PEDIATRICS Vol. 110 No. 4 October 2002, pp. 833-835


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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.

Robert D. Baker, MD, PhD


Digestive Disease and Nutrition Center
Children’s Hospital of Buffalo
Buffalo, NY 14222

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:
[log in to unmask]

REFERENCES


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Nutritional Products, Labeling and Dietary Supplements. Available at:
www.cfsan.fda.gov/dms/inf-ltr3.html
American Dietetic Association. Preparation of formula for infants:
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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics

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Esther Grunis, IBCLC
Lis Maternity Hospital
Tel Aviv, Israel

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