What is Enterobacter sakazakii?
Enterobacter sakazakii
is a bacterium from the Enterobacteriaceae family of micro organisms, some of which have been implicated in an extremely rare but severe form of neonatal (newborn) meningitis.

Why is Enterobacter sakazakii a particular problem for infant formula?
Problems of this kind are extremely rare, but the presence of high numbers of these micro organisms can cause severe illness in infants. Unfortunately E.sakazakii are everywhere in the environment and even though we operate very strict manufacturing procedures, and E.sakazakii is destroyed during pasteurization of the liquid milk before it is dried, recontamination of products can occur during handling and filling. This recontamination could also occur in the home or hospital if handled incorrectly. If the product is subsequently reconstituted or stored incorrectly this may allow micro organisms to grow, then problems can occur in immuno-compromised infants.

How common is the problem?
Thankfully this form of neonatal meningitis is extremely rare. There have been approximately 46 cases reported worldwide, 2 of which were in the UK in 1961.  The 2 UK cases were believed to have been caused by a contaminated incubator, and there have been no other reported incidents since then.

How do babies get infected with E sakazakii?
Little is known about Enterobacter sakazakii. In some cases, infection is thought to be due to organisms present in the birth canal of the mother that go on to infect the infant, but this is not the case for infants delivered by caesarean or who develop the disease after birth. The two cases in England in 1961 were believed to have been caused by a contaminated incubator. Powdered infant formula has been implicated in a few cases of E. sakazakii infection elsewhere in the world. In these cases the most probable reason is that the formula has been incorrectly prepared or stored allowing contamination and growth of bacteria in the feed.

What are the symptoms of E. sakazakii infection?
Neonatal (newborn) meningitis is an acute inflammation of the membranes of the brain and spinal cord. It is a severe condition in pre-term, low birth weight or immuno-compromised babies which can be fatal. The symptoms include severe headache, fever, loss of appetite, convulsions, vomiting and sensitivity to light.

Can infant formulas infect babies?
Infant formulas are intrinsically very safe provided they are prepared, stored and used correctly. There have been a few extremely rare cases worldwide where powdered infant formulas have been implicated in the infection. Mostly these were in premature babies or other babies with weakened immune systems being cared for in hospitals. There have been no reported cases among healthy full-term infants in home settings.

What measures are taken to ensure powdered infant formulas are safe?
Infant formulas are produced under stringent hygienic conditions and comply with strict international microbiological specifications. All infant formulas are heat-treated. Liquid ready-to-use infant formulas are commercially sterile. Powdered infant formulas cannot undergo a final sterilization process in pack because this would adversely affect the product, but they too are heat treated during manufacture using temperatures that aim to kill all micro organisms that are likely to be present and pose a health risk to babies. Explicit instructions are provided on how to make up, store and use infant formulas correctly through labelling and educational leaflets. In addition health professionals are advised to complement this education process through advice and demonstrations to parents about how to make up feeds.

Are bottle-fed babies more at risk of infection with E Sakazakii than breastfed babies?
We don't know the answer to this as so little information on E. sakazakii is available. However, infant formulas are intrinsically very safe as they are produced to very strict microbiological standards under stringent hygienic conditions. Temperatures used during the processing of infant formulas aim to kill those bacteria that are likely to be present and pose a health risk to babies. However, contamination and/or growth of bacteria can occur when making up the feeds and during subsequent storage.

Does processing destroy the organism?
Pasteurisation destroys E. sakazakii.  Liquid ready-to-use infant formulas are commercially sterile. Powdered infant formulas cannot undergo a final sterilisation in pack because this would adversely affect the nutritional quality of the product. However, they are heat-treated (pasteurised) during processing using temperatures that aim to kill all bacteria that are likely to be present and pose a health risk to babies. However, this does not stop contamination and/or bacterial growth occurring later, for example, while making up feeds with water or during subsequent storage. Research confirms that proper temperature control during preparation, usage and storage of infant formulas is important in preventing growth.





Why are we getting more enquiries about preparation and storage of powdered formulas? The Department of Health (DH) has revised the Birth to Five book (May 05) and the bottle-feeding leaflet (Nov 05) to remove all references to advance preparation of formulas. Mothers are advised to “make up only one feed at a time and throw away any left over milk”. UNICEF UK have followed suit (August 05), but HCPs are looking for the evidence to justify this change. DH/FSA have issued guidance for HCPs on their websites, but this is causing more confusion (December 06)


Why did DH change the Birth to Five book and the Bottle feeding leaflet?

At the end of 2004, the European Food Safety Authority (EFSA) issued an Opinion on the Microbiological Safety of Infant Formulas. EFSA has issued a number of recommendations relating to good hygiene practices in the factory, hospital and home, including advice to use commercial sterile liquid formula in hospitals and advice to parents to use reconstituted formula immediately. The Food Standards Agency (FSA) and DH have assessed this advice, and issued the updated advice to consumers, using these 2 publications. We await the hospital communication.


What do other agencies say?

NHS Direct recommends that carers use “cooled, boiled water” and “feeds should be made up fresh for each feed”.

NCT recommend that members make up feeds at or above 70oC, and suggests practical ways of doing this such as only boiling the required amount of water which will cool more quickly to 70oC in the kettle.

UNICEF UK BFI says that if mothers decide to bottle feed, they will be asked if they want to be taught how to make up a bottle properly, and staff will be able to answer any questions. There is a UNICEF UK BFI bottle feeding leaflet that reflects the FSA advice.

NICE Routine Postnatal Care of Women and their Babies (July 06) says that any woman who wishes to use formula milk should be taught how to make feeds


Why are carers asking about mixing at 70oC?

DH advice recommends that carers leave the kettle for at least 30 minutes. However, the Food Standards Agency website recommends mixing at 70oC. Leaving the kettle for 30 minutes will achieve a temperature of 70oC, but the FSA advice has generated a number of questions from HCPs and carers


Is there a quicker way to cool the boiled water in the kettle to 70oC?

1 litre of water (filling the kettle half full) takes 15 minutes to cool to 70oC


Following the new DH advice, carers are asking how to make up feeds when travelling

Either: Use ready made formula available in 200 or 500ml tetrapacks. This is recommended in the DH Bottle feeding leaflet.

Or: Boil the freshly run tap water, and fill the sterilised feeding bottle(s) to the required level.

Seal with a sterilised cap. Measure out the required number of scoops per feed into a portable sealable container. When the baby is ready to feed, add the powder to the sterilised water, shake well and feed immediately. As long as the baby is fed immediately, it is not necessary to reheat the boiled water.

Or: Store the made up feed for at least 1 hour in the fridge at 5oC before leaving the house, carry the feed in a cool bag with a frozen ice brick, and feed to the baby within 4 hours. This is suggested by DH/FSA but is not the safest option.


Can carers use a flask when travelling?

This is suggested in the DH Bottle feeding leaflet. However we have some concerns about the recommendation to put freshly boiled water into the flask leading to scalding issues when mixing, combined with the possible inability to cool the feed to feeding temperature. Therefore we recommend using the sterilised feeding bottle as the means of carrying the boiled water.

Should the same advice apply to follow-on formulas?
The EFSA advice is precautionary as there is very little risk for healthy babies and older infants. As with any food product, it is always important to follow manufacturer’s instructions in making up follow-on formulas.


Why aren’t powdered infant formulas labelled to warn that they are not sterile?
Industry is currently discussing the provision of this information to carers within neonatal units with the FSA/DH, as the EFSA Opinion showed this to be particularly important. Breastmilk Fortifier labels do warn that the product is not sterile. For carers in the home, it is far better to provide positive advice on labels on how to handle, prepare, and store infant feeds safely. Any information of this nature has to be worded in such a way that makes sense to the carer, and the FSA/DH agree with this principle. The agreed wording is “Failure to follow instructions may make your baby ill”.




What advice has the US FDA issued?
The US Food & Drug Administration (FDA) have recommended that powdered infant formulas should not be used in neonatal intensive care settings unless there is no liquid formula available. The FDA issued advice in 2003 that specifically relates to the use of powdered infant formulas in hospitalised newborn babies. It does not apply to liquid infant formulas, nor the use of powdered infant formulas for the full-term healthy infant. The reason for the warning is because premature infants and other infants with weakened immune systems are particularly at risk from developing E. sakazakii infection and there have been a growing number of cases among these infants in the USA (24 out of 45 cases worldwide since 1961).  The FDA believes that milk-based powdered infant formulas may have been the source of some of the infections. Infant formulas nutritionally designed for premature babies are generally in liquid form and are commercially sterile, but there has been a growing use of 'transition' infant formulas that are available in powdered form. Powdered products need to be made up with water and this extra handling can involve opportunities for contamination and growth of E. sakazakii. They have issued advice to reduce the risk of infection in these situations.



What advice has the European Food Safety Authority (EFSA) issued?

EFSA recommends that sterile liquid infant formulas are used wherever available for infants at the highest risk of infection. The following table shows their recommendations for the use of powders:



EFSA Guidelines for reconstitution, handling, storage and use of powdered infant formulae


in the home

at hospitals

Good hygienic measures are essential to avoid contamination.

Caregivers should be trained to deal with dried formula in centralized units for reconstitution and in the neonatal health-care units.


Prepare powdered infant formula fresh for each meal.

Good hygienic measures are essential to avoid contamination.


Use “sanitized” containers to reconstitute the formula (e.g. a clean container, “sterilized” by immersion in hot water or chemically).

Use sterile containers to reconstitute the formula (e.g. sterile cabinet) avoiding the possibility of recontamination by the environment.


Always reconstitute formulae in hot water (>70°C) or water that has been boiled and cooled, avoiding recontamination.

Always reconstitute formulae in hot water (>70°C) avoiding recontamination.


Cool the reconstituted formula rapidly to use temperature.

If continued feeding is necessary, the reconstituted formula should be used within four hours.

Use the reconstituted formula immediately.

Cool the reconstituted formula rapidly to temperatures below the growth range of E. sakazakii (below 4-5ºC).


After feeding discard any remaining formula.


Why has EFSA recommended 70oC to reconstitute feeds?

Tests have shown that if E.sakazakii were present in very low quantities in the powdered formula, it would be destroyed at this temperature. Therefore, even if the made up formula was incorrectly stored, there would not be a problem with E.sakazakii. However, EFSA also recommend that home carers could safely use water that has been boiled and cooled if fed immediately. We feel this is a more practical option for home carers.

What advice has WHO issued?

WHO is actively working on worldwide recommendations. The UK FSA is part of the Expert Group looking into the issues. After their last meeting in May 2006, WHO issued draft Guidelines on Safe Preparation, Storage & Handling of Powdered Infant Formulae. These are undergoing stakeholder consultation and we await the results of this consultation. The draft Guidelines recommend mixing all infant formulas at 70oC, but acknowledges that no formulas are currently designed to mix well at this temperature. They also confirm that minimising the time from preparation to consumption reduces the risk, as does storage below 4oC.


I have heard that New Zealand has issued hospital guidelines, what are they?

New Zealand has issued guidelines to all their hospitals that sterile liquid infant formula is recommended for infants at the highest risk of infection.