- Email: [email protected]
IN-UTERO PLATELET TRANSFUSION FOR ALLOIMMUNE THROMBOCYTOPENIA
1307 of delusions is moulded by the spirit of the report describes the delusional belief of being infected with HIV.1 Delusional beliefs may also influence the reporting of child sexual abuse. We have encountered three patients who believed themselves responsible for abuse. Two men were convinced they were guilty of gross acts of abuse, and this belief was the main factor underlying their presentation. One was diagnosed schizophrenic and the second had alcoholic hallucinosis. No evidence could be found to substantiate their beliefs and they disappeared after treatment with neuroleptic medication. The third patient believed that she had uncovered a string of child abuse cases in her neighbourhood, for which she held herself ultimately responsible. Investigations were initiated by the local social services department. The woman had a long history of paranoid psychosis. A further six patients believed, whilst ill, that they had been sexually abused as children. Five were women, and the ages of the six ranged from 19 to 51. Two were schizophrenic, three were depressed, and one had a bipolar affective disorder. Their beliefs disappeared upon recovery from illness. Concerns on television and in newspapers can influence fears and beliefs in people in states of mental and emotional turmoil. It might be argued that the "disclosure" of abuse in our patients represented the release of repressed experience under the disinhibition of illness. However, it could equally well be argued that the patients’ statements represented the release of primitive fantasies, or simply constituted a form of retrospective rationalisation. There have been several surveys and reports suggesting links between childhood sexual abuse and psychiatric illness.24> They need to be interpreted with caution.
SiR,—The
times, and
content
a recent
Department of Psychological Medicine, Royal Free Hospital London NW3 2QG
DAVID V. JAMES SUNNY COLLINGS
Mahoney SL, Cavenar JO. Anew and timely delusion: the complaint of having AIDS. Am J Psychiatry 1988, 145: 1130-32. 2. Mullen PE, Romans-Clarkson SE, Walton VA, Herbison GP. Impact of sexual and physical abuse on women’s mental health. Lancet 1988; i. 841-45. 3 Rippere V. Childhood sexual abuse and women’s health Lancet 1988; i: 1106-07. 4 Beck JC, van der Kolk B. Reports of childhood incest and current behaviour of chronically hospitalised psychotic women. Am J Psychiatry 1987; 144: 1474-76 5. Jacobsen A, Richardson B. Assault experiences of 100 psychiatric in-patients; evidence of the need for routine enquiry. Am J Psychiatry 1987; 144: 908-13. 6 Bryer JB, Nelson BA, Miller JB, Krol PA. Childhood sexual and physical abuse as factors in adult psychiatric illness. Am J Psychiatry 1987; 144: 1426-30. 1
ARE IMMUNOLOGICAL MARKERS OF GLUTEN-SENSITIVE ENTEROPATHY DETECTABLE IN IgA NEPHROPATHY?
SIR,-IgA immune complexes have been implicated in the development of idiopathic IgA nephropathy. A role for dietary antigens, especially gluten, in the production of IgA-containing circulating immune complexes has been proposed,’ and anti-gliadin antibodies in IgA glomerulonephritis have been reported.2-4 Lagrue and co-workers2 found a 70% frequency of anti-gliadin antibodies in IgA glomerulonephritis by single-step ELISA and a 100% frequency by a more sensitive two-step ELISA. In contrast Fomasieri et als reported that only 30% of patients with IgA glomerulonephritis had anti-gliadin antibodies and suggested the coexistence of coeliac disease and IgA glomerulonephritis. These discrepancies were attributed to differences in methodology. Rodriguez-Soriano et a16 corroborated the findings of Fomasieri et al. Lagrue’s group2,7 showed that IgA-class anti-gliadin antibodies are not associated with latent coeliac disease in IgA nephropathy since reticulin and endomysial antibodies, markers of glutensensitive enteropathy, were absent. We have reported the specificity and sensitivity of IgA-class endomysial antibodies and a comparison with reticulin and gliadin antibodies.8-9 We have now examined sera from 23 patients with IgA glomerulonephritis for anti-gliadin antibodies (DIG-ELISA’°) and for IgA class reticulin and endomysial antibodies (indirect immunofluorescence’1). Anti-gliadin antibodies were found in 3 patients whereas reticulin and endomysial antibodies were not found in any
case.
These results indicate
a
lack of association
between IgA glomerulonephritis and coeliac disease in the group studied. The presence of anti-gliadin antibodies without reticulin and endomysial antibodies raises a question about the specificity of anti-gliadin antibodies for gluten-sensitive enteropathy. Antigliadin antibodies are not disease-specific markers of coeliac disease,12 occurring not only in coeliac disease but also in other inflammatory bowel disease, bullous diseases, and even in 10-20% of normal subjects. The presence of anti-gliadin antibodies in some patients with IgA glomerulonephritis is thus not surprising. IgA-class endomysial antibodies, which are specific and sensitive markers of gluten-sensitive enteropathy, should be tested for in cases in which gluten-associated enteropathy is suspected. Departments of Microbiology and Dermatology, University at Buffalo, State University of New York, Buffalo, New York 14214, USA; and Departments of Nephrology and Dermatology, Medical Academy, Warsaw, Poland 1.
VIJAY KUMAR MARIA SIENIAWSKA ERNST H. BEUTNER TADEUSZ P. CHORZELSKI
Emancipator S, Gallo G, Lamm M. IgA nephropathy: perspectives on pathogenesis and classification Clin Nephrol 1985; 24: 161-79.
2. Rostoker G, Laurent J, André C, Cholin S, Lagrue G. High levels of IgA antigliadin antibodies in patients who have IgA mesangial glomerulonephritis but not coeliac disease. Lancet 1988; i: 356-57. 3. Laurent J, Branellec A, Heslan JM, et al. An increase in circulating IgA antibodies to gliadin in IgA mesangial glomerulonephritis. Am J Nephrol 1987, 7: 178-83. 4. Coppo R, Basolo B, Rollino C, et al. Dietary gluten and primary IgA nephropathy. N Engl J Med 1986; 315: 1167-68. 5. Fornasieri A, Sinico RA, Maldifassi P, et al. IgA-antigliadin antibodies in IgA mesangial nephropathy (Berger’s disease). Br Med J 1987; 295: 78-80. 6. Rodriguez-Soriano J, Arrieta A, Vallo A, Sebastian MJ, Vitoria JC, Masdevall MD. IgA antigliadin antibodies in children with IgA mesangial glomerulonephritis. Lancet 1988; i: 1109-10. 7. Rostaker G, Andre C, Branellec A, et al. Lack of antireticulin and antiendomysium antibodies in patients with primary IgA nephropathy associated with IgA antibodies to gliadin. Kidney Int 1987; 32: 426 (abstr). 8. Kapuscinska A, Zalewski T, Chorzelski TP, et al. Disease specificity and dynamics of changes in IgA class anti-endomysial antibodies in celiac disease. J Pediatr Gastroenterol Nutr 1987; 6: 529-34. 9. Reunala T, Chorzelski TP, Viander M, et al. IgA anti-endomysial antibodies in dermatitis herpetiformis: correlation with jejunal morphology, gluten-free diet and
anti-gliadin antibodies Br J Dermatol 1987; 117: 185-91. 10. Kilander AF, Dotevall G, Fallstrom SP, et al. Evaluation of gliadin antibodies for detection of coeliac disease. Scand J Gastroenterol 1983; 18: 377-83 11. Kumar V, Hemedinger E, Chorzelski TP, et al. Reticulin and endomysial antibodies in bullous diseases: comparison of specificity and sensitivity. Arch Dermatol 1987; 123: 1179-82. 12. Kumar V, Jain N, Lemer A, et al. Comparative studies of different gliadin preparations m detecting anti-gliadin antibodies. J Pediatr Gastroenterol Nutr 1986; 5: 730-34.
IN-UTERO PLATELET TRANSFUSION FOR ALLOIMMUNE THROMBOCYTOPENIA
SiR,—Dr Nicolini and colleagues (Aug 28, p 506) describe management of a fetus with alloimmune thrombocytopenia by weekly in-utero platelet transfusions. We feel that this approach was too invasive since it involved seven percutaneous umbilical blood samplings and seven in-utero transfusions, and was followed by delivery of an infant who was 8 weeks premature. While these multiple procedures and the premature delivery did not lead to complications the risks were appreciable. This is especially true for in-utero transfusions, which prolong the time required for the needle to remain within an umbilical blood vessel. An alternative to this invasive approach is treatment of the mother with intravenous gammaglobulin (IVIG), which we have done in 7 mother/fetus pairs. The mothers had a previous pregnancy severely affected with neonatal alloimmune thrombocytopenia, in 2 cases, the previous fetus had had intracranial haemorrhage. Serial fetal platelet counts were measured by percutaneous umbilical blood sampling and the count increased in all cases (mean 70 x 109/1, median 43 x 10/1). Comparison of the treated fetuses with their affected untreated siblings showed a similar increase in platelet count at delivery in the treated infants and no haemorrhages occurred in the treated cases. Our approach eliminates the need for any in-utero transfusions and the number of percutaneous umbilical blood samplings was less than four.
1308 The degree of intervention required in a pregnancy subsequent to complicated by neonatal alloimmune thrombocytopenia depends not only upon the damage suffered by the previous fetus but also on whether the haemorrhage occurred antenatally. While antenatal haemorrhage is not rare,2 it is probably still true that in most of the damaged children, the haemorrhage is not antenatal but occurs with vaginal delivery. Another factor to be considered is whether the father is homozygous for the incompatible antigen (ie, P1A1) because if so, the fetus is virtually guaranteed to be at least as affected as the previous sibling. Also, Nicolini and colleagues claim that percutaneous umbilical blood sampling "seems unnecessary" at 20-22 weeks since the platelet count can fall at this time. This is true, but some fetuses will already have a very low platelet count by 20 weeks’ gestationl3and they are probably the ones at greatest risk for antenatal haemorrhage, which might occur before 26 weeks. If thrombocytopenia is found in mid-second trimester, then IVIG can be started early. Much basic information, such as the incidence of intracranial haemorrhage in infants with alloimmune thrombocytopenia, the percentage of such haemorrhages which occur antenatally, and the timing of these haemorrhages, is not well defined. No therapeutic approach is justified unless it does more good than harm and we believe that the risks to individual fetuses for antenatal haemorrhage should be better defined and therapy shown to be ineffective before subjecting the fetuses to numerous invasive antenatal manipulations. This accords with the view of Dr Daffos and
OBSERVED AND EXPECTED MORTALITY FROM LEUKAEMIAS
(OTHER THAN CHRONIC LYMPHOCYTIC LEUKAEMIA) IN FIVE
one
colleagues (Oct 15, p 910). Department of Pediatrics, Cornell Medical Center, and Department of Obstetrics, Mount Sinai Medical Center, New York, USA; and Southeast Wisconsin Blood Milwaukee, Wisconsin
J. BUSSEL R. BERKOWITZ
J. MCFARLAND Center,
L. LYNCH U. CHITKARA
1 Busseli JB, Bercowitz RL, McFarland JG,
Lynch L, Chitkara U Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319: 1374-78 2. Herman JH, Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage m alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8: 312-17. 3. Kaplan C, Daffos F, Forestier F, et al. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood 1988; 72: 340-43.
LEUKAEMIA NEAR PILGRIM NUCLEAR POWER PLANT, MASSACHUSETTS
SIR,-Clapp et all reported an increase in leukaemia incidence during 1982-84 in five Massachusetts coastal towns near the Pilgrim nuclear power plant, Plymouth. The known releases of radioactive effluents are too small (by several orders of magnitude) to account for the increase, but Clapp et al hypothesised "a mechanism by which airborne releases are contained in a coastal pattern". This meteorological theory did not explain how the increased rate of leukaemia was almost wholly concentrated among adult males. We have examined more recent data on Massachusetts towns to see if the increase in the five coastal towns has persisted. The new data cover 1985 and 1986. We excluded chronic lymphocytic leukaemia, which is thought not to be caused by radiation. For all leukaemia (apart from chronic lymphocytic) Clapp et al reported, for both genders and all ages, a 60% increase for 1982-84, with 27 cases observed and 16-9 expected based on the statewide rates. For 1985 and 1986, there were 6 cases with 11-8 expected based on the rates for the remainder of Massachusetts. Thus, there was a 49% deficit during the additional two-year period. The likelihood of observing the 6 cases can easily be compared for two hypotheses of interest-that the people in these five towns have a 60% risk of leukaemia (as Clapp et al reported), and the null hypothesis of no excess risk of leukaemia. The likelihood ratio (LR) for the alternative versus the null hypothesis, assuming a Poisson model, is: RRx - exp (RR-1) À, where RR is the multiplier of disease risk under the alternative hypothesis, x is the observed number of cases, and À is the number of cases expected under the null hypothesis. For the 6 observed cases, with RR =1.60 and=11-8, the likelihood ratio is 0-014. Thus, it is 71 times more probable that 6 cases would
MASSACHUSETTS
TOWNS,* 1969-86
Obs = observed cases, Exp = expected cases; SMR = standardised mortality ratio Exp); CI = confidence interval. *Duxbury, Kingston, Marshfield, Plymouth, and Scituate. tConfidence mtervals by exact (mid-P) method.
(Obs/
have been observed if the null hypothesis were correct than if RR =1-60. For the five-year period 1982-86 there were 33 cases, with 28-8 expected, for a standardised incidence ratio of 1’ 14 (95% confidence interval 0-79-1-61). Massachusetts has computerised mortality data back to 1969. The Pilgrim plant began operating in late 1972. The observed number of deaths and the number expected based on non-chronic leukaemia mortality rates in the remainder of Massachusetts are given in the table for each of four time periods since 1969. There was no excess in any time period. It seems that the transient excess of leukaemia incidence reported by Clapp et al was largely nullified by the more recent data. Furthermore, mortality data, available for earlier time periods than incidence data, indicate no historical record of excess leukaemia in these towns. It would be possible to embellish the meteorological hypothesis to postulate a time-localised effect of a one-time environmental exposure, but such an attempt would conflict with the wealth of data on the time for induction of leukaemia by radiation2 and still would not explain how the effect was limited to adult males. The finding of a small increase of leukaemia in a restricted age range, in one gender, in a few selected towns, for a short time period is better explained as a minor statistical fluctuation than as an effect of radioactive releases into the environment.
Epidemiology Resources Inc, Brookline, Massachusetts 02167, USA
CHARLES POOLE KENNETH J. ROTHMAN NANCY A. DREYER
Clapp RW, Cobb S, Chan CK, et al. Leukaemia near Massachusetts nuclear power plant. Lancet 1987; i: 1324-25 2. National Institutes of Health Ad Hoc Working Group to Develop Radioepidemiologic 1.
Tables. NIH Publ Report (85-2748).
IS IMPAIRED VISUAL DEVELOPMENT CAUSED BY PERINATAL HYPOXIA?
SIR,-Infants with a history of perinatal hypoxia are at risk of developmental disorders. Visual development after perinatal hypoxia has only been studied retrospectively.1 We describe visual development during the first 6 months of corrected age of infants with a well-documented history of perinatal hypoxia. 79 infants with a history of severe perinatal hypoxia on at least two criteria (abnormal fetal heart rate pattern, Apgar score less than 6 at 5 min, pH of umbilical arterial blood below 7 -20, or neonatal arterial p02 below 40 mm Hg) bom in 1986 and admitted within 24 h of birth were divided into three groups on gestational age. 10 died from perinatal hypoxia and 11did not attend for follow-up clinic, leaving 58 infants. The children were examined at corrected ages of 6, 13, and 26 weeks. Visual function was tested by use of behavioural techniques, with acuity cards2 and kinetic perimetry.3 Results were compared with normal values from our laboratory.3,4 Binocular optokinetic nystagmus (OKN) was elicited by moving a 105 x 40 cm paper covered with random dots slowly clockwise and counterclockwise in front of the infant. Ocular movements were observed. Normally, binocular OKN is symmetrical from birth onwards.5 Impaired visual acuity, visual field, and binocular OKN were detected in all three groups (table), especially in preterm infants (groups 1 and 2) with perinatal hypoxia (p < 001). The frequency of
SiR,—The
times, and
content
a recent
Department of Psychological Medicine, Royal Free Hospital London NW3 2QG
DAVID V. JAMES SUNNY COLLINGS
Mahoney SL, Cavenar JO. Anew and timely delusion: the complaint of having AIDS. Am J Psychiatry 1988, 145: 1130-32. 2. Mullen PE, Romans-Clarkson SE, Walton VA, Herbison GP. Impact of sexual and physical abuse on women’s mental health. Lancet 1988; i. 841-45. 3 Rippere V. Childhood sexual abuse and women’s health Lancet 1988; i: 1106-07. 4 Beck JC, van der Kolk B. Reports of childhood incest and current behaviour of chronically hospitalised psychotic women. Am J Psychiatry 1987; 144: 1474-76 5. Jacobsen A, Richardson B. Assault experiences of 100 psychiatric in-patients; evidence of the need for routine enquiry. Am J Psychiatry 1987; 144: 908-13. 6 Bryer JB, Nelson BA, Miller JB, Krol PA. Childhood sexual and physical abuse as factors in adult psychiatric illness. Am J Psychiatry 1987; 144: 1426-30. 1
ARE IMMUNOLOGICAL MARKERS OF GLUTEN-SENSITIVE ENTEROPATHY DETECTABLE IN IgA NEPHROPATHY?
SIR,-IgA immune complexes have been implicated in the development of idiopathic IgA nephropathy. A role for dietary antigens, especially gluten, in the production of IgA-containing circulating immune complexes has been proposed,’ and anti-gliadin antibodies in IgA glomerulonephritis have been reported.2-4 Lagrue and co-workers2 found a 70% frequency of anti-gliadin antibodies in IgA glomerulonephritis by single-step ELISA and a 100% frequency by a more sensitive two-step ELISA. In contrast Fomasieri et als reported that only 30% of patients with IgA glomerulonephritis had anti-gliadin antibodies and suggested the coexistence of coeliac disease and IgA glomerulonephritis. These discrepancies were attributed to differences in methodology. Rodriguez-Soriano et a16 corroborated the findings of Fomasieri et al. Lagrue’s group2,7 showed that IgA-class anti-gliadin antibodies are not associated with latent coeliac disease in IgA nephropathy since reticulin and endomysial antibodies, markers of glutensensitive enteropathy, were absent. We have reported the specificity and sensitivity of IgA-class endomysial antibodies and a comparison with reticulin and gliadin antibodies.8-9 We have now examined sera from 23 patients with IgA glomerulonephritis for anti-gliadin antibodies (DIG-ELISA’°) and for IgA class reticulin and endomysial antibodies (indirect immunofluorescence’1). Anti-gliadin antibodies were found in 3 patients whereas reticulin and endomysial antibodies were not found in any
case.
These results indicate
a
lack of association
between IgA glomerulonephritis and coeliac disease in the group studied. The presence of anti-gliadin antibodies without reticulin and endomysial antibodies raises a question about the specificity of anti-gliadin antibodies for gluten-sensitive enteropathy. Antigliadin antibodies are not disease-specific markers of coeliac disease,12 occurring not only in coeliac disease but also in other inflammatory bowel disease, bullous diseases, and even in 10-20% of normal subjects. The presence of anti-gliadin antibodies in some patients with IgA glomerulonephritis is thus not surprising. IgA-class endomysial antibodies, which are specific and sensitive markers of gluten-sensitive enteropathy, should be tested for in cases in which gluten-associated enteropathy is suspected. Departments of Microbiology and Dermatology, University at Buffalo, State University of New York, Buffalo, New York 14214, USA; and Departments of Nephrology and Dermatology, Medical Academy, Warsaw, Poland 1.
VIJAY KUMAR MARIA SIENIAWSKA ERNST H. BEUTNER TADEUSZ P. CHORZELSKI
Emancipator S, Gallo G, Lamm M. IgA nephropathy: perspectives on pathogenesis and classification Clin Nephrol 1985; 24: 161-79.
2. Rostoker G, Laurent J, André C, Cholin S, Lagrue G. High levels of IgA antigliadin antibodies in patients who have IgA mesangial glomerulonephritis but not coeliac disease. Lancet 1988; i: 356-57. 3. Laurent J, Branellec A, Heslan JM, et al. An increase in circulating IgA antibodies to gliadin in IgA mesangial glomerulonephritis. Am J Nephrol 1987, 7: 178-83. 4. Coppo R, Basolo B, Rollino C, et al. Dietary gluten and primary IgA nephropathy. N Engl J Med 1986; 315: 1167-68. 5. Fornasieri A, Sinico RA, Maldifassi P, et al. IgA-antigliadin antibodies in IgA mesangial nephropathy (Berger’s disease). Br Med J 1987; 295: 78-80. 6. Rodriguez-Soriano J, Arrieta A, Vallo A, Sebastian MJ, Vitoria JC, Masdevall MD. IgA antigliadin antibodies in children with IgA mesangial glomerulonephritis. Lancet 1988; i: 1109-10. 7. Rostaker G, Andre C, Branellec A, et al. Lack of antireticulin and antiendomysium antibodies in patients with primary IgA nephropathy associated with IgA antibodies to gliadin. Kidney Int 1987; 32: 426 (abstr). 8. Kapuscinska A, Zalewski T, Chorzelski TP, et al. Disease specificity and dynamics of changes in IgA class anti-endomysial antibodies in celiac disease. J Pediatr Gastroenterol Nutr 1987; 6: 529-34. 9. Reunala T, Chorzelski TP, Viander M, et al. IgA anti-endomysial antibodies in dermatitis herpetiformis: correlation with jejunal morphology, gluten-free diet and
anti-gliadin antibodies Br J Dermatol 1987; 117: 185-91. 10. Kilander AF, Dotevall G, Fallstrom SP, et al. Evaluation of gliadin antibodies for detection of coeliac disease. Scand J Gastroenterol 1983; 18: 377-83 11. Kumar V, Hemedinger E, Chorzelski TP, et al. Reticulin and endomysial antibodies in bullous diseases: comparison of specificity and sensitivity. Arch Dermatol 1987; 123: 1179-82. 12. Kumar V, Jain N, Lemer A, et al. Comparative studies of different gliadin preparations m detecting anti-gliadin antibodies. J Pediatr Gastroenterol Nutr 1986; 5: 730-34.
IN-UTERO PLATELET TRANSFUSION FOR ALLOIMMUNE THROMBOCYTOPENIA
SiR,—Dr Nicolini and colleagues (Aug 28, p 506) describe management of a fetus with alloimmune thrombocytopenia by weekly in-utero platelet transfusions. We feel that this approach was too invasive since it involved seven percutaneous umbilical blood samplings and seven in-utero transfusions, and was followed by delivery of an infant who was 8 weeks premature. While these multiple procedures and the premature delivery did not lead to complications the risks were appreciable. This is especially true for in-utero transfusions, which prolong the time required for the needle to remain within an umbilical blood vessel. An alternative to this invasive approach is treatment of the mother with intravenous gammaglobulin (IVIG), which we have done in 7 mother/fetus pairs. The mothers had a previous pregnancy severely affected with neonatal alloimmune thrombocytopenia, in 2 cases, the previous fetus had had intracranial haemorrhage. Serial fetal platelet counts were measured by percutaneous umbilical blood sampling and the count increased in all cases (mean 70 x 109/1, median 43 x 10/1). Comparison of the treated fetuses with their affected untreated siblings showed a similar increase in platelet count at delivery in the treated infants and no haemorrhages occurred in the treated cases. Our approach eliminates the need for any in-utero transfusions and the number of percutaneous umbilical blood samplings was less than four.
1308 The degree of intervention required in a pregnancy subsequent to complicated by neonatal alloimmune thrombocytopenia depends not only upon the damage suffered by the previous fetus but also on whether the haemorrhage occurred antenatally. While antenatal haemorrhage is not rare,2 it is probably still true that in most of the damaged children, the haemorrhage is not antenatal but occurs with vaginal delivery. Another factor to be considered is whether the father is homozygous for the incompatible antigen (ie, P1A1) because if so, the fetus is virtually guaranteed to be at least as affected as the previous sibling. Also, Nicolini and colleagues claim that percutaneous umbilical blood sampling "seems unnecessary" at 20-22 weeks since the platelet count can fall at this time. This is true, but some fetuses will already have a very low platelet count by 20 weeks’ gestationl3and they are probably the ones at greatest risk for antenatal haemorrhage, which might occur before 26 weeks. If thrombocytopenia is found in mid-second trimester, then IVIG can be started early. Much basic information, such as the incidence of intracranial haemorrhage in infants with alloimmune thrombocytopenia, the percentage of such haemorrhages which occur antenatally, and the timing of these haemorrhages, is not well defined. No therapeutic approach is justified unless it does more good than harm and we believe that the risks to individual fetuses for antenatal haemorrhage should be better defined and therapy shown to be ineffective before subjecting the fetuses to numerous invasive antenatal manipulations. This accords with the view of Dr Daffos and
OBSERVED AND EXPECTED MORTALITY FROM LEUKAEMIAS
(OTHER THAN CHRONIC LYMPHOCYTIC LEUKAEMIA) IN FIVE
one
colleagues (Oct 15, p 910). Department of Pediatrics, Cornell Medical Center, and Department of Obstetrics, Mount Sinai Medical Center, New York, USA; and Southeast Wisconsin Blood Milwaukee, Wisconsin
J. BUSSEL R. BERKOWITZ
J. MCFARLAND Center,
L. LYNCH U. CHITKARA
1 Busseli JB, Bercowitz RL, McFarland JG,
Lynch L, Chitkara U Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319: 1374-78 2. Herman JH, Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage m alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8: 312-17. 3. Kaplan C, Daffos F, Forestier F, et al. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood 1988; 72: 340-43.
LEUKAEMIA NEAR PILGRIM NUCLEAR POWER PLANT, MASSACHUSETTS
SIR,-Clapp et all reported an increase in leukaemia incidence during 1982-84 in five Massachusetts coastal towns near the Pilgrim nuclear power plant, Plymouth. The known releases of radioactive effluents are too small (by several orders of magnitude) to account for the increase, but Clapp et al hypothesised "a mechanism by which airborne releases are contained in a coastal pattern". This meteorological theory did not explain how the increased rate of leukaemia was almost wholly concentrated among adult males. We have examined more recent data on Massachusetts towns to see if the increase in the five coastal towns has persisted. The new data cover 1985 and 1986. We excluded chronic lymphocytic leukaemia, which is thought not to be caused by radiation. For all leukaemia (apart from chronic lymphocytic) Clapp et al reported, for both genders and all ages, a 60% increase for 1982-84, with 27 cases observed and 16-9 expected based on the statewide rates. For 1985 and 1986, there were 6 cases with 11-8 expected based on the rates for the remainder of Massachusetts. Thus, there was a 49% deficit during the additional two-year period. The likelihood of observing the 6 cases can easily be compared for two hypotheses of interest-that the people in these five towns have a 60% risk of leukaemia (as Clapp et al reported), and the null hypothesis of no excess risk of leukaemia. The likelihood ratio (LR) for the alternative versus the null hypothesis, assuming a Poisson model, is: RRx - exp (RR-1) À, where RR is the multiplier of disease risk under the alternative hypothesis, x is the observed number of cases, and À is the number of cases expected under the null hypothesis. For the 6 observed cases, with RR =1.60 and=11-8, the likelihood ratio is 0-014. Thus, it is 71 times more probable that 6 cases would
MASSACHUSETTS
TOWNS,* 1969-86
Obs = observed cases, Exp = expected cases; SMR = standardised mortality ratio Exp); CI = confidence interval. *Duxbury, Kingston, Marshfield, Plymouth, and Scituate. tConfidence mtervals by exact (mid-P) method.
(Obs/
have been observed if the null hypothesis were correct than if RR =1-60. For the five-year period 1982-86 there were 33 cases, with 28-8 expected, for a standardised incidence ratio of 1’ 14 (95% confidence interval 0-79-1-61). Massachusetts has computerised mortality data back to 1969. The Pilgrim plant began operating in late 1972. The observed number of deaths and the number expected based on non-chronic leukaemia mortality rates in the remainder of Massachusetts are given in the table for each of four time periods since 1969. There was no excess in any time period. It seems that the transient excess of leukaemia incidence reported by Clapp et al was largely nullified by the more recent data. Furthermore, mortality data, available for earlier time periods than incidence data, indicate no historical record of excess leukaemia in these towns. It would be possible to embellish the meteorological hypothesis to postulate a time-localised effect of a one-time environmental exposure, but such an attempt would conflict with the wealth of data on the time for induction of leukaemia by radiation2 and still would not explain how the effect was limited to adult males. The finding of a small increase of leukaemia in a restricted age range, in one gender, in a few selected towns, for a short time period is better explained as a minor statistical fluctuation than as an effect of radioactive releases into the environment.
Epidemiology Resources Inc, Brookline, Massachusetts 02167, USA
CHARLES POOLE KENNETH J. ROTHMAN NANCY A. DREYER
Clapp RW, Cobb S, Chan CK, et al. Leukaemia near Massachusetts nuclear power plant. Lancet 1987; i: 1324-25 2. National Institutes of Health Ad Hoc Working Group to Develop Radioepidemiologic 1.
Tables. NIH Publ Report (85-2748).
IS IMPAIRED VISUAL DEVELOPMENT CAUSED BY PERINATAL HYPOXIA?
SIR,-Infants with a history of perinatal hypoxia are at risk of developmental disorders. Visual development after perinatal hypoxia has only been studied retrospectively.1 We describe visual development during the first 6 months of corrected age of infants with a well-documented history of perinatal hypoxia. 79 infants with a history of severe perinatal hypoxia on at least two criteria (abnormal fetal heart rate pattern, Apgar score less than 6 at 5 min, pH of umbilical arterial blood below 7 -20, or neonatal arterial p02 below 40 mm Hg) bom in 1986 and admitted within 24 h of birth were divided into three groups on gestational age. 10 died from perinatal hypoxia and 11did not attend for follow-up clinic, leaving 58 infants. The children were examined at corrected ages of 6, 13, and 26 weeks. Visual function was tested by use of behavioural techniques, with acuity cards2 and kinetic perimetry.3 Results were compared with normal values from our laboratory.3,4 Binocular optokinetic nystagmus (OKN) was elicited by moving a 105 x 40 cm paper covered with random dots slowly clockwise and counterclockwise in front of the infant. Ocular movements were observed. Normally, binocular OKN is symmetrical from birth onwards.5 Impaired visual acuity, visual field, and binocular OKN were detected in all three groups (table), especially in preterm infants (groups 1 and 2) with perinatal hypoxia (p < 001). The frequency of