PEDIATRICS Vol. 110 No. 4 October 2002, pp. 833-835
COMMENTARY |
Infant Formula Safety
Abbreviations: CDC, Centers for Disease Control and Prevention • NICU, neonatal intensive care unit • FDA, Food and Drug Administration • ADA, American Dietetic Association
In the April 12th issue of Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention (CDC) reported on a fatal case of meningitis in an intensive care nursery in Tennessee.1 The infecting organism was Enterobacter sakazakii, an unusual but often fatal, invasive pathogen. In the fatal Tennessee case, the infection was traced to contaminated powdered infant formula. Other infants in the same nursery were screened for E sakazakii. Of 49 screened infants, 10 events were discovered (1 proven infection, 2 assumed infections, and 7 colonizations). E sakazakii has been reported to cause or be associated with bacteremia,2,3 necrotizing enterocolitis,4 meningitis,5,6 and colonization.7 There are also reports of E sakazakii contaminating infant formula8–10; however, this report detailed for the first time a direct link to an unopened product. The manufacturer voluntarily recalled the contaminated batch of powdered formula identified as the source. The editorial comment after the report, pointed out that powdered infant formula is not sterile. The CDC concluded its report with the following recommendations for the use of powdered infant formula in the neonatal intensive care unit (NICU): 1) use alternatives to powdered formula whenever possible, 2) use aseptic technique in the preparation of infant formula, 3) refrigerate prepared formula and discard any reconstituted formula stored for longer than 24 hours, 4) limit ambient temperature "hang time" to no >4 hours, and 5) have written guidelines on how to deal with a manufacturer’s recall.
In a letter addressed to "Health Care Professionals" and dated April 11, 2002, the Food and Drug Administration (FDA) outlined the problems with E sakazakii and other organisms with respect to powdered infant formula11 (www.cfsan.fda.gov/
dms/inf-ltr3.html). The FDA published its own set of recommendations similar to the CDC’s, but added that small quantities of formula should be made up at a time and that boiling water should be used to reconstitute powdered formulas.
Infant formula, like no other food, is regulated by its own law, the Infant Formula Act of 1980 as amended in 1986. The act sets lower limits on 29 nutrients (so called "table nutrients" because they appear in table form. US Code of Federal Regulations 21 CFR 107.100). It requires that the formula supports normal growth and that contents are clearly labeled. Manufacturers are required to follow "good manufacturing practice," but no requirement for sterility is specified. In fact, the FDA performs bacterial counts on infant formula, and up to 10 000 colony forming units per gram powder are acceptable. Powdered formula is not guaranteed nor required to be free of pathogenic organisms.
Powdered formula is made from pasteurized (ie, sterile) liquid that is then freeze-spray dried into a powder. It is possible for organisms to be introduced in the final stages of production. The preparation of infant formula for special care nurseries within institutions is not regulated by law. The most widely followed guidelines are those of the American Dietetic Association (ADA) issued in 1991 and amended since the E sakazakii warning12 (www.eatright.org/formulaguide.html). These guidelines are presently being reviewed and updated. The amended guidelines suggest using ready-to-feed or concentrated formulas rather than powdered formulas in neonatal intensive care nurseries. As they stand, the guidelines call for the use of aseptic technique in a designated formula preparation room. The guidelines call for the refrigeration of prepared formula so that a temperature of 2° to 3°C is reached by 4 hours after reconstitution.
The recommendation to use boiling water (recommended by the FDA but not the CDC) is controversial. First, adding boiling water may not accomplish the job of killing E sakazakii13 or other organisms. Second, boiling water certainly alters the ingredients of the formula, destroying an unknown amount of vitamins, and possibly also altering other substances such as proteins. It is not clear to what extent boiling water will alter the formulas or if formula mixed in boiling water will meet the requirements of the Infant Formula Act. Third, boiling water changes the dissolution characteristics of the formula causing it to clump. Fourth, these recommendations cannot be applied to Human Milk Fortifier, because it is generally added as a powder directly to mother’s milk. Finally, adding boiling water directly to powdered formula may endanger those preparing the formula. Most formula labs are not equipped to perform this maneuver, risking spills and burns. The risks of using boiling water to reconstitute powered formula outweigh the benefits. This recommendation is not supported.
There is an urgent need to minimize the dangers and insure the safety of formulas given to infants. Improvement should start with the manufacturing process. Manufacturers should explore new methods or change present practices that could assure sterility at the end of production (eg, irradiation). The cleanliness and practices of formula labs need to be examined, improved when necessary, and undergo continuing monitoring by an established process. As a consequence of the additional scrutiny given formula labs, it is clear that a greater level of oversight is necessary. When Joint Commission reviews hospitals for accreditation, formula labs should be an element included for inspection. For the present, institutions should assure that formula labs are adhering to the ADA guidelines. Premature infants in the intensive care setting do not exist in a sterile environment. Yet the risk of introducing an infecting organism in formula at the time of administration can be reduced. Nursing units should review and update policies and procedures regarding the administration of enteral feeds. Hygienic handling of delivery systems at the bedside, limiting "hang-time" to 4 hours and avoiding open delivery systems will decrease the risk of contamination.
The recommendations by the CDC and the FDA pertain to intensive care nurseries only, suggesting that these vulnerable infants are at most risk. Present practice leads to early discharge from the NICU, so a significant number of premature infants are being cared for at home. Should the precautions be extended to this group? A few term infants will be immune compromised. Are they at risk and can they be identified? Perhaps newborns could be protected from enterically introduced pathogens in other ways—for example, probiotics or prebiotics.
A number of problems and questions have been brought to the forefront by the E sakazakii issue that require urgent answers: 1) No universally followed standards exist for formula labs. Physicians should take the lead in examining their institutions’ formula lab policies and should work with clinical nutrition departments and pharmacies to develop standardized policies and procedures for formula preparation and handling. Surveillance policies should also be developed to monitor quality and safety of formulas prepared and used in hospitals. The present ADA guidelines should be updated, but for now, offer practical guidance. 2) Infant formula needs to be handled in a way to reduce the chance of infection. This starts with the manufacture and finishes with the way the formula is administered. 3) The CDC and FDA recommendations, if implemented, will improve the safety of formula feeding in the NICU. The preponderance of evidence does not support using boiling water as recommended by the FDA. 4) It is presently unknown whether powdered formula contamination effects groups other than premature infants in NICUs. Other populations need to be studied and new ways of protecting all infants from foodborne diseases sought.
Digestive Disease and Nutrition Center
Children’s Hospital of Buffalo
Buffalo, NY 14222
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FOOTNOTES
Received for publication Aug 15, 2002; Accepted Aug 15, 2002.
Reprint requests to (R.D.B.) Digestive Disease and Nutrition Center, Children’s Hospital of Buffalo, 219 Bryant St, Buffalo, NY 14222. E-mail: rbaker{at}upa.chob.edu
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[Abstract/Free Full Text] - Nazarowec-White M, Farber JM. Incidence, survival and growth of Enterobacter sakazakii in infant formula. J Food Protect.1997; 60 :226 –230
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- Taylor CJ. Health professionals: Enterobacter sakazakii infections associated with the use of powdered (dry) infant formulas in neonatal intensive care units [letter]. April 11, 2002. US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling and Dietary Supplements. Available at: www.cfsan.fda.gov/dms/inf-ltr3.html
- American Dietetic Association. Preparation of formula for infants: guidelines for health-care facilities. Chicago, IL: American Dietetic Association; 1991. Abbreviated version, updated April 2002. Available at: http://www.eatright.org/formulaguide.html
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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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