- Email: [email protected]
Helicobacter pylori among siblings
CORRESPONDENCE
Authors’ reply Sir—We would be the first to admit that our study was quite complex and in the space allowed it was not possible to include data on speciality needs. The issue of separating general and speciality-based beds is not as simple as it first might seem. In our area all the major critical-care specialities are provided for within the study boundary, we nevertheless made efforts to identify those patients with local postcodes being treated in units elsewhere. Since individual units may be under more or less pressure it is not appropriate simply to remove specialist beds from the analysis. The only sensible method of assessing general and specialist critical-care-bed requirement is to base it on the population served regardless of where patients may be treated. Patients considered appropriate for treatment in coronary-care units accounted for 40% of total highdependency-unit bed needs. When patients with burns or those treated in cardiac surgical, thoracic surgical, and neurosurgical units are excluded our results show that for a population of 500 000 people the general intensivecare-unit average daily bed requirement is 15·97 (23 to meet needs on 95% of occasions) and the figures for high-dependency-unit are 39·57 (52) or 23·63 (34), if patients on the coronary-care units are excluded. The criticism that critical-care bed need should be based on an individual hospital rather than the population it serves is a simplistic and erroneous solution to a complex problem. The problem lies in the fact that hospitals do not have fixed catchment areas. Indeed, different services or specialties within a hospital will have different illdefined catchment areas. Intensivists around the UK will recognise the all too frequent occurrence of patients from within the catchment area having to be transferred elsewhere because of the lack of hospital beds, or the reciprocal arrangement. It is extremely unlikely that individual hospitals will be provided with the resources to support all intensive-care eventualities. Local hospitals share an inter-dependency, and so planning for adequate critical-care facilities should take this into account. Table 4 of our paper showed the calculation of bed needs by individual hospitals; if an individual hospital approach is followed the bed requirements (and costs) are substantially higher. We do not
1998
suggest that it is desirable to collect patients into one very large unit, we merely point out that to do so would require fewer beds. Our population-based approach indicates a large shortfall of adult critical-care beds, which will require a substantial injection of money to address. We are aware of the disquiet our study has produced in those responsible for financing the UK National Health System. Whatever the chances are for funding the bed requirements indicated by the population approach, we believe that this approach is the correct one. *Ronan Lyons, Ed Major Welsh Combined Centres for Public Health, University of Wales College of Medicine, Swansea SA1 1LT, UK; and Intensive Therapy Unit, Morriston Hospital, Morriston, Swansea. (e-mail: [email protected])
Thus in western countries, H pylori transmission seems not to be all “child’s play”, and extrapolation of Goodman and Correa’s analysis to western populations may not be justified and misleading when targeting further research strategies and preventive approaches. We also find that mother-tochild transmission may be less efficient if the mother smokes, an observation which could indicate an oral-oral transmission pathway.5 This pathway, might not be so relevant in a developing country where a faecal-oral pathway or other extrafamilial sources might predominate. *Dietrich Rothenbacher, Günter Bode, Hermann Brenner Department of Epidemiology, University of Ulm, D-89081 Ulm, Germany 1
2
Helicobacter pylori among siblings Sir—Karen Goodman and Pelayo Correa (Jan 29, p 358),1 report an analysis of Helicobacter pylori transmission in rural Colombia, concluding that there is a “major role for siblings in the transmission of H pylori infection”. Their analysis does not address a key question—who or what is responsible for the 63% infection prevalence in children with no sibling? H pylori prevalence in all children was 69%. Goodman and Correa could not address the role of parent-child transmission, which is difficult to assess if almost all parents are potentially infected (estimates reach over 90% in the population studied). Our work indicates that other transmission pathways may be important in western countries. Our three independent population-based studies in southern Germany in three consecutive years showed consistently that the parents, especially the mother, may have a key role in transmitting H pylori to the child. This was the case for an indirect measure of parental H pylori infection status such as history of peptic ulcer (almost everyone with peptic ulcer carries H pylori)2 or if the infection status of the parents was measured directly by 13C-urea breath test.3 Even if the infection status of both parents was adjusted for by multivariate methods, the mother clearly showed the strongest association with the infection status of her child.4 Another consistent finding was that number of siblings and birth order had only a minor role. In Germany, families are smaller than they are in Colombia.
3
4
5
Goodman KJ, Correa P. Transmission of Helicobacter pylori among siblings. Lancet 2000; 355: 358–62. Brenner H, Rothenbacher D, Bode G, Adler G. Parental history of gastric or duodenal ulcer and Helicobacter pylori infection among pre-school children: evidence of mother-infant transmission. BMJ 1998; 316: 556. Rothenbacher D, Bode G, Berg G, et al. Helicobacter pylori among pre-school children and their parents; evidence for parent-child transmission. J Infect Dis 1999; 179: 398–402. Rothenbacher D, Winkler M, Gonser T, Adler G, Brenner H. More evidence for major role of an infected mother in transmission of H pylori. Gut 1999; 45 (suppl III): A44. Brenner H, Bode G, Adler G, Rothenbacher D. Does maternal smoking hinder mother-child transmission of Helicobacter pylori? Epidemiology 2000; 11: 71–75.
Sir—Karen Goodman and Pelayo Correa1 report on the transmission of Helicobacter pylori in 2–9-year-old children in southern Colombia. A positive 13C-urea breath test was better predicted by the number of older than of younger siblings and Goodman and Correa conclude that H pylori transmission from older to younger siblings is of major importance in this population. The breath test, although it has shown excellent sensitivity and specificity in other paediatric studies, mostly in school-age children, has not been validated against invasive methods in infants, toddlers, and pre-school children. We have studied a standardised breath test in 1499 children. The protocol included a fast of at least 4 h, ingestion of 75 mg 13C urea dissolved in apple juice (pH 3·4), breath sampling before and 15 and 30 min after tracer ingestion, and a cut-off of 肁5%o for a positive test result.2 Compared with biopsy-proven H pylori status, specificity was 98% in 96 children >6 years of age but only 88% in 53 younger children. Sensitivity was 100%, independent of age.
THE LANCET • Vol 355 • June 3, 2000
CORRESPONDENCE
We now have breath-test results in 85 children under 6 years of age with biopsy-confirmed H pylori status (culture, histology, rapid urease test). All 16 H pylori infected children had changes from baseline (DOB) values above 5 per 1000 at 15 min (range 22–80) and at 30 min (range 23–82). However, eight of 69 non-infected children had a false-positive test (range 5·0–20·2 per 1000). Thus, although the test gave excellent results in school-aged children2 one-third of positive results in children below 6 years of age were false positive. A similar false-positive rate in young children has been reported by Imrie and colleagues.3 In 18 infants (mean age 12·8 months, SD 6·6) undergoing endoscopy, a test protocol found to be 100% sensitive and 97% specific in a previous study of 88 children of mean age 10·6 years (SD 4·2). The breath test was false positive in 55% at 20 min and in 18% at 30 min. The higher rate of false-positive results in younger children may lead to findings in older children being misinterpreted as a decrease in H pylori prevalence or a spontaneous clearance of the infection within the first years of life, a conclusion in longitudinal and cross-sectional studies.4,5 Goodman and Correa’s test protocol was unusual in that they gave 2·5 mg/kg 13 C-urea diluted in a glucose solution after a test meal of bread and butter; breath samples were taken before and 20 and 40 min after the tracer; and the cutoff was 6 per 1000. This protocol has never been validated against invasive methods, and if it yields the same age dependency of DOB values that we found, with more false-positive results in younger children, some of Goodman and Correa’s findings may be explained by this systematic error. Diagnostic tests used for clinical and epidemological purposes should be validated in the population in which they are applied. *Sibylle Koletzko, Hans Demmelmair, Angelika Kindermann Kinderpoliklinik im Dr. v. Haunerschen Kinderspital, D-80336 München, Germany 1
2
3
4
Goodman KJ, Correa P. Transmission of Helicobacter pylori among siblings. Lancet 2000; 355: 358–61. Kindermann A, Demmelmair H, Koletzko B, Krauss-Etschmann S, Wiebecke B, Koletzko S. Influence of age on 13C-urea breath test results in children. J Pediatr Gastroenterol Nutr 2000; 30: 85–91. Imrie C, Rowland M, Bourke B, Drumm B. Low specificity of 13C-urea breath testing in young children. Gut 1999; 45 (suppl V): A71 (abstr). Kehrt R, Becker M, Brosicke H, Kruger N, Helge H. Prevalence of Helicobacter pylori infection in Nicaraguan children with persistent diarrhea, diagnosed by the 14C-urea breath test. J Pediatr Gastroenterol Nutr 1997; 25: 84–88.
THE LANCET • Vol 355 • June 3, 2000
5
Klein PD, Gilman RH, Leon BR, Diaz F, Smith EO, Graham DY. The epidemiology of Helicobacter pylori in Peruvian children between 6 and 30 months of age. Am J Gastroenterol 1994; 89: 2196–200.
Author’s reply Sir—We agree that the role of siblings in Helicobacter pylori transmission may depend on population characteristics, as suggested by published studies we summarised.1 We presented data on children with no sibling aged 2–9 years. Only 9% of our study population had no sibling of any age, and 53% of them were infected, possibly, as with many childhood infections, by children they interacted with outside the home. Among the Colombian children, for the age groups 2–4, 5–7, and 8–9 years, the respective prevalences were 21%, 67%, and 85% among those without siblings in contrast with 61%, 75%, and 82% among children with siblings. Thus, those without siblings appear to become infected at older ages, a pattern that does not suggest frequent parent-child transmission. Dietrich Rothenbacher and colleagues mention studies showing concordant infection status in parents and 5-8-year-old children but this is weak evidence of parent-child transmission. A study that followed 67 Belgian infants of H pylori positive mothers, found only one who was positive by urea breath test at 12–15 months of age.2 Inadequate validation of the breath test in young children is a crucial problem. However, validation against biopsy-based diagnoses does not resolve all difficulties. Biopsy sampling may miss patchy or recent infection, and methods used to identify H pylori in biopsy material are not error-free.3,4 Against biopsy-based diagnosis, reduced breathtest specificity is compatible with reduced sensitivity of biopsy-based methods. The breath test may even be the more accurate method, picking up infections missed by biopsy sampling. Young children may have recent and sparse colonisation so that biopsy-based methods may be especially insensitive in young children. Most of the family-composition attributes we examined are not related to age, so the results we reported are not likely due to differential specificity by age. Even for age-related factors, a specificity of 88% among younger children would not substantially alter the effects we observed. Although a breath test with such specificity has a positive predictive value of 67% in German gastroenterology patients under age 6, in whom the observed prevalence is 19%, the positive predictive value for the same specificity is over 90% in the Colombian
2-5-year-olds, in whom the observed prevalence is 61%. The data discussed by Sibylle Koletzko and colleagues have limited statistical power to detect a difference in specificity by age (95% CI for 88% [61/69] is 0·78–0·95 while for 98% [45/46]5 it is 0·88–1·0; p=0·14). In our population, older children were about as likely as younger children to have lowpositive breath-test values (14% of positive 2-5-year-olds and 13% of positive 6-9-year-olds had delta-overbaseline values <20 per 1000). Validating the breath test in every epidemiologic study population may be desirable but the accuracy of the test in children being investigated for gastrointestinal symptoms may not apply to healthy children. For populationbased studies, a valid and feasible gold standard is lacking. *Karen J Goodman, Pelayo Correa *School of Public Health, University of TexasHouston Health Science Center, PO Box 20186, Houston, TX 77225, USA; and Department of Pathology, Louisiana State University Medical Center, 1901 Perdido St, New Orleans, LA 70112, USA 1
2
3
4
5
Goodman KJ, Correa P. Helicobacter pylori transmission among siblings. Lancet 2000; 355: 358–62. Blecker U, Lanciers S, Keppens E, Vandenplas Y. Evolution of Helicobacter pylori positivity in infants born from positive mothers. J Pediatr Gastroenterol Nutr 1994; 19: 87–90. El-Zimaity HMT, Graham DY, Al-Assi MT, et al. Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis. Hum Pathol 1996; 27 (1): 35–41. Misawa K, Kumagai T, Shimuzu T, et al. A new histological procedure for re-evaluation of the serological test for Helicobacter pylori. Eur J Clin Microbiol Infect Dis 1998; 17: 14–19. Kindermann A, Demmelmair H, Koletzko B, Krauss-Etschmann S, Wiebecke B, Koletzko S. Influence of age on 13C-urea breath test results in children. J Pediatr Gastroenterol Nutr 2000; 30: 85–91.
A check on limiting multiple births Sir—As Ian Craft and colleagues (March 25, p 1103)1 indicate, the guidelines of the Royal College of Obstetricians and Gynaecologists recommend that in all women under 40 years undergoing invitro fertilisation, no more than two embryos should be transferred. The purpose of this recommendation, as Craft and colleagues concede, is to reduce multiple, and particularly, triplet births. They quote statistics from three units—Aberdeen, Hammersmith, and their own—but fail to indicate that during the past 2 years, each of the first two units had generated only one triplet birth each, while in their own unit nine triplet births had been recorded, despite
1999
Authors’ reply Sir—We would be the first to admit that our study was quite complex and in the space allowed it was not possible to include data on speciality needs. The issue of separating general and speciality-based beds is not as simple as it first might seem. In our area all the major critical-care specialities are provided for within the study boundary, we nevertheless made efforts to identify those patients with local postcodes being treated in units elsewhere. Since individual units may be under more or less pressure it is not appropriate simply to remove specialist beds from the analysis. The only sensible method of assessing general and specialist critical-care-bed requirement is to base it on the population served regardless of where patients may be treated. Patients considered appropriate for treatment in coronary-care units accounted for 40% of total highdependency-unit bed needs. When patients with burns or those treated in cardiac surgical, thoracic surgical, and neurosurgical units are excluded our results show that for a population of 500 000 people the general intensivecare-unit average daily bed requirement is 15·97 (23 to meet needs on 95% of occasions) and the figures for high-dependency-unit are 39·57 (52) or 23·63 (34), if patients on the coronary-care units are excluded. The criticism that critical-care bed need should be based on an individual hospital rather than the population it serves is a simplistic and erroneous solution to a complex problem. The problem lies in the fact that hospitals do not have fixed catchment areas. Indeed, different services or specialties within a hospital will have different illdefined catchment areas. Intensivists around the UK will recognise the all too frequent occurrence of patients from within the catchment area having to be transferred elsewhere because of the lack of hospital beds, or the reciprocal arrangement. It is extremely unlikely that individual hospitals will be provided with the resources to support all intensive-care eventualities. Local hospitals share an inter-dependency, and so planning for adequate critical-care facilities should take this into account. Table 4 of our paper showed the calculation of bed needs by individual hospitals; if an individual hospital approach is followed the bed requirements (and costs) are substantially higher. We do not
1998
suggest that it is desirable to collect patients into one very large unit, we merely point out that to do so would require fewer beds. Our population-based approach indicates a large shortfall of adult critical-care beds, which will require a substantial injection of money to address. We are aware of the disquiet our study has produced in those responsible for financing the UK National Health System. Whatever the chances are for funding the bed requirements indicated by the population approach, we believe that this approach is the correct one. *Ronan Lyons, Ed Major Welsh Combined Centres for Public Health, University of Wales College of Medicine, Swansea SA1 1LT, UK; and Intensive Therapy Unit, Morriston Hospital, Morriston, Swansea. (e-mail: [email protected])
Thus in western countries, H pylori transmission seems not to be all “child’s play”, and extrapolation of Goodman and Correa’s analysis to western populations may not be justified and misleading when targeting further research strategies and preventive approaches. We also find that mother-tochild transmission may be less efficient if the mother smokes, an observation which could indicate an oral-oral transmission pathway.5 This pathway, might not be so relevant in a developing country where a faecal-oral pathway or other extrafamilial sources might predominate. *Dietrich Rothenbacher, Günter Bode, Hermann Brenner Department of Epidemiology, University of Ulm, D-89081 Ulm, Germany 1
2
Helicobacter pylori among siblings Sir—Karen Goodman and Pelayo Correa (Jan 29, p 358),1 report an analysis of Helicobacter pylori transmission in rural Colombia, concluding that there is a “major role for siblings in the transmission of H pylori infection”. Their analysis does not address a key question—who or what is responsible for the 63% infection prevalence in children with no sibling? H pylori prevalence in all children was 69%. Goodman and Correa could not address the role of parent-child transmission, which is difficult to assess if almost all parents are potentially infected (estimates reach over 90% in the population studied). Our work indicates that other transmission pathways may be important in western countries. Our three independent population-based studies in southern Germany in three consecutive years showed consistently that the parents, especially the mother, may have a key role in transmitting H pylori to the child. This was the case for an indirect measure of parental H pylori infection status such as history of peptic ulcer (almost everyone with peptic ulcer carries H pylori)2 or if the infection status of the parents was measured directly by 13C-urea breath test.3 Even if the infection status of both parents was adjusted for by multivariate methods, the mother clearly showed the strongest association with the infection status of her child.4 Another consistent finding was that number of siblings and birth order had only a minor role. In Germany, families are smaller than they are in Colombia.
3
4
5
Goodman KJ, Correa P. Transmission of Helicobacter pylori among siblings. Lancet 2000; 355: 358–62. Brenner H, Rothenbacher D, Bode G, Adler G. Parental history of gastric or duodenal ulcer and Helicobacter pylori infection among pre-school children: evidence of mother-infant transmission. BMJ 1998; 316: 556. Rothenbacher D, Bode G, Berg G, et al. Helicobacter pylori among pre-school children and their parents; evidence for parent-child transmission. J Infect Dis 1999; 179: 398–402. Rothenbacher D, Winkler M, Gonser T, Adler G, Brenner H. More evidence for major role of an infected mother in transmission of H pylori. Gut 1999; 45 (suppl III): A44. Brenner H, Bode G, Adler G, Rothenbacher D. Does maternal smoking hinder mother-child transmission of Helicobacter pylori? Epidemiology 2000; 11: 71–75.
Sir—Karen Goodman and Pelayo Correa1 report on the transmission of Helicobacter pylori in 2–9-year-old children in southern Colombia. A positive 13C-urea breath test was better predicted by the number of older than of younger siblings and Goodman and Correa conclude that H pylori transmission from older to younger siblings is of major importance in this population. The breath test, although it has shown excellent sensitivity and specificity in other paediatric studies, mostly in school-age children, has not been validated against invasive methods in infants, toddlers, and pre-school children. We have studied a standardised breath test in 1499 children. The protocol included a fast of at least 4 h, ingestion of 75 mg 13C urea dissolved in apple juice (pH 3·4), breath sampling before and 15 and 30 min after tracer ingestion, and a cut-off of 肁5%o for a positive test result.2 Compared with biopsy-proven H pylori status, specificity was 98% in 96 children >6 years of age but only 88% in 53 younger children. Sensitivity was 100%, independent of age.
THE LANCET • Vol 355 • June 3, 2000
CORRESPONDENCE
We now have breath-test results in 85 children under 6 years of age with biopsy-confirmed H pylori status (culture, histology, rapid urease test). All 16 H pylori infected children had changes from baseline (DOB) values above 5 per 1000 at 15 min (range 22–80) and at 30 min (range 23–82). However, eight of 69 non-infected children had a false-positive test (range 5·0–20·2 per 1000). Thus, although the test gave excellent results in school-aged children2 one-third of positive results in children below 6 years of age were false positive. A similar false-positive rate in young children has been reported by Imrie and colleagues.3 In 18 infants (mean age 12·8 months, SD 6·6) undergoing endoscopy, a test protocol found to be 100% sensitive and 97% specific in a previous study of 88 children of mean age 10·6 years (SD 4·2). The breath test was false positive in 55% at 20 min and in 18% at 30 min. The higher rate of false-positive results in younger children may lead to findings in older children being misinterpreted as a decrease in H pylori prevalence or a spontaneous clearance of the infection within the first years of life, a conclusion in longitudinal and cross-sectional studies.4,5 Goodman and Correa’s test protocol was unusual in that they gave 2·5 mg/kg 13 C-urea diluted in a glucose solution after a test meal of bread and butter; breath samples were taken before and 20 and 40 min after the tracer; and the cutoff was 6 per 1000. This protocol has never been validated against invasive methods, and if it yields the same age dependency of DOB values that we found, with more false-positive results in younger children, some of Goodman and Correa’s findings may be explained by this systematic error. Diagnostic tests used for clinical and epidemological purposes should be validated in the population in which they are applied. *Sibylle Koletzko, Hans Demmelmair, Angelika Kindermann Kinderpoliklinik im Dr. v. Haunerschen Kinderspital, D-80336 München, Germany 1
2
3
4
Goodman KJ, Correa P. Transmission of Helicobacter pylori among siblings. Lancet 2000; 355: 358–61. Kindermann A, Demmelmair H, Koletzko B, Krauss-Etschmann S, Wiebecke B, Koletzko S. Influence of age on 13C-urea breath test results in children. J Pediatr Gastroenterol Nutr 2000; 30: 85–91. Imrie C, Rowland M, Bourke B, Drumm B. Low specificity of 13C-urea breath testing in young children. Gut 1999; 45 (suppl V): A71 (abstr). Kehrt R, Becker M, Brosicke H, Kruger N, Helge H. Prevalence of Helicobacter pylori infection in Nicaraguan children with persistent diarrhea, diagnosed by the 14C-urea breath test. J Pediatr Gastroenterol Nutr 1997; 25: 84–88.
THE LANCET • Vol 355 • June 3, 2000
5
Klein PD, Gilman RH, Leon BR, Diaz F, Smith EO, Graham DY. The epidemiology of Helicobacter pylori in Peruvian children between 6 and 30 months of age. Am J Gastroenterol 1994; 89: 2196–200.
Author’s reply Sir—We agree that the role of siblings in Helicobacter pylori transmission may depend on population characteristics, as suggested by published studies we summarised.1 We presented data on children with no sibling aged 2–9 years. Only 9% of our study population had no sibling of any age, and 53% of them were infected, possibly, as with many childhood infections, by children they interacted with outside the home. Among the Colombian children, for the age groups 2–4, 5–7, and 8–9 years, the respective prevalences were 21%, 67%, and 85% among those without siblings in contrast with 61%, 75%, and 82% among children with siblings. Thus, those without siblings appear to become infected at older ages, a pattern that does not suggest frequent parent-child transmission. Dietrich Rothenbacher and colleagues mention studies showing concordant infection status in parents and 5-8-year-old children but this is weak evidence of parent-child transmission. A study that followed 67 Belgian infants of H pylori positive mothers, found only one who was positive by urea breath test at 12–15 months of age.2 Inadequate validation of the breath test in young children is a crucial problem. However, validation against biopsy-based diagnoses does not resolve all difficulties. Biopsy sampling may miss patchy or recent infection, and methods used to identify H pylori in biopsy material are not error-free.3,4 Against biopsy-based diagnosis, reduced breathtest specificity is compatible with reduced sensitivity of biopsy-based methods. The breath test may even be the more accurate method, picking up infections missed by biopsy sampling. Young children may have recent and sparse colonisation so that biopsy-based methods may be especially insensitive in young children. Most of the family-composition attributes we examined are not related to age, so the results we reported are not likely due to differential specificity by age. Even for age-related factors, a specificity of 88% among younger children would not substantially alter the effects we observed. Although a breath test with such specificity has a positive predictive value of 67% in German gastroenterology patients under age 6, in whom the observed prevalence is 19%, the positive predictive value for the same specificity is over 90% in the Colombian
2-5-year-olds, in whom the observed prevalence is 61%. The data discussed by Sibylle Koletzko and colleagues have limited statistical power to detect a difference in specificity by age (95% CI for 88% [61/69] is 0·78–0·95 while for 98% [45/46]5 it is 0·88–1·0; p=0·14). In our population, older children were about as likely as younger children to have lowpositive breath-test values (14% of positive 2-5-year-olds and 13% of positive 6-9-year-olds had delta-overbaseline values <20 per 1000). Validating the breath test in every epidemiologic study population may be desirable but the accuracy of the test in children being investigated for gastrointestinal symptoms may not apply to healthy children. For populationbased studies, a valid and feasible gold standard is lacking. *Karen J Goodman, Pelayo Correa *School of Public Health, University of TexasHouston Health Science Center, PO Box 20186, Houston, TX 77225, USA; and Department of Pathology, Louisiana State University Medical Center, 1901 Perdido St, New Orleans, LA 70112, USA 1
2
3
4
5
Goodman KJ, Correa P. Helicobacter pylori transmission among siblings. Lancet 2000; 355: 358–62. Blecker U, Lanciers S, Keppens E, Vandenplas Y. Evolution of Helicobacter pylori positivity in infants born from positive mothers. J Pediatr Gastroenterol Nutr 1994; 19: 87–90. El-Zimaity HMT, Graham DY, Al-Assi MT, et al. Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis. Hum Pathol 1996; 27 (1): 35–41. Misawa K, Kumagai T, Shimuzu T, et al. A new histological procedure for re-evaluation of the serological test for Helicobacter pylori. Eur J Clin Microbiol Infect Dis 1998; 17: 14–19. Kindermann A, Demmelmair H, Koletzko B, Krauss-Etschmann S, Wiebecke B, Koletzko S. Influence of age on 13C-urea breath test results in children. J Pediatr Gastroenterol Nutr 2000; 30: 85–91.
A check on limiting multiple births Sir—As Ian Craft and colleagues (March 25, p 1103)1 indicate, the guidelines of the Royal College of Obstetricians and Gynaecologists recommend that in all women under 40 years undergoing invitro fertilisation, no more than two embryos should be transferred. The purpose of this recommendation, as Craft and colleagues concede, is to reduce multiple, and particularly, triplet births. They quote statistics from three units—Aberdeen, Hammersmith, and their own—but fail to indicate that during the past 2 years, each of the first two units had generated only one triplet birth each, while in their own unit nine triplet births had been recorded, despite
1999