COWS’ MILK PROTEIN ALLERGY & LACTOSE INTOLERANCE:

THE USE & ABUSE OF SPECIALISED INFANT FORMULAE 2011

Aim

 To outline the differences between cows’ milk protein allergy (CMPA) and lactose intolerance  To give guidance on how to suspect lactose intolerance & CMPA  To show the algorithm for CMPA in bottle fed babies; Vandenplas 2007, including the use of specialised infant formulae  To discuss the role of soya, rice & goat’s milks etc  To show some illustrative cases

CMPA and lactose intolerance

 Allergy is a reaction to a foreign protein (allergen)  Allergy involves the immune system  Intolerance does not  Lactose is a sugar, therefore not an allergen  Lactose is present in all animal milks including breast milk  Cows’ milk protein allergy (CMPA) & lactose intolerance are two very different things

Lactose intolerance

Allergy

Lactose; “milk sugar”

Lactose

Lactase

Glucose Galactose

Lactase; brush border of duodenum

Lactase levels highest at birth, tend reduce thereafter

Lactose intolerance; 3 types

Congenital Primary Acquired

Congenital lactose intolerance

 Extremely rare autosomal recessive disorder associated with a complete absence of lactase expression.  Finns & Russians

Primary lactose intolerance; childhood/teenage & adult onset

 Lactase deficiency: extremely common in this age group  Lactase levels genetically programmed to decline steadily after 2 years of age, but rarely become

symptomatic until after 7

years of age

Acquired lactose intolerance

 Transient by nature  After gastroenteritis, bowel surgery etc  Takes about 3 months to resolve

Who gets it? Prevalence

 Northern Europeans (ie most of UK!) have the lowest prevalence of primary lactose intolerance; usually only manifest over the age of 5 years  Central & Southern Europeans have higher rates  Hispanic, African and Indians have much higher prevalence, maybe apparent over the age of 2+ years  Premature babies; < 34 weeks gestation (70% term lactase levels at 34 weeks)

So what happens to the lactose?

 Reaches large bowel undigested  Creates abnormal osmotic load to bowel This causes;  Bacterial fermentation of lactose to hydrogen gas,  Increased faecal water,  Increased gut transit time,  Explosive acid stools with  Excoriated bottom

Lactose intolerance; clinical

 Mainly relating to

(bacterial fermentation of lactose in)

the large bowel  Bloating  Pain & discomfort  “Gassy”  Diarrhoea  Explosive stools; no blood except from  Sore bottom

Lactose intolerance; investigation

 Making the diagnosis;

History is the key

Stool pH & reducing substances (hot fresh sample, within the hour!)  Normal stool pH ~6  < 5.3 is acidic and diagnostic of carbohydrate (sugar) malabsorption  Breath hydrogen test; rarely done in children

Lactose intolerance; management

 Lactose intolerance; suitable milks; Enfamil O Lac SMA LF Soya over 6 months of age

Colief is lactase drops

CMPA

Cows milk protein allergy; CMPA

 CMPA is;  Much more common than lactose intolerance  Easily missed, can be difficult to diagnose  Causes infant distress, impaired growth & a wide variety of clinical symptoms  Spectrum of disease; no one pathognomonic symptom  There is no diagnostic test

CMPA; how big is the problem?

 5-15% of infants show symptoms suggestive of adverse reaction to cows’ milk protein

Symptoms of CMPA

 Often, but not always occur within first few weeks after introduction of CMP, e.g. after period of breast feeding Median onset of symptoms from exposure =24 hrs Many develop symptoms in at least 2 systems; Gastro intestinal tract: Skin : Respiratory tract: 50-60% 50-60% 20-30% Mild, moderate or severe

Most frequent symptoms of CMPA

 Irritability, distress, colic, arching, regurgitation, vomiting, difficulty feeding  Loose stools, bloody stools  Iron deficiency anaemia  Atopic dermatitis/eczema  Swelling of lips & tongue  Runny nose, otitis media, chronic cough & wheeze

Alarm symptoms; refer when

 Failure to thrive  Macroscopic blood loss; colitis  Hypoalbuminaemia (Protein Losing Enteropathy)  Severe, difficult to manage eczema  Acute laryngeal oedema or bronchospasm  Anaphylaxis

Management of cows milk allergy in the UK Guest et al 2008 1000 infants with CMPA Study period =12 month period following initial visit to GP Mean age at presentation to GP; 3 months Time to be put on a diet; Time to symptom resolution; Time to diagnosis; 2.2 months 2.9 months 3.6 months Average of 18.2 visits to GP in 12 month period, 4.2 visits before appropriate milk introduced 42% referred to a specialist Average of 7.6 visits before specialist referral

 How did they initially present?

 Combination of GI & atopic/skin symptoms = 55%  GI symptoms alone = 22%  Atopic/skin symptoms alone = 9%  Acute IgE symptoms in less than 10% What other milks were they put on initially?

 60% soya formula  18% with extensively hydrolysed formula  3% with an amino acid formula

Diagnosis and management of CMPA in formula-fed infants*

*Adapted from Vandenplas Y

et al.

Arch Dis Child. 2007; 92 (10): 902-908.

What is a suitable alternative to cows’ milk?

 Any extensively hydrolysed protein formula (EHF) will be suitable for ~80-90% Extensively hydrolysed protein With added MCT (55%) Aptamil Pepti Nutramigen (whey) (casein) Aptamil Pepti Junior Pregestimil  For the other 10-20%: Single amino acid (“elemental”) formula Neocate LCP Nutramigen AA

Standard infant formula Extensively hydrolysed formula EHF + MCT

Danone Nutricia/Cow & Gate/Milupa

Cow and Gate 1 & 2 Aptamil products Aptamil Pepti Whey formula Contains LCPs (omega 3&6) 80-85% short peptide chains 15-20% single amino acids 63% protein chains < 1000 daltons Calcium & iron enriched 34% residual lactose Per 400g tin £8.62

Pepti Junior (+50% MCT) Appropriate for malabsorption disorders 63% protein chains < 1000 daltons Lactose free Per 400 g tin £10.68

Single amino acid formulae Neocate LCP 100% amino acid formula Calcium enriched Produced in a milk free environment Lactose free Per 400g tin £23.83

SMA products Mead Johnson Nutramigen Casein formula Lactose free 95% protein chains < 1000 daltons Per 400 g tin £8.95

Pregestimil (+55% MCT) Appropriate for malabsorption disorders Per 400 g tin £9.81

Cost Taste Allergen -icity Low Good High Nutramigen AA with LIPIL* present in breast milk) Lactose free Per 400 g tin £22.05

(blend of Omega 3 (DHA and Omega 6 ARA fatty acids High Poor Low

Formula fed infants with mild – moderate CMPA     Diagnostic elimination diet (DED) >80% will respond to an EHF (extensively hydrolysed formula) Some casein based (Nutramigen, Pregestimil) Some whey based – taste better! (Aptamil Pepti) Allow at least 2 weeks, up to 4 weeks for some symptoms to resolve.

 But many improve in 48-72 hours ~10-20% will not respond and will need single amino acid formula (Neocate LCP, Nutramigen AA) Infants < 6 months of age Stop all supplementary feeds/weaning during DED

Prescribable indications

 Aptamil Pepti Extensively hydrolysed protein formula Whey based (improved palatability) >97% of infants with CMPA will respond clinically Low levels of lactose (not lactose free) May be some clinical benefits to small amounts of residual lactose (improves calcium absorption & lactase is an inducible enzyme)

What about breast fed babies?

 Continue to breast feed CMP elimination diet in mum, exclude egg too Supplement with calcium Vandenplas guidelines

Prognosis

 Cows’ milk protein allergy persists in only a minority Most outgrow by teenage years (~75%)  20% by 4 years of age  Those with positive IgE based tests more likely to have persistent allergy  Risk factors for persistent allergy: Co existent asthma & rhinitis

FAQs-1 Why not soya milk?

   CMO update 37 January 2004 “Soya should not be used as first line management of CMPA, lactose intolerance or galactokinase deficiency” Soya milks have high phyto-oestrogen content; long term risk to reproductive health of infants (COT 2003) Significant risk of cross reactivity of ~30% (-50%); soy is a potential allergen  SACN advises no unique clinical condition which particularly requires the use of soya based formulae www.sacn.gov.uk

www.foodstandards.gov.uk

FAQs-2 Is soya ever ok?

 Child over 6 months of age Refusing to drink EHF or AA formula Vegans

FAQs-3 Why not goat’s milk?

 2006 DoH advice; Goat’s milk protein formulae not suitable for infants under 12 months of age High chance of cross reaction, ~30%; proteins are very similar Low in folate Similar levels of lactose to cows’ milk (all animal milks contain lactose)  Rice milk High levels of arsenic Not recommended under 4 years of age

FAQs-4 What about investigations?

 GOLD standard is history + improvement on DED  Other tests not usually necessary, unless history of anaphylaxis  Problems with IgE based tests eg RAST & Skin Prick Tests:  Only about 50% of CMPA is IgE mediated  50% of healthy newborns have circulating IgE to cow’s milk  IgE antibodies may appear & be present with no clinical history of CMPA  Negative tests do NOT exclude allergy

FAQs-5 CMPA and associations

 Significant overlap between CMPA and Gastro oesophageal reflux disease of infancy (~40% of those with GORDI have CMPA)  Associated with other food allergies (eg soya up to 50%)  Associated with atopic dermatitis  Associated with positive family history of food allergy and atopy

FAQs -6 What about the lactose?

 Theoretical reasons to suggest that a lactose-free formula may not be beneficial in the longer term.

 Lactase is an inducible enzyme and requires the presence of some lactose in the intestine for optimal development (Shulman et al, 2005)  Removing lactose unnecessarily from diet risks lactase levels permanently declining

Illustrative case 1 Corey aged 3 months  Presented to children’s ward with bloody stool for 2 months Began when mum stopped breast feeding and changed to formula @ 4 weeks of age No vomiting, irritability or colic Mother has allergy to cats, dogs, peanuts, and has asthma Dad’s sister had problems tolerating cows milk as a baby Clinical diagnosis of CMPA; start EHF (Aptamil Pepti in this case) No tests necessary Clinic 4 weeks later, 4 months old Thriving Well No blood in stools since 36 hours after EHF introduced Referral to dietitian for weaning advice

Corey

Illustrative case 2 Oliver aged 2 months  Admitted at 2 months of age with vomiting, loose stools & colic Formula fed (“hungry baby” formula as not settling with feeds) Taking Colief with little effect Mum allergic to cows milk (diagnosed at 3 years of age) Clinical diagnosis of CMPA Changed to EHF  Seen 3 weeks later: “much better” Diarrhoea stopped Less irritable, much happier, sleeping longer No longer on Colief Still some vomiting and regurgitation Started on anti reflux treatment

 Best Practice: Identifying and managing cow's milk protein allergy  George du Toit et al Archives of Disease in Childhood; 2010;95:134-144

References and resources

      http://www.cks.nhs.uk/colic_infantile/evidence/references Vandenplas et al Archives of Disease in Childhood October 2007: 92; 10; 902 Lactose Intolerance in Infants, Children, and Adolescents Pediatrics 2006;118;1279- 1286 Melvin B. Heyman and for the Committee on Nutrition Influence of changes in lactase activity and small intestinal mucosel growth on lactose digestion and absorption in preterm infants, Robert J. Shulman, William W. Wong, and E. O’Brian Smith, Am J Clin Nutr 2005; 81: 472-9 Early feeding, feeding tolerance, and lactase activity in preterm infants, Robert J. Shulman, Richard J. Schanler, Chantal Lau, Margaret Heitkemper, Ching-Nan Ou, and E. O’Brian Smith,, J Pediatr 1998; 133: 645-9 NICE guidelines April 2011

Any questions?