4/5/2015

Jill Mallory, MD, IBCLC Wildwood Family Clinic Madison, WI

 Define a food allergy and a food intolerance.  20 yo living w/ her mom  List 2 risk factors for the development of food  First baby allergies in children?  10 lbs at birth!  Describe the prognosis of food allergies in children.  Vaginal delivery  What is the role of in the prevention of  41 weeks gestation food allergies?  No complications  What is the role of alteration in maternal diet in the allergic child?  Took right to the  Is ever advisable in the setting of food  2 weeks old allergies or intolerances?  Well above  List 3 reasons why a nursing baby who has food allergies should continue to nurse.  Exclusively breastfed

 Very colicky baby  Her sister only breastfed  Seems to be in pain all her daughter for 4 mo the time because she was so colicky. When she  “About the only time he isn’t crying is when he’s switched to , asleep or nursing” it was like magic, and the baby was happy.  Very runny, mucous stools  Afraid of months of colic  Grandmother can’t take  “What’s wrong with my ?” the crying and rec formula

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 Definition: an adverse health effect arising  Food allergies result in IgE-mediated from a specific immune response that occurs immediate reactions reproducibly on exposure to a specific food.  (e.g., anaphylaxis)  and several chronic diseases  (e.g., enterocolitis syndromes, eosinophilic Burks AW, et al. NIAID-sponsored 2010 guidelines for managing food esophagitis, etc), allergy: applications in the pediatric population. . 2011  in which IgE may not an important role. Nov;128(5):955-65. doi: 10.1542/peds.2011-0539. Epub 2011 Oct 10.

Burks AW, et al. NIAID-sponsored 2010 guidelines for managing food Gupta RS, et al. Childhood food allergies: current diagnosis, treatment, allergy: applications in the pediatric population. Pediatrics. 2011 and management strategies. Mayo Clin Proc. 2013 May;88(5):512-26 Nov;128(5):955-65. doi: 10.1542/peds.2011-0539. Epub 2011 Oct 10.

Gupta RS, et al. Childhood food allergies: current diagnosis, treatment, and management strategies. Mayo Clin Proc. 2013 May;88(5):512-26

 In the nursling:  GE reflux  Bloody stools  Eczema  Colic  In older children or adults:  Itching in the mouth or swelling  Vomiting, diarrhea, or abdominal cramps  Hives or eczema  Tightening of the throat and wheezing  Drop in blood pressure

 Milk   Wheat  Soy  Peanut – affects 1-2% of children!  Treenut  Fish  Shellfish

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 IgE presence + symptoms = IgE mediated allergy  Allergens are usually proteins

http://www.ifr.ac.uk/protall/infosheet.htm

 Less well-defined  In the United States, affects an estimated  NOT IgE mediated 12% of children and 13% of adults (self- reported)  Symptoms occur after eating a certain food  Headaches  In double-blind food challenges, incidence  Muscle and joint aches and pains looks more like 3% for adults and children  Tiredness  Rise in prevalence in the past 20 years  Abdominal pain and diarrhea  No effective treatment exists  Examples  Management = avoidance  Celiac disease  Burks AW, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics. 2011 Nov;128(5):955-65. doi: 10.1542/peds.2011-0539. Epub 2011 Oct 10.

 Incidence is poorly defined  Eczema and GI sxs most common  0.5-1% of EBF will develop allergy to  Most common GI sx is bloody stools cow’s milk proteins excreted into ’s  Generally “well-appearing” milk  Sxs can be present at birth  50-65% of allergic colitis in EBF is due  Typically develop at 2-6 weeks of age to cow’s milk protein

 19% to egg, 6% to corn, and 3% to soy ABM Clinical Protocol #24: Allergic Proctocolitis in the Exclusively Breastfed Infant.  EBF infants have significantly lower rates of Breastfeed Med. 2011 Dec;6(6):435-40. doi: 10.1089/bfm.2011.9977. Epub 2011 Nov 3. cow’s than those exposed to formula ABM Clinical Protocol #24: Allergic Proctocolitis in the Exclusively Breastfed Infant. Breastfeed Med. 2011 Dec;6(6):435-40. doi: 10.1089/bfm.2011.9977. Epub 2011 Nov 3.

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 2-4 x more likely to have asthma, eczema,  Biologic or siblings with a hx of respiratory problems allergic rhinitis, asthma, atopic dermatitis  May co-exist with eosinophilic esophagitis (eczema), or food allergy.  Food exposure may cause severe asthma  Child themselves have other preexisting attacks or anaphylaxis allergic disease  37% of children with eczema have IgE- Burks AW, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications mediated food allergy in the pediatric population. Pediatrics. 2011 Nov;128(5):955-65. doi: 10.1542/peds.2011-0539. Epub 2011 Oct 10. Burks AW, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics. 2011 Nov;128(5):955-65. doi: 10.1542/peds.2011-0539. Epub 2011 Oct 10.

 Difficult to predict by  AAP Recommends  Severity of past reactions  At risk = at least 1 first degree relative, or  Food specific IgE levels sibling with food allergy  Wheal size in skin-prick testing  All children at risk of should be exclusively breastfed  Co-existence of asthma =  If exclusive is not possible marker for severity of hydrolyzed infant formulas should be used food allergy  Complementary food should not be restricted at 6 mo

 Intact proteins from the mother’s diet can  Maternal gut cross the gut barrier and enter the breastmilk  Infant gut  These proteins can trigger an allergic response and symptoms in some infants. The crux of it all!

Vadas P, et al. Detection of peanut allergens in of lactating women. JAMA 2001;285:1746-1748. Sorva R, et al. Beta-lactoglobulin secretion in milk varies widely after cow’s milk ingestion in of infants with cow’s milk allergy. J Allergy Clin Immunol.1994;93:787-792. Casas R, et al. Detection of IgA to cat, beta-lactoglobulin, and ovalbumin allergens in human milk. J Allergy Clin Immunol. 2000;105:1236-1240. Pittschieler K. Cow’s milk protein-induced colitis in the breastfed infant. J Pediatr Gastroenterol Nutr. 1990;10:548-549.

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 A healthy gut  Physical barriers – tight junctions  Allows nutrients to pass from food into the  Our bacteria friends bloodstream  Oligosaccharides  Prevents the entrance of pathogenic bacteria and toxins from the environment into the blood

 Breakdown of these barriers occur  Large food particles pass into the blood stream and interact with the immune system  This leads to the development of food allergies

C. Perrier et al. Gut permeability and food allergies. Clinical & Experimental Allergy. Volume 41, Issue 1, pages 20–28, January 2011

Your body houses 10 x more bacterial cells  May start prenatally? than human cells  Modulated by mode of birth  Further modulated by feeding method

Thum C et al. Can nutritional modulation of maternal intestinal microbiota influence the development of the infant gastrointestinal tract? J Nutr. 2012 Nov;142(11):1921-8.

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Maternal gut bacteria are  Our gut bacterial population = a hidden organ thought to contribute  Breaks down our food towards the microbial,  Biotransformation of bile acids metabolic, and  Degradation of oxalate immunological  Breakdown of plant polysaccharides  Production of short chain programming of the fatty acids  Synthesis of biotin, folate, child. and vitamin K

• Lindsay K et al. Probiotics in and maternal outcomes; a systematic review. J Matern Fetal Neonatal Med. 2013 Jan 11. [Epub ahead of print] O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO • Cilieborg MS et al. Bacterial colonization and gut Rep. 2006 Jul;7(7):688-93. development in preterm neonates. Early Hum Dev. 2012 Mar;88 Suppl 1:S41-9.

Affects:  A systematic review . Mucosal immunity  7 studies: 6 RCT’s and 1 prospective cohort . Intestinal disorder  33,399 women in the prospective cohort .Development of allergies  Altered . Energy homeostasis  Breast milk composition . Inflammation . Glucose metabolism  Infant gut bacterial population  Reduced: • Guarner F, et al. Gut flora in health and disease. Lancet 2003; 361:512-9.  Infant allergic disease • Guarner F. Inulin and oligofructose:impact on intestinal diseases and disorders, Br J Nutr 2005;93:S61-5. • Hatakka K et al. Probiotics in intestinal and non-intestinal infectious disease – clinical evidence. Curr Pharm Des 2008;14:1351-67. • Cani PD et al. Interplay between obesity and associated metabolic disorders: new Lindsay, K et al. Probiotics in Pregnancy and Maternal Outcomes. The Journal of insights into the gut microbiota. Curr Opin Pharmacol 2009;9:737-43. Maternal-Fetal & Neonatal Medicine 2013 May;26(8):772-8. • Greiner T et al. Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab 2011;22:117-23.

 Infants born by c-section  Infants who are exclusively breastfed have different gut develop a specific flora by 1 week bacteria than children born vaginally after birth that reaches dominance by 1 month. (Langhendries JP, et al.1995)  Infants born by c-section have a higher incidence of  Prebiotic factors in breast milk → a food allergy and other flora predominant in lactobacilli and atopic disease bifidobacteria (Balmer SE, et al.1989)

 Several factors in breastfed infants

contribute to an intestine that favors

proliferation of these healthy

bacteria (Bernt KM, et al.1999) Koplin J, Allen K, Gurrin L, Osborne N, Tang ML, Dharmage S. Is caesarean delivery associated with sensitization to food allergens and IgE- mediated food allergy: a systematic review.

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 The good microorganisms in breastmilk also  This mixture of bacteria and prebiotics produce antibiotic molecules that directly alters the strength and permeability of prevent the growth of harmful organisms. the barrier between the intestinal lumen and the circulating blood

Dai D, Walker WA. Protective nutrients and bacterial colonization in the immature human gut. Adv Pediatr 1999; 46:353-82.

 In contrast, in newborns who receive formula at birth an intestinal flora develops that is high in enterobacteria and gram- negative organisms.  Tight junctions do not develop properly in these babies.

Majamas H, Isolauri E. Probiotics: A novel approach in the management of food allergy. J Allergy Clin Immunol 1997; 99:178- 85. Isolauri E, Majamas H, Hrvola T, et al. Lactobacillus casei strain reverses increased intestinal permeability induced by cow's milk in suckling rats. Gastroenterology 1993; 105:1643-50

 When damage to the gut barrier occurs from  C-section + formula exposure one exposure to formula, it takes a full month of exclusive breastfeeding to heal it.  The intestinal permeability increases with exposure to formula in a dose-related

manner

Taylor SN, et al. Intestinal permeability in preterm infants by feeding type: mother's milk versus formula. Breastfeed Med. 2009 Mar;4(1):11-5.

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 Poor maternal gut health in pregnancy  Hypothesis: decline in gut health  Allows larger food particles to cross the  Both infant and maternal and get into fetal circulation  Rise in c-sections  Affects what bacteria are passed to baby  Decrease in exclusive breastfeeding prenatally, at birth, postpartum  Antibiotic and pharmaceutical exposure  Affects what bacteria are present in the  Processed foods breastmilk  Poor diets

 Chemical exposure  A mechanism for inheritance of allergic  Environment disease? 

 Historically MDs recommended stopping  This resolved symptoms BUT . . . breastfeeding in:  Deprived the mother and infant of the  Severely allergic infants benefits of breastfeeding AND . . .  Blood in the stool  Will make the leaky gut issue worse  Started on hydrolyzed or elemental formulas  Specialized formulas are very expensive!

 Generally a benign and self-limiting disorder  Most common cause: breastmilk  Not an automatic dx of cow’s milk protein allergy oversupply  Anal tear (fissure) from baby straining with the passage of the stool

 Mom has a cracked or other bleeding, then baby may ingest some blood from mom  Mucous and/or blood in the stool after starting vitamin/fluoride drops

 Infectious: C. Difficile, campylobacter??? Arvola T, Ruuska T, Keränen J, Hyöty H, Salminen S, Isolauri E. Rectal bleeding in infancy: clinical, allergological, and microbiological examination. Pediatrics. 2006 Apr;117(4):e760-8.

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 Incidence is 0.5-1% in breastfed infants  Prognosis  2-3 % in infants overall in the first year of life  Remission rate of  Most develop sxs before 1 mo of age  45-50% by 1 year of age  Often within 1 week of exposure to formula  60-75% by 2 years of age  50-60% GI sxs  85-90% by 3 years of age  50% rash  50% will develop allergies to other foods as well  20-30% wheezing  50-80% will develop environmental allergic reactions such as asthma and rhinoconjunctivitis

 If GI sxs are the only sxs, remission rates are high

Høst A. Frequency of cow's milk allergy in childhood. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):33-7. Høst A. Frequency of cow's milk allergy in childhood. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):33-7.

 Proteins are made of chains of amino acids  Some other mammalian are similar to breastmilk  Some research suggests that exposure to proteins of other may trigger an actual human milk protein allergy  Sx: poor weight gain, GI sxs, not resolving with hypoallergenic diet  This may be one food allergy situation where weaning is advisable

Restani P, et al. Evaluation of the presence of bovine proteins in human milk as a possible cause of allergic symptoms in breast-fed children. Ann Allergy Asthma Immunol.1999;84:353-360. Bernard H, et al. Molecular basis of IgE cross-reactivity between human beta-casein and bovine beta-casein, a major allergen of milk. Mol Immunol 2000;37:161-167.

 Hemoglobin or albumin levels dropping  Rule of 3’s:  Use of hypoallergenic formula may be  3 weeks of age advisable while awaiting pediatric GI  More than 3 hours of crying evaluation  3 days a week or more  Put mom on hypoallergenic diet (rice, lamb,  Lasts for more than 3 weeks pears, squash) for 2 weeks  If baby still symptomatic, may need to wean

ABM Clinical Protocol #24: Allergic Proctocolitis in the Exclusively Breastfed Infant. Breastfeed Med. 2011 Dec;6(6):435-40. doi: 10.1089/bfm.2011.9977. Epub 2011 Nov 3.

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 Behavioral theory  Infant should be assessed by a medical  Crying results from a disequilibrium in the professional for: maternal/infant interaction/bond  GERD  Immunologic model  Malrotation of the intestine  Possible allergens in breastmilk or  Intussuscetion as a causative agent  Malabsorption syndromes  Other things to consider  Blood in stools  Oversupply, undersupply  Other medical conditions

 The family should also be assessed  Other common foods that can cause colic  Diet symptoms in nurslings:  Food allergies in mom or other family  Peanuts  Asthma   Eczema  Soy  Environmental allergies  Wheat  Atopic disease  Tree nuts  Corn  Strawberries

 Elimination of cow’s milk protein (CMP) from  One high quality RCT (n = 90) reported a the maternal diet has led to a decrease in reduction >37% (95% CI 15–56%) of colic colicky symptoms in a large number of symptoms when mothers changed from a infants standard diet to a hypoallergenic diet  A positive challenge test is considered  Elimination of , eggs, peanuts, tree nuts, diagnostic wheat, soy, and fish  For seven days  For some infants, multiple foods may be the culprit  Other studies have had mixed results

Iacovou, Marina et al. Dietary Management of Infantile Colic: A Systematic Review Matern Child Health J (2012) 16:1319–1331 Iacovou, Marina et al. Dietary Management of Infantile Colic: A Systematic Review Matern Child Health J (2012) 16:1319–1331

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 Mom and baby to be evaluated by MD  RAST testing – no longer recommended  Consider allergy testing - controversial  IgE testing  Mom and baby to start probiotic and eat  False negatives plenty of prebiotics  False positives  Burdock, raw chicory root, raw jerusalem  Food challenge artichoke , raw dandelion greens, garlic, leek,  Skin testing onion, wheat bran, banana  IgG testing - not recommended  OK to go ahead and advise mom to start an elimination diet while awaiting MD  Applied kinesiology – not recommended evaluation

 Overused  Varying degrees of success  Symptoms may resolve within 48-72 hours, but may take up to 2 weeks  There may be a big decrease in symptoms without 100% resolution  Burdensome on mothers emotionally  Nutritional risks  Financial risks  Lots of education needed

 Start with dairy  Mother takes 2 tablets of pancrease MT4- elimination: two weeks, strength tablets with each meal or snack followed by re-introduction  Pancrease is a digestive enzyme that further  Consider soy, corn, egg breaks down fats, proteins, and carbohydrates before they enter the mother’s bloodstream.  Lastly: citrus, nuts, wheat, strawberries, chocolate  First phase of elimination:  Dairy, soy, nuts, strawberries, chocolate  Once problem foods are identified, they should be  Second phase of elimination: eliminated for at least 6  Wheat, eggs, corn mo  Avoid until 9-12 mo of age

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 Decreased symptoms of colic  What might be causing Leo’s  Decreased blood in infant’s stool colic  13/16 were able to continue lactation  Should she wean? without use of specialized formulas  Why not?  What should she try instead?

Repucci A. Resolution of stool blood in breast-fed infants with maternal ingestion of pancreatic enzymes. J Pediatr Gastroenterol Nutr. 1999;29:500A.

 Does it play a role in some of our “low milk  No benefit to limiting exposure supply” cases? to non-food allergens (e.g.,  Case study dust mites or pollen)  Baby #4, exclusively BF  Insufficient evidence to  Mom had no hx low supply recommend allergy testing in  at 6mo at-risk children without  “Whimpy nurser” symptoms, prior to food  Happy baby introduction  Eczema  Varied maternal diet may be  Food allergy testing: dairy helpful  Maternal elimination -> growth

 No benefit to delaying allergenic foods That’s right!  Start eggs, dairy, fish, nut , soy, strawberries, citrus, wheat all right at 6 mo when other foods are introduced

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 Studies on allergic food elimination in  The role of breastfeeding in prevention is pregnant women are conflicting debated, mainly due to problems with the  Restriction of maternal diet during pregnancy or lactation is not recommended quality of studies  AAP recommends all children with risk factors for food allergy be exclusively  Why? breastfed for 4-6 months

 Many don’t look at exclusivity and think in terms of breastmilk exposure as a magic

Greer FR et al. Effects of early nutritional interventions on the development of atopic bullet disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008 Jan;121(1):183-91.

 They really should be thinking from the  12 criteria for a valid study perspective of formula exposure as a gut  Non-reliance on late maternal recall of barrier disruptor breastfeeding  Sufficient duration of exclusive breastfeeding  Strict diagnostic criteria for allergy  Assessment of effects of children at high risk of allergies  Adequate statistical power  Unfortunately, no studies to date have completely fulfilled these criteria. Kramer MS. Does breast feeding help protect against atopic disease? Biology, methodology, and golden jubilee of controversy. J Pediatr. 1988;112:181–190

 In order to decrease the risk:  Probiotics  Avoid both early (<4 months) and late (≥7 months)  Present in breastmilk introduction of gluten  Introduce gluten while the infant is still being  Review of 10 studies breastfed  Given to pregnant and postpartum women or newborns reduces incidence of allergies  Given to children with eczema, reduced the severity  Did not specify feeding type

Foolad N, et al. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol. Szajewska H et al. Systematic review: early infant feeding and the prevention of 2013 Mar;149(3):350-5. Review. coeliac disease. Aliment Pharmacol Ther. 2012 Oct;36(7):607-18. doi: 10.1111/apt.12023. Epub 2012 Aug 21.

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 Prebiotics –  Formula exposure oligosaccharides (OS)  At least 25% of BF infants are exposed to formula  Present in breastmilk by day #2 of life in the US  Formula fed kids who were supplemented  By 3 mo of age, that is up to 80% in some studies with OS had a decreased risk of  Type of Formula developing eczema  Mixed results on the benefits of amino acid or (50% reduction) hydrolyzed formulas over standard cow’s milk

formulas Foolad N, et al. Effect of nutrient supplementation on atopic dermatitis in  There may be a benefit in prevention of dairy children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA allergy Dermatol. 2013 Mar;149(3):350-5. Review.

 Formula exposure  Fatty acids  Use of soy formula is not beneficial in prevention  US pregnant and lactating women have the of dairy allergy lowest DHA levels in the developed world  There is no evidence that suggests use of  Gamma-linolenic acid (GLA) and omega-3’s both hydrolyzed formulas offer any preventative components of breastmilk benefit over breastmilk  If a mother has allergic disease, GLA supplementation in pregnancy may reduce severity of allergic disease in infants

Foolad N, et al. JAMA Dermatol. 2013 Mar;149(3):350-5. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids.

 Fatty acids  GLA also appears to reduce severity when given to infants  Infants and mother’s supplemented with omega- 3’s had lower incidence of allergic disease  Black currant seed oil = GLA + omega 3’s, beneficial in incidence reduction  Again, does not specify feeding method

Foolad N, et al. JAMA Dermatol. 2013 Mar;149(3):350-5. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. Hibbeln, Joseph. NIH

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 Likely to occur over time with dairy, soy, egg  Sublingual Immunotherapy (SLIT) and wheat  Liquid or tabs placed under the tongue  Kids with peanut, tree nut, fish and shellfish  More research needed allergies are less likely to outgrow them  Oral Immunotherapy (OIT)  Younger children may be re-tested annually  May lessen the severity of reactions  More research needed

1. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 2012;129(2)448-‐55,455.e1‐5. 2. Burks AW, Jones SM, Wood RA, et al. Oral Immunotherapy for treatment of egg allergy in children. N Engl J Med 2012;367(3):233‐43

 Food Allergy and Anaphylaxis Network  AAP Section on Allergy and Immunology www.foodallergy.org www.aap.org/sections/allergy   Consortium of Food Allergy Research’s American Academy of Allergy, Asthma & Immunology online educational program (AAAAI) www.aaaai.org/ https://web.emmes.com/study/cofar/  American College of Allergy, Asthma and EducationProgram.htm Immunology  The Whole Life Nutrition Cookbook (ACAAI) www.acaai.org/ https://wholelifenutrition.net/store/  Asthma and Allergy Foundation of America books/whole-life-nutrition-cookbook (AAFA) www.aafa.org/

 Food Allergy Initiative (FAI) www.faiusa.org/  Kids With Food Allergies (KFA) www.kidswithfoodallergies.org/  National Institute of Allergy and Infectious Diseases (NIAID) www.niaid.nih.gov/  Infant Proctocolitis – printable handouts! http://infantproctocolitis.org/

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