Summary
Cross-sectional study from Pakistan measuring essential minerals (Ca, Mg, P, Fe, Cu, Mn, Zn, Se, Na) and nonessential or potentially toxic elements (Al, Ba, chromium (Cr), Sr, Ti) in preterm breast milk, term breast milk, and preterm commercial infant formula (n=5 formula samples) using inductively coupled plasma-optical emission spectrometry (ICP-OES). The study evaluated mineral adequacy against ESPGHAN reference intakes for preterm infants at an assumed enteral intake of 165 mL/kg/day. For the ready-to-feed formula page, the key findings are aluminum and chromium concentrations in preterm infant formula powder samples (prepared for feeding, reported as µg/mL, which is equivalent to µg/L for a liquid formula).
Key numbers
Table 5 — Nonessential/potentially toxic elements (µg/mL, as prepared liquid; mean ± SD):
| Element | Preterm MM (n=10) | Full-term MM (n=10) | Preterm infant formula (n=5) | P-value |
|---|---|---|---|---|
| Aluminum (Al) | 16.20 ± 15.70 | 5.90 ± 4.30 | 1.16 ± 1.70 | 0.028* |
| Barium (Ba) | 1.25 ± 1.20 | 0.89 ± 1.41 | 0.26 ± 0.31 | 0.331 |
| Strontium (Sr) | 0.16 ± 0.21 | ND | 0.35 ± 0.14 | n/a |
| Titanium (Ti) | 1.90 ± 1.97 | 1.33 ± 0.86 | 0.21 ± 0.10 | 0.105 |
| Chromium (Cr) | 0.06 ± 0.14 | 0.44 ± 0.91 | 0.03 ± 0.07 | 0.290 |
Values are µg/mL (equivalent to µg/L for a liquid). To convert to µg/kg as-consumed liquid (assuming density approximately 1 g/mL), multiply by 1,000: aluminum (Al) in preterm formula = 1160 µg/kg (1.16 µg/mL); Cr = 30 µg/kg (0.03 µg/mL).
Key pairwise comparisons (Table 5 footnotes):
- Al was significantly greater in both preterm MM and full-term MM than in formula (preterm MM vs formula mean difference 15.01 µg/mL, P=0.035; full-term MM vs formula mean difference 4.79 µg/mL, P=0.023). Formula Al (1.16 µg/mL) was lowest of the three groups.
- Authors note this contradicts some studies reporting prominent formula Al contamination; the authors attribute the lower formula Al to manufacturing process controls.
Se findings: Se was detected only in preterm infant formula samples (0.044 ± 0.050 µg/mL). Se was below the LOD (1.0 µg/L) in all human milk samples. Se was conservatively classified as “below” ESPGHAN requirements for all milk types. The authors note that the apparent absence of Se in breast milk may reflect the LOD rather than true absence.
Adequacy assessment (Table 3): For preterm infant formula (n=5 samples):
- Calcium: 40% of samples below ESPGHAN requirements, 20% meeting, 40% above
- Manganese: 100% of samples exceeded ESPGHAN requirements
- Zinc: 60% below, 40% meeting, 0% above
- Chromium: 80% below, 30% meeting — but Cr ESPGHAN requirement is trace (0.056-4.185 µg/kg/day) and the paper’s classification differs from typical toxic-metal assessments
Methods (brief)
Milk samples expressed 48-72 h after delivery by members of preterm mothers and analyzed with ICP-OES (Milestone Ethos Up, 0.1 mol/L HNO3 digestion). Mineral adequacy assessed against ESPGHAN per-kg intake requirements at 165 mL/kg/day assumed intake for a preterm infant weighing 1.86 kg (mean preterm cohort birth weight). Reference standard NIST 2710a and NIST 1570a. Recovery 89-103%. LODs: 3-500 µg/L for elements. Multilevel element wavelengths set to minimize spectral interferences.
Limitations
Very small formula sample (n=5). Single Pakistani institution. Preterm formula results may not be representative of term infant formula or of non-preterm product markets. Se results may reflect LOD limitations rather than true absence in breast milk. Chromium values are total Cr; hexavalent chromium (Cr-VI) not speciated. Only 5 preterm formula samples with limited brand diversity.
Implications
- Certification: Al in preterm infant formula (mean 1.16 µg/mL = approximately 1160 µg/kg as-consumed liquid) is consistent with the global meta-analysis range (Largueza 2026 WMD 946.75 µg/kg). Cr values (0.03 µg/mL = approximately 30 µg/kg) are substantially lower than the Largueza 2026 pooled estimate (250.37 µg/kg); the small n and Pakistani market context are likely explanations.
- Courses: Useful for teaching the distinction between breast milk and formula concentrations of aluminum, and for illustrating that formula Al concentration varies substantially across studies and manufacturing controls.
- App: Adds Pakistani/UAE preterm infant formula concentration data for Al, Cr, Ba, Ti as-consumed liquid basis.
- Microbiome: No direct microbiome endpoint.
Provenance notes
Open-access CC BY-NC article. PDF retrieved from PMC (PMC13523657). SHA256 verified against MANIFEST.csv for HMI-PROD-ready-to-feed-formula-1.
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