Infant milks and health/feeding issues
Partially hydrolysed proteins are created using enzymatic processes to break proteins naturally found in a food into smaller fragments. In the UK, infant formula marketed as ‘comfort milks’ are based on partially hydrolysed whey protein and more recently manufacturers have introduced several standard infant formula to the market which are also based on partially hydrolysed whey proteins.
Partially hydrolysed proteins are advertised as being easier for infants to digest, for example one manufacturer claimed on their website ‘Whey dominant formulas containing partially hydrolysed protein accelerate gastric emptying time making the formula easy to digest’
A Nestlé sponsored study using NAN and NAN H.A products, Staelens et al (2008), found no significant difference in the rate of gastric emptying when infants were given a partially hydrolysed whey protein formula and a standard whey based infant milk with intact protein. Another reference given to support claims around digestibility comes from one small under powered study measuring gastric emptying in infants with and without reflux (Billeaud et al, 1990).
In the UK ‘Comfort’ milks are based on partially hydrolysed whey protein and more recently manufacturers have introduced several standard infant milk products to the market which are based on partially hydrolysed whey proteins. There is no evidence to suggest any benefit to infants from using these infant milks over those based on intact cows’ or goats’ milk protein. More information on comfort milks can be found at www.infantmilkinfo.org.
Billeaud C, Guillet J, Sandler B (1990). Gastric emptying in infants with or without gastro-oesophageal reflux according to the type of milk. European Journal of Clinical Nutrition, 44, 577-583.
Staelens S, Van Den Driessche M, Barclay D et al (2008) Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula.Clinical Nutrition,doi:10.1016/j.clnu.2007.12.009.
There is good evidence that breastfeeding is the best way to protect infants from developing allergies, even where there is a family history of allergy. Some infant formula may claim to reduce the risk of a baby developing an allergy, however there is no good evidence to support this claim.
Infant milks containing partially hydrolysed proteins were originally marketed with claims that the use of these formula could prevent allergies in infants from families with a history of allegies (atopic families). Much of the evidence used to support this hypothesis is based on industry funded studies with a high risk of bias, as highlighted in a recent Cochrane review (Osborn et al, 2018). A systematic review, commissioned by the Food Standards Agency, into the evidence on diet and allergy in the first year of life also found no evidence that use of partially hydrolysed formula reduced the risk of allergy or autoimmune outcomes in infants at high risk (Boyle et al, 2016).A recent study has also raised the possibility of adverse effects from the use of partially hydrolysed whey protein based infant formula, although their clinical significance is unknown (Davisse-Paturet et al 2019). It is important to note that infant formula containing partially hydrolysed proteins are not suitable for infants diagnosed with cows’ milk protein allergy. For more information on H.A formula marketed in the UK see the section in ‘Type of infant milk’ at www.infantmilkinfo.org.
Boyle RJ, Ierodiakonou D, Khan T et al (2016) Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. British Medical Journal; 352; i974
Davisse‐Paturet, C, Raherison, C, Adel‐Patient, K, et al. (2019). Use of partially hydrolysed formula in infancy and incidence of eczema, respiratory symptoms or food allergies in toddlers from the ELFE cohort. Pediatric Allergy Immunol, 30, 614– 623.
Osborn DA, Sinn JKH, Jones LJ (2018). Infant formulas containing hydrolysed protein for prevention of allergic disease. Cochrane Database of Systematic Reviews, 10. Art. No.: CD003664. DOI: 10.1002/14651858.CD003664.pub6.
There is no consistent evidence that comfort milks improve babies’ wind, colic or fussiness, and these will pass as the baby gets older. Often small changes to the timing and quantity of feeds can be effective in managing periods of fussiness. No convincing evidence is presented by manufacturers to support the efficacy of these milks in preventing colic, wind or gastrointestinal discomfort. NICE clinical guidance is clear there is no infant formula solution for colic (NICE CKS, 2017) and NICE advise against a change in formula type
More information for healthcare professionals on management of colic can be found on the GP Infant Feeding Network Website https://gpifn.org.uk
Information for parents on managing colic can be found at www.nhs.uk
NICE CK (2017) NICE Clinical Knowledge Summaries: Infant colic. Available at https://cks.nice.org.uk
Will a comfort milk help with constipation?
Breastfed babies rarely get constipated. Most infant milks containing partially hydrolysed proteins are marketed as ‘comfort milks’ and claim to be easier to digest and designed for the management of colic and constipation in formula-fed infants.
Other modifications made to comfort milks that have been used as a basis for claims of improved symptoms of colic and constipation include reduced lactose, the use of partially hydrolysed whey protein, increasing the proportion of fats supplied as beta-palmitate and the addition of oligosaccharides. Increasing the proportion of magnesium (but to within the parameters specified by the current delegated regulation for infant milks marketed as foods for special medical purposes) is the most recent modification that has been used as the basis for claims of efficacy in the management of constipation. However, manufacturers do not present any convincing evidence to support the efficacy of these milks in preventing gastrointestinal discomfort, colic or constipation. For more information about claims made for infant milks, or their ingredients, see www.firststepsnutrition.org/infant-milks-health-workers
The NHS website suggests that constipation in formula-fed infants can be treated with additional drinks of water but there is no advice to change formula (NHS, 2020). It is important that families do not add more to feeds and use the reconstitution guidance on the product. Some additional activity may stimulate a baby’s bowels – for example gentle bicycling movement with their legs or gently massaging their tummy.
(NHS, 2020) https://www.nhs.uk/conditions/constipation/
Lactose intolerance is a clinical syndrome which can cause abdominal pain, diarrhoea, flatulence and/or bloating after ingestion of food containing lactose. The underlying physiological problem is lactose malabsorption, which is caused by an imbalance between the amount of lactose ingested and the capacity of the enzyme lactase to hydrolyse it, and therefore the amount of lactose that can cause symptoms varies (Heyman et al, 2006).
Heyman et al (2006) identify the following different types of lactose intolerance:
- Primary lactose intolerance is caused by an absolute or relative lack of the enzyme lactase and is the most common cause of lactose malabsorption worldwide. It is known to be more prevalent among black and Asian populations but is extremely rare in infants.
- Secondary lactose intolerance results from injury to the small bowel such as might occur during acute gastroenteritis and persistent diarrhoea and is likely to be temporary.
- Congenital lactase deficiency is a rare condition in infants, in which the infant develops persistent diarrhoea as soon as any lactose, from human milk or formula, is introduced.
- Developmental lactase deficiency is observed among premature infants. Lactase production is deficient in the immature gastrointestinal tract until at least 34 weeks’ gestation.
In the very rare cases of primary or congenital lactose intolerance, lactose-free formula are necessary, but infants should be managed by a clinician. The continued use of breastmilk does not seem to have any adverse effects on pre-term infants with developmental lactose intolerance (Shulman et al, 1995).
In the UK lactose free infant milks available over the counter suggest they are suitable for infants who have been diagnosed with lactose intolerance following a bout of gastroenteritis.In developed countries, the use of lactose-free milks as a treatment for acute gastroenteritis has been shown to have no clinical advantage over standard lactose-containing formula (Kukuruzovic and Brewster, 2002). The most recent ESPGHAN guidelines for the management of acute gastroenteritis in children (Guarino et al, 2014) suggest that there is weak evidence for the use of lactose-free milk for the treatment of acute diarrhoea in hospital settings, but that the routine use of lactose free milks in community settings is not recommended. It is also suggested that diets without lactose might have disadvantages for the composition of the infants’ colonic microflora and colonic physiological function, and they might compromise calcium absorption (Ziegler & Fomon, 1983).
There are also potential risk associated with the use of lactose free formula. Diets without lactose might have disadvantages for the composition of the infants’ colonic microflora and colonic physiological function, and they might compromise calcium absorption (Ziegler& Fomon, 1983). Moreover, feeding lactose free diets from birth (for example, for preventive purposes), will cause false negative results of most neonatal screening tests for galactosaemia (Hðst et al, 1999).
Some newer evidence also suggests that infants fed a lactose free formula will have higher blood glucose and some circulating amino acid levels after 120 minutes than infants fed standard infant formula, suggesting that lactose free formula may have a negative impact on the infant metabolism which require further investigation (Slupsky et al, 2017).
Lactose-free milk has a greater potential to cause dental caries. Lactose is a non-cariogenic sugar whereas the common replacement carbohydrate maltodextrin has greater cariogenic potential (Grenby and Mistry, 2000). It is therefore vital that parents using lactose-free milk follow advice to avoid prolonged contact of milk feeds with their baby’s teeth and ensure that they clean their baby’s teeth after the last feed at night.
Grenby TH, Mistry M (2000). Properties of maltodextrins and glucose syrups in experiments in vitro and in the diets of laboratory animals, relating to dental health. British Journal of Nutrition, 84, 565-574.
Guarino A, Ashkenazi S, Gendrel D et al (2014) ESPGHAN and Nutrition/European Society for Pediatric Infectious Diseases: Evidence based guidelines for the management of acute gastroenteritis in children in Europe: Update 2014. JPGN, 59, 1320 152.
Heyman B for the Committee on Nutrition of the American Academy of Pediatrics (2006). Lactose intolerance in infants, children and adolescents. Pediatrics, 118, 1279-1286.
Hðst A, Koletzko B, Dreborg S, et al (1999). Joint Statement of the European Society for Paediatric Allergology and Clinical Immunology (ESPACI) Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition. Dietary products used in infants for treatment and prevention of food allergy. Archives of Disease in Childhood, 81, 80-84.
Kukuruzovic R, Brewster D (2002). Milk formulas in acute gastroenteritis and malnutrition: a randomised trial. Journal of Paediatrics and Child Health, 38, 571-577.
Shulman R, Feste A, Ou C (1995). Absorption of lactose, glucose polymers or combination in premature infants. Journal of Pediatrics, 127, 626-631.
Slupsky CM, He X, Hernell O, Andersson Y et al (2017). Postprandial metabolic response of breastfed infants and infants fed lactose-free vs regular infant formula: A randomized control trial. Scientific Reports, 7:3640. DOI: 10.1038/s41598-017-03975-4.
Ziegler EE, Fomon SJ (1983) Lactose enhances mineral absorption in infancy. Gastroenterol Nutr2, 288–294
Many babies will bring up small amounts of milk after feeds or if they burp, and this causes them no distress. Crying, vomiting milk after feeds, and back-arching or being unsettled are not symptoms of reflux in most babies. Reflux is rare and should be properly diagnosed by a paediatrician. Babies bringing up milk after feeds may need smaller milk feeds more often or more frequent winding during a feed. Where babies are growing adequately, many of these problems will disappear as they grow.
Advice on managing reflux for families can be found here www.nhs.uk
In 2015 NICE published guidelines to support health professionals, including GPs and hospital doctors, to help everyone provide consistent, evidence-based support for anyone concerned about infant reflux and regurgitation. They state:
- Reflux is very common. It affects nearly half (at least 4 out of 10) of babies younger than 1 year.
- Usually no tests or treatments are needed.
- It tends to start before the baby is 8 weeks old.
- It can happen a lot – some babies bring up milk 6 or more times a day.
- It normally happens less often as the baby gets older.
- It gets better on its own in most babies (9 out of 10) by the time they are 1 year old
For bottle‑fed babies who regurgitate often and are very distressed, for example, if they cry inconsolably and they seem to be in obvious pain then changing the amount of milk and giving smaller feeds more often (but the same overall amount of milk) are the first recommendations made. A trial of changing to a thickened feed or adding a thickener to the feed for a trial period is recommended after these practical feeding changes have been tried. A thickened formula is not necessary and a standard infant formula can be given with thickener given in the milk or on a spoon before the feed.
This guidance has also been reiterated in NICE Quality Standards published in 2016 available at www.nice.org.uk
Thickened (anti-reflux) milks do not have to comply with infant formula regulations in the UK, and they should only be used under medical supervision. Thickened (anti-reflux) milks contain locust or carob bean gum or potato starch. Manufacturers recommend that anti-reflux milks are made up at lower temperatures than the temperature currently recommended for safety (water at a temperature >70oC). Powdered infant formula are not sterile and making them up at lower temperatures will not kill any harmful bacteria that might be present. It may not be advisable for infants on certain medications to be given an anti-reflux milk.
For more information on infant formula and follow-on formula based on cows’ or goats’ milk follow the links from types of infant milks.
The first line of support for infants with cows’ milk protein allergy (CMPA) is to encourage continued breastfeeding for breastfed babies. A return to or establishment of exclusive breastfeeding for infants who are fed using a combination of breastmilk and infant formula may be recommended. For breastfed infants, healthcare professionals should advise the mother to exclude cows’ milk protein from her diet and consider prescribing a daily supplement of 1000 mg of calcium and 10 micrograms of vitamin D to the mother.
For infants who are exclusively formula fed, an extensively hydrolysed formula (eHF)is generally suitable. These infant formula) are based on cows’ milk but the protein is extensively broken down into smaller peptides that are less well recognised by the immune system. For the very few infants with severe allergy or multiple food allergies an infant formula which contains fully broken down proteins in the form of amino acids (amino acid-based formula) should be used. Both these infant formula are only available on prescription.
It is important to note that soy protein–based formulas, partially hydrolysed infant formula, hydrolysed pre-term formulaor infant formula made from goats’ milk are notsuitable breastmilk substitutes for cows’ milk protein allergy treatment.
For guidance on how to manage suspected or diagnosed cows’ milk protein allergy, please refer to the NICE guidance on cows’ milk protein allergy management cks.nice.org.uk
For more information on specialised milks see www.infantmilkinfo.org.
There is good evidence that breastfeeding is the best way to protect infants from developing allergies, even where there is a family history. Some infant formula may claim to reduce the risk of a baby developing an allergy, however there is no good evidence to support this claim.
The UK government advises that soya protein-based infant formula should only ever be used if it has been recommended or prescribed by a health visitor or GP, and then only from 6 months. This is primarily due to concerns over the potential allergenic effect of soya protein-based infant formula in infants at high risk of atopy and the effects that the phyto-oestrogens present in soya protein-based formula might have on future reproductive health. Additionally, as the carbohydrate source in soya protein-based infant formula is maltodextrin rather than lactose, these milks have a greater potential to cause dental caries than animal milk based infant formula.
Soya protein-based formula contain much higher levels of phyto-oestrogens than formula based on cows’ milk protein. Setchell et al (1998) estimated that infants aged 1 to 4 months who were fed soya protein-based formula would receive 6-12mg/kg of body weight of phyto-oestrogens per day, compared to 0.7-1.4mg/kg bw per day for adults consuming soya protein-based products. There has been very little research into the effects of consumption of phyto-oestrogens from soya protein-based formula in very young infants. However, research in animals suggests that phyto-oestrogens can have detrimental effects on reproductive function, immune function and carcinogenesis. In a review of the scientific evidence on soya protein-based formula, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) concluded that the high levels of phyto-oestrogens present in soya protein-based formula posed a potential risk to the future reproductive health of infants (Committee on Toxicity, 2003).
There have been a number of more recent studies and the outcomes have not been consistent, but some studies have shown potential risks. Harlid et al (2017) fed soya-based infant formula or cows’ milk formula to infant girls who provided vaginal swab samples at 2 weeks and 4 weeks of age and monthly up to 9 months of age. These samples were analysed by pyrosequencing for methylation levels. Samples from girls receiving soya-based infant formula were found to have a significantly higher degree of methylation in vaginal epithelial cells compared to those receiving cows’ milk formula. The long-term implications of this are currently unknown however the precautionary principle would suggest that caution should be observed where evidence is not conclusive.
In a review of trials comparing the effect of prolonged feeding of soya protein based infant formula and of cows’ milk protein based infant formula, meta-analysis found no significant difference in childhood asthma incidence, childhood eczema incidence or childhood rhinitis. The authors concluded that soya protein-based formula cannot be recommended for allergy prevention or food intolerance in infants at high risk of atopy (Osborn and Sinn, 2006).
ESPGHAN recommends that soya protein based infant formulas should not be used for infants under 6 months of age and that the use of therapeutic milks based on extensively hydrolysed proteins (or amino acid preparations if hydrolysates are not tolerated) should be preferred to the use of soya protein formula in the treatment of cows’ milk protein allergy (Agostoni et al, 2006). Soy protein-based formula can be used in some cases for infants with cows’ milk protein allergy over 6 months of age if tolerance to soya protein has been established (Koletzko et al, 2012).
Agostoni C, Axelsson I, Goulet O, et al (2006). Soya protein infant formula and follow-on formula: a commentary by the ESPGHAN Committee on Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 42, 352-361.
Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (2003). Phytoestrogens and Health. Available at: http://cot.food.gov.uk/pdfs/phytoreport0503
Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, Stallings VA, Williams CJ, Rogan WJ, Taylor JA. (2017). Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Environ Health Perspect125, 447–452
Koletzko B, Niggeman B, Arato A, Dias JAS, Heuschkel R et al (2012).Diagnostic Approach and Management of Cow’s-Milk Protein Allergyin Infants and Children: ESPGHAN GI Committee Practical Guidelines.Journal of Pediatric Gastroenterology and Nutrition,55, 221-229
Osborn D, Sinn J (2006). Soya formula for prevention of allergy and intolerance in infants. Cochrane Database of Systematic Reviews.Issue 4. Art. No.: CD003741. DOI: 10.1002/14651858.CD003741.pub4
Setchell K, Zimmer-Nechemias L, Cai J, Heubi J (1998). Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life. American Journal of Clinical Nutrition, 68, 1453S-1461S.
Periods of fussy eating are common in young children and in most cases resolve themselves if families continue to offer a range of foods, eat with their children and act as a good role model for eating a range of foods. Occasionally a child will have a more serious case of food refusal, and advice should be sought on how to manage this most effectively. Giving a fussy child a sweet milkshake drink will not help them eat better in the long term, and we discourage the use of any fortified milks for this purpose.