J. Paediatr. Child Health(1991) 27, 164-166
Aluminium absorption in infancy F. CHEDID, A. FUDGE, J. TEUBNER, S. L. JAMES and K. SIMMER Departments of Paediatrics and Chemical Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia
Abstract The use of aluminium-containing medications and aluminium contamination of infant formulae is common. We aimed to determine whether aluminium absorption occurs after antacid ingestion. Plasma and urinary levels of aluminium were measured before and after antacid therapy in seven infants whose mean gestational age was 3 6 k 2 weeks and postnatal age 1 1 f 5 days. Antacid therapy (400-800 pmol aluminium) was given with feeds for 2 days. Plasma aluminium levels increased and reached toxic levels (0.64f0.33 pmol/L vs 3.48f2.86 pmoliL, P = 0.029). Urinary a1uminium:creatinine ratio also increased. These results demonstrate that infants absorb aluminium from antacids and raise the concern of aluminium toxicity. Key words:
absorption; aluminium; infancy.
INTRODUCTlON
Aluminium is the most abundant metal in the earth’s crust and contamination of foodstuffs with aluminium is common. Aluminium is not required by the body and is toxic to brain, bone and liver if accumulation occurs. Aluminium toxicity was first described in 1976’ and is associated with a dementing encephalopathy, osteomalacia and anaemia.’r2 Aluminium is normally excreted by the kidneys and toxicity is well described in patients with renal failure who receive large doses of aluminium in their dialysis fluid and medication^.'*^^^ Parenteral nutrition solutions are also frequently contaminated with aluminium and parenterally fed preterm infants have been shown to have raised aluminium levels in serum, urine and bone? Healthy infants may be at risk of aluminium toxicity because of chronic exposure through artificial feeds and medications. Several of the infant milk formulae available in Australia and all of the soy preparations contain relatively high concentrations of aluminium (>40 pmol/L)6 In addition, aluminium-containing antacids are often recommended for infants with gastrooesophageal reflux or colic. The amount of aluminium absorbed by infants is unknown but is generally believed to be minimal. The aim of this study was to assess whether infants absorb aluminium. This was done by measuring plasma and urine levels of aluminium after shortterm antacid therapy.
PATIENTS AND METHODS
To be eligible for the study, patients had to be >35 week gestation, >5 days of age and have never received intravenous Correspondence: Dr Karen Simmer, Department of Paediatrics, Flinders Medical Centre, Bedford Park, SA 5042, Australia. F. Chedid. MB, BS, Paediatric Registrar. A. Fudge, BSc, Scientific Officer. J. Teubner, MB. BS. PhD, FRACP, Biochemist. S. L. James, MB, BCh. FRACP. Neonatologist K. Simmer, MB. BS. PhD. MRCP. FRACP, Neonatologist. Accepted for publication 25 February 1991.
nutrition or medications. Seven infants were studied, three female and four male. Their mean gestational age (,s.d.) was 36+2 weeks (range 33-40 weeks) and their mean birthweight (+s.d.), 2410f722 g (range 1460-3415 9). Five were preterm (3.7 p m ~ l / LIn. ~six of the seven infants studied, plasma levels exceeded 1 pmol/Land in three, levels in excess of 3.7 pmol/L (up to 8.4 pmol/L) were recorded. Birthweight, gestational age, postnatal age and dose had no effect on plasma aluminium levels in this small study. The cause of the variability in absorption between infants is not clear, but changes in gastric pH and complexing with nutrients have been suggested to alter the bioavailability of aluminium. Previous studies have shown the absorption of aluminium from This is, to our knowledge, the first study confirming absorption of aluminium from antacids in infants. There has been concern about absorption of aluminium from contaminated infant formulae but the limited data available do not support significant absorption. A recent study of healthy infants receiving human milk or soy formulae (60-63 pmol/L aluminium) demonstrated the two groups to have similar plasma levels of aluminium but urinary aluminium levels were not reported.I2 Infant formulae have been incriminated as a cause of aluminium toxicity in two uraemic infants,I3 but this study was criticized, as the quantity of aluminium retained was greater than the total exposure suggesting an additional source of a~uminium.’~ Infants may be at risk of aluminium toxicity as a result of chronic exposure to aluminium-containing medications and aluminium contamination of infant feeds. Aluminium intake can be limited by encouraging breast feeding, avoiding soy milks and ensuring levels of aluminium in infant formulae are kept to a minimum. Such recommendations exist in Australia, America, Canada and the United Kingdom. The indiscriminate use of aluminium-containing drugs is of concern as the dose of aluminium is high. Commonly used doses of antacids far exceed the normal dietary intake of aluminium in infancy. For example, a 6 kg infant fed soy formula will receive 63 pmol aluminium per day (1 pmol = 27 pg aluminium). If he also receives antacids his aluminium intake will increase to 3700-7400 pmol. Until more data are available, aluminium-containing drugs should be used cautiously in infancy and only when medically indicated.
166
REFERENCES 1 Alfrey A. C., LeGendreG. R.. Kaehny W. D. The dialysis encephalopathy syndrome: Possible aluminium intoxication. N. Engl. J. Med. 1976; 294: 184-8. 2 Short A. K., Winney R. I., Robson J. S. Reversible microcytic hyperchromic anaemia in dialysis patients due to aluminium intoxication. Proc. Eur. Dial. Transplant Assoc. 1980; 17: 226-33. 3 Ward M. K.. Feest T. G., Ellis H. A. et a/. Osteomalacic dialysis osteodystrophy. Evidence for a waterborne aetiological agent, probably aluminium. Lancet 1978; 1: 841-5. 4 Andreoli S. P., Bergstein J. M., Sherrard D. J. Aluminium intoxication from aluminium-containing phosphate binders in children with azotaemia not undergoing dialysis. N. Engl. J. Med. 1984; 310: 1079-84. 5 Sedman A. B., Klein G. L., Merriti R. J. et a/. Evidence of aluminium loading in infants receiving intravenous therapy. N. Engl. J. Med. 1984; 312: 1337-43. 6 Simmer K., Fudge A., Teubner J., James S. L. Aluminium concentrations in infant formulae. J. Paediatr. Child Health 1990; 26: 9-11.
F. Chedid et a/.
7 Kitchen, W. H.,Robinson H. P., Dickinson A. J. Revised intrauterine growth curves for an Australian hospital population. Aust. Paediatr. J. 1983; 19: 157-61. 8 Heinegard D., Tiderstrom G. Determination of serum creatinine by a direct colorimetric method. Clin. Chim. Acta 1973; 43: 305-10. 9 Trompeter R. S., Polinsky M. S..Andreoli S. A. 81 a/. Neurologic complications of renal failure. Am. J. Kidney Dis. 1986; 7: 318-23. 10 Kaehny W. D., Hegg A. P., Alfrey A. C.. Gastrointestinal absorption of aluminium from aluminium-containing antacids. N. Engl. J. Med. 1977; 296: 1389-90. 11 Gorsky J. F., Dietz A. A., Spencer H., Osis D. Metabolic balance of aluminium studied in six men. Clin. Chem. 1979; 25: 1739-43. 12 Litov R. E., Sickles V. S., Chan G. M., Springer M. A,. Cordano A. Plasma aluminium measurements in term infants fed human milk or a soy based infant formulae. Paediatrics 1989; 84: 1105-7. 13 Freundlich M., Zilleruelo G., Abitol C., Straus J., Faugere M., Malluche H. H. Infant formula as a cause of aluminium toxicity in neonatal uraemia. Lancet 1985; 2: 527-30. 14 Koo W. W., Kaplan L. A. Aluminium and bone disorders with specific reference to aluminium contamination of infant nutrients. J. Am. Coll. Nutr. 1988; 7: 199-21 4.
Aluminium absorption in infancy F. CHEDID, A. FUDGE, J. TEUBNER, S. L. JAMES and K. SIMMER Departments of Paediatrics and Chemical Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia
Abstract The use of aluminium-containing medications and aluminium contamination of infant formulae is common. We aimed to determine whether aluminium absorption occurs after antacid ingestion. Plasma and urinary levels of aluminium were measured before and after antacid therapy in seven infants whose mean gestational age was 3 6 k 2 weeks and postnatal age 1 1 f 5 days. Antacid therapy (400-800 pmol aluminium) was given with feeds for 2 days. Plasma aluminium levels increased and reached toxic levels (0.64f0.33 pmol/L vs 3.48f2.86 pmoliL, P = 0.029). Urinary a1uminium:creatinine ratio also increased. These results demonstrate that infants absorb aluminium from antacids and raise the concern of aluminium toxicity. Key words:
absorption; aluminium; infancy.
INTRODUCTlON
Aluminium is the most abundant metal in the earth’s crust and contamination of foodstuffs with aluminium is common. Aluminium is not required by the body and is toxic to brain, bone and liver if accumulation occurs. Aluminium toxicity was first described in 1976’ and is associated with a dementing encephalopathy, osteomalacia and anaemia.’r2 Aluminium is normally excreted by the kidneys and toxicity is well described in patients with renal failure who receive large doses of aluminium in their dialysis fluid and medication^.'*^^^ Parenteral nutrition solutions are also frequently contaminated with aluminium and parenterally fed preterm infants have been shown to have raised aluminium levels in serum, urine and bone? Healthy infants may be at risk of aluminium toxicity because of chronic exposure through artificial feeds and medications. Several of the infant milk formulae available in Australia and all of the soy preparations contain relatively high concentrations of aluminium (>40 pmol/L)6 In addition, aluminium-containing antacids are often recommended for infants with gastrooesophageal reflux or colic. The amount of aluminium absorbed by infants is unknown but is generally believed to be minimal. The aim of this study was to assess whether infants absorb aluminium. This was done by measuring plasma and urine levels of aluminium after shortterm antacid therapy.
PATIENTS AND METHODS
To be eligible for the study, patients had to be >35 week gestation, >5 days of age and have never received intravenous Correspondence: Dr Karen Simmer, Department of Paediatrics, Flinders Medical Centre, Bedford Park, SA 5042, Australia. F. Chedid. MB, BS, Paediatric Registrar. A. Fudge, BSc, Scientific Officer. J. Teubner, MB. BS. PhD, FRACP, Biochemist. S. L. James, MB, BCh. FRACP. Neonatologist K. Simmer, MB. BS. PhD. MRCP. FRACP, Neonatologist. Accepted for publication 25 February 1991.
nutrition or medications. Seven infants were studied, three female and four male. Their mean gestational age (,s.d.) was 36+2 weeks (range 33-40 weeks) and their mean birthweight (+s.d.), 2410f722 g (range 1460-3415 9). Five were preterm (3.7 p m ~ l / LIn. ~six of the seven infants studied, plasma levels exceeded 1 pmol/Land in three, levels in excess of 3.7 pmol/L (up to 8.4 pmol/L) were recorded. Birthweight, gestational age, postnatal age and dose had no effect on plasma aluminium levels in this small study. The cause of the variability in absorption between infants is not clear, but changes in gastric pH and complexing with nutrients have been suggested to alter the bioavailability of aluminium. Previous studies have shown the absorption of aluminium from This is, to our knowledge, the first study confirming absorption of aluminium from antacids in infants. There has been concern about absorption of aluminium from contaminated infant formulae but the limited data available do not support significant absorption. A recent study of healthy infants receiving human milk or soy formulae (60-63 pmol/L aluminium) demonstrated the two groups to have similar plasma levels of aluminium but urinary aluminium levels were not reported.I2 Infant formulae have been incriminated as a cause of aluminium toxicity in two uraemic infants,I3 but this study was criticized, as the quantity of aluminium retained was greater than the total exposure suggesting an additional source of a~uminium.’~ Infants may be at risk of aluminium toxicity as a result of chronic exposure to aluminium-containing medications and aluminium contamination of infant feeds. Aluminium intake can be limited by encouraging breast feeding, avoiding soy milks and ensuring levels of aluminium in infant formulae are kept to a minimum. Such recommendations exist in Australia, America, Canada and the United Kingdom. The indiscriminate use of aluminium-containing drugs is of concern as the dose of aluminium is high. Commonly used doses of antacids far exceed the normal dietary intake of aluminium in infancy. For example, a 6 kg infant fed soy formula will receive 63 pmol aluminium per day (1 pmol = 27 pg aluminium). If he also receives antacids his aluminium intake will increase to 3700-7400 pmol. Until more data are available, aluminium-containing drugs should be used cautiously in infancy and only when medically indicated.
166
REFERENCES 1 Alfrey A. C., LeGendreG. R.. Kaehny W. D. The dialysis encephalopathy syndrome: Possible aluminium intoxication. N. Engl. J. Med. 1976; 294: 184-8. 2 Short A. K., Winney R. I., Robson J. S. Reversible microcytic hyperchromic anaemia in dialysis patients due to aluminium intoxication. Proc. Eur. Dial. Transplant Assoc. 1980; 17: 226-33. 3 Ward M. K.. Feest T. G., Ellis H. A. et a/. Osteomalacic dialysis osteodystrophy. Evidence for a waterborne aetiological agent, probably aluminium. Lancet 1978; 1: 841-5. 4 Andreoli S. P., Bergstein J. M., Sherrard D. J. Aluminium intoxication from aluminium-containing phosphate binders in children with azotaemia not undergoing dialysis. N. Engl. J. Med. 1984; 310: 1079-84. 5 Sedman A. B., Klein G. L., Merriti R. J. et a/. Evidence of aluminium loading in infants receiving intravenous therapy. N. Engl. J. Med. 1984; 312: 1337-43. 6 Simmer K., Fudge A., Teubner J., James S. L. Aluminium concentrations in infant formulae. J. Paediatr. Child Health 1990; 26: 9-11.
F. Chedid et a/.
7 Kitchen, W. H.,Robinson H. P., Dickinson A. J. Revised intrauterine growth curves for an Australian hospital population. Aust. Paediatr. J. 1983; 19: 157-61. 8 Heinegard D., Tiderstrom G. Determination of serum creatinine by a direct colorimetric method. Clin. Chim. Acta 1973; 43: 305-10. 9 Trompeter R. S., Polinsky M. S..Andreoli S. A. 81 a/. Neurologic complications of renal failure. Am. J. Kidney Dis. 1986; 7: 318-23. 10 Kaehny W. D., Hegg A. P., Alfrey A. C.. Gastrointestinal absorption of aluminium from aluminium-containing antacids. N. Engl. J. Med. 1977; 296: 1389-90. 11 Gorsky J. F., Dietz A. A., Spencer H., Osis D. Metabolic balance of aluminium studied in six men. Clin. Chem. 1979; 25: 1739-43. 12 Litov R. E., Sickles V. S., Chan G. M., Springer M. A,. Cordano A. Plasma aluminium measurements in term infants fed human milk or a soy based infant formulae. Paediatrics 1989; 84: 1105-7. 13 Freundlich M., Zilleruelo G., Abitol C., Straus J., Faugere M., Malluche H. H. Infant formula as a cause of aluminium toxicity in neonatal uraemia. Lancet 1985; 2: 527-30. 14 Koo W. W., Kaplan L. A. Aluminium and bone disorders with specific reference to aluminium contamination of infant nutrients. J. Am. Coll. Nutr. 1988; 7: 199-21 4.
