Table 4 Summary of studies on heated milk challenge

Nowak et al. [4]

Eligible subjects aged 0.5–21 years, with positive SPT responses or detectable serum milk-specific IgE, and had a history of an allergic reaction to milk within 6 months before study entry or milk-specific IgE levels or SPT responses greater than 95 % of predicted value for clinical reactivity N = 100

7.5 (2.1–17.3)

Prospective

Muffin (baked at 350 F for 30 min in an oven) and waffle containing 1.3 g milk protein (cooked in a waffle maker at 500 F for 3 min) Total 2.6 g of CM protein

77 (77 %)

23 (23 %)

7 (2.5–19)

9.5 (5–24)

2.43 (0–79.1)

11.6 (0.69–101)

1.4 (0–101)

14.15 (0.71–101)

Among 100 children who undertook HM challenges: 68 tolerated extensively HM only, 23 reacted to HM, and 9 tolerated both heated and unheated milk. HM reactive children had significantly larger SPT wheals and higher milk-specific and casein-specific IgE levels than other groups

Kim et al. [1]

Eligible subjects same as [4] N = 89

Comparison group matched to active subjects (N = 60)

6.6 (2.1–17.3)

Prospective

Each muffin contained 1.3 g of milk protein (baked at 350 F for 30 min). And cheese pizza containing 4.6 g of milk protein (baked at 425 F for 13 min or longer)

65 (74 %)

23 (26.1 %)

NA

NA

NA

NA

NA

NA

Among 65 children initially tolerant to HM, 39 (60 %) now tolerate unheated milk,. Among the HM reactive group (n = 23), 2 (9 %) tolerate unheated milk, 3 (13 %) tolerate HM and baked cheese, whereas the majority (78 %) avoid milk strictly. Children initially tolerant to HM were more likely to become unheated milk tolerant compared with HM reactive children (p < 0.001) and those who incorporated dietary baked milk were more likely than the comparison group to become unheated milk tolerant (p < 0.001)

Caubet et al. [17]

Two cohorts of milk allergic children N = 97 from [4] and a second cohort of N = 128. Eligibility criteria same as [4] and [1] Total N = 225

Second cohort HM tolerant: 7.5 (4.0–11.0) HM reactive 8.0 (4–10)

Prospective

Same as [4]

83 (64.8 %)

38 (29.7 %)

NA

NA

(0.2–42.3)

11.9 (0.8–50.5)

2.3 (0.2–30.5)

12.2 (0.5–67.0)

The two cohorts of milk allergic children demonstrated the levels of IgE to cow’s milk, casein and β-lactoglobulin were significantly higher in HM reactive patients compared with HM tolerant patients. Casein-specific IgE had the highest positive and negative predictive values compared with specific IgE to cow’s milk or b-lactoglobulin, and casein-specific and b-lactoglobulin specific IgE/IgG4 ratios were significantly higher in HM reactive children with compared with HM -tolerant children

Ford et al. [13]

Eligible subjects were between the ages of 4 and 10 years and had a positive SPT response to milk or detectable serum milk-specific IgE levels and a history of an allergic reaction to milk N = 132

7.6 (4.0–11.0)

Prospective

Muffin same as [4] pizza (4 g of milk protein baked at 425 F for at least 13 min), rice pudding (7.7 g of milk protein baked at 325 F for 90 min)

95 (72 %)

37 (28 %)

NA

NA

NA

12.4 (0.6–43.6)

NA

13.75 (0.36–49.9)

The majority of patients with milk allergy are able to tolerate some forms of HM in their diets. Casein- and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to HM than among those who tolerate it

Bartnikas et al. [12]

All patients had a history of prior allergic reactions to milk (either baked or unheated) documented in the medical record by an allergist and detectable milk protein sIgE, as determined by a positive SPT result or elevated serum sIgE level. N = 35

8.1 (3.1–18)

Retrospective

Each muffin or cup-cake of milk protein (baked at 350 F for 30 min) (total of 2.6 g of milk protein)

29 (83 %)

6 (17 %)

10 (0–20)

15 (7–20)

1.93 (<0.35–20.6)

2.39 (<0.35–31.0)

1.05 (<0.35–10.3)

1.07 (<0.35–31.5)

Most children allergic to cow’s milk tolerated baked milk. Milk protein SPT wheal may be more reliable than sIgE level in predicting outcomes of baked milk challenges. There is a possibility of late reactions to ongoing baked milk exposure at home

Mehr et al. [14]

Previous convincing clinical reaction to CM with SPT reaction or sIgE to CM N = 70

HM tolerant 4.5 (2.5–8)

HM reactive 7.3 (4.9- 7.3)

Not mentioned

A standard recipe was used for the muffin, baked at 180 ℃ for 20 min (containing 0.5 g of cow’s milk protein)

51 (72.9 %)

19 (27.1 %)

8 (7.0–10)

8.5 (7.5–10.0)

NA

NA

NA

NA

51 (73 %) passed the OFC and successfully incorporated baked CM into their diet. 19 children (27 %) reacted to their challenge. Of reactors, 4 (21 %) developed anaphylaxis and required intramuscular adrenalin. Predictors of clinical reactivity to baked CM were asthma, asthma requiring preventer therapy, IgE mediated clinical reactions to >3 food groups, and those with a history of CM anaphylaxis

This study

To be included, the patients should have a prior history of allergic reaction to milk and detectable milk protein sIgE as determined by a positive skin prick test (SPT) and/or elevated serum milk-specific IgE. N = 39

9 (4.0–17.0)

Restrospective

A glass of instant skim milk powder that was equivalent to a total of 4 g of cow’s milk protein (approximately 120 mL)

30 (76.9 %)

9 (23.1 %)

7.5 (4–13)

7.5 (4–16)

0.86 (<0.35–9.8)

4.19 (0.89–>100)

0.38 (<0.35–3.65

1.65 (0.51–80.8)

30 (76.9 %) passed the powder milk challenge. Compared to those who were HM tolerant, HM reactive children had higher specific IgE levels to cow’s milk (p < .004), casein (p < .006) and α-lactalbumin (p < .01). In comparison to other studies on HM challenge, our study demonstrates comparable children characteristics. This study shows a similar rate of positive challenge to HM compared to previously published studies and demonstrates a new technique of HM challenge that is user-friendly and safe