Cow's Milk Allergic Infants on Elemental Formula Maintain Adequate Mineral Status Despite Using Acid-suppressive Drugs.

To the Editor: We recently presented data in this Journal showing that cow's milk allergic infants who received an amino acid–based formula (AAF) for 16 weeks as oral feeding had adequate mineral status (1). One factor that may negatively affect mineral solubility and bioavailability and hence mineral status, is a high gastric pH (2). Therefore, we currently present data on mineral status of a subgroup of infants on AAF receiving acid-suppressive drugs.

We analysed retrospectively the data of infants (0–8 months) with confirmed immunoglobulin E or non-immunoglobulin E–mediated cow's milk allergy who were randomized between 2008 and 2012 in a double-blind fashion to either an AAF with or without synbiotics (3). In- and exclusion criteria of the study and baseline characteristics of the enrolled infants have been reported before in our original paper (1). Details about the composition of the study formulae (Neocate; SHS International Ltd, Nutricia Advanced Medical Nutrition, Liverpool, UK) can be found in Table 1.

TABLE 1

Macronutrient and mineral profile of study products per 100 kcal of prepared product

	Neocate with synbiotics	Neocate without synbiotics*
Energy	67 kcal/100 mL	67 kcal/100 mL
Macronutrients
Proteins, g	2.8	3.1
Carbohydrates, g	11.3	11.7
Fats, g	4.8	4.5
Dietary fibre, g	1.1	–
Bifidobacterium breve M16-V, CFU	2.11 × 109	–
Minerals
Sodium, mg	40	37
Potassium, mg	105	155
Chloride, mg	75	77
Calcium, mg	90	124
Phosphorus, mg	63	93
Magnesium, mg	11.2	12.4
Iron, mg	1.5	1.9
Zinc, mg	1.1	1.7
Copper, μg	76	124
Manganese, μg	76	90
Selenium, μg	2.8	3.7
Iodine, μg	17.5	15.4
Mineral sources
	Calcium phosphate dibasic, tripotassium citrate, sodium chloride, magnesium chloride, tricalcium citrate, magnesium l-aspartate, ferrous slphate, zinc sulphate, calcium d-pantothenate, manganese sulphate, cupric sulphate, potassium iodide, chromium chloride, sodium selenite, sodium molybdate

*Differences in blood chemistry parameters (at baseline, week 16, and change from baseline) between the study products have been analysed before and were not found to be statistically significant or clinically relevant (1,3) and are therefore presented for the combined (Neocate with or without synbiotics) group.

Serum concentrations of phosphorus, calcium, and magnesium were determined at baseline (n = 82) and after 16 weeks (n = 66) on AAF and compared to age-specific reference ranges. Subgroup analysis was performed for infants who were receiving acid-suppressive drugs (proton-pump-inhibitors/H2-antagonists), that is, approximately one-third (35%) of our sample. Between-group comparisons were made by 2-tailed Student t tests. P values >0.05 were considered as not significant.

Serum concentrations of phosphorus, calcium, and magnesium for the total population and for the subgroups of infants receiving or not receiving acid-suppressive drugs are presented in Tables 2 and 3. After 16 weeks, mineral concentrations of all infants were within the reference range.

TABLE 2

Serum concentrations (mean, 95% confidence interval) of phosphorus (P), calcium (Ca), and magnesium (Mg) and number (n, %) of infants having P, Ca, and Mg concentration below the lowest range of the reference value at baseline

				Acid-suppressive drugs
	Total population (n = 82)			Users (n = 29)			Non-users (n = 53)
	Mean	95% CI	n (%)	Mean	95% CI	n (%)	Mean	95% CI	n (%)	P value: users vs nonusers
P, mmol/L	2.05	2.00–2.11	1 (1%)	2.10	2.00–2.19	0	2.03	1.96–2.10	1 (2%)	ns
Ca, mmol/L	2.67	2.64–2.70	1 (1%)	2.67	2.63–2.71	0	2.66	2.62–2.71	1 (2%)	ns
Mg, mmol/L	0.95	0.93–0.96	0	0.95	0.93–0.97	0	0.94	0.93–0.96	0	ns

Reference ranges—P: 1.36–2.62 (<1 years) and 1.03–1.97 (≥1 years) mmol/L; Ca: 2.25–2.74 mmol/L; Mg: 0.70–0.98 (<30 days), 0.66–1.03 (males, ≥30 days), and 0.78–0.98 (females, ≥30 days) mmol/L.

ns = not significant.

TABLE 3

Serum concentrations (mean, 95% confidence interval) of phosphorus (P), calcium (Ca), and magnesium (Mg) and number (n, %) of infants having P, Ca, and Mg concentration below the lowest range of the reference value after 16 weeks intervention with an amino acid–based formula

				Acid-suppressive drugs
	Total population (n = 66)			Users (n = 25)			Non-users (n = 41)
	Mean	95% CI	n (%)	Mean	95% CI	n (%)	Mean	95% CI	n (%)	P value: users vs nonusers
P, mmol/L	1.96	1.91–2.01	0	1.95	1.88–2.03	0	1.97	1.90–2.04	0	ns
Ca, mmol/L	2.62	2.59–2.65	0	2.63	2.59–2.68	0	2.61	2.58–2.65	0	ns
Mg, mmol/L	0.95	0.94–0.97	0	0.96	0.94–0.99	0	0.95	0.92–0.97	0	ns

Reference ranges—P: 1.36–2.62 (<1 years) and 1.03–1.97 (≥1 years) mmol/L; Ca: 2.25–2.74 mmol/L; Mg: 0.70–0.98 (<30 days), 0.66–1.03 (males, ≥30 days), and 0.78–0.98 (females, ≥30 days) mmol/L.

ns = not significant.

Our data show that, although doses, compliance, and the neutralizing effect of the acid-suppressive drugs were not measured and infants were not randomized for acid-suppressive drug use, cow's milk allergic infants orally fed with AAF for 16 weeks maintain target serum concentrations of phosphorus, calcium, and magnesium even when receiving acid-suppressive drugs. Regular review of the ongoing need for acid-suppressive drugs remains recommended.