, or a mixture; and can be useful for infants with lactose intolerance,7,15 Vitamin and mineral levels in infant formulas meet FDA regulations and AAP recommendations. Manufacturer product labeling and literature provide specific information about the vitamin and mineral content of each formula. The bioavailability of certain elements is lower in formula than in human milk, so infant formulas have higher levels of these elements to ensure adequate intake. 4,7 For example, iron is better absorbed from human milk than from formula. AAP recommends the use of iron-fortified infant formulas to prevent the development of iron deficiency anemia in formulafed infants. 16 Iron-fortified infant formulas contain 12 mg of elemental iron per liter, compared with 1.5 mg of elemental iron per liter in low-iron formulas. The use of iron-fortified formula has almost eliminated iron deficiency anemia in early childhood. 16 Parents may be reluctant to use iron-fortified formulas, believing that it increases fussiness, colic, cramps, or constipation in their infants. A recent study showed no observed difference in behavior between infants fed iron-fortified formula and those fed low-iron formula; the only difference noted was a darker stool color with iron-fortified formula users.17 Pharmacists should recommend iron-fortified formulas for the majority of infants. Parents may also have questions about vitamin and mineral or fluoride supplementation for the formula-fed infant. The pharmacist should advise the parent to discuss supplementation with the pediatrician. The age and health of the infant, timing of introduction of solid food, amount of formula use, and local water supply influence the pediatrician's decision on supplementation use. Vol. NS33, No. 10

October 1993

Resources for Information on Breast-Feeding and Drug Use American Academy of Pediatrics. Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 1989;84(5):924-36.

Anderson PO. Drug use during breast-feeding. Clin Pharm. 1991;10:594-624. Bennett PN, Matheson I, Dukes NMG, et al., eds. Drugs and Human Lactation. Amsterdam: Elsevier; 1988. Briggs GG, Freeman RK, Yaffee SJ. Drugs in Pregnancy and Lactation. 3rd ed. Baltimore: William and Wilkins; 1990. Olin BR, Hebel SK, Dombek CE, et al., eds. Facts and Comparisons. St. Louis: Facts and Comparisons, Inc., 1993. Updated monthly. Individual drug monographs may contain information under "Warnings: Lactation."

Types of Formula The types of formula available for full-term infants, their composition, and representative products are shown in Table 2. The three basic types are milk-based, soy-based, and casein hydrolysate-based. Milk-based formulas are indicated for full-term infants with no known medical problems or allergies. They can be used as supplementation to or substitution for breast-feeding. As previously indicated, many milkbased formulas contain added whey protein to better simulate the ratio of whey and casein proteins in human milk. Although the issue is still debated, the added whey protein may result in plasma amino acid concentrations that are closer to those produced by human milk. 4,7 For infants unable to tolerate milk-based formulas, several options are available. Soy-based formulas have become a popular alternative for the full-term infant. Approximately 20% of all infants consume soy-based formulas during the frrst year of life. 2 Soy formulas were originally developed for use in infants allergic to cow's milk protein or intolerant to lactose; however, infants allergic to cow's milk protein can also become allergic to soy protein, so caution is warranted. 7,15 Soy protein formulas can be safely recommended for use during the temporary lactose intolerance that often follows viral gastroenteritis,7,15 They are also indicated for infants with lactase deficiency. A strict vegetarian family may wish to use soy formula to avoid animal protein. While all soy formulas contain soy protein as the protein source, the fat and carbohydrate sources vary with each formula. The infant may prefer the taste of one formula to another because of the specific fat and carbohydrate sources of that formula. AMERICAN PHARMACY

"I"able 2 I

Composition of Infant Formulas by Brand and Type Protein Source

Simi lac with Iron

Nonfat cow's milk

Soy and coconut oils

Lactose

Enfamil with Iron

Reduced-minerals whey and nonfat cow's milk

Coconut and soy oils

Lactose

Gerber Baby: Formula

Nonfat cow's milk

Palm olein, soy, coconut, and sunflower oils

Lactose

Carnation Good Start

Whey protei n

Palm olein, soy, coconut, and safflower oils

Lactose and maltodextrin

Isomil

Soy protein isolate and L-methionine

Soy and coconut oils

Corn syrup and sucrose

Prosobee

Soy protein isolate and L-methionine

Coconut and soy oils

Corn syrup solids

Nursoy

Soy protein isolate

Oleo, coconut, oleic, and soy oils

Sucrose

Nutramigen

Casein hydrolysate, cystine, tyrosine, and tryptophan

Corn oil

Alimentum

Casein hydrolysate, cystine, tyrosine, and tryptophan

Medium chain triglycerides, safflower and soy oils

*

Sucrose and modified tapioca starch

For full-term infants with no known medical problems or allergies.

t For infants allergic to. cow's milk protein, intolerant to lactose, or having a lactase deficiency. :t: For infants with gastrointestinal problems or allergic to cow's milk protein. Source: References5!6, 18-24.

Another option to the traditional milk-based formulas is the casein hydrolysate-based formulas, developed for the infant sensitive to intact protein or unable to digest intact protein. 7 The protein source for these formulas is completely hydrolyzed casein. A drawback to these "predigested" formulas is their less desirable taste and smell compared with traditional milk-based formulas. These characteristics seem to bother parents more than infants; most infants accept them readily. These formulas are recommended for use by infants with a variety of gastrointestinal problems or allergies to intact protein. 7 Infants with severe diarrhea or proven allergy AMERICAN PHARMACY

to cow's milk protein may be placed on a casein hydrolysate-based formula. 7 Formula manufacturers have also developed special formulas for premature infants and infants with serious medical problems. These infants will be under dose medical supervision. Similac, SMA Preemie, and Enfamil Premature Formula are a few examples of special-use formulas designed for the pre-term or low birth weight infant. The pharmacist should be aware of the macronutrient content of common formulas, be familiar with several examples of milk-based and soy-based formulas, and know how to October 1993

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obtain special formulas if the need arises. The pharmacist will always want to obtain a brief history of the infant from the parent inquiring about formulas. Table 3 gives several questions to ask the parent before recommending a formula product.

Preparation and Storage Once an infant formula is selected, the pharmacist should instruct the parent on preparing and storing it. Formula manufacturers publish useful pamphlets describing appropriate procedures and the proper equipment, which can be helpful in counseling the parent. Infant formulas are available in three forms: liquid requiring no dilution, liquid concentrate, and powder. The appearance of the labels on all three forms is similar. The pharmacist should make sure that parents understand which formulation they are purchasing. The formula requiring no dilution is called liquid ready-to-use, liquid ready-to-feed, or nursette, depending on the manufacturer and packaging of the product. This formulation may be placed directly into a bottle after being shaken, if supplied in a can. It may also be supplied in a glass bottle with an accompanying nipple that the parent will attach to the bottle when ready to feed the infant. Both the liquid concentrate and the powder must be diluted before use. On the labels of the products are directions written in English and Spanish and accompanied by illustrations. All of the powder must be dissolved before feeding the formula to the infant. The pharmacist should stress the importance of proper dilution because ingestion of improperly diluted formula can result in infant illness or even death. 22 For example, an infant who consumes too concentrated a formula could develop hypernatremia, hyperkalemia, and dehydration. 22 With proper dilution, problems with formula use are rare. 11 The pharmacist should also be aware that under special circumstances a pediatrician may instruct a parent to dilute formula differently from the product label instructions. For example, pediatricians often give parents special instructions for formula dilution and use when an infant has a gastrointestinal illness. A parent will need to purchase eight to 12 bottles for an infant who is fed only formula. Plastic bottles are preferred by most parents. Bottles come in two sizes-4 oz and 8 oz; 4oz bottles hold enough formula for the newborn, but 8-oz bottles will be needed in several months. Common nipple types available include the Gerber Nuk nipple, the Evenflo nipple, and the Playtex nurser. Manufacturers also have special newborn nipples, which are smaller in size and have smaller holes than the nipples used for the older infant. Traditionally, pediatricians have advised parents to boil the water they use to prepare formula, especially for newborns. However, a recent study of lead intoxication in children linked lead poisoning from parent-prepared formula to the Vol. NS33, No. 10

October 1993

Table 3 ;I

Questions the Pharmacist Should Ask the Parent 1. Did your pediatrician recommend a particular formula or type of formula? Pediatricians often recommend a specific formula for infants with special needs. 2. Have you previously used a formula product for another infant?

If a sibling was intolerant to a type of formula, this infant may be also. 3. Will the formula be used to supplement breastfeeding when the mother is absent or as the infant's sole source of milk? Parents often ask about formula use when the baby will be away from the mother. 4. How old is your infant? Was your infant born full term? Premature or low-birth-weight infants often require special formulas. 5. Does your infant have any medical or health problems? Is your infant taking any medications or dietary supplements? Infants with health problems or taking medications may require a specific formula. 6. Did your pediatrician discuss preparation of the infant formula with you? Do you have the necessary bottles and nipples, and access to clean water and refrigeration? Once the parent selects a formula product, the pharmacist should counsel the parent on appropriate preparation and storage.

use of water that was excessively boiled, water that was boiled in a lead-based kettle, and water that was drawn in the morning (when lead levels are highest).23,24 The pharmacist should suggest that the parent ask the pediatrician about the issue of boiling water before using it in formula preparation. Parents should always flush the water system before preparing formula and make sure their kettle is not lead based if they boil the water before use. 17 ,18 Parents may want to check the lead level of the water supply or purchase bottled water. They could also purchase only the ready-to-use formula that requires no dilution. Once formula is prepared, it should be refrigerated. Most manufacturers recommend using prepared bottles within 24 hours. Some infants will accept cold formula, but most prefer it warm. Formula should be warmed in a pan of hot water or by using one of the commercial steam bottle warmers available. Most pediatricians discourage the use of a microwave oven to warm formula because it can heat the formula unevenly, creating hot spots that can bum the infant. After AMERICAN PHARMACY

Infant Formula Recalled

3. Ryan AS, Martinez GA. Breast-feeding and the working mother: a profile. Pediatrics. 1989;83:524-31.

Products dried or packaged by Maple Island, Inc., of Wanamingo, Minn., after November 4, 1992, have been recalled at the Food and Drug Administration's request because of Salmonella contamination. Among the products recalled was Soyalac Powder infant formula (14-0z. cans), sold by Nutricia Inc., of Mt. Vernon, Ohio. The agency is not aware of any illnesses in the United States caused by the products under recall. Other products spray-dried or packaged at the plant and recalled are Sumacal, a medical food supplement; Propac, a protein supplement; and several products sold only abroad, including: Formance, a nutritional supplement for women who are pregnant or nursing; Promil, a weaning formula; Enercal, a diet beverage; and Enercal Plus, for convalescing patients. Consumers should return these products to the stores where they were purchased.

4. Picciano MF. Nutrient needs of infants. Nutr Today. January!February 1987:8-13. 5. Forbes GB, Woodruff CW, eds. Appendix. Pediatric Nutrition Handbook. 2nd ed. Elk Grove Village, III: American Academy of Pediatrics; 1985:363-70. 6. Ross laboratories. Composition of Feedings for Infants and Young Children at Home. Columbus, Ohio: September 1991. 7. Hansen JW, Cook DA, Cordano A, et al. Human milk substitutes. In: Tsang RC, Nichols Bl, eds. Nutrition During Infancy. Philadelphia: Hanley and Belfus, Inc. 1988:378-98. 8. Report of the task force on the assessment of the scientific evidence relating to infant-feeding practices and infant health. Pediatrics. 1984;74:579-762. 9. Cunningham AS, Jelliffe DB, Jelliffe EF. Breast-feeding and health in the 1980's: a global epidemiologic review. J Pediatrics. 1991;118: 659-66. 10. Howie PW, Forsyth JS, Ogston SA, et al. Protective effect of breast feeding against infection. Brit Med J. 1990;300:11-6. 11. Miller SA, Chopra JG. Problems with human milk and infant formulas. Pediatrics. 1984;74(S):639-47. 12. Anderson PO. Drug use during breast-feeding. Clin Pharm. 1991;10: 594-624. 13. Forbes GB, Woodruff CW, eds. Current legislation and regulations regarding infant formulas. In: Pediatric Nutrition Handbook. 2nd ed. Elk Grove Village, III: American AcademY'of Pediatrics; 1985:185-7. 14. Polczer R.lnfant nutrition. On Continuing Practice. 1989;16:9-13.

warming, caregivers should check the temperature of the formula on the inside of their wrist before feeding the infant. It should feel warm, not hot.

Conclusion Formula use has increased over the past decades, and a large variety of infant formulas are available today. Most American infants now consume part or all of their milk supply as infant formula. The use of whole cow's milk is recommended only after the child is 12 months old. The pharmacist may be asked for advice by parents or caregivers about infant formula products.

15. Forbes GB, Woodruff CW, eds. Formula feeding of infants. In: Pediatric Nutrition Handbook. 2nd ed. Elk Grove Village, III: American Academy of Pediatrics; 1985:16-27. 16. American Academy of Pediatrics. Committee on Nutrition. Iron-fortified infant formulas. Pediatrics. 1989;84:1114-5. 17. Nelson SE, Zeigler EE, Copeland AM, et al. lack of adverse reactions to iron-fortified formula. Pediatrics. 1988;81:36{}-4. 18. Tsang RC, Nichols Bl, eds. Nutrition During Infancy. Philadelphia: Hanley and Belfus, Inc. 1988:41~24. 19. Carnation Nutritional Products. Product information. Glendale, Calif: 1991. 20. Mead Johnson Nutritionals. Pediatric Products Handbook. Evansville, Ind: 1990. 21. Gerber Products Company. Product information. Fremont, Mich: 1992. 22. Coodin FJ, Gabrielson IW. Formula Fatality. Pediatrics. 1972;47:438-9. 23. Shannon MW, Graef JW. lead intoxication in infancy. Pediatrics. 1992;89:87-90. 24. Shannon MW, Graef JW. Hazard of lead in infant formula. N Engl J Med. 1992;326:137. letter.

Leisa L. Marshall is instructor and externship coordinator, Department of Pharmacy Practice, Mercer University Southern School of Pharmacy, Atlanta, Ga. This series is coordinated by the Section of Clinical/Pharmacotherapeutic Practice in the APhA Academy of Pharmacy Practice and Management. Dennis M. Williams, PharmD, BCPS, is the editor. The reviewers for this monograph were Deborah Edwards, MS, Arkansas Children's Hospital, Little Rock, Ark.; Victoria Strandhoy, North Carolina Baptist Hospital, Winston-Salem, NC; and Loni Garcia, pharmacist-in-charge, Health South Rehabilitation Hospital, Kingsport, Tenn.

References 1. American Academy of Pediatrics. Committee on Nutrition. The use of whole cow's milk in infancy. Pediatrics. 1992;89:1105-9. 2. American Academy of Pediatrics. Policy statement based on task force report: the promotion of breast-feeding. Pediatrics. 1982;69:654-61.

AMERICAN PHARMACY

October 1993

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