Externally Reviewed Key Facts
- In 1865, Justus von Liebig developed infant food first in liquid form and then in a powdered form for better preservation. The original formula consisted of cow’s milk, wheat and malt flour, and potassium bicarbonate.
- The percentage of infants in the U.S. supplemented with formula is 19.2%
- There are 3 types of pediatric infant formula: soy-based, protein hydrosolyte, and cow-milk based formula and can be purchased as a powder, ready to use, or concentrated liquid. Adulteration reports of pediatric infant formula have been noted to involve melamine and phlatate-contaminated product.
- According to the National Outbreak Reporting System’s (NORS) 2010-2020 Data, there has been one outbreak related to infant food formula, 6 illnesses, 3 hospitalizations, 0 deaths; however due to several new outbreaks since 2020, this has been altered.
- One of the most recent infant formula-related outbreaks occurred in 2021, due to several Salmonella and Cronobacter sakazakii infections among infants leading to several infant-deaths.
- The production process for infant formula makes it well suited for potentially harboring pathogens including Salmonella and Cronobacter sakazakii.
- The largest infant formula companies include Abbott Laboratories, Mead Johnson, Perrigo Company PLC and Nestle SA.
Externally Reviewed Content
As noted by the Institute of Medicine, “infant formulas are unique because they are the only source of nutrition for many infants during the first 4 to 6 months of life. They are critical to infant health because they must safely support growth and development during a period when the consequences of inadequate nutrition are most severe.” (Institute of Medicine, 2004).
In 1865, Justus von Liebig developed infant food in liquid form and then in a powdered form for better preservation. The original formula consisted of cow’s milk, wheat and malt flour, and potassium bicarbonate (Stevens, et al., 2009).
Pediatric infant formulas (PIF) are classified by the FDA as a food designed to feed babies and infants less than 12 months of age. Infant formula is prepared for bottle-feeding to replace breast milk. Powdered formula is mixed with water or another liquid. Manufacturers claim that the composition of infant formula is almost the same as breast milk (Martin, et al., 2016); however, breast milk has better overall absorption of nutrients and provides antibodies/immune factors from the mother (Steube, 2009). There are 3 types of infant formula: soy-based, protein hydrosolyte, and cow-milk based formula and can be purchased as a powder, ready to use, or concentrated liquid (Medline Plus, 2021).
In the United States infant formulas and ingredients added to infant formulas fall within the purview of the Office of Food Additive Safety and the Office of Nutritional Products, Labeling and Dietary Supplements of FDA‘s Center for Food Safety and Applied Nutrition. The safety of new ingredients added to infant formulas is regulated under Section 409 of the Federal Food, Drug and Cosmetic (FD&C) Act (21 U.S.C. §348), which was the primary focus of the committee.
The Infant Formula Acts of 1980 (P.L. 96-359) and 1986 (P.L. 99-570) were incorporated into the FD&C Act as Section 412 (21 U.S.C §350a), which deals with proper manufacturing, formulation, and quality factors of infant formulas. This chapter will focus mainly on safety issues of ingredients (Section 409), but it should be noted that some aspects of Section 412 (quality factors) also play a critical role in the safety assessment process. (IOM, 2004)
Foodborne Outbreaks and Recalls
One of the most recent and notable outbreaks related to infant formula was due to Cronobacter sakazakii contamination. C. sakazakii is a microbe that can live in dry foods for long periods of time and can be found in products such as powdered infant formula, powdered milk, herbal teas, and starches. The most notable symptoms of Cronobacter infection include diarrhea, urinary tract infections, and is especially serious in infants leading to death in approximately 50% of infant illnesses (Center for Disease Control and Prevention, 2022).
Cronobacter is a gram-negative rod within the family Enterobacteriaceae and is found in the environment with the ability to survive in dry environments and low-moisture foods, e.g., powdered infant formula, for long periods. Research results demonstrated over a 12-month storage period, the pathogen survived better in dried formula and cereal at low aw (0.25–0.30) than at high aw (0.69–0.82) and at 4 °C compared to 30 °C. C. sakazakii grew in formulas and cereals reconstituted with water or milk and held at 12–30 °C. The composition of formulas or cereals did not markedly affect the rate of growth. (Beauchat, et al., 2009)
Most cases associated with C. sakazakii come from powdered infant formula that has been contaminated with the bacterium. During production, high temperatures are reached to create the powdered formula and to kill bacteria. It has been found that powdered infant formula is most likely contaminated after production. However, if the powder is produced using the dry blending process, and not heated, Cronobacter bacteria can survive in the formula (Ingham, 2022). Addition of heat sensitive ingredients to improve nutritional value of the formula and meeting the strict nutritional regulatory requirement and difficulties in pasteurizing/sterilizing a product in powdered form are main concerns for safe production of infant formula. Other transmission routes of C. sakazakii to infants can be associated with the preparation methods at home or care settings. C. sakazakii can affect infants by contaminated bottles, nipples, scoops, and other utensils not being properly cleaned as well as hands not being washed properly (Henry, 2019).
As noted above, Cronobacter spp. survives desiccation in dried foods like powdered infant formula (PIF) and thrives in reconstituted formula (Forsythe 2018). Linked to outbreaks among hospitalized neonates in the 1980s, contaminated PIF was identified as the transmission vehicle in nearly all Cronobacter infections for which a source was found. Some of the identified US outbreaks of Cronobacter infections linked to intrinsic contamination of a formula product (i.e., Cronobacter isolated from sealed formula containers) occurred in 2001 at a Tennessee hospital. Since then, the WHO issued broader recommendations aimed at preventing Cronobacter transmission through hygienic PIF reconstitution and storage practices, emphasizing the importance of hand hygiene and advising that caregivers reconstitute PIF with water heated to >70°C (WHO, 2007). In 2014, FDA issued quality control standards aimed at safer PIF production, including requiring manufacturers to routinely test for Salmonella and Cronobacter before distribution (Strysko, et al., 2022).
The first reported infant outbreak related to PIF and/or infant care settings was in 1958 in England (Henry and Fouladkha, 2019). A summary of Cronobacter outbreaks is available in a public repository that can be accessed at https://doi.org/10.7910/DVN/TZ5PV9 (accessed on 21 February 2019). According to the National Outbreak Reporting System’s (NORS) 2010-2020 Data, there has been one outbreak related to infant food formula, 6 illnesses, 3 hospitalizations, 0 deaths; however due to several new outbreaks after 2020, these data from the US have been updated.
Abbott Nutrition’s voluntarily recalled several brands of their powdered formula products due to bacterial contamination from Cronobacter sakazakii or Salmonella (FDA 2022) and shutdown of their Michigan facility in February, 2022 (Abrams and Duggan 2022). The U.S. Food and Drug Administration (FDA) reports investigating complaints of bacterial infections in four infants. This infant formula was produced in Abbott Nutrition’s facility in Sturgis, Michigan. All four infants were hospitalized, and the bacterial infection may have contributed to death in two patients (Office of the Commissioner, 2022). All four of these ill cases had C. sakazakii infection in Minnesota, Ohio, and Texas between September 6, 2021 and January 4, 2022.
Cronobacter bacteria can causes severe infections including sepsis and meningitis. Newborns are at increased risk for Cronobacter complications. Additionally, fifteen infants tested positive for Salmonella after consuming a Similac product. Brands that have issued a recall in the most recent recall include Similac, Alimentum and EleCare powdered infant formulas produced in Sturgis, Michigan. The plant producing the recalled product was shut down from February 2022 to July 2022 for additional sanitization and changes to safety production protocols. Additionally, in September 2022, the FDA announced new guidance that will help provide a pathway for infant formulas operating under enforcement discretion in the US to remain on the market. This will help ensure the US continues diversifying its infant formula market and make families less susceptible to shocks in the infant formula market (https://www.fda.gov/news-events/press-announcements/fda-infant-formula-update-november-14-2022).
Cronobacter infection surveillance is not handled the same way as infection with other foodborne pathogens, e.g. Salmonella or E. coli O157:H7. It is not nationally reportable, though reporting is required in Minnesota and Michigan, which means in most US states doctors and labs are not required to report cases to their health department (https://www.cdc.gov/nndss/about/index.html).
Thus, the FDA relies on consumer complaints of illness sent to the Agency as well as information from health care providers directly about infants with Cronobacter infections. When single cases of Cronobacter are reported, the FDA conducts a thorough review of each complaint. FDA collaborates with CDC, which has developed a detailed questionnaire specifically for Cronobacter infections that is often used by state health departments in instances of C. sakazakii infection.
In 2008, infant formula was produced from milk in China to which melamine had been added to provide a higher protein content. The additive caused urolithiasis and related damage in a large number of infants (Shang, et al., 2012). Approximately 300,000 infants were exposed to such adulterated formula, with six reported deaths and thousands of hospitalizations (Gossner, et al., 2009). This milk contamination with melamine had international implications due to the global distribution of these products and delayed reporting.
The exposure of phthalates to infants is of concern since exposure to in early life has been associated with endocrine disrupting effects, impaired growth, mental and motor development, and increased risk for heart defects (Yen, et al., 2011). In 2011, a major incident of phthalate-contaminated food stuffs occurred when the addition of di-(2-ethylhexyl) phthalate and diisononyl phthalate were used to substitute for an emulsifier, including foods that were consumed by infants (Wu, et al., 2012).
The largest U.S. infant formula companies include Abbott Laboratories, Mead Johnson, Perrigo Company PLC and Nestle SA. The primary production areas in the U.S. include Sturgis, Michigan (Similac) and Chicago, Illinois (Enfamil).
To ensure quality assurance in infant formulas, there are several steps taken in order to create a healthy and safe product for infants to consume. This quality assurance is taken very seriously due to the severity of the consequences from unsafe formulas. Laws and regulations require food chain stakeholders to have streamlined, systematic process controls in place such as the Hazard Analysis and Critical Control Points (HACCP). The HACCP breaks down the formula manufacturing process into steps to identify physical (e.g., glass), chemical (e.g., allergens), and biological (e.g., Salmonella spp.) hazards for every step in the whole process. The responsible zones include the participation of the HACCP assurance of homogeneity in whole batches, in-process control testing of raw materials to meet infant formula specifications, detection of Cronobacter sakazakii and Bacillus cereus, monitoring including production, filling, and packaging, and several other avenues. Quality formula production methods are highly important to ensure that infants are consuming a safe product (Hoeft, 2012). If there’s any concern about adulteration, it should be dealt with at the source by assuring that in-plant processes and procedures are adequately defined and controlled. The overarching principle is that microbiological quality must inherently come via controlling the process, and not solely by testing of raw materials and finished products. It is recommended that efforts should be directed toward microbiological control of raw materials, products and processes in manufacturing environments to assure microbiological quality (e.g., HACCP programs)
For more information on production, please visit the US FDA website.
The percentage of US infants supplemented with formula only is 19.2% (Center for Disease Control and Prevention, 2021). There are several U.S. government initiatives recommending women to breastfeed their infants due to the numerous health benefits for their baby.
There has been an increased rate of formula-feeding to infants due to a rise in the number of women participating in labor force. The high nutritional content of infant formula has driven the growth of the U.S. formula market. However, this rate has not increased as hoped by formula markets due to government initiatives striving to promote the action of breastfeeding rather than formula-feeding (Allied Market Research, 2021).
Infant formulas contain a protein, fat, carbohydrate, and mineral source. Formula contains purified whey and casein from cow’s milk for protein, vegetable oils for fat, lactose for carbohydrates, as well as a mixture of vitamins and minerals including vitamins A, B, C, D and E, calcium, phosphorus and iron (Martin, et. al., 2016). The codex specifies that formulas should have 1.8–3.0 g of protein, 4.4–6.0 g of fat, and 9.0–14.0 g of carbohydrates (specifically lactose or glucose) per 100 kcal, a typical infant-sized serving of formula.
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