By Ewing, Whitney Merrill; Allen, Patricia Jackson
Cow milk protein intolerance (CMPI) affects 3% of infants under the age of 12 months and is often misdiagnosed as GERD or colic, risking dangerous exposure to antigens. Most infants out grow CMPI by 12 months; however, those with IgE-mediated reactions usually continue to be intolerant to cow’s milk proteins and also develop other allergens including environmental allergens that cause asthmatic symptoms. Clinical manifestations of CMPI include diarrhea, bloody stools, vomiting, feeding refusal, eczema, atopic dermatitis, urticaria, angioedema, allergic rhinitis, coughing, wheezing, failure to thrive, and anaphylaxis. The research and literature showed that CMPI is easily missed in the primary care setting and needs to be considered as a cause of infant distress and clinical symptoms. This article focuses on correctly diagnosing CMPI and managing it in the primary care setting.
The advent of pasteurization and improved hygiene in farming over the last 100 years has led to the dramatic increase in consumption of cow milk-based products by infants and breast-feeding mothers (Brown, 2002). Despite the numerous health benefits of milk, there are potential detrimental effects, such as gastrointestinal complaints, colic, eczema, rhinitis, asthma, and anaphylaxis (Lake, 2001; Nocerino & Guandalini, 2003). The health risks are no surprise since cow’s milk was not intended for human infants. Two conditions that explain these symptoms are cow milk protein intolerance (CMPl) and cow milk allergy (CMA). Both involve the body’s inability to digest the cow milk protein (CMP), but they are differentiated by the body’s immune response. The literature cites CMPI occurring in 2 to 15% of infants with CMA, accounting for 53 to 64% of these cases (Anderson, 1997; Nocerino & Guandalini, 2003; Vanto et al., 2004). Actual occurrence of CMPI in developed countries is likely around 3% of infants under a year of age (Salvatore & Vandenplas, 2002).
Due to the varied clinical symptoms, there is often a delay in diagnosis, and symptoms can progress to bloody diarrhea, anemia, dehydration, poor growth, and failure to thrive (Lake, 2001). CMPI is responsible for 50 to 80% of gastrointestinal symptoms in children under one year of age (Nocerino & Guandalini, 2003). There is evidence that CMA is a precursor for childhood and adult diagnoses of asthma, environmental and food allergies, and reflux disease (Brown, 2002; Hill, Heine et al., 2000; lacono, 1996). Knowing this, it is imperative that pediatric nurse practitioners know how to recognize and treat CMPI so that symptom progression and failure to thrive are prevented, and the source of future allergies is stunted (Isolauri & Turjanmaa, 1996).
CMA is differentiated from CMPl by elevated levels of IgE specific antibodies (Heine, Elsayed, Hosking, & Hill, 2002). Non- IgE mediated CMPI may cause elevated T-cell levels, and does not have the same long-term adverse effects of CMA. Clinically, it is impossible to diagnose CMPI versus CMA, and they are often discussed and treated without differentiation since the immunologic basis of the involved mechanism often is not determined (Salvatore & Vandenplas, 2002). For the purpose of this article, the term CMPI will be used to refer to both conditions unless CMA is specifically mentioned.
Pathophysiology
A useful framework for understanding CMPI is the body’s immunologic response to cow milk protein (CMP) as described by Brown (2002). Brown diagrams how each system of the body is in contact with ingested CMP through the blood and extracellular fluids ( see Figure 1). Based on this, it is not surprising that CMPI manifests in several body systems. It is therefore important to treat CMPI and not just specific symptoms.
Immunologic Response. The protein in cow’s milkbased formulas acts as an antigen in the sensitized infant’s body, and in the case of CMA, stimulates the production of IgE antibodies. CMPI occurs when large molecules, such as intact CMP, pass thru the infant’s permeable gastrointestinal (GI) tract and are absorbed rather than broken down (Cirgin Ellett, 2003). As the infant’s GI tract matures, the lining also matures, and fewer proteins get through, resolving the CMPI symptoms and reducing the production of IgE.
Pathophysiology. The difference between CMPI and CMA lies in the antibodies. CMA reactions are mediated by immunoglobulin E antibodies (IgE). CMPI reactions are similar but have no IgE component. When an allergic infant is exposed to milk protein, either prenatally or post natally. his or her body makes more IgE antibodies to the cow milk protein than a nonallergic infant. These IgE antibodies connect with mast cells in the skin, the gastrointestinal tract, and the sinopulmonary tract (Burks. 2003; Sicherer, 2003). With continued exposure, the affected mast cells release mediators that cause the signs and symptoms of an allergic reaction (Brown. 2002; Hill, Heine, Cameron, Francis. & Bines. 1999; lsolauri & Turjanmaa. 1996; Lake. 2001; Odze, Wershil, Leichtner, & Antonioli. 1995). IgE food reactions are usually caused by milk, eggs, peanuts, tree nuts, soy, wheat, and seafood (Sicherer. 2003). Providers recommend to parents to avoid these foods in the first year and some foods until after the second year because of their potentially highly allergic status. However, milk proteins are in all of the first line formulas and may be in the pregnant/breast- feeding mother’s diet therefore, they are harder to avoid completely. Clinical tolerance to milk, eggs, wheat, and soy usually develops within a few years of diagnosis, despite continuing presence of IgE antibodies to the allergenic foods (Anderson. 1997).
Figure 1. Effect of CMP on Sensitized Infants
Stages of CMPI. Researchers have categorized three stages of CMPI associated with severity of reaction; and immediate, intermediate, and late stage reactions to CMP (Heine et al.. 2002). Within 30 minutes, the immediate stage shows signs of urticaria (skin rashes, perioral erythema), angioedema of the face, and or anaphylaxis. accompanied by CMP IgE antibodies (Dupont & de Boissieu. 2003: Heine et al., 2002). The intermediate stage is a non IgF sensitized reaction, and gastrointestinal symptoms develop within hours post contact/consumption of CMP (Dupont & de Boissieu, 2003; Heine et al., 2002). The late stage reaction has gastrointestinal symptoms with or without respiratory or cutaneous symptoms, and develops one to five days post contact or consumption (Dupont & de Boissieu. 2003; Heine et al., 2002). IgE involvement in the late stage is uncertain.
Urticaria and angioedema are immediate reactions to CMP: atopic dermatitis, infantile colic, gastroesophageal reflux, esophagitis, infantile proctocolitis, food-protein enterocolitis. and constipation are all intermediate and late-onset reactions (Dupont & de Boissieu, 2003). The literature does not mention whether infants can progress from one stage to the next, but it does indicate that early atopy can progress to asthma later in life.
Clinical Manifestations
Symptomatically, there is no difference in the way CMPI and CMA present, and it is important to refer to allergy or gastroenterology for diagnostic testing if symptoms are severe (Brown. 2002: Heine et al., 2002; Klish et al., 1998; Lake, 2001; Odze et al., 1995; Salvatore & Vandenplas, 2002). Providers need to be aware that infants with CMPI may present with gastrointestinal symptoms only, cutaneous symptoms only, respiratory symptoms only, or anaphylaxis in the rare case, and any combination of all four systems. CMPI symptoms usually begin by one month of age or within one week of starting a CMP based formula (Dupont & de Boissie. 2003), up to 42% of infants with CMPl are symptomatic within 7 days of starting a cow’s milk-based formula (Nocerino & Guandalini, 2003). For a full list of potential symptoms, see Table 1.
Symptoms suggestive of CMH in breast-fed babies are similar to those seen in formula-fed babies (Brown, 2002). Because there is less CMP in breast-milk than regular formula, if the breast-fed baby is symptomatic, it has a high degree of sensitivity, increased likelihood of CMA, and greater potential for long-term sequelae (Brown, 2002).
Table 1. Common Symptoms of CMPI
Gastrointestinal Manifestations. Gastrointestinal (QI) symptoms are the most common symptom of CMPI, presenting clinically 58 to 80% of the time (Dupont & de Boissieu, 2003; Nocerino & Guandalini, 2003). GI symptoms commonly present alone (Nocerino & Guandalini, 2003). Diarrhea, bloody stools, nausea, vomiting, constipation, and feeding refusal make up the GI symptoms associated with CMPI (Heine et al., 2002; Hill, Heine et al., 2000; Iacono, 1996; lacono et al., 1998; Nocerino & Guandalini, 2003; Salvatore & Vandenplas, 2002; Sicherer, Eigenmann, & Sampson, 1998; Vanderhoof et al., 1997). With CMPI, nausea and vomiting typically occur within minutes or hours after food ingestion, followed by diarrhea. Left untreated, diarrhea can progress to bloody diarrhea. CMPI is the most common cause of bloody stools in infants.
Cutaneous Manifestations. Eczema and atopic dermatitis, urticaria, pruritus, and angioedema are the main skin reactions associated with CMPI and occurin 50 to 60% of infants with CMPI (Burks, 2003; de Boissieu & Dupont, 2000; Heine et al., 2002; Hill, Sporik, Thorburn, & Hosking, 2000; Isolauri & Turjanmaa, 1996; Salvatore & Vandenplas, 2002). Eczema describes a generic inflammatory skin condition characterized by erythematous, itchy, potentially infected skin lesions. It may or may not have an allergic cause. Atopic dermatitis, also known as atopic allergy, describes eczema caused by an allergen. It is one of the symptoms of atopy, an allergic, hereditary disorder characterized by hay fever, asthma, chronic urticaria, and atopic dermatitis. Differentiation between eczema and atopic dermatitis is done with radioallergosorbent testing.
Eczema before the age of 4 months has been found to be associated with allergy to several foods (de Boissieu & Dupont, 2000). “Eczema or urticaria on contact with spilt milk is a clear indication that milk is the cause, but this is rare” (Brown, 2002).
Table 2. Differential Diagnosis for CMPI in the Infant
Respiratory Manifestations. CMPI-associated respiratory symptoms occur in 20 to 30% of sensitive infants, usually develop after infancy, and are considered a sign of further IgE sensitization (Brown, 2002). Allergic rhinitis symptoms are indicative of upper airway involvement, and asthma is indicative of lower airway involvement (Anderson, 1997). A cough or wheeze that develops while on a cow’s milk-containing diet, or after rechallenge with cow’s milk, are considered allergy-related respiratory symptoms (Heine et al., 2002).
General Manifestations. General symptoms of CMPI . are anaphylaxis and failure to thrive. Anaphylaxis related to CMP is very rare (Anderson, 1997; Heine et al., 2002; Salvatore & Vandenplas, 2002; Taubman, 1988). When anaphylaxis occurs, the child becomes pale, cool, and perspires; and has urticaria and angioedema progressing to shock within minutes (ISocerino & Guandalini, 2003). Anaphylaxis happens within minutes of ingesting CMP.
Failure to thrive (FTT) can result from serious, untreated CMPl (Brown, 2002; Field, 2002; Hill et al., 1999; Isolauri, Siitas, Salo, Isosomppi, & Kaila, 1998; Isolauri, Tahvanainen, Peltola, & Arvola, 1999; Salvatore & Vandenplas, 2002; Wyllie, 1996). As infants refuse food, absorb fewer nutrients, and have prolonged vomiting and diarrhea, their height and weight may drop down several growth percentiles.
Differential Diagnosis
Gastroesophageal reflux disease (GERD) and colic are the main differentials of CMPI in infants less than 12 months old (Anderson, 1997; Lucassen et al., 1998; Nocerino & Guandalini, 2003; Sicherer, 2003). CMPl, GERD, and colic present similarly and are often misdiagnosed. Other less likely differentials are included in Table 2.
Gastroesophageal Reflux. The research reveals that CMPI is found in up to 50% of infants diagnosed with gastroesophageal reflux (GER) (Salvatore & Vandenplas, 2002). GER is defined as the involuntary passage of gastric contents into the esophagus and is classified as either primary physiologic, primary pathologic, or secondary GER (Salvatore & Vandenplas, 2002). usually, there are clinical manifestations in only one system of the body (GI) with primary GER. If more than one system is involved (GI, cutaneous, or respiratory), it is more suspicious of primary CMPI. Secondary GER is known in the literature as GER disease (GERD), and CMPI is often its causative agent (Salvatore & Vandenplas, 2002). Vomiting and irritability seen in CMPI is sometimes mistaken for the vomiting and irritability often seen with GERD. However, the infant will have relief of symptoms when CMP is removed from the diet. CMPI often precedes gastrointestinal problems and should be ruled out as the underlying pathology of GERD (Staiano et al., 1995). Table 3 lists the symptoms of GERD, CMPI, and their overlap. As with CMPI, GERD improves with age; 98% of infants with GERD have no symptoms by two years of age (Salvatore & Vandenplas, 2002).
Figure 2. CMPI Tolerance Development in Infants
Intestinal permeability tests, β-lactoglobulin antibody presence, and pH tracings can help with GERD-CMPI diagnosis, but they are costly, time-consuming, and have variable reliability. Clinical response to an elimination diet is the safest and most frequent diagnostic clue for CMPI-associated GERD. If symptoms persist, then treatment directed at GERD is indicated (Salvatore & Vandenplas, 2002).
Colic. About 20% of infants have colic in the first four months of life. Of these, 10 to 35% are caused by CMPI (Anderson, 1997: Cirgin Ellett, 2003). Colic is defined as irritability lasting for a total of more than three hours a day and happening more than three days per week for three weeks in an otherwise healthy infant. Along with persistent crying, infants with colic are less able to be soothed and are restless. According to the literature, there are at least five possible causes of colic: CMPI and soy protein allergy/ intolerance: immature gastrointestinal system; immature central nervous system; difficult infant temperament; and parent-infant interaction problems (Cirgin Ellett, 2003). Unless there are other symptoms consistent with CMPI, it is difficult to clinically determine CMPI involvement in colic. Cirgin Ellett (2003) found 10 to 35% of infants studied with colic improved after cow’s milk or soy protein was removed from the infant or breast-feeding mother’s diet. The only way to conclude CMPI is the cause of colic in an infant is through a trial CMP elimination diet. If the infant improves, CMPI is the likely cause of colic.
Prognosis
CMPI affects infants from birth to one year, and those at greatest risk have a history of CMPI or atopic disease in their family (Klish et al., 1998). When a child develops tolerance to cow’s milk depends on the severity of the initial reaction. Children whose initial reaction is limited to cutaneous symptoms, such as contact urticaria around the mouth or simple hives, usually develop tolerance to CMP earlier than children who initially react with anaphylaxis (Anderson, 1997). CMPI usually spontaneously resolves by one to three years of age (Brown. 2002). Reports vary, but between 15 to 50% of CMPI infants are tolerant of cow’s milk protein by one year, and 90% by three years of age (Vanto et al., 2004). When GI symptoms present alone, total resolution of CMPI can be expected (see Figure 2) (Dupont & de Boissieu, 2003).
Once sensitized to CMP, even through breast feeding, an elimination diet does not reverse sensitization that has developed into allergic disease (Isolauri & Arvola, 2000). Early IgE antibodies to CMP is an indicator for possible other food allergies persisting into childhood and adult life, as well as developing asthma and rhinoconjunctivitis (Dupont & de Boissieu, 2003). About 10% of infants with CMA go on to have CMA in their adult life (Dupont & de Boissieu, 2003).
In infants thought to have CMA, low-allergen solids (for example, rice cereal, apples, pears, potatoes, and pumpkins) are usually well tolerated at six months of age, but highly allergic foods (such as eggs, milk, peanuts, soy) should be delayed until the second year of life (Heine et al., 2002).
Diagnostic Testing
The main reason to determine allergy verses intolerance is so that parents and providers can have epinephrine on hand in the event of an anaphylactic reaction to an accidental exposure (Anderson, 1997). Differentiating will also help predict infants who will outgrow the intolerance and those who will go on to develop further allergies. Because it is less costly and time consuming to simply switch the infant formula and wait to see if the infant becomes tolerant at one year of age. testing is often delayed until one year of age.
It is the allergic gene that gets passed on, not specific allergies, so it is important to discover if there are any allergies in the family to food, the environment, or medications. This and the infant feeding history are helpful in diagnosis (Brown, 2002). Families with multiple food allergies are more likely to have infants with CMPI, and atopy in the family is a strong predictor for CMA (Anderson, 1997; Brown, 2002; Sicherer, 2003).
Diagnostic testing for CMPI and CMA should be done by an allergist if the infant has significant symptoms, does not respond to treatment, or has a strong family history of allergies. If CMPI is suspected, a referral should be made to a local allergy clinic. Tests likely to be done include radioallergosorbent testing (RAST), skin prick testing (SPT), atopy patch testing (APT), and double- blind placebo controlled food challenge (DBPCFC).
The definitive test for CMPI is the double-blind placebo controlled food challenge (DBPCFC) that must be done in a provider’s office or hospital over several hours (Heine et al., 2002). It is very costly, takes a lot of time, and places the infant at risk for further sensitizing and anaphylaxis. For these reasons, it is not used very often in infants. The other options for diagnostic testing include screening for specific serum IgE antibodies (RAST), SPT, and AFT. These tests have limited value on their own and are used in combination to diagnose CMPI and CMA.
Clinically, diagnosis is made when symptoms improve with a CMP- free diet, and two or more challenge tests reproduce the symptoms. If atopic disease develops, along with proctitis and proctocolitis, further testing for IgE antibody involvement is indicated (Sicherer, 2003). In the presence of suspected CMP-related anaphylaxis, a presumptive diagnosis of CMA is generally preferred to testing that will further expose and sensitize the infant, but an allergy referral is needed regardless (Anderson, 1997). This diagnosis can be made based on a consistent history of food anaphylaxis and a positive RAST test for allergen-specific IgE antibodies (Heine et al., 2002).
Table 3. CMPI and GERD Manifestations Compared
Tests not normally used but that are occasionally helpfulinclude fecal leukocyte testing, upper endoscopy, colonoscopy, and colon biopsy. If fecal eosinophils are found, they are a diagnostic clue for allergic colitis (Nocerino & Guandalini, 2003). upper endoscopy is helpful in the diagnostic work up of esophagitis and in children presenting with symptoms of enteropathy. If the child has lower GI bleeding (colitis, proctitis), a colonoscopy is helpful. If CMP is the cause, the test will show linear erosions and mucosal edema (Nocerino & Guandalini, 2003). Biopsy can also help determine the cause of GI signs and symptoms.
Management
The specific treatment approach used is modeled after a clinical care pathway (Brown, 2002; Currie & Harveyk, 1998; Rohrbach, 1999). The clinical care pathway is useful in this situation because it combines multidisciplinary interventions aimed at agreed upon goals for the child. Pediatric care has been divided into many sub- specialties and it is important to follow a uniform approach. The clinical management issues will be supported by the research evidence and the critical pathway model (Rohrbach, 1999). The nurse practitioner (NP) coordinates care with an allergist, and possibly nutritionist, gastroenterologist, and dermatologist.
The primary treatment for CMPI is restricting milk and milk products from the diet (Anderson, 1997). Avoiding CMP is important because it allows the intestinal lining to heal and prevents further CMP antigen absorption through the gut (Dupont & de Boissieu, 2003). This is done by either breast-feeding mothers restricting milk and milk products from their diet while breast-feeding, or replacing the cow’s milk based formula with soy-based formula, extensively hydrolyzed formula (eHF), or amino acid formula (AAF). Symptoms should resolve within 2 to 4 weeks. In infants with CMPI, it is best to also avoid eggs, milk, peanuts, tree nuts, fish, and shellfish for the first two years of life. This includes exclusion from the breast-feeding mother’s diet (Nocerino & Guandalini, 2003; Sampson, 2003). The infant’s presenting symptoms as well as breast-feeding status must be taken into consideration when determining which formula to use in the elimination diet.
Breast-feeding. Breast-fed infants are not immune to CMPI. CMPI in exclusively breast-fed infants has a prevalence of 0.37% (de Boissieu, Matarazzo, & Dupont, 1997). Exclusively breast-fed infants are sensitized to CMP through dietary antigens in the breast milk from the mother’s diet (Isolauri & Arvola, 2000). It is rare because there are so few CMP antigens present in breast milk. Though rare, the incidence of CMPI in breast-fed babies has increased in the past two decades coinciding with increased numbers of breast-fed infants (Isolauri et al., 1999). A recent study showed that children with persistent CMPI past the age of four years were breast-fed longer than those who became tolerant, regardless of atopic family history (Vanto et al., 2004). It was suggested that there are cellular, cytokine, or other components in breast milk that increase the persistence of CMPI. There are no other reports of this and further study is needed.
Breast-feeding remains the best source of nutrition for infants and should be encouraged. The only treatment as the child continues to breast-feed is complete avoidance of CMP in the mother’s diet. Infants are most likely to be allergic to cow’s milk; however, egg and peanut allergies also begin in infancy with less frequency. It is therefore best for the mother to seek allergist and nutritionist counseling concurrent with a structured elimination diet to avoid depleting important nutrition during lactation (Isolauri & Arvola, 2000).
When determining if an infant should continue to be breast-fed, four factors must be considered: infant growth, nutrition, clinical symptoms, and the mother’s perceived benefit and ability to maintain the elimination diet. A study conducted by Isolauri et al (1999) determined that breast-fed allergic infants’ growth with an unrestricted diet was slower, first in length and then weight, compared to expected growth for breast-fed infants at the same age. Infants breast-fed during CMP-elimination diets showed similar growth restrictions, as well as general nutritional inadequacy. The study measured the levels of albumin, prealbumin, urea, zinc, and alkaline phosphatase during breast-feeding and after. The levels improved with cessation of breast-feeding, correlating with resolution of atopic eczema and improved growth. In fact, the longer the infants were breast-fed while symptomatic, the more significant their decreased growth and nutrition. The study also found that more mothers considered the elimination diet (either of a single food, milk, and milk products only; or milk, milk products, and cereals) more difficult and demanding than it was helpful to their infant. The study concluded that if allergic symptoms and normal growth cannot be achieved while breast-feeding on an elimination diet, it is not recommended to continue breast-feeding (Isolauri et al., 1999). Another study found that breast-fed infants with GI and cutaneous symptoms did not have symptom resolution with the mother’s CMP elimination diet (Lake, 2001). For these reasons, it is important to consult with an allergist and nutritionist when putting a breast-feeding mother on a CMP-elimination diet.
Formula. There are three categories of formula used for infants with CMPI: soy-based formula, eHF, and AAF. Clinical presentation often indicates which formula should be used. The standard formulas used (Similac, Enfami, Good Start, and store brands) use cow’s milk protein, casein, or whey, which cannot be part of an elimination diet (Morrow, 2004). Extensively hydrolyzed formula (eHF) and AAF are the only formulas that meet hypoallergenicity standards (Salvatore & Vandenplas, 2002).
Soy-based formula. Soy-based formulas (including Enfamil Prosobee, Similac Isomil, and Good Start Soy) are the first-line treatment for CMPI infants (Morrow, 2004). According to one study, soy-based formula is better tasting and less expensive than eHF (Anderson, 1997). Soy-based formula is well tolerated in most CMPI infants. However, it is not tolerated by all infants with CMPI. In the general population, soy intolerance occurs in about 1.1% of all infants (Salvatore & Vandenplas, 2002). Among infants with CMPI, soy- based formula intolerance ranges from 10 to 35% (Dupont & de Boissieu, 2003; Salvatore & Vandenplas, 2002). The American Academy of Pediatrics (AAP) finds that soy intolerance increases up to 60% if the infant has CMP-induced enterocolitis (for example, bloody diarrhea, ulcerations, and evidence of inflammatory bowel disease) (American Academy of Pediatrics [AAP], 1998). A study done in 2003 states it is more common for CMPI infants without IgE involvement to be intolerant of soy (Dupont & de Boissieu, 2003). Infants with IgE involvement (CMA) are likely to tolerate soy-based formula. Age is a contributing factor; infants less than six months are less likely to tolerate soy formula, while infants with CMA who are older than six months are more likely to tolerate soy formula (Salvatore & Vandenplas, 2002).
Soy intolerance is more likely if the infant is younger than six months, has a family history of atopic disease (for example, asthma, allergic rhinitis, or eczema), presents with severe GI symptoms (including bloody diarrhea), and/or has non-IgE associated CMPI (Dupont & de Boissieu, 2003; Lake, 2001; Salvatore & Vandenplas, 2002). The pediatric nurse practitioner (PNP) must decide whether or not to use soy formula based on the incidence of soy intolerance in the literature, infant age, clinical presentation, and likelihood that immunologic differences between CMPI and CMA have not yet been determined.
Table 4. Web Sites for Family Referral
Extensively hydrolyzed formula. The second-line formulas for treating CMPI are extensively hydrolyzed formulas (eHF). eHFs such as Nutramigen, Progestimil, and Alimentum are made with casein, a CMP that has been processed to become “hypoallergenic” (Morrow, 2004). eHF is tolerated by about 90% of infants with CMPI (CMA included) (Salvatore & Vandenplas, 2002). Conversely, it is estimated that about 10 to 19% of infants with CMPI are also sensitive to eHF (D de Boissieu et al., 1997; Heine et al., 2002). Infants who do not tolerate eHFs are more likely to have several other food allergies and tolerance of CMP develops later than one year of age (Dupont & de Boissieu, 2003). Infants unresponsive to eHF are treated with AAF.
Amino-acid based formula. Those with severe CMPI will probably respond best to AAF (Anderson, 1997; Dupont & de Boissieu, 2003; Lucassen et al., 1998). A study by de Boissier et al. (1997), showed that infants who are put on an eHF (such as Nutramigen, Progestimil and Alimentum) and are still experiencing symptoms like irritability, vomiting, diarrhea, eczema, and failure to thrive (FTT), had relief of symptoms when on an AAF, which is safe to use in infants up to 30 months of age (D de Boissieu et al., 1997: Dupont & de Boissieu, 2003). The difficulty is that AAFs are extremely costly and available by prescription only. Neocate and Ross’s Elecare are the only formulas available in this class (Morrow, 2004). Both are approved for use in infants less than one year of age. Neocate has a similar fatty acid profile to that of breast milk and is well tolerated by infants with CMPI (Isolauri et al., 1999). If an infant does not respond to AAF or eHF, the diagnosis of CMPI may be in error and referral for additional testing is warranted. Infants requiring an AAF diet can expect to take longer than one year of age to develop tolerance to CMP (de Boissieu & Dupont, 2000).
Anaphylaxis. Infants who have severe or immediate reactions to CMP may need an emergency medication. Epinephrine (Epipen Jr.) is prescribed for infants/children who have had a sever\e immediate reaction to CMP, or any reaction affecting their ability to breathe. This should be carried with the infant at all times in case of an accidental exposure.
When to Refer. Most allergists would like to see all infants suspected of having CMPI for diagnostic testing. However, most infants with CMPI can be managed in primary care. An allergy referral is necessary if symptoms are severe, unresponsive to an elimination diet, or persist past 12 months of age. Clinical symptoms should guide referrals to gastroenterology or dermatology.
Family Education
A family history of atopy is a significant predictor for allergy. According to the literature, incidence of CMA without atopy in the family is about 12% (Salvatore & Vandenplas, 2002). Incidence rises to 20% if there is 1 atopic parent, to 32% if a sibling is atopic, 43% if both parents are atopic, and up to 72% if the parents have matching types of atopic disease (for example, both have eczema or hives) (Salvatore & Vandenplas, 2002). In families with known allergies, it is wise to counsel the mother if she intends to breast- feed to avoid the most highly allergic foods (milk, eggs, peanuts, and occasionally fish) in her own diet during the third trimester and while breast-feeding (Nocerino & Guandalini, 2003). Regardless of whether breast-fed or formula-fed, in these families, introduction of solids should wait until the child is six months of age with a slow progression of new foods.
It is important for families to know that CMPI usually resolves, sometimes as soon as one year of age and in most children by four years of age (Nocerino & Guandalini, 2003). The literature varies, but between 13 to 49% of children with CMPI are still intolerant at age three; these are usually the children who have immediate reactions to CMP (Vanto et al., 2004). Children with a delayed reaction to CMP will usually develop tolerance more quickly than children who have an immediate reaction.
Family Support. It is important for parents to have support from their primary care provider and other parents experiencing similar situations with CMPl. This can be done informally in a provider’s office and on the Internet. Table 4 contains Web sites have been reviewed for accuracy and are appropriate for family referral. Pediatric providers should be aware of the multiple strains on the family; emotional stress as they try to comfort their fussy, crying baby; financial strains of costly formula; and relational stress of welcoming a new baby into the family.
Further Research
For infants who do not outgrow CMPI, immunotherapy may be considered. It is uncertain if this would prevent future allergies, and there is inconclusive evidence that food allergen immunotherapy works (Anderson, 1997). This research is in the experimental stages and may provide a long-term answer for CMPI. Further research also needs to be conducted to determine if avoiding CMP in atopic families from infancy through the first two years prevents developing asthma or other allergic symptoms later in life. Knowing this will add weight to the importance of diagnosing CMPI early in infancy.
Conclusion
CMPI is present in approximately 3% of infants. A small percentage has IgE-mediated reactions known as cow’s milk allergy. CMPI manifests in the gastrointestinal system, cutaneous system, and respiratory system. Very few CMPI infants have anaphylactic reactions. CMPI must be differentiated from GERD and colic in the primary care setting. Elimination of CMP in the diet of the breast- feeding mother or a change in infant formula to a non-CMP formula usually eliminates symptoms. Referral to allergy is necessary if symptoms are severe or if they persist past 12 months of age. The long-term consequences of early IgE stimulation with CMA are unknown. Pediatric providers must offer education and support to families with CMPI infants.
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Whitney Merrill Ewing, RN, MSN, PNP, is Pediatric Nurse Practitioner, Advance Pediatrics, Advance, NC.
Patricia Jackson Allen, RN, MS, PNP, FAAN, is Professor and Director, Pediatric Nurse Practitioner Specialty, Yale University School of Nursing, New Haven, CT.
The Primary Care Approaches section f\ocuses on physical and developmental assessment and other topics specific to children and their families. If you are interested in author guidelines and/or assistance, contact Patricia L. Jackson Allen at [email protected].
Copyright Anthony J. Jannetti, Inc. Nov/Dec 2005
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