At birth, a baby’s immune system is still maturing and all babies are vulnerable and at risk of bacterial infections. Breastfeeding contains live cells and provides active and passive immunity to protect infants. Powdered baby milk products do not contain these anti-infective factors and may contain dangerous bacteria that can multiply in warm conditions to cause severe infection.
Recent life-threatening infections in newborns in the USA were caused by harmful Cronobacter bacteria detected in reconstituted powdered baby milks. These products are referred to collectively as powdered infant formula, PIF; they include powdered infant and follow-up formulas and breastmilk fortifiers (Note 1). The cases of infection serve as a reminder that PIF is not a sterile product and focus attention on the risks of incorrect use. Extra precautions must therefore be taken, as warned by the World Health Organization, WHO(1).
Correct preparation and handling reduces the risk of illness.
Infections in the USA
In November and December, 2011, four newborns became ill in Florida, Illinois, Missouri and Oklahoma. Tragically, two of the babies died as a result of their infection, and two others survived. Cronobacter sakazakii bacteria can cause severe and potentially fatal infections in infants, such as bacterial sepsis or meningitis. Cronobacter sakazakii was formerly called Enterobacter sakazakii. However, when the name of the bacteria was changed in 2008, the alteration did not bury its bad reputation.
Infections caused by Cronobacter are severe and can cause lasting neurological impairment and developmental delays. These are explained in the study by Oonaka (2) “Subsequent reports … showed that there is a high risk of the bacteria infecting infants (including premature and low-birth-weight infants) and causing brain abscess, necrotizing enterocolitis, and sepis. In severe cases the bacteria cause hydrocephaly and meningitis, with a fatality rate as high as approx. 40-50%, accompanied by severe neurological sequelae”.
These are by no means the first cases in the USA. The fact that Wal-Mart issued a voluntary withdrawal of Enfamil Premium newborn baby formula reflects concern over 2 earlier cases of infection in March 2011. These were in Michigan and Ohio and also showed a possible link to contaminated PIF, prompting a call by the Centers for Control and Prevention of Disease, CDC, to obtain all recently- and currently-used containers and unopened containers of PIF associated with infant infections, so that they can be tested by state public health laboratories, the CDC, and the Food and Drug Administration, FDA.
How is Cronobacter detected in powdered infant formula?
Even previously unopened containers of powdered formulas can contain harmful bacteria. These are found in the environment, including in factories. Being heat-resistant and able to survive drying processes, they can be introduced in the factory during the manufacturing process. This is called intrinsic contamination, while contamination coming from household work surfaces and sinks is called extrinsic contamination.
Scientists have examined samples of previously unopened packages of PIF. A 2006 study in Indonesia analysed packages and found 47% of the 35 samples tested positive for members of the large Enterobacteriaceae family, and 10 of them (13.5%) contained Cronobacter sakazakii (3). In 2010, Oonaka et al (2) reconstituted PIF with distilled water and analysed the samples. They identified 52 strains of the Enterobacteriaceae family. These were isolated from the reconstituted PIF samples, all of them either domestic or imported products purchased in Japan. “In 36 of the 149 samples, 11 bacterial types were isolated, including Cronobacter sakazakii, Enterobacter cloacae, E. coli, Klebsiella pneumoniae … Cronobacter sakazakii was isolated from 9 (6.6%) of the 149 samples”. Salmonella bacteria have also been detected and caused fatal infections in France in 2005.
However, testing for the presence of Cronobacter sakazakii is not an easy process. Samples are not always available from the bodies of infected infants, nor from unopened or opened containers of PIF.In the USA, the CDC reports that none of the products given to the infant in Florida were available for testing, and neither were samples of bacteria from the infants in Oklahoma and Florida.
Tests on the remaining available samples and products are still underway in the USA, but are made more complicated by the fact that the genetic fingerprints of the Cronobacter bacteria are not identical. The FDA is inspecting facilities that manufacture the products which had been used by the infants. To date these recent infections have not been linked to previously unopened containers of PIF, but rather to opened containers of PIF or of bottled nursery water.
Recommendations issued by health authorities in the USA
While investigations are ongoing, the US CDC and FDA issued a joint statement on December 31 2011: “Investigation of Cronobacter Bacteria Illness in Infants”: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm285401.htm
This was updated by the CDC on January 13 2012:
http://www.cdc.gov/foodsafety/diseases/cronobacter/2011-investigation/index.html and now gives the following advice to parents and other care-givers, with breastfeeding coming first:
“Breastfeed: breastfeeding helps to prevent many kinds of infection among infants
If your baby is given powdered infant formula, there are things you can do to protect your baby from infections – not just Cronobacter infections. Good hygiene, mixing the formula with water hot enough to kill germs, and safely storing formula can prevent growth of Cronobacter bacteria and other germs”
What is “water hot enough to kill germs”? The definition is in the link to “there are things you can do” at http://www.cdc.gov/Features/Cronobacter/ and is more specific:
“Use hot water (158 degrees F/70 degrees C and above) to make formula : A simple way to heat water to this temperature is to boil a kettle of fresh water and to use it to make formula within 30 minutes of boiling”.
These “things you can do” are critical, because Cronobacter sakazakii has been shown to be resistant to heat, as well as presenting increasing resistance to some antibiotics. The bacteria show luxuriant growth at warm temperatures, especially around between 37 and 43°C – these are the temperatures often used to mix powdered formula with water, and then to store the prepared formula. At these temperatures, even low levels of bacteria present in the unopened or opened containers of PIF or in bottled water can multiply rapidly to levels that pose a risk for infant health.
WHO therefore includes a lethal decontamination step to kill harmful bacteria in the 2007 Guidelines (1):
IBFAN calls for government action
Since 2002, the International Baby Food Action Network, IBFAN, has shared information on infections caused by PIF all over the world. Our experience shows us that recorded cases are merely the tip of the iceberg, because even in countries such as the USA with advanced testing facilities, testing for the presence of Cronobacter sakazakii is so difficult.Based on the information collected, IBFAN calls upon governments to take the following measures:
Protect, promote and support breastfeeding by implementing the International Code of Marketing of Breastmilk Substitutes and its subsequent, relevant resolutions. (Note 2)
Make infections caused by Cronobacter a notifiable disease. In Canada, Ottawa Public Health says that “All cases of bacterial meningitis must be immediately reported”. However, in the USA, the CDC only “encourages clinicians and laboratories to inform their local or state health department”. Reporting of Cronobacter infections is thus not required, despite the fact that the CDC and FDA report between 12 and 13 documented cases of Cronobacter infections in 2011, when the agencies state that there are normally 4 to 6 cases per year.
Enforce the obligations of formula manufacturers to provide clear alerts on product labels, warning that PIF are not sterile products, in accordance with the recommendations in the 2007 WHO Guidelines (1). As well as their responsibilities under article 9.2 of the International Code, formula manufacturers have an ethical obligation to follow the principles of corporate responsibility, which includes providing correct labelling information to help product users avoid unsafe preparation and storage of PIF. In many countries, manufacturers do not print the warning that PIF is not a sterile product on packages; in other countries, the information on preparation and storage is inconsistent or incomplete.
Implement as a matter of urgency all the recommendations of the 2007 WHO Guidelines (1). Several government authorities already provide detailed guidance and advice to parents and care-givers, for example, the UK:
and Canada: http://www.hc-sc.gc.ca/fn-an/securit/kitchen-cuisine/pif-ppn-eng.php
and Hong Kong: http://www.cfs.gov.hk/english/programme/programme_rafs/programme_rafs_fm_02_04.html
These governmental health and food safety agencies have included the lethal decontamination step in their directions on how to prepare PIF more safely. Surely it is time now for governments all over the world to follow these examples, and ensure that the industry puts this information on product labels and in all their documents.
So why has so little action been taken up to now?
Resistance from the formula industry
Infant formula manufacturers have strongly opposed the recommendations made by the World Health Assembly and the WHO that there should be warnings on containers of powdered infant formulas.
Mixing the powder with water that is no cooler than 70°C can kill heat-sensitive vitamins and probiotics, which are added to the milk powder after pasteurisation (Note 3). If the reconstituted powdered formula no longer contains these added active ingredients, the health and nutrition claims made by manufacturers fall apart and they can no longer charge premium prices or use these ingredients as a sales strategy.
Corporate profits above healthy infants?
The infections in the USA are not isolated cases. Over the past 10 years, IBFAN has compiled a list of recalls of contaminated formulas (4), while WHO has compiled a list of Recorded Cases of Enterobacter sakazakii (Cronobacter ssp.)Infections and Colonisations in infants and young children (5). These Recorded cases show the urgent need for information for parents and care-givers on how to avoid unsafe preparation and storage to prevent infections. Frequent unsafe practices that allow any bacteria present in PIF, in bottled water or on work surfaces to multiply rapidly have been well-documented, as in the study by Carletti and Cattaneo (6).
How many more babies have to fall sick or die before governments and the formula industry take action, as strongly urged by the World Health Assembly resolutions in 2005 and 2008 (7)?
WHO provides detailed guidance in the 2007 Guidelines on Preparation, Storage and Handling of Powdered Infant Formula, issued jointly with the UN Food and Agriculture Organization, FAO:
Oonaka K et al. Powder infant formula milk contaminated with Enterobacter sakazakii. Jpn. J. Infect.Dis. 2010 63: 103-107
Estuningsih S et al. Enterobacteriaceae in dehydrated powdered infant formula manufactured in Indonesia and Malaysia. J. Food Prot. 2006 Dec; 69(12): 3013-7
IBFAN ICDC Recall Lists: http://www.ibfan.org/art/85-27.pdf
WHO 2008 Meeting Report on Enterobacter sakazakii in powdered follow-on formulae, Annex 1: http://www.who.int/foodsafety/micro/jemra/meetings/formula/en/index.html
Carletti C and Cattaneo A. Home preparation of powdered infant formula: is it safe? Acta Paediatrica 2008 97:1131-1132
World Health Assembly resolution WHA 58.32, 2005: http://apps.who.int/gb/ebwha/pdf_files/WHA58/WHA58_32-en.pdf
and World Health Assembly resolution WHA 61.20, 2008:
Report of the second 2006 WHO/FAO Joint Meeting on Enterobacter sakazakii and Salmonella in PIF (MRA series no. 10) on page 5 defines powdered infant formula as: “PIF was considered to include products in powdered form specially manufactured and presented to be used by infants, either as a breastmilk substitute after preparation with water, or to modify prepared breastmilk substitutes or to fortify human milk. Included products are, therefore, infant formula (as defined in Codex Standard 72-1981), follow-up formula (as defined in Codex Standard 156-1987), formula for special medical purposes for the partial feeding of infants (as defined in Codex Alinorm 04/27/26 Appendix V) and human milk fortifiers as defined in the 2004 meeting (FAO/WHO 2004). Throughout the report, the term “Powdered infant formula “ or PIF includes as the products mentioned above, but does not include cereals or any other product added to breastmilk or used as a breastmilk substitute that are not specifically manufactured for that purpose”: http://www.who.int/foodsafety/micro/jemra/meetings/jan2006/en/index.html
Government obligations: the Report of the second 2006 WHO/FAO Joint Meeting on Enterobacter sakazakii and Salmonella in PIF (MRA series no. 10) makes the key point on page 43 that: “Several international reference documents specify that labelling should include adequate information to enable safe use of the product. For example the International Code of Marketing of Breastmilk Substitutes, article 9 on labelling states in section 9.2 that manufacturers and distributors of infant formula should include “instructions for appropriate preparation, and a warning about the health hazards of inappropriate preparation”. The General Principles of Food Hygiene (CAC/RCP 1-1969, Rev. 4-2003) states in section 9.3 on labelling: “Pre-packaged foods should be labelled with clear instructions to enable the next person in the food chain to handle, display, store, and use the product safely”. See url on Note 1.
Report of the second 2006 WHO/FAO Joint Meeting on Enterobacter sakazakii and Salmonella in PIF (MRA series no. 10), page 90: “It was also noted in the course of the meeting that some PIF products may contain added probiotics; these would be killed by reconstitution at 70°C”. See url in Note 1.
The recommendations of the second 2006 WHO/FAO Joint Meeting on Enterobacter sakazakii and Salmonella in PIF (MRA series no. 10) addressed to member countries, WHO and FAO state: “Review and revise product labels, as appropriate, to enable caregivers to handle, store and use the product safely, and to make clear the health hazards of inappropriate preparation”. See url in Note 1.
More information, please visit: the study by Carletti and Cattaneo