550001 PENXXX10.1177/0148607114550001Journal of Parenteral and Enteral NutritionLima-Rogel et al
`
`research-article2014
`
`Original Communication
`
`Aluminum Contamination in Parenteral Nutrition
`Admixtures for Low-Birth-Weight Preterm Infants
`in Mexico
`
`Victoria Lima-Rogel, MD, MSc1; Silvia Romano-Moreno, PhD2;
`Esperanza de Jesús López-López, BSc2; Francisco de Jesús Escalante-Padrón, MD, MSc1;
`and Gilberto Fabian Hurtado-Torres, MD, MEd3
`
`Journal of Parenteral and Enteral
`Nutrition
`Volume 40 Number 7
`September 2016 1014 –1020
`© 2014 American Society
`for Parenteral and Enteral Nutrition
`DOI: 10.1177/0148607114550001
`jpen.sagepub.com
`hosted at
`online.sagepub.com
`
`Abstract
`Background: Aluminum contamination from intravenous solutions still represents an unsolved clinical and biochemical problem.
`Increased aluminum intake constitutes a risk factor for the development to metabolic bone disease, anemia, cholestasis, and neurocognitive
`alterations. Low-birth-weight preterm infants (LBWPIs) are one of the most exposed populations for aluminum toxicity. Methods: To
`determine the presence of aluminum in components employed in the preparation of parenteral nutrition (PN) admixtures in Mexico and
`compare with the maximal aluminum recommended intake from the Food and Drug Administration. Results: Cysteine, trace elements,
`levocarnitine, phosphate, and calcium salts tested positive for aluminum contamination. All components analyzed were contained in glass
`vials. Total aluminum intake for 2 sample PN admixtures were calculated in basis to cover nutrition requirements of 2 hypothetical LBWPIs.
`Aluminum contents, stratified in micrograms per kilogram of weight, exceeded maximal aluminum recommendations, particularly for
`the very LBWPIs. Substituting sodium phosphate for potassium phosphate salts reduced aluminum intake by 52.7%. Calcium gluconate
`was the leading aluminum contamination source and confers the greatest risk for aluminum overdose, even with the salt substitution of
`potassium phosphate by sodium phosphate salts. Adding cysteine and trace elements might increase aluminum content in PN admixtures.
`Conclusion: Cysteine, trace elements, phosphate, and gluconate salts are the main sources of aluminum in PN prepared in Mexico.
`Substituting sodium phosphate for potassium phosphate salts reduces aluminum intake but does not resolve aluminum contamination risk.
`Mineral salts contained in plastic vials should be explored as an additional measure to reduce aluminum contamination. (JPEN J Parenter
`Enteral Nutr. 2016;40:1014-1020)
`
`Keywords
`aluminum; toxicity; metabolic bone disease; osteomalacia; low-birth-weight preterm infants; parenteral nutrition
`
`Clinical Relevancy Statement
`
`Excessive aluminum intakes from intravenous solutions,
`drugs, and parenteral nutrition still represent an unsolved
`problem. Potential toxicities and side effects have been
`widely described. Low-birth-weight preterm infants, long-
`term home parenteral nutrition adult patients, and patients
`with chronic kidney disease are particularly exposed and con-
`sidered high-risk populations. Aluminum determination
`facilities are not usually available in most hospital scenarios;
`therefore, inadvertent high-aluminum concentrations might
`be provided. Efforts should be implemented to identify and
`subsequently reduce the amount of aluminum in parenteral
`solutions.
`
`Background
`
`As part of the quality standards in the care of patients hospital-
`ized in neonatal, pediatric, and adult intensive care units
`(ICUs),1 medical nutrition interventions have shown a positive
`impact on prognosis and survival, reflected in the preservation
`of body composition, multiorgan functionality, and modulation
`
`of the metabolic, immune, and inflammatory responses that
`underlie the condition of critically ill patients.2,3
`Despite a progressive decline in the prescriptions of paren-
`teral nutrition (PN) admixtures in the past years, a significant
`
`From the 1Neonatology Unit, Hospital Central Dr Ignacio Morones
`Prieto and Faculty of Medicine, University of San Luis Potosí, México;
`2Pharmacy Division, Faculty of Chemistry, University of San Luis Potosí,
`México; and 3Internal Medicine and Clinical Nutrition Department,
`Hospital Central Dr Ignacio Morones Prieto and Faculty of Medicine,
`University of San Luis Potosi, México.
`
`Financial disclosure: None declared.
`
`Conflicts of interest: None declared.
`
`Received for publication July 1, 2014; accepted for publication August
`11, 2014.
`
`This article originally appeared online on September 16, 2014.
`
`Corresponding Author:
`Gilberto Fabian Hurtado-Torres, MD, MEd, University of San Luis
`Potosi, Av. V. Carranza 2395, Col. Universitaria, CP 78210, San Luis
`Potosí SLP, México.
`Email: gilberto.hurtado@uaslp.mx
`
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`percentage of patients still require administration of intravenous
`(IV) nutrients, which, even with the proven benefits, are not
`exempt from potential side effects and toxicity.4-6
`One of the reported hazards of PN is the inadvertent and
`excessive provision of aluminum (Al), a condition especially
`described in low-birth-weight preterm infants (LBWPIs) and
`in patients with renal failure.7
`Aluminum contamination is primarily derived from the
`glass containers of the components, required for the formula-
`tion of PN admixtures.8,9 Commercial preparations of cyste-
`ine , calcium, and phosphate are reportedly the main sources of
`aluminum as a contaminant.10-15
`Excessive intake of aluminum predisposes to osteomalacia,
`dementia, impaired neurocognitive development, encephalop-
`athy, jaundice, and anemia.9,10,15-19 The risk of aluminum toxic-
`ity depends on the dose, route of administration, and duration
`of exposure.9 The greatest risk occurs when it is administered
`parenterally, in comparison with the enteral route, because in
`the former, intestinal regulatory mechanisms of absorption are
`bypassed.10
`The Food and Drug Administration (FDA) has recom-
`mended limiting aluminum exposure from contamination of
`parenteral additives to <5 µg/kg/d.20 However, in clinical prac-
`tice, this amount is often exceeded.8,10,16,21-25
`To our knowledge, in Mexico, no studies have addressed the
`amount of aluminum administered in PN admixtures, particularly
`in the neonatal population. The aim of this study was to determine
`the concentration of aluminum in theoretical formulated samples
`of PN admixtures, designed to be administered to LBWPIs, and to
`establish the potential toxicity risk of this mineral.
`
`Methods
`
`Commercial preparations of energy substrates, electrolytes,
`multivitamins, and trace elements usually employed for the
`formulation of PN admixtures as individual components were
`evaluated in this study. In addition, the theoretical aluminum
`content of 2 typical PN admixtures was estimated with regard
`to 2 hypothetical PN admixtures similar to the ones routinely
`prescribed in our neonatal unit.
`Samples analyzed were randomly chosen from vials of
`sodium chloride, potassium phosphate, sodium acetate, sodium
`phosphate, magnesium sulfate, zinc sulfate, levocarnitine,
`multivitamin solution, selenium, cysteine hydrochloride, com-
`mercial trace element presentations, 10% crystalline amino
`acid solution, 20% lipid emulsion, and 50% dextrose.
`In addition, from 2 formulations of PN admixtures (identi-
`cal to the ones routinely prescribed for LBWPIs, with weights
`of 1800 g [admixture 1] and 1230 g [admixture 2]), patients’
`total daily intakes of aluminum were calculated from the sum
`of aluminum provided by each individual component and
`according to the volumes routinely prescribed to LBWPIs.
`The total estimated aluminum amounts for each of the 2
`admixtures were divided by the selected neonatal weights used
`
`for the formulations to obtain the theoretical clinical provision
`of aluminum expressed as µg/kg/min and to compare them
`with the safe thresholds established by the FDA.
`In Mexico, phosphate is usually provided as potassium
`phosphate. To compare potential differences in aluminum con-
`tent between potassium phosphate and sodium phosphate, we
`performed 2 different aluminum estimations, one using potas-
`sium phosphate as the main phosphate source and the other by
`substituting the former with sodium phosphate.
`Aluminum determinations were performed at the Institute
`of Metallurgy from the University of San Luis Potosi, Mexico.
`
`Aluminum Determination
`
`The method used to measure levels of aluminum was derived
`from D’Haese et al.26 Aluminum concentrations were deter-
`mined by flame atomic absorption spectrometry (Model 3110;
`Perkin-Elmer, Waltham, MA) with a nitrous oxide–acetylene
`flame (temperature, 2600–2800°C). An aluminum hollow
`cathode lamp (Perkin Elmer) was used for the measurements at
`309.3 nm, slit 0.7 nm. Aluminum concentrations in the samples
`were interpolated using a calibration curve (range, 2–20 ppm).
`Standard solutions were prepared from a commercial standard
`of aluminum (Perkin Elmer) (1000 mg/L−1 in HNO
`), using
`3
`deionized water as dissolvent (Millipore, Billerica, MA).
`Detection limit was 1 mg/L−1. Calibration method and instru-
`mental conditions were optimized for this study. To avoid alu-
`minum contamination, all laboratory materials were in plastic
`(polyethylene) and immersed in HNO
` for 48 hours and washed
`3
`with deionized water. Aliquots were taken directly from the
`original vials of each component analyzed.
`All measurements were performed in triplicate from the
`same batch; sodium phosphate and levocarnitine were tested
`just in 1 sample due to institutional restrictions in availability.
`Reported results correspond to mean ± standard deviation.
`
`Results
`
`Calcium gluconate, potassium phosphate, trace elements, levo-
`carnitine, and L-cysteine were positive for the presence of alu-
`minum in the 3 processed commercial batches. The single
`sample of sodium phosphate analyzed was also positive for
`aluminum. Table 1 shows the individual components analyzed
`and their aluminum concentrations.
`Table 2 shows the total aluminum content of the 2 typical
`PN admixtures, derived from the sum of the theoretical alumi-
`num content of individual components administered according
`to the required volume.
`According to the amount of aluminum measured in phos-
`phate salts, individual aluminum provision from phosphate
`salts can be reduced by 52.7% by replacing potassium phos-
`phate with sodium phosphate salts (Table 3).
`Theoretically, replacing potassium phosphate with sodium
`phosphate in the 2 typical PN admixtures would reduce the
`
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`Journal of Parenteral and Enteral Nutrition 40(7)
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`Table 1. Aluminum Concentration of Parenteral Nutrition Individual Components.
`
`Components Evaluated: Generic (Trade Name, Manufacturer)
`
`20% Lipid emulsion MCT/LCT (SMOF lipids, Fresenius Kabi, Austria)
`50% Dextrose (SOLUCION D-50, PISA Farmaceutica, Mexico)
`10% Crystalline amino acids (LEVAMIN PAD, PISA Farmaceutica)
`Intravenous multivitamin solution (MVI-12 pediatric, Grossman, Mexico)
`Sodium acetate (SOLUCION AC-S, PISA Farmaceutica)
`Intravenous trace elementsa (TRACEFUSIN, PISA Farmaceutica)
`Selenium (SELEFUSIN, PISA Farmaceutica)
`Zinc sulfate (ZN-FUSIN, PISA Farmaceutica)
`L-cysteine (FISCARNAT, PISA Farmaceutica)
`Magnesium sulfate 20% (MAGNEFUSIN, PISA Farmaceutica)
`Sodium chloride 17.7% (SOLUCION CS-S 17.7%, PISA Farmaceutica)
`Potassium phosphate (FP-20, PISA Farmaceutica)
`Sodium phosphate (FOSFUSIN, PISA Farmaceutica)
`Calcium gluconate 10% (SOLUCION GC 10%, PISA Farmaceutica)
`Potassium chloride (KELEFUSIN, PISA Farmaceutica)
`Levocarnitine (EFE-CARN, PISA Farmaceutica)
`
`Lot of Commercial
`Product
`
`Aluminum Concentration,
`Mean (SD), mg/L
`
`160K0090
`A024551
`J3L027
`84152
`C113125
`C091852
`C034246
`C014202
`C013601
`B052773
`B14A369
`B042654
`C14Y347
`B013298
`B034325
`B014218
`
`ND
`ND
`ND
`ND
`ND
`2.3 (0.18)
`ND
`ND
`2.56 (0.39)
`ND
`ND
`3.78 (0.45)
`1.78b
`3.89 (0.37)
`ND
`1.10b
`
`LCT, long-chain triglyceride; ND, not detected; MCT, medium-chain triglyceride.
`aIntravenous trace elements (TRACEFUSIN, PISA Farmaceutica): each 100 mL contains zinc chloride, 55 mg; copper sulfate, 16.90 mg; manganese
`sulfate, 38.10 mg; sodium iodide, 1.30 mg; sodium fluoride, 14.0 mg; and sodium chloride, 163.90 mg.
`bSodium phosphate and levocarnitine were tested just in 1 sample.
`
`Table 2. Aluminum Daily Intake for 2 Hypothetical Neonates According to the Sum of the Amounts of Aluminum Detected in
`Individual Parenteral Nutrition Components, Underscoring, for Admixture 2, Aluminum Content That Surpassed the FDA Safe
`Maximal Aluminum Threshold.
`
`Component
`
`Volume, mL
`
`Aluminum Content, µg
`
`Aluminum Intake, µg/kg/d
`
`Admixture 1 (hypothetical weight = 1800 g)
` 50% Dextrose
` 10% Crystalline amino acids
` Sodium chloride 17.7%
` Potassium phosphate
` Magnesium sulfate 20%
` Calcium gluconate 10%
` Selenium
` Zinc sulfate
` Multivitamins
` Water
` Total contribution
`Admixture 2 (hypothetical weight = 1230 g)
` 50% Dextrose
` 10% Crystalline amino acids
` 20% Lipid emulsion MCT/LCT
` Sodium chloride 17.7%
` Potassium phosphate
` Magnesium sulfate 20%
` Calcium gluconate 10%
` Selenium
` Zinc sulfate
` Multivitamins
` Water
` Total contribution
`
`37
`21.4
`2.9
`0.7
`0.5
`1.3
`0.1
`0.1
`0.3
`105
`
`31.8
`43
`12.3
`1.2
`1.2
`0.3
`2.4
`0.1
`0.2
`2.4
`89.1
`
`—
`—
`—
`3.01
`—
`5.07
`—
`—
`—
`—
`8.08
`
`—
`—
`—
`—
`5.16
`—
`9.36
`—
`—
`—
`—
`14.52
`
`FDA, Food and Drug Administration; LCT, long-chain triglyceride; MCT, medium-chain triglyceride; —, not detected.
`
`
`—
`—
`—
`2.82
`—
`1.67
`—
`—
`—
`—
`4.49
`
`—
`—
`—
`—
`4.2
`—
`7.61
`—
`—
`—
`—
`11.8
`
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`Table 3. Effect of Substitution of Potassium Phosphate (KPO
`4
`Nutrition Admixture Contents.
`
`) Salts With Sodium Phosphate (NaPO
`4
`
`) Salts in Aluminum Parenteral
`
`Characteristic
`
`mL
`
`Aluminum
`per mL
`
`Aluminum
`Content, µg
`
`Total Aluminum
`Content, µg
`
`Aluminum,
`µg/kg/d
`
`Admixture for neonate 1, hypothetical weight 1800 g
` Original admixture with KPO
`
` KPO
`4
`
` Calcium gluconate 10%
`
` Substituting KPO
`4
`
` NaPO
`4
`
` Calcium gluconate 10%
`
`Admixture for neonate 2, hypothetical weight 1230 g
` Original admixture with KPO
`4
`
` KPO
`4
`
` Calcium gluconate 10%
`
` Substituting KPO
`4
`
` NaPO
`4
`
` Calcium gluconate 10%
`
`
`4
`
` with NaKPO
`4
`
` with NaKPO
`4
`
`3.78
`3.89
`
`1.78
`3.89
`
`3.78
`3.89
`
`1.78
`3.89
`
`0.7
`1.3
`
`0.7
`1.3
`
`1.2
`2.4
`
`1.2
`2.4
`
`2.64a
`5.06b
`
`1.25a
`5.06b
`
`4.53a
`9.34
`
`2.14a
`9.34
`
`7.70c
`
`6.31c
`
`13.87f
`
`11.48f
`
`1.47
`2.81
`4.27d
`
`0.69
`2.81
`3.50d
`
`3.68
`7.6e
`11.27g
`
`1.74
`7.6e
`9.33g
`
`aPercent reduction in aluminum content derived from phosphate salts, 52.7%.
`bPercent reduction in total aluminum content, 18.1%.
`cCalcium gluconate, main source of aluminum.
`dAluminum intake, below Food and Drug Administration (FDA) recommendations.
`eCalcium gluconate, main source of aluminum.
`fPercent reduction in total aluminum content, 17.2%.
`gAluminum intake, exceeding FDA recommendations.
`
`final aluminum concentration by 18.1% and 17.2% for admix-
`ture 1 and admixture 2, respectively. Nevertheless, total con-
`tent of aluminum was still found outside the safety margins
`recommended by the FDA in admixture 2, with calcium gluco-
`nate as the main source of aluminum contamination.
`
`Discussion
`
`Aluminum contamination in PN admixtures remains an unsolved
`problem.11,27 Given its potential implications, in terms of mor-
`bidity and long-term side effects, physicians who care for
`patients with risk of aluminum toxicity must be aware of the
`potential sources of excessive amounts of this element.28
`In the present analysis in Mexico and in accordance with
`previous international reports, calcium and phosphate salts,
`levocarnitine, cysteine, and trace elements are the main sources
`of contamination of aluminum,12 so that neonatal PN routinely
`exceeds the upper safety limit established by the FDA of <5
`µg/kg/d for aluminum provision.20 Sodium phosphate salts
`also were positive for aluminum contamination but contained
`nearly 50% less compared with potassium phosphate.
`The importance of preventing aluminum toxicity derives
`from the adverse effects that have been extensively described
`in patients receiving PN for prolonged periods, with particular
`
`emphasis on the neonatal or pediatric population, in whom
`renal excretion mechanisms are still immature27; hence, expo-
`sure to high concentrations of aluminum, usually inadvertently,
`can have toxic side effects.11
`The association between exposure to aluminum and impaired
`neurodevelopment is well documented. Bishop et al17 reported a
`cohort of preterm infants who received PN with concentrations up
`to 45 µg/kg/d; surviving infants were evaluated at age 18 months,
`and the authors noticed patients previously exposed to higher alu-
`minum doses had lower neurodevelopment scores compared with
`infants receiving PN with concentrations of aluminum no greater
`than 5 µg/kg/d. Subsequently, the same authors documented the
`presence of high concentrations of aluminum in the central ner-
`vous system in an infant who previously received high aluminum
`concentrations in a PN solution.29 This finding confirms the dele-
`terious role of aluminum in neurocognitive development, particu-
`larly in susceptible populations such as LBWPIs.
`Another potential and serious negative effect of aluminum
`toxicity is the role it exerts in bone metabolism. Metabolic bone
`disease (MBD), defined as the presence of patchy osteomalacia,
`bone pain, reduced bone turnover, and suppressed parathyroid
`hormone secretion,10,30 represents a multifactorial entity31 and is
`the result of several risk factors usually present in critically ill
`patients, including infants. These include vitamin D and vitamin
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`K deficiency, metabolic acidosis, immobility, lack of sun expo-
`sure, and inadequate intake of calcium and phosphate.32
`Preventing aluminum toxicity might contribute to reducing
`the incidence of MBD in high-risk populations.19 Excess of
`aluminum accumulates in bone mineralization fronts, affecting
`new bone formation and increasing osteoblast activity,10,19,33-35
`an aspect particularly relevant in pediatric and neonatal popu-
`lations,10 since preterm infants receiving PN longer than 3
`weeks have 10 times higher bone aluminum concentrations
`compared with infants who receive enteral nutrition, predis-
`posing them to develop osteomalacia.35,36
`Current guidelines for bone metabolic disease prevention
`underscore the aluminum contamination from PN solutions as
`a preventable risk factor for osteomalacia, and the reduction of
`excessive aluminum intake should be pursued as a preventive
`measure.37
`Aluminum toxicity has also been implicated as a risk factor
`for cholestasis in patients receiving PN regimens.11 Alemmari
`et al38 demonstrated the role of aluminum in the development
`of intestinal failure–PN-associated liver disease (IF-PNLAD),
`a clinical and biochemical entity highly prevalent in neonatal
`populations.39
`The role of aluminum for the development of IF-PNLAD is
`related to mechanisms such as oxidative stress, lipid peroxida-
`tion, and DNA damage.11 In experimental models, reducing the
`intake of aluminum and adding taurine have successfully pre-
`vented the presentation of liver complications associated with
`the use of PN.40,41
`In clinical practice, several strategies to reduce aluminum
`intake from PN admixtures have been established. Diverse
`authors support the recommendation to substitute calcium salt
`presentations employed in the parenteral nutrition compound-
`ing, preferring the form of calcium chloride instead of calcium
`gluconate.14,25,42
`Calcium chloride salts have lower contents of aluminum as
`a contaminant and could help to reduce final aluminum content
`by 34%.42,43 Others authors have doubts about the utility of this
`intervention, under the rationale that excessive chloride may
`be a risk for the development of metabolic acidosis, an associ-
`ated factor also involved in the development of MBD; in addi-
`tion, calcium chloride also can affect calcium availability and
`the interaction with phosphate.10,42
`In our study, we found that calcium gluconate is the main
`source of aluminum contamination. In Mexico, calcium salts
`are available only in the form of calcium gluconate, which
`show high aluminum content. From our findings, we postulate
`that the incorporation of chloride salts could be an attractive
`field of research to explore in our context as an additional way
`to reduce aluminum parenteral intake, particularly in LBWPIs.
`Replacing potassium phosphate salts with sodium phos-
`phate also represents a valuable measure to reduce the contri-
`bution of aluminum.42 Sodium phosphate salts have a lower
`aluminum content compared with potassium phosphate, and
`their effectiveness has been widely documented.11
`
`In our trial, we demonstrated that sodium phosphate salts
`can be considered a feasible substitute of potassium phosphate
`salts as a low-aluminum component in PN, leading to a reduc-
`tion in aluminum content, derived from phosphate salts, by
`more than half.
`In addition, aluminum contamination can be reduced by
`replacing glass burettes and syringes with plastic materials and
`by choosing commercial preparations of electrolytes and trace
`elements in plastic (polyethylene) vials instead of glass.44 The
`rationale is supported by extensive evidence that shows glass
`contains more aluminum impurities in comparison with plas-
`tic.27,45 We could not evaluate such an alternative, because all
`the PN components we tested were originally contained in
`glass vials. Electrolyte salts contained in plastic vials should be
`evaluated to confirm whether plastic containers provide lower
`amounts of aluminum.
`Theoretical calculations of aluminum intake were per-
`formed according to 2 low-birth-weight preterm requirements.
`Although PN admixtures calculations were derived just from 2
`hypothetical low-birth-weight infants, we confirmed that vari-
`ations in body weight and in the requirements for calcium and
`phosphate were the main determinants related to exceeding the
`safety limit for daily intake of aluminum due to the volume of
`additives used.46 The PN admixture, designed for very low-
`birth-weight preterm infants, represented the greatest risk for
`exceeding safe FDA aluminum intake thresholds.
`Although only 2 sample PN admixtures as a finished prod-
`uct were evaluated and with a limited number of individual
`components, this study allows us an initial approach to estab-
`lish the safety of the use of commercial products available in
`Mexico for the preparation of PN admixtures and to know their
`aluminum contents.
`
`Limitations
`
`We are aware that other medications also given to preterm
`infants, such as antibiotics, steroids, vasoactive amines, dilu-
`ents, and loop diuretics, were not evaluated and might serve as
`unrecognized and potential sources of aluminum.9,47
`The PN admixtures analyzed did not contain cysteine or
`trace elements, additives in which aluminum has been found as
`a contaminant. In diverse clinical scenarios, the addition of
`these products could potentially increase aluminum content
`and exceed the upper safe threshold proposed by the FDA (<5
`µg/kg/d).20
`No serum, tissue, or bone aluminum determinations were
`performed in infants receiving PN.10,24,48,49 Preterm infants are
`not exempt from receiving aluminum from other sources and
`are exposed to the risk of developing aluminum-related long-
`term complications, even when PN admixtures are reduced in
`aluminum content. Aluminum determination facilities are not
`widely available in most hospital scenarios, so choosing prod-
`ucts labeled as having a low aluminum content would help to
`reduce aluminum exposure.28,50
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`The method employed in this study did not allow the detec-
`tion of aluminum concentrations lower than 1 mg/L−1; how-
`ever, this did not limit our ability to report positive aluminum
`contamination in commercial products used for the preparation
`of PN admixtures in Mexico.
`There was no evaluation of mineral salts filled in plastic
`containers because the availability in Mexico is mainly in glass
`presentations. A future analysis must be extended to plastic
`vials if they are available in Mexico.
`
`Conclusions
`
`In Mexico, calcium and phosphate salts, cysteine, and trace
`elements are the main sources of aluminum contamination in
`PN admixtures. The safety margins established by the FDA to
`prevent aluminum toxicity are easily exceeded with the use of
`commercial preparations available in Mexico.
`Monitoring and control of aluminum concentrations in
`the components usually employed in the PN admixtures
`would allow implementation of effective strategies to pre-
`vent aluminum toxicity and avoid potential side effects, par-
`ticularly in high-risk populations (ie, LBWPIs). Mineral
`salts and IV components filled in plastic containers should
`be further evaluated as an effective measure to reduce alumi-
`num intake.
`
`Statement of Authorship
`V. Lima-Rogel, F. J. Escalante-Padrón, and G. F. Hurtado-Torres
`contributed to conception/design of the research; S. Romano-
`Moreno and E. J. López-López equally contributed to biochemical
`analysis of samples; G. F. Hurtado-Torres contributed to analysis
`and interpretation of the data; and V. Lima-Rogel, G. F. Hurtado-
`Torres, and F. J. Escalante-Padrón equally drafted the manuscript.
`All authors critically revised the manuscript, agree to be fully
`accountable for ensuring the integrity and accuracy of the work,
`and read and approved the final manuscript.
`
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