Analysis of the Elemental Composition of Milk Formulae: Impact on the Nutritional Status of Infants From Birth to 1 Year of Age

Overview

Dobrzyńska and colleagues measured nine basic elements (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn) and seven toxic or potentially toxic elements (As, cadmium (Cd), Co, chromium (Cr), mercury (Hg), tin (Sn), Ni) by ICP-MS in 149 powdered milk formulae available on the Polish market between 2019 and 2023. Cadmium, mercury, and arsenic were below the analytical detection limit in every sample; nickel was detected in 62 of 149 samples (highest 17 µg/kg wet weight in a powder formula) and the estimated daily intake exceeded the EFSA lowest-observed-adverse-effect level of 4.3 µg/kg body weight for eczematous skin reactions in one-month-old infants for every formula category analyzed. Copper exceeded the EU compositional maximum in 18 samples and was below the minimum in 43; potassium exceeded the EU maximum in 63 samples; and manganese varied across roughly two orders of magnitude (1-91 µg/100 kcal). Lead and selenium were excluded from this paper — lead (Pb) due to spectral interference in the analytical run, Se reported in a separate publication.

Key numbers

The corpus is 149 powdered formulae purchased on the Polish market between 2019 and 2023 (Materials, p. 386). The 0-6 month infant-formula stratum was 37 samples, the 7-12 month follow-on stratum was 34 samples, and the formulae for special medical purposes (FSMP) stratum was 78 samples. Within FSMP, the breakdown was extensively hydrolyzed n=26, amino-acid-based n=6, manufactured from goat milk proteins n=15, comfort n=12, anti-reflux n=7, lactose-free n=5, preterm n=4, and soy-based n=3.

The reference material was ERM-BD150 (skimmed milk powder, European Reference Materials, Belgium); recovery was 80-120% for most elements. Analyses were performed in triplicate following Yaman et al. ICP-MS sample digestion used a CEM MARS6 microwave system with 10 mL of 69% ultrapure nitric acid (ROMIL, Cambridge, UK) on 0.5 g sample, ramping from ambient to 180 °C over 20 min and holding for 20 min, then diluted to 15 mL with ultrapure water. The propagated uncertainty (RSD) for the whole procedure was below 20%. Limits of detection (µg/L) were arsenic (As) 6.0, Ca 250, Cd 0.45, Co 1.5, Cr 0.77, Cu 2.4, Fe 61, Hg 18, K 140, Mg 150, Mn 1.2, Na 110, nickel (Ni) 13, P 3100, Zn 5.6, Sn 0.27 (p. 386-387).

Table 9 — toxic and potentially toxic elements, µg/kg wet weight. Cd, Hg, and As were < DL in every infant-formula, follow-on, and FSMP sample (Cd EU limit 10 µg/kg; As EU limit 20 µg/kg; Hg unrestricted under the cited regulation). Sn medians were 0.3 (1st-3rd quartile 0.1-0.5; range 0-2.2) for infant formulae, 0.2 (0.2-0.4; range 0-1.1) for follow-on, and 0.4 (0.2-0.6; range 0-11) for FSMP, far below the Sn maximum of 50,000 µg/kg. Co was 0 (0-0; range 0-1.0) for infant formulae, 0 (0-0; range 0-1.1) for follow-on, and 0 (0-0; range 0-9.6) for FSMP. Cr medians were 0 (range 0-23) for infant formulae, 0 (range 0-13) for follow-on, and 0 (range 0-1.7) for FSMP. Ni medians were 0 (range 0-17) for infant formulae, 0 (range 0-13) for follow-on, and 0 (range 0-12) for FSMP. The text records that Ni was detected in 62 of 149 samples (p. 395).

Estimated daily intake of toxic and potentially toxic elements (Table 10). Sn EDI for the 0-6 month infant-formula stratum was median 1.86 µg/day at 1 month (1st-3rd quartile 0.00-3.11; range 0.00-15.66), 2.37 µg/day at 3 months (range 0.00-19.86), and 2.56 µg/day at 6 months (range 0.00-21.47). For follow-on formulae the Sn EDI was 0.91 µg/day at 7 months and 0.57 µg/day at 10 months. For FSMP the Sn EDI reached 3.31 µg/day at 6 months (range 0.00-104.97), with a stratum maximum of approximately 105 µg/day at 6 months.

Ni EDI (Table 10) for infant formulae (0-6 months, 100% energy coverage) was median 0 µg/day at every age band, but the upper bound of the range was 18.36 µg/day at 1 month, 19.08 µg/day at 3 months, and 19.29 µg/day at 6 months. For follow-on formulae (45% energy coverage at 7 months, 25% at 10 months), Ni EDI ranges reached 6.80 µg/day and 3.84 µg/day respectively. For FSMP (100% coverage at 1 and 6 months), Ni EDI ranges reached 12.49 µg/day at 1 month and 13.13 µg/day at 6 months. The authors converted Ni EDI to µg/kg body weight and compared against the EFSA tolerable daily intake of 13 µg/kg body weight and the LOAEL of 4.3 µg/kg body weight for eczematous flare-up reactions (EFSA 2020). The Ni EDI per kg body weight exceeded the TDI of 13 µg/kg in four FSMP formulae at 6 months and two infant formulae at 1 month; the Ni EDI per kg body weight exceeded the LOAEL of 4.3 µg/kg in all formulae regardless of category for infants aged 1-6 months (Discussion, p. 395-396).

Cr EDI was 0.00-210.40 µg/day across the corpus with the highest medians among infant formulae and the lowest among FSMP. The text reports that the chromium EDI did not exceed the National Research Council’s “estimated safe and adequate daily dietary intake” of 0.01-0.04 mg/day, nor the UK Committee on Medical Aspects “adequate level of chromium intake” range of 0.0001-0.001 mg/body weight/day.

Co EDI was below the limit of detection in most preparations. The infant-formula maximum was 6.77 µg/day at 1 month and 9.27 µg/day at 6 months. Follow-on EDI maxima were 4.52 and 2.95 µg/day for 45% coverage at 7 months and 25% coverage at 10 months. FSMP Co EDI reached 64.49 µg/day at 1 month and 6 months.

Essential-element findings against EU compositional norms. For the 37 infant formulae (Table 1), P and Mn were within EU limits for all 37 samples. Na was below the minimum in two samples (11-17% lower). K exceeded the EU maximum in 16 samples by an average of 13% (range 1-32%). Ca was below the minimum in 1 sample (27.5% lower). Mg exceeded the maximum in 2 samples (4-6%). Fe exceeded the maximum in 2 samples (23-69%). Zn was below minimum in 1 sample (20% lower) and exceeded the maximum in 1 sample (27.5%). Cu was inappropriate in 21 of 37 samples: below the minimum in 16 (5-90% lower; one sample below the detection limit) and above the EU maximum in 5 samples.

For the 34 follow-on formulae (Table 2), Mn was within limits for all 34. Na exceeded the maximum in 2 samples (by 2%). K exceeded the maximum in 14 samples (one by 28%). P exceeded the maximum in 7 samples (1-15%, average 15%). Mg exceeded the maximum in 8 samples (1-172%). Fe was below the minimum in 1 sample (50% lower). Zn exceeded the maximum in 4 samples (7-39%). Cu was below the minimum in 1 sample (80% lower) and exceeded the maximum in 7 samples (10-238%).

For the 78 FSMP (Table 3), Ca, Fe, Zn, and Mn were within acceptable limits for all samples. Na exceeded the maximum in extensively hydrolyzed (1 sample, 3%), goat-milk-protein (1 sample, 20%), and preterm (2 samples, 3-72%) formulae; Na was below the minimum in the extensively hydrolyzed and goat-milk formulae. K exceeded the maximum in 33 samples regardless of formulae type (1-98%) except the soya-based formula which met the limits. P exceeded the maximum in 1 goat-milk sample (39%) and 1 soya-based sample (7%). Mg exceeded the maximum in 2 extensively hydrolyzed, 4 amino-acid-based, 2 goat-milk-protein, 1 comfort, and 1 anti-reflux sample. Cu was below the minimum in 26 samples (mostly hydrolyzed) and exceeded the maximum in 6 (maximum 47%).

Across the full 149-formulae corpus: Cu was below minimum in 43 samples and above maximum in 18 samples; K exceeded the maximum in 63 samples; Mn ranged from 1-91 µg/100 kcal across formulae. Cu median was 72 µg/100 kcal across all formulae (66 µg/100 kcal infant; 81 µg/100 kcal follow-on; 68 µg/100 kcal FSMP), all somewhat higher than the European breast-milk reference range of 51-60 µg/100 kcal.

Methods (brief)

Inductively coupled plasma mass spectrometry (ICP-MS), Department of Analytical Chemistry, Adam Mickiewicz University, following the analytical method of Yaman et al. Triplicate analyses per sample, with one to twenty parallel samples per formula depending on availability and study cost. Sample digestion: 0.5 g formula powder + 10 mL 69% ultrapure HNO₃ in a CEM MARS6 microwave (Matthews, NC, USA), 15 min pre-digestion, ramp ambient → 180 °C over 20 min, hold 20 min, dilute to 15 mL with ≥18 MΩ·cm ultrapure water (Milli-Q, Merck Millipore). High-pure (99.999%) Ar, He, and H₂ gases (Linde, Poland). Commercial standards (Romil, UK) and Suprapur® 65% HNO₃ used for calibration and standard preparation. Certified reference material: ERM-BD150 (European Reference Materials, Belgium); recoveries 80-120%. RSD < 20% (propagated uncertainty for the full procedure). Limits of detection are listed in the Key Numbers section above.

EDI was calculated by converting concentrations to mg or µg per 100 kcal and dividing into three age groups (infant 0-6 mo, follow-on 7-12 mo, FSMP). For 7-month-olds the model assumes 45% of energy from formula; for 10-month-olds, 25%. Body weights were taken from current WHO infant percentiles; energy needs from Stan et al. Toxic-element EDI was compared against EU Commission Regulation 2023/915 of 25 April 2023 (repealing Regulation (EC) No 1881/2006) maximum levels and, for Ni, against EFSA’s TDI of 13 µg/kg body weight and LOAEL of 4.3 µg/kg body weight for eczematous flare-up reactions.

Reported limitations. Pb and Se were excluded from this paper. The authors state that the Pb assessment was limited “due to significant elemental interference in Pb concentrations” and that Se concentrations will appear in a separate publication (p. 396). The corpus is limited to powdered formulae and to the Polish market 2019-2023; ready-to-feed and concentrated liquid forms were not analyzed. Brand identification is not provided in the manuscript.

Related evidence

• Infant Formula Powder
• Infant Formula, Powder (Non-Soy)
• Infant Formula, Powder (Soy-Based)
• Cow Milk Infant Formula
• Soy-based infant formula
• Milk Based Infant Formula
• Non-soy infant formula
• Nickel
• Tin
• Cobalt
• Chromium
• Cadmium
• Mercury, Total
• Arsenic, Total
• Copper
• Manganese
• EU Regulation 2023/915 maximum levels for contaminants in food
• EFSA — Nickel Tolerable Daily Intake (13 µg/kg b.w./day)

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