- Email: [email protected]
Recovery of failing liver after auxiliary heterotopic transplantation
1156
family history of anencephaly. Selective termination was decided complications, such as acute polyhydramnois or premature delivery due to the abnormal fetus. This was done at 19 weeks by intracardiac injection of sterile air.1 At the same procedure blood from the malformed fetus and amniotic fluid from the normal fetus were sampled for karyotyping; both were normal. The remainder of the pregnancy was uneventful, and
no
on, in view of the risk of obstetric
normal healthy baby was delivered at 39 weeks. A 30-year-old primigravida had a quadruplet pregnancy. A transvaginal scan revealed no anomaly of the four embryos, all in separate sacs. A twin pregnancy was achieved as in the first case. At 17 weeks a scan revealed isolated anencephaly-like malformation of one twin and selective feticide was done as previously. No family history of anencephaly was noted. Karytypes of both fetuses were normal. The pregnancy was complicated by rupture of membranes at 32 weeks and the preterm delivery of a baby, who is now well. In neither case did examination of the placenta after delivery allow recognition of the reduced products of conception because of maceration. The obstetric outcome after pregnancy reduction in the first trimester is often complicated.z°3 Our two cases suggest that remaining embryos can be damaged by pregnancy reduction. Possible explanations include: (a) an adverse effect of the saline solution, which may have gained access to the other embryos despite the muiltizygosity; and (b) a fetal malformation present before reduction which could not be demonstrated by earlier scans’ - however, we had used transvaginal scanning, which permits accurate examination of embryo morphology at this stage of gestation. There is also the possibility of cerebral disease in a surviving twin caused by the reduced twin; this has been described where one twin dies at a late stage of gestation. 6 We suggest use of potassium chloride solution as lethal agent rather than hypertonic saline since no fetal malformation after reduction by potassium chloride has been reported. Patients must be told that the outcome of reduced pregnancies is unpredictable, and ultrasound scans of the surviving embryos should be done monthly. Data on malformations and embryo reduction should be collected so that the possible role of these procedures in fetal malformations can be defined.
FETAL LOSSES FOUND AT THE DIFFERENT STAGES OF CVS FOLLOW-UP
a
P. BOULOT B. HEDON F. DESCHAMPS F. LAFFARGUE J. L. VIALA C. HUMEAU F. ARNAL
Fetology Centre, Department of Obstetrics and Gynaecology, and In Vitro Fertilisation Unit, 34059 Montpellier, France
P, Deschamps F, Galand B, et al. Terminaison selective des grossesses gemellaires bi-amniotiques a 20 semaines d’amenorrhée pour malformation foetale: à propos de deux cas realises avec succès. Pres Méd 1989; 18: 494-95. 2. Berkowitz RL, Lynch L, Chitkara U, Wilkins IA, Mehalek KE, Alvarez E. Selective reduction of multifetal pregnancies in the first trimester. N Engl J Med 1988; 318: 1. Boulot
1043-47. 3.
Wapner RJ, Davis GH, Johnson A, et al. Selective reduction of multiple pregnancies.
Lancet 1990; 335: 90-93. 4. Goldstein RB, Filly RA, Callen PW. Sonography of anencephaly: pitfalls in early pregnancy. J Clin Ultrasound 1989; 17: 397-102. 5. Shalev J, Frenkel Y, Goldenberg M, et al. Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures. Fert Steril 1989; 52: 416-20. 6. Dudley DK, D’Alton ME. Single fetal death in twin gestation. Semin Perinatol 1986; 10: 65-72.
in assessing fetal losses after chorion villus sampling
Complete follow-up
SIR,-Losses in follow-up are a source of bias in any prospective study. Unfortunately, in most studies of fetal losses attributable to chorion villus sampling (CVS) follow-up of pregnancy outcome has been less than 100%. Coordination of prenatal diagnosis by the Victorian Clinical Genetics Services (VCGS) is possible because of notification of all procedures by participating obstetricians. A three-stage follow-up is then undertaken. The first stage yields data on most
pregnancy outcomes These are notified
gestation).
(ie, birth
routinely
after 20 weeks’ the perinatal data
at or
to
collection unit (PDCU). When birth outcomes are not received by the PDCU, a stage 2 is carried out by the VCGS, by writing to the doctor looking after the pregnancy. The third stage involves sending another letter to doctors still not responding, and this may have to be followed with a telephone call to persistent non-
responders. Data for 1986 and 1987 are shown in the table. Transcervical and transabdominal CVS have not been separated. No attempt is made here to estimate attributable loss rates. In 1986,12% of pregnancy outcomes required stage 3 follow-up. The fetal loss rate doubled when outcome information on these last pregnancies was obtained. In 1987, there were only 8% of pregnancy outcomes in the stage 3 follow-up, but again it was in this group that a significant number of losses were found. The total loss rate was 2-3% rather than 1-0% as first recorded. The 1988 outcomes, on 518 CVS monitored pregnancies, have been collected more easily as doctors now realise the importance of notification. There was a small group lost to follow-up and, again, additional fetal losses (spontaneous and induced) have been found when these outcomes were finally traced. This follow-up is not yet complete, with results from interstate and overseas outstanding, The total loss rate for 1988, with 2% of outcomes missing, is 37%. The effort required to obtain information on every pregnancy outcome is substantial, and different study centres will have different sources of outcome data, some more efficient and complete than others. Whatever the method of follow-up, it will be amongst those outcomes most difficult to trace that a significant proportion of losses is to be found. Studies that do not achieve 100% follow-up will underestimate the fetal loss rate. Murdoch Institute, Royal Children’s Hospital, Parkville, 3052 Victoria, Australia Perinatal Data Unit, Health Department, Victoria
JANE HALLIDAY LESLIE SHEFFIELD DAVID DANKS
JUDITH LUMLEY
1. Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Mulocentre randomised clinical tnal of chorion villus sampling and amniocentesis. Lancet 1989; i: 1-6. 2. Brambati B, Lanzani A, Tului L. Transabdominal and transcervical chononic villus sampling: efficiency and risk evaluation of 2,411 cases. Am J Med Genet 1990; 35: 160-64.
Recovery of failing liver after auxiliary heterotopic transplantation SIR,-Orthotopic liver transplantation (OLT) has much improved the short-term outlook in acute hepatic failure.1 However, this treatment negates the potential recovery of the patient’s own liver. In theory, auxiliary heterotopic liver transplantation (HL T? should give the diseased liver a chance to regenerate so that immunosuppression can be discontinued, allowing the graft to atrophy once it is no longer required. However, successful auxiliary HLT in patients with acute liver failure has not yet been reported so far, though the procedure has been effective in animal models.3 The main causes of failure have probably been lack of room in the peritoneal cavity or inadequate splanchnic blood flow. Recently, we reported success with HLT in patients with chronic liver disease’ We now report a case of auxiliary HLT in a patient with subacute hepatic failure, followed by recovery of the patient’s own liver.
1157
The recovery of the diseased liver could be due to several factors. Cyclosporin and prednisone may have suppressed the original disease, a hepatotrophic factor synthesised in the graft could have stimulated regeneration (one such factor has been characterised); or, since ultrasonography during follow-up revealed flow through venous collaterals to the patient’s own liver, despite surgical interruption of the portal vein, portal hepatotrophic factors could have contributed to the restitution of liver function. Auxiliary HLT in acute liver failure may be difficult technically but it does seem able to provide the metabolic support essential for the recovery of diseased liver. In this patient immunosuppression has been reduced to the level customary in chronic active hepatitis (10 mg prednisone, 50 mg azathioprine daily), and further graft atrophy is awaited.
Diisopropyliminodiacetic acid, scintiscans. Left: on discharge (day 45) showing uptake, concentration, excretion exclusively in graft. Right: after 6 months, clearance mainly by host liver.
and
Departments of Internal Medicine, General Surgery, Pathology, Radiology, and Anaesthesiology,
University Hospital "Dijkzigt",
year-old woman was referred to our hospital because of progressive jaundice and ascites in January, 1989. After investigations the probable diagnosis was subacute hepatitis (autoimmune), and corticosteroid treatment was started, with non-resorbable antibiotics, lactulose, and diuretics. When hepatic encephalopathy developed with persistently high bilirubin and transaminase levels and worsening clotting factors HLT was decided on. The operation is described in detail elsewhere.4 A 35
Segments II and III of the donor liver were removed and the reduced liver was placed in the subhepatic region with anastomosis of the suprahepatic portion of the graft vena cava to the infrahepatic vena cava of the recipient. The graft portal vein was anastomosed end-to-side to that of the recipient and the hepatic artery was anastomosed to the infrarenal aorta. Drainage of bile was restored by an anastomosis of the common bileduct and a Roux-en-Y jejunum loop. The postoperative course was complicated by portal vein thromboses, necessitating thrombectomy of the portal vein to the graft with ligation of the portal vein to the host liver on day 1. During a second re-exploration, on day 25, a new end-to-end anastomosis was created between the portal veins; at that time the host liver showed severe liver cell necrosis without hepatocyte
regeneration. The patient was discharged on day 45 in good general conditon with a serum bilirubin level 24 ltmol/1 and normal clotting profile. Scintigraphy showed good uptake, concentration, and excretion of radioisotope, almost exclusively in the graft (figure). She was taking cyclosporin, prednisone, and acenocoumarol. 6 months after transplantation liver function was normal (table) but a scintiscan now revealed uptake, concentration, and excretion mainly in the patient’s own liver (figure). Biopsy of graft showed liver tissue with a normal architecture; the hepatocytes were small. The recipient’s own liver had few abnormalities, consisting of small irregular fibrous bands and some mononuclear infiltrate. Doppler sonography and angiography demonstrated preferential flow of portal blood to the patient’s own liver through venous collaterals. 1 year after transplantation liver function is still normal and a scan and biopsy confirm the findings at 6 months. LIVER FUNCTION TESTS BEFORE AND AFTER HETEROTOPIC LIVER TRANSPLANTATION
AP=albaline phosphatase. ACAT=alanine aminoprosferase ASPAT asparate amino transferase.
3015 G D Rotterdam,
Netherlands, and Department of Surgery, Municipal Hospital Rijnstate, Arnhem
H. J. METSELAAR E. J. HESSELINK S. DE RAVE F. J. W. TEN KATE J. S. LAMERIS T. H. N. GROENLAND C. B. REUVERS W. WEIMAR O. T. TERPSTRA S. W. SCHALM
J, Perkins JD, Gross JB, et al. Acute hepatic failure: the emerging role of orthotopic liver transplantation. Mayo Clin Proc 1989; 64: 424-28. 2. Editorial. Auxiliary liver transplantation. Lancet 1989; i: 523-24. 3. Terpstra OT, Reuvers CB, Schalm SW. Auxiliary heterotopic liver transplantation. Transplantation 1988; 45: 1003-07. 4. Terpstra OT, Schalm SW, Weimar W, et al. Auxiliary partial liver transplantation for end-stage chronic liver disease. N Engl J Med 1988; 319: 1507-11. 5. Nakamura T, Nishizawe T, Hogiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1987; 342: 440-43. 1. Rakela
Diarrhoea and catch-up growth SiR,—The further debate (March 10, p 599) about our paper on diarrhoea and malnutrition1 could be clarified by a reminder that the argument is whether diarrhoea control programmes reduce childhood malnutrition in the community in poor countries. There is no doubt that repeated attacks of diarrhoea can sometimes lead to a lower weight gain or even to weight loss. We are surprised by Dr Schorling and Dr Guerrant’s report from Brazil that children with several consecutive months of diarrhoea gained less weight than did those without diarrhoea. Diarrhoea, however, could be regarded as an important cause of malnutrition in this community only if a large proportion of children had a high prevalence of diarrhoea for several consecutive months. This proportion is not provided but it can be estimated, if we assume that diarrhoea episodes are not clustered and occur randomly among all children. In Schorling and Guerrant’s study, 25-4% of intervals had a high prevalence of diarrhoea and the proportionality of two and three consecutive high-diarrhoea intervals would be 0-065 (0-2542) and 0-016 (02543). The 312 g weight-gain deficit, in comparison with children who had no diarrhoea, accumulated over these six months by the 1 6% of children who went through three consecutive high-diarrhoea intervals, averaged on all children, would represent only 5 g per child. At 24 months a weight-for-age of 83 % of the NCHS median (the average in that community) is about 2080 g below the median. The contribution of repeated attacks of diarrhoea to the weight-forage deficit seems small in Brazil. Attempts to assess the nutritional impact of diarrhoea by comparing growth during short time intervals with and without diarrhoea cannot show whether catch-up growth occurs after diarrhoea (figure). Large differences in weight gain between short intervals may be due to a major effect of diarrhoea on growth during the interval with diarrhoea or to important catch-up growth after diarrhoea in the absence of long-term effect of diarrhoea on growth. When weight-gain differences between intervals with and without diarrhoeas are small this may mean either that diarrhoea does not affect growth or that there was no catch-up after diarrhoea. This ambiguity is clearly shown by Schorling and Guerrant’s graph which, they argue, suggests no catch-up after diarrhoea among
family history of anencephaly. Selective termination was decided complications, such as acute polyhydramnois or premature delivery due to the abnormal fetus. This was done at 19 weeks by intracardiac injection of sterile air.1 At the same procedure blood from the malformed fetus and amniotic fluid from the normal fetus were sampled for karyotyping; both were normal. The remainder of the pregnancy was uneventful, and
no
on, in view of the risk of obstetric
normal healthy baby was delivered at 39 weeks. A 30-year-old primigravida had a quadruplet pregnancy. A transvaginal scan revealed no anomaly of the four embryos, all in separate sacs. A twin pregnancy was achieved as in the first case. At 17 weeks a scan revealed isolated anencephaly-like malformation of one twin and selective feticide was done as previously. No family history of anencephaly was noted. Karytypes of both fetuses were normal. The pregnancy was complicated by rupture of membranes at 32 weeks and the preterm delivery of a baby, who is now well. In neither case did examination of the placenta after delivery allow recognition of the reduced products of conception because of maceration. The obstetric outcome after pregnancy reduction in the first trimester is often complicated.z°3 Our two cases suggest that remaining embryos can be damaged by pregnancy reduction. Possible explanations include: (a) an adverse effect of the saline solution, which may have gained access to the other embryos despite the muiltizygosity; and (b) a fetal malformation present before reduction which could not be demonstrated by earlier scans’ - however, we had used transvaginal scanning, which permits accurate examination of embryo morphology at this stage of gestation. There is also the possibility of cerebral disease in a surviving twin caused by the reduced twin; this has been described where one twin dies at a late stage of gestation. 6 We suggest use of potassium chloride solution as lethal agent rather than hypertonic saline since no fetal malformation after reduction by potassium chloride has been reported. Patients must be told that the outcome of reduced pregnancies is unpredictable, and ultrasound scans of the surviving embryos should be done monthly. Data on malformations and embryo reduction should be collected so that the possible role of these procedures in fetal malformations can be defined.
FETAL LOSSES FOUND AT THE DIFFERENT STAGES OF CVS FOLLOW-UP
a
P. BOULOT B. HEDON F. DESCHAMPS F. LAFFARGUE J. L. VIALA C. HUMEAU F. ARNAL
Fetology Centre, Department of Obstetrics and Gynaecology, and In Vitro Fertilisation Unit, 34059 Montpellier, France
P, Deschamps F, Galand B, et al. Terminaison selective des grossesses gemellaires bi-amniotiques a 20 semaines d’amenorrhée pour malformation foetale: à propos de deux cas realises avec succès. Pres Méd 1989; 18: 494-95. 2. Berkowitz RL, Lynch L, Chitkara U, Wilkins IA, Mehalek KE, Alvarez E. Selective reduction of multifetal pregnancies in the first trimester. N Engl J Med 1988; 318: 1. Boulot
1043-47. 3.
Wapner RJ, Davis GH, Johnson A, et al. Selective reduction of multiple pregnancies.
Lancet 1990; 335: 90-93. 4. Goldstein RB, Filly RA, Callen PW. Sonography of anencephaly: pitfalls in early pregnancy. J Clin Ultrasound 1989; 17: 397-102. 5. Shalev J, Frenkel Y, Goldenberg M, et al. Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures. Fert Steril 1989; 52: 416-20. 6. Dudley DK, D’Alton ME. Single fetal death in twin gestation. Semin Perinatol 1986; 10: 65-72.
in assessing fetal losses after chorion villus sampling
Complete follow-up
SIR,-Losses in follow-up are a source of bias in any prospective study. Unfortunately, in most studies of fetal losses attributable to chorion villus sampling (CVS) follow-up of pregnancy outcome has been less than 100%. Coordination of prenatal diagnosis by the Victorian Clinical Genetics Services (VCGS) is possible because of notification of all procedures by participating obstetricians. A three-stage follow-up is then undertaken. The first stage yields data on most
pregnancy outcomes These are notified
gestation).
(ie, birth
routinely
after 20 weeks’ the perinatal data
at or
to
collection unit (PDCU). When birth outcomes are not received by the PDCU, a stage 2 is carried out by the VCGS, by writing to the doctor looking after the pregnancy. The third stage involves sending another letter to doctors still not responding, and this may have to be followed with a telephone call to persistent non-
responders. Data for 1986 and 1987 are shown in the table. Transcervical and transabdominal CVS have not been separated. No attempt is made here to estimate attributable loss rates. In 1986,12% of pregnancy outcomes required stage 3 follow-up. The fetal loss rate doubled when outcome information on these last pregnancies was obtained. In 1987, there were only 8% of pregnancy outcomes in the stage 3 follow-up, but again it was in this group that a significant number of losses were found. The total loss rate was 2-3% rather than 1-0% as first recorded. The 1988 outcomes, on 518 CVS monitored pregnancies, have been collected more easily as doctors now realise the importance of notification. There was a small group lost to follow-up and, again, additional fetal losses (spontaneous and induced) have been found when these outcomes were finally traced. This follow-up is not yet complete, with results from interstate and overseas outstanding, The total loss rate for 1988, with 2% of outcomes missing, is 37%. The effort required to obtain information on every pregnancy outcome is substantial, and different study centres will have different sources of outcome data, some more efficient and complete than others. Whatever the method of follow-up, it will be amongst those outcomes most difficult to trace that a significant proportion of losses is to be found. Studies that do not achieve 100% follow-up will underestimate the fetal loss rate. Murdoch Institute, Royal Children’s Hospital, Parkville, 3052 Victoria, Australia Perinatal Data Unit, Health Department, Victoria
JANE HALLIDAY LESLIE SHEFFIELD DAVID DANKS
JUDITH LUMLEY
1. Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Mulocentre randomised clinical tnal of chorion villus sampling and amniocentesis. Lancet 1989; i: 1-6. 2. Brambati B, Lanzani A, Tului L. Transabdominal and transcervical chononic villus sampling: efficiency and risk evaluation of 2,411 cases. Am J Med Genet 1990; 35: 160-64.
Recovery of failing liver after auxiliary heterotopic transplantation SIR,-Orthotopic liver transplantation (OLT) has much improved the short-term outlook in acute hepatic failure.1 However, this treatment negates the potential recovery of the patient’s own liver. In theory, auxiliary heterotopic liver transplantation (HL T? should give the diseased liver a chance to regenerate so that immunosuppression can be discontinued, allowing the graft to atrophy once it is no longer required. However, successful auxiliary HLT in patients with acute liver failure has not yet been reported so far, though the procedure has been effective in animal models.3 The main causes of failure have probably been lack of room in the peritoneal cavity or inadequate splanchnic blood flow. Recently, we reported success with HLT in patients with chronic liver disease’ We now report a case of auxiliary HLT in a patient with subacute hepatic failure, followed by recovery of the patient’s own liver.
1157
The recovery of the diseased liver could be due to several factors. Cyclosporin and prednisone may have suppressed the original disease, a hepatotrophic factor synthesised in the graft could have stimulated regeneration (one such factor has been characterised); or, since ultrasonography during follow-up revealed flow through venous collaterals to the patient’s own liver, despite surgical interruption of the portal vein, portal hepatotrophic factors could have contributed to the restitution of liver function. Auxiliary HLT in acute liver failure may be difficult technically but it does seem able to provide the metabolic support essential for the recovery of diseased liver. In this patient immunosuppression has been reduced to the level customary in chronic active hepatitis (10 mg prednisone, 50 mg azathioprine daily), and further graft atrophy is awaited.
Diisopropyliminodiacetic acid, scintiscans. Left: on discharge (day 45) showing uptake, concentration, excretion exclusively in graft. Right: after 6 months, clearance mainly by host liver.
and
Departments of Internal Medicine, General Surgery, Pathology, Radiology, and Anaesthesiology,
University Hospital "Dijkzigt",
year-old woman was referred to our hospital because of progressive jaundice and ascites in January, 1989. After investigations the probable diagnosis was subacute hepatitis (autoimmune), and corticosteroid treatment was started, with non-resorbable antibiotics, lactulose, and diuretics. When hepatic encephalopathy developed with persistently high bilirubin and transaminase levels and worsening clotting factors HLT was decided on. The operation is described in detail elsewhere.4 A 35
Segments II and III of the donor liver were removed and the reduced liver was placed in the subhepatic region with anastomosis of the suprahepatic portion of the graft vena cava to the infrahepatic vena cava of the recipient. The graft portal vein was anastomosed end-to-side to that of the recipient and the hepatic artery was anastomosed to the infrarenal aorta. Drainage of bile was restored by an anastomosis of the common bileduct and a Roux-en-Y jejunum loop. The postoperative course was complicated by portal vein thromboses, necessitating thrombectomy of the portal vein to the graft with ligation of the portal vein to the host liver on day 1. During a second re-exploration, on day 25, a new end-to-end anastomosis was created between the portal veins; at that time the host liver showed severe liver cell necrosis without hepatocyte
regeneration. The patient was discharged on day 45 in good general conditon with a serum bilirubin level 24 ltmol/1 and normal clotting profile. Scintigraphy showed good uptake, concentration, and excretion of radioisotope, almost exclusively in the graft (figure). She was taking cyclosporin, prednisone, and acenocoumarol. 6 months after transplantation liver function was normal (table) but a scintiscan now revealed uptake, concentration, and excretion mainly in the patient’s own liver (figure). Biopsy of graft showed liver tissue with a normal architecture; the hepatocytes were small. The recipient’s own liver had few abnormalities, consisting of small irregular fibrous bands and some mononuclear infiltrate. Doppler sonography and angiography demonstrated preferential flow of portal blood to the patient’s own liver through venous collaterals. 1 year after transplantation liver function is still normal and a scan and biopsy confirm the findings at 6 months. LIVER FUNCTION TESTS BEFORE AND AFTER HETEROTOPIC LIVER TRANSPLANTATION
AP=albaline phosphatase. ACAT=alanine aminoprosferase ASPAT asparate amino transferase.
3015 G D Rotterdam,
Netherlands, and Department of Surgery, Municipal Hospital Rijnstate, Arnhem
H. J. METSELAAR E. J. HESSELINK S. DE RAVE F. J. W. TEN KATE J. S. LAMERIS T. H. N. GROENLAND C. B. REUVERS W. WEIMAR O. T. TERPSTRA S. W. SCHALM
J, Perkins JD, Gross JB, et al. Acute hepatic failure: the emerging role of orthotopic liver transplantation. Mayo Clin Proc 1989; 64: 424-28. 2. Editorial. Auxiliary liver transplantation. Lancet 1989; i: 523-24. 3. Terpstra OT, Reuvers CB, Schalm SW. Auxiliary heterotopic liver transplantation. Transplantation 1988; 45: 1003-07. 4. Terpstra OT, Schalm SW, Weimar W, et al. Auxiliary partial liver transplantation for end-stage chronic liver disease. N Engl J Med 1988; 319: 1507-11. 5. Nakamura T, Nishizawe T, Hogiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1987; 342: 440-43. 1. Rakela
Diarrhoea and catch-up growth SiR,—The further debate (March 10, p 599) about our paper on diarrhoea and malnutrition1 could be clarified by a reminder that the argument is whether diarrhoea control programmes reduce childhood malnutrition in the community in poor countries. There is no doubt that repeated attacks of diarrhoea can sometimes lead to a lower weight gain or even to weight loss. We are surprised by Dr Schorling and Dr Guerrant’s report from Brazil that children with several consecutive months of diarrhoea gained less weight than did those without diarrhoea. Diarrhoea, however, could be regarded as an important cause of malnutrition in this community only if a large proportion of children had a high prevalence of diarrhoea for several consecutive months. This proportion is not provided but it can be estimated, if we assume that diarrhoea episodes are not clustered and occur randomly among all children. In Schorling and Guerrant’s study, 25-4% of intervals had a high prevalence of diarrhoea and the proportionality of two and three consecutive high-diarrhoea intervals would be 0-065 (0-2542) and 0-016 (02543). The 312 g weight-gain deficit, in comparison with children who had no diarrhoea, accumulated over these six months by the 1 6% of children who went through three consecutive high-diarrhoea intervals, averaged on all children, would represent only 5 g per child. At 24 months a weight-for-age of 83 % of the NCHS median (the average in that community) is about 2080 g below the median. The contribution of repeated attacks of diarrhoea to the weight-forage deficit seems small in Brazil. Attempts to assess the nutritional impact of diarrhoea by comparing growth during short time intervals with and without diarrhoea cannot show whether catch-up growth occurs after diarrhoea (figure). Large differences in weight gain between short intervals may be due to a major effect of diarrhoea on growth during the interval with diarrhoea or to important catch-up growth after diarrhoea in the absence of long-term effect of diarrhoea on growth. When weight-gain differences between intervals with and without diarrhoeas are small this may mean either that diarrhoea does not affect growth or that there was no catch-up after diarrhoea. This ambiguity is clearly shown by Schorling and Guerrant’s graph which, they argue, suggests no catch-up after diarrhoea among