- Email: [email protected]
UK nuclear-test veterans
CORRESPONDENCE
antibodies to pertussis toxin and filamentous haemagglutinin (the basic components of acellular pertussis vaccine) do not correlate with child protection.5 We need antibodies to fimbrial and outer-membrane proteins (agglutinogens 1, 2, and 3), deficiency in one or more of which has led to vaccination failure in various countries.5 Assay of these agglutinins is provided by our Pertussis Reference Laboratory at Manchester University, Manchester, UK. To achieve the dual goals of herd immunity and immunological memory in the individual,1-4 the basal immune response in each child needs to be optimised. Surely we should revert to an immunisation schedule at 3, 4, and 5 months, which is still used effectively in many countries. Noel W Preston University Department of Medical Microbiology, Clinical Sciences Building, Manchester Royal Infirmary, Manchester M13 9WL, UK (e-mail: [email protected]) 1
2
3 4
5
McVernon J, Andrews N, Slack MPE, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003; 361: 1521–23. Trotter CL, Ramsay ME, Slack MPE. Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign. Commun Dis Public Health 2003; 6: 55–58. Steinhoff M, Goldblatt D. Conjugate Hib vaccines. Lancet 2003; 361: 360–61. Rijkers GT, Vermeer-de Bondt PE, Spanjaard L, Breukels MA, Sanders EAM. Return of Haemophilus influenzae type b infections. Lancet 2003; 361: 1563–64. Preston NW. Pertussis (whooping cough): the road to eradication is well sign-posted but erratically trodden. Infect Dis Rev 2000; 2: 5–11.
decreased risk for invasive H influenza infection of 5% for each added week of exclusive breastfeeding.4 Additionally, breastfeeding enhances the specific IgG2 anti-Hib response to invasive Hib infection that arises years after breastfeeding has stopped.5 Finally, findings of a vaccine trial (SA Silfverdal, unpublished data) show that those children less adequately protected against Hib (<1 g/mL) after 3 doses of vaccine, given at 3, 5, and 12 months (the Swedish schedule), were breastfed exclusively for only 31 days or less (p=0·007). *Sven Arne Silfverdal, Lennart Bodin, Per Olcén *Department of Paediatrics (SAS), Biostatistics and Epidemiology (LB), and Clinical Microbiology and Immunology (PO), Örebro University Hospital, SE 701 85 Örebro, Sweden (e-mail: [email protected]) 1
2
3
4
5
McVernon J, Andrews N, Slack MPE, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003; 361: 1521–23. Pabst HF, Spady DW. Effect of breastfeeding on antibody response to conjugate vaccine. Lancet 1990; 336: 269–70. Silfverdal SA, Bodin L, Olcén P. Protective effect of breastfeeding: an ecological study on Haemophilus influenzae meningitis and breastfeeding in a Swedish population. Int J Epidemiol 1999; 28: 152–56. Silfverdal SA, Bodin L, Hugosson S, et al. Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case control study in Swedish preschool children. Int J Epidemiol 1997; 26: 443–450. Silfverdal SA, Bodin L, Ulanova M, HahnZoric M, Hanson LÅ, Olcén P. Long term enhancement of the IgG2 antibody response to Haemophilus influenzae type b by breastfeeding. Pediatr Infect Dis J 2002; 21: 816–21.
UK nuclear-test veterans Sir—Breastfeeding is an important factor not considered in the debate about the cause of the increase in invasive Hib infections reported in the UK.1 We believe breastfeeding could explain the rise in invasive Hib infections caused by reduced protection for various reasons. In Sweden and Finland, countries where exclusive breastfeeding is extended, no increase in invasive Hib disease has been noted. Furthermore, Pabst and Spady2 reported that antibody concentrations in Canadians were significantly higher in the breastfed than in the formula-fed group after vaccination with a conjugate Hib vaccine. In Sweden, before general Hib immunisation was introduced, results of an ecological study3 indicated a protective effect of breastfeeding against Haemophilus influenza meningitis at a population level, and those of a case-control study showed a
Sir—We wish to respond to Keith Baverstock’s Commentary (May 24, p 1759)1 on our study2 of UK nucleartest veterans. First, Baverstock notes that Sue Rabbitt Roff3 has criticised our study for not including what she regards as eligible cases of multiple myeloma. However, it is crucial that test participants and controls in a cohort study such as ours should be identified in the same way so that the extent of ascertainment of cancers in the two groups is the same. To supplement cases in an ad-hoc way could introduce bias, which we were careful to avoid. For example, self-response bias has been suggested in an analysis of US test veterans4 that used multisource tracing of participants along the lines suggested by Baverstock. Second, Baverstock is unconvinced that, “so long after the records were
compiled”, the estimated 15% of eligible test participants not in our cohort were excluded for a reason unrelated to their health. However, his reasoning is incorrect. Most of the deaths and cancers arose after the cohort was identified nearly 20 years ago. We took great care to avoid bias when assembling the cohort. Furthermore, no such bias could have occurred to any material extent—if at all—in subsequent years. Third, both we and Baverstock agree that test participants might have an increased risk of leukaemia other than chronic lymphatic leukaemia, but he suggests that we offer no explanation— other than chance—for the low mortality relative to national rates for non-chronic lymphatic leukaemia in the control group. We have considered this topic previously5 and did not identify any social, behavioural, or environmental factors that could lead to such low mortality relative to national rates; chance is the most likely explanation. In an approximate analysis, Baverstock suggests that rates of nonchronic lymphatic leukaemia were low (and similar to controls) in those who participated in Australian tests, and close to national rates for those at tests in the Pacific. However, the small numbers and lack of a prior hypothesis make interpretation difficult. Indeed, Baverstock’s arguments about local fallout suggest that, if anything, he should have applied a one-sided test for a raised risk among Australian relative to Pacific participants, rather than using a one-sided test for Pacific relative to Australian participants. To conclude, Baverstock’s commentary does not alter the conclusions of our study—namely, that test participation might be associated with a small increase in the risk of nonchronic lymphatic leukaemia, but not with multiple myeloma, which was the main reason for undertaking our analysis. Funding for the maintenance of the test veterans database and for its analysis has been provided by the Ministry of Defence.
*Colin R Muirhead, Gerry M Kendall National Radiological Protection Board, Chilton, Didcot, Oxon OX11 0RQ, UK (e-mail: [email protected]) 1
2
Baverstock K. The 2003 NRPB report on UK nuclear-test veterans. Lancet 2003; 361: 1759–60. Muirhead CR, Bingham D, Haylock RG, et al. Follow up of mortality and incidence of cancer 1952–98 in men from the UK who participated in the UK’s atmospheric nuclear weapons tests and experimental programmes. Occup Environ Med 2003; 60: 165–72.
THE LANCET • Vol 362 • July 26, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
331
CORRESPONDENCE
3
4
5
Roff SR. Underascertainment of multiple myeloma challenges robustness of third NRPB study of nuclear veterans. Published online March 7, 2003. http://bmj.com/cgi/eletters/326/7387/468/d# 30234 (accessed June 30, 2003). Johnson JC, Thaul S, Page WF, Crawford H. Mortality of Veteran Participants in the CROSSROADS Nuclear Test. Washington, DC: National Academy Press, 1996. Darby SC, Kendall GM, Fell TP, et al. A summary of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom’s atmospheric nuclear weapon tests and experimental programmes. BMJ 1988; 296: 332–38.
longer incubation period, can be treated with plasma exchange or other measures.3 The complex logistics of distant organ procurement, large recipient pools, and surgical urgencies invite errors. The last-minute tests that protect against a mistake are the redcell and HLA crossmatching tests. Is it not time that red-cell crossmatching, which has been obligatory for blood transfusions, also be compulsory for organ transplantation? Paul I Terasaki Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA (e-mail: [email protected])
ABO mismatching errors in heart transplants
1
2
Sir—Recent adverse publicity in the USA about a patient who received an ABO mismatched heart transplant is a tragedy that will reoccur unless steps are taken to preclude such an event. Standard procedures need to be instituted so that such mistakes cannot be made. 12 years ago, ABO mismatching errors in heart transplants resulted in eight deaths, and prompted me to to suggest a remedy.1 I proposed that a red-cell crossmatch be done for all organ transplantations. This final check, has been universally mandatory for all blood transfusions for many years. Because an error would be equally disastrous for organ transplantation, there is no reason why the same test would not be used. Almost all the ABO mismatching errors that have occurred were because of clerical, administrative errors. I recommended that hearts for transplantation be sent to the blood bank, not to the operating room. The red-cell crossmatching should be done in the blood bank, and then the heart can be released to the operating room. This simple 10-min test should be mandatory for heart transplantations, where an error invariably leads to certain death. An HLA-antibody crossmatch test is also important for organ transplantations. It is usually argued that the urgency to proceed with the operation supersedes the need for an HLA crossmatch. However, for kidney transplantation, as Nishikawa and I have shown,3 even 1 h extra cold ischaemia time has no adverse effect on 3-year graft survival rate. For heart and liver grafts, one possible procedure would be a 30-min cytotoxic crossmatch test to identify strong positive crossmatches. Weak crossmatches, if identified within a
332
3
Terasaki PI. Red cell crossmatching for heart transplants. N Engl J Med 1991; 325: 1748. Nishikawa K, Terasaki PI. Annual trends and triple therapy—1991–2000. In: Cecka JM, Terasaki P. eds. Clinical transplants 2001. Los Angeles: UCLA Immunogenetics Center, 2001: 247–69. McCarthy JF, Cook DJ, Massad MG, et al. Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching. Eur J Cardio-Thoracic Surg 1998; 14: 197–200.
Blood transfusions: a hidden source of lead exposure Sir—Lead is toxic to the developing and blood nervous system,1,2 transfusions are a potential source of Extremely low lead exposure.3 birthweight (ELBW) infants (who need repeated blood transfusions), together with those who need doublevolume exchange transfusions, cardiac surgery necessitating bypass, extracorporeal membrane oxygenation (ECMO), or chronic transfusions, are extensively exposed to donated blood. In 1991, we showed3 that premature infants were exposed to unacceptably high amounts of lead through blood transfusions. To ascertain if hazardous concentrations of lead (PbB) are still present in transfused blood, we measured the PbB of 100 units of blood by atomic absorption spectroscopy. The mean PbB was 0·11 mol/L (SD 0·17) and the median was 0·07 mol/L (range 0·02–1·37). Two units had PbBs of 0·99 mol/L and 1·37 mol/L, respectively, representing an unacceptable hazard of lead exposure, particularly for ELBW infants, who often receive multiple transfusions from the same donor.
In 2001, ELBW infants received an average of 3·3 transfusions each of about 15 mL/kg during their admission to Rainbow Babies and Children’s Hospital. If a unit contains 0·97 mol/L PbB, the infant would receive 3 g/kg intravenously on the day of transfusion. Infants undergoing exchange transfusion receive twice their volume of blood (160 mL/kg), equivalent to 32 g/kg of lead. After exchange, 90% of the infant’s blood is donor blood, thus their PbB would be 0·87 mol/L.4 Acceptable concentrations of intravenous lead exposure are unknown. WHO has set a provisional tolerable weekly oral intake of 25 g/kg.5 We have calculated a daily permissible value of intravenous lead based on the following: given that only 10% of lead is absorbed from the gastrointestinal tract, a weekly permissible intravenous dose would be 2·5 g/kg, and therefore a daily permissible dose would be 0·36 g/kg. To limit the dose of a premature infant receiving a 20 mL/kg blood transfusion to less than 0·36 g/kg (and assuming blood transfusion is the only route of exposure to lead), the donor unit must have a lead concentration of less than 0·09 mol/L. 64% of our measured units fit this criteria. To achieve these lower exposures, we recommend that all units designated for paediatric patients be screened for lead concentration, and that only units with lead concentrations of less than 0·09 mol/L be used in these patients. *Cynthia F Bearer, Natalie Linsalata, Roslyn Yomtovian, Michele Walsh, Lynn Singer *Division of Neonatology, Department of Pediatrics, Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA (CFB, NL, MCW); Department of Pathology, University Hospitals of Cleveland, Cleveland (RY); and Case Western Reserve University, Cleveland (LS) (e-mail: [email protected]) 1
2
3
4
5
Lanphear BP, Dietrich K, Auinger P, Cox C. Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents. Public Health Rep 2000; 115: 521–29. Canfield RL, Henderson CR, CorySlechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 mg per deciliter. N Engl J Med 2003; 348: 1517–26. Bearer CF, O’Riordan MA, Powers R. Lead exposure from blood transfusion in VLBW infants. J Pediatr 2000; 137: 549–54. Luchtman-Jones L, Schwartz AL, Wilson DB. Blood component therapy for the neonate. In: Fanaroff AA, Martin RJ, eds. Neonatal-perinatal medicine. (7th edn). St Louis: Mosby, 2002: 1239–47. WHO. Guidelines for drinking-water quality 2nd edn. Geneva: World Health Organization, 1996.
THE LANCET • Vol 362 • July 26, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
antibodies to pertussis toxin and filamentous haemagglutinin (the basic components of acellular pertussis vaccine) do not correlate with child protection.5 We need antibodies to fimbrial and outer-membrane proteins (agglutinogens 1, 2, and 3), deficiency in one or more of which has led to vaccination failure in various countries.5 Assay of these agglutinins is provided by our Pertussis Reference Laboratory at Manchester University, Manchester, UK. To achieve the dual goals of herd immunity and immunological memory in the individual,1-4 the basal immune response in each child needs to be optimised. Surely we should revert to an immunisation schedule at 3, 4, and 5 months, which is still used effectively in many countries. Noel W Preston University Department of Medical Microbiology, Clinical Sciences Building, Manchester Royal Infirmary, Manchester M13 9WL, UK (e-mail: [email protected]) 1
2
3 4
5
McVernon J, Andrews N, Slack MPE, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003; 361: 1521–23. Trotter CL, Ramsay ME, Slack MPE. Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign. Commun Dis Public Health 2003; 6: 55–58. Steinhoff M, Goldblatt D. Conjugate Hib vaccines. Lancet 2003; 361: 360–61. Rijkers GT, Vermeer-de Bondt PE, Spanjaard L, Breukels MA, Sanders EAM. Return of Haemophilus influenzae type b infections. Lancet 2003; 361: 1563–64. Preston NW. Pertussis (whooping cough): the road to eradication is well sign-posted but erratically trodden. Infect Dis Rev 2000; 2: 5–11.
decreased risk for invasive H influenza infection of 5% for each added week of exclusive breastfeeding.4 Additionally, breastfeeding enhances the specific IgG2 anti-Hib response to invasive Hib infection that arises years after breastfeeding has stopped.5 Finally, findings of a vaccine trial (SA Silfverdal, unpublished data) show that those children less adequately protected against Hib (<1 g/mL) after 3 doses of vaccine, given at 3, 5, and 12 months (the Swedish schedule), were breastfed exclusively for only 31 days or less (p=0·007). *Sven Arne Silfverdal, Lennart Bodin, Per Olcén *Department of Paediatrics (SAS), Biostatistics and Epidemiology (LB), and Clinical Microbiology and Immunology (PO), Örebro University Hospital, SE 701 85 Örebro, Sweden (e-mail: [email protected]) 1
2
3
4
5
McVernon J, Andrews N, Slack MPE, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003; 361: 1521–23. Pabst HF, Spady DW. Effect of breastfeeding on antibody response to conjugate vaccine. Lancet 1990; 336: 269–70. Silfverdal SA, Bodin L, Olcén P. Protective effect of breastfeeding: an ecological study on Haemophilus influenzae meningitis and breastfeeding in a Swedish population. Int J Epidemiol 1999; 28: 152–56. Silfverdal SA, Bodin L, Hugosson S, et al. Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case control study in Swedish preschool children. Int J Epidemiol 1997; 26: 443–450. Silfverdal SA, Bodin L, Ulanova M, HahnZoric M, Hanson LÅ, Olcén P. Long term enhancement of the IgG2 antibody response to Haemophilus influenzae type b by breastfeeding. Pediatr Infect Dis J 2002; 21: 816–21.
UK nuclear-test veterans Sir—Breastfeeding is an important factor not considered in the debate about the cause of the increase in invasive Hib infections reported in the UK.1 We believe breastfeeding could explain the rise in invasive Hib infections caused by reduced protection for various reasons. In Sweden and Finland, countries where exclusive breastfeeding is extended, no increase in invasive Hib disease has been noted. Furthermore, Pabst and Spady2 reported that antibody concentrations in Canadians were significantly higher in the breastfed than in the formula-fed group after vaccination with a conjugate Hib vaccine. In Sweden, before general Hib immunisation was introduced, results of an ecological study3 indicated a protective effect of breastfeeding against Haemophilus influenza meningitis at a population level, and those of a case-control study showed a
Sir—We wish to respond to Keith Baverstock’s Commentary (May 24, p 1759)1 on our study2 of UK nucleartest veterans. First, Baverstock notes that Sue Rabbitt Roff3 has criticised our study for not including what she regards as eligible cases of multiple myeloma. However, it is crucial that test participants and controls in a cohort study such as ours should be identified in the same way so that the extent of ascertainment of cancers in the two groups is the same. To supplement cases in an ad-hoc way could introduce bias, which we were careful to avoid. For example, self-response bias has been suggested in an analysis of US test veterans4 that used multisource tracing of participants along the lines suggested by Baverstock. Second, Baverstock is unconvinced that, “so long after the records were
compiled”, the estimated 15% of eligible test participants not in our cohort were excluded for a reason unrelated to their health. However, his reasoning is incorrect. Most of the deaths and cancers arose after the cohort was identified nearly 20 years ago. We took great care to avoid bias when assembling the cohort. Furthermore, no such bias could have occurred to any material extent—if at all—in subsequent years. Third, both we and Baverstock agree that test participants might have an increased risk of leukaemia other than chronic lymphatic leukaemia, but he suggests that we offer no explanation— other than chance—for the low mortality relative to national rates for non-chronic lymphatic leukaemia in the control group. We have considered this topic previously5 and did not identify any social, behavioural, or environmental factors that could lead to such low mortality relative to national rates; chance is the most likely explanation. In an approximate analysis, Baverstock suggests that rates of nonchronic lymphatic leukaemia were low (and similar to controls) in those who participated in Australian tests, and close to national rates for those at tests in the Pacific. However, the small numbers and lack of a prior hypothesis make interpretation difficult. Indeed, Baverstock’s arguments about local fallout suggest that, if anything, he should have applied a one-sided test for a raised risk among Australian relative to Pacific participants, rather than using a one-sided test for Pacific relative to Australian participants. To conclude, Baverstock’s commentary does not alter the conclusions of our study—namely, that test participation might be associated with a small increase in the risk of nonchronic lymphatic leukaemia, but not with multiple myeloma, which was the main reason for undertaking our analysis. Funding for the maintenance of the test veterans database and for its analysis has been provided by the Ministry of Defence.
*Colin R Muirhead, Gerry M Kendall National Radiological Protection Board, Chilton, Didcot, Oxon OX11 0RQ, UK (e-mail: [email protected]) 1
2
Baverstock K. The 2003 NRPB report on UK nuclear-test veterans. Lancet 2003; 361: 1759–60. Muirhead CR, Bingham D, Haylock RG, et al. Follow up of mortality and incidence of cancer 1952–98 in men from the UK who participated in the UK’s atmospheric nuclear weapons tests and experimental programmes. Occup Environ Med 2003; 60: 165–72.
THE LANCET • Vol 362 • July 26, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
331
CORRESPONDENCE
3
4
5
Roff SR. Underascertainment of multiple myeloma challenges robustness of third NRPB study of nuclear veterans. Published online March 7, 2003. http://bmj.com/cgi/eletters/326/7387/468/d# 30234 (accessed June 30, 2003). Johnson JC, Thaul S, Page WF, Crawford H. Mortality of Veteran Participants in the CROSSROADS Nuclear Test. Washington, DC: National Academy Press, 1996. Darby SC, Kendall GM, Fell TP, et al. A summary of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom’s atmospheric nuclear weapon tests and experimental programmes. BMJ 1988; 296: 332–38.
longer incubation period, can be treated with plasma exchange or other measures.3 The complex logistics of distant organ procurement, large recipient pools, and surgical urgencies invite errors. The last-minute tests that protect against a mistake are the redcell and HLA crossmatching tests. Is it not time that red-cell crossmatching, which has been obligatory for blood transfusions, also be compulsory for organ transplantation? Paul I Terasaki Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA (e-mail: [email protected])
ABO mismatching errors in heart transplants
1
2
Sir—Recent adverse publicity in the USA about a patient who received an ABO mismatched heart transplant is a tragedy that will reoccur unless steps are taken to preclude such an event. Standard procedures need to be instituted so that such mistakes cannot be made. 12 years ago, ABO mismatching errors in heart transplants resulted in eight deaths, and prompted me to to suggest a remedy.1 I proposed that a red-cell crossmatch be done for all organ transplantations. This final check, has been universally mandatory for all blood transfusions for many years. Because an error would be equally disastrous for organ transplantation, there is no reason why the same test would not be used. Almost all the ABO mismatching errors that have occurred were because of clerical, administrative errors. I recommended that hearts for transplantation be sent to the blood bank, not to the operating room. The red-cell crossmatching should be done in the blood bank, and then the heart can be released to the operating room. This simple 10-min test should be mandatory for heart transplantations, where an error invariably leads to certain death. An HLA-antibody crossmatch test is also important for organ transplantations. It is usually argued that the urgency to proceed with the operation supersedes the need for an HLA crossmatch. However, for kidney transplantation, as Nishikawa and I have shown,3 even 1 h extra cold ischaemia time has no adverse effect on 3-year graft survival rate. For heart and liver grafts, one possible procedure would be a 30-min cytotoxic crossmatch test to identify strong positive crossmatches. Weak crossmatches, if identified within a
332
3
Terasaki PI. Red cell crossmatching for heart transplants. N Engl J Med 1991; 325: 1748. Nishikawa K, Terasaki PI. Annual trends and triple therapy—1991–2000. In: Cecka JM, Terasaki P. eds. Clinical transplants 2001. Los Angeles: UCLA Immunogenetics Center, 2001: 247–69. McCarthy JF, Cook DJ, Massad MG, et al. Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching. Eur J Cardio-Thoracic Surg 1998; 14: 197–200.
Blood transfusions: a hidden source of lead exposure Sir—Lead is toxic to the developing and blood nervous system,1,2 transfusions are a potential source of Extremely low lead exposure.3 birthweight (ELBW) infants (who need repeated blood transfusions), together with those who need doublevolume exchange transfusions, cardiac surgery necessitating bypass, extracorporeal membrane oxygenation (ECMO), or chronic transfusions, are extensively exposed to donated blood. In 1991, we showed3 that premature infants were exposed to unacceptably high amounts of lead through blood transfusions. To ascertain if hazardous concentrations of lead (PbB) are still present in transfused blood, we measured the PbB of 100 units of blood by atomic absorption spectroscopy. The mean PbB was 0·11 mol/L (SD 0·17) and the median was 0·07 mol/L (range 0·02–1·37). Two units had PbBs of 0·99 mol/L and 1·37 mol/L, respectively, representing an unacceptable hazard of lead exposure, particularly for ELBW infants, who often receive multiple transfusions from the same donor.
In 2001, ELBW infants received an average of 3·3 transfusions each of about 15 mL/kg during their admission to Rainbow Babies and Children’s Hospital. If a unit contains 0·97 mol/L PbB, the infant would receive 3 g/kg intravenously on the day of transfusion. Infants undergoing exchange transfusion receive twice their volume of blood (160 mL/kg), equivalent to 32 g/kg of lead. After exchange, 90% of the infant’s blood is donor blood, thus their PbB would be 0·87 mol/L.4 Acceptable concentrations of intravenous lead exposure are unknown. WHO has set a provisional tolerable weekly oral intake of 25 g/kg.5 We have calculated a daily permissible value of intravenous lead based on the following: given that only 10% of lead is absorbed from the gastrointestinal tract, a weekly permissible intravenous dose would be 2·5 g/kg, and therefore a daily permissible dose would be 0·36 g/kg. To limit the dose of a premature infant receiving a 20 mL/kg blood transfusion to less than 0·36 g/kg (and assuming blood transfusion is the only route of exposure to lead), the donor unit must have a lead concentration of less than 0·09 mol/L. 64% of our measured units fit this criteria. To achieve these lower exposures, we recommend that all units designated for paediatric patients be screened for lead concentration, and that only units with lead concentrations of less than 0·09 mol/L be used in these patients. *Cynthia F Bearer, Natalie Linsalata, Roslyn Yomtovian, Michele Walsh, Lynn Singer *Division of Neonatology, Department of Pediatrics, Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA (CFB, NL, MCW); Department of Pathology, University Hospitals of Cleveland, Cleveland (RY); and Case Western Reserve University, Cleveland (LS) (e-mail: [email protected]) 1
2
3
4
5
Lanphear BP, Dietrich K, Auinger P, Cox C. Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents. Public Health Rep 2000; 115: 521–29. Canfield RL, Henderson CR, CorySlechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 mg per deciliter. N Engl J Med 2003; 348: 1517–26. Bearer CF, O’Riordan MA, Powers R. Lead exposure from blood transfusion in VLBW infants. J Pediatr 2000; 137: 549–54. Luchtman-Jones L, Schwartz AL, Wilson DB. Blood component therapy for the neonate. In: Fanaroff AA, Martin RJ, eds. Neonatal-perinatal medicine. (7th edn). St Louis: Mosby, 2002: 1239–47. WHO. Guidelines for drinking-water quality 2nd edn. Geneva: World Health Organization, 1996.
THE LANCET • Vol 362 • July 26, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.