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The web site itself may have changed. You can check the current page or check for previous versions at the Internet Archive. Yahoo! is not affiliated with the authors of this page or responsible for its content. centre: retrospective study Ten years of neonatal autopsies in tertiary referral doi:10.1136/bmj.324.7340.761 2002;324;761-763 BMJ Malcolm Brodlie, Ian A Laing, Jean W Keeling and Kathryn J McKenzie centre: retrospective study Ten years of neonatal autopsies in tertiary referral http://bmj.com/cgi/content/full/324/7340/761 Updated information and services can be found at: These include: Data supplement http://bmj.com/cgi/content/full/324/7340/761/DC1 "Tables" References http://bmj.com/cgi/content/full/324/7340/761#otherarticles 11 online articles that cite this article can be accessed at: http://bmj.com/cgi/content/full/324/7340/761#BIBL This article cites 22 articles, 11 of which can be accessed free at: Rapid responses http://bmj.com/cgi/eletter-submit/324/7340/761 You can respond to this article at: http://bmj.com/cgi/content/full/324/7340/761#responses at: 2 rapid responses have been posted to this article, which you can access for free service Email alerting the top left of the article Receive free email alerts when new articles cite this article - sign up in the box at Notes To order reprints follow the "Request Permissions" link in the navigation box http://resources.bmj.com/bmj/subscribers go to: BMJ To subscribe to on 23 July 2008 bmj.com Downloaded from Ten years of neonatal autopsies in tertiary referral centre:
retrospective study Malcolm Brodlie, Ian A Laing, Jean W Keeling, Kathryn J McKenzie Abstract Objectives To measure the neonatal autopsy rate at a
tertiary referral centre and identify trends over the
past decade. To identify factors that may influence the
likelihood of consent being given for autopsy. To
examine any discordance between diagnoses before
death and at autopsy. Design Retrospective review of patients records. Setting Tertiary neonatal referral centre affiliated to
university. Outcome measures Sex, gestational age, birth weight,
type of delivery, and length of stay in neonatal unit for
baby. Maternal age, marital status, history of previous
pregnancies, and details of who requested permission
for autopsy. Concordance between diagnoses before
death and at autopsy. Results An autopsy was performed in 209/314 (67%)
cases. New information was obtained in 50 (26%)
autopsies. In six (3%) cases this information was
crucial for future counselling. In 145 (74%) there was
complete concordance between the clinical cause of
death and the findings at autopsy. From 1994 onwards
the autopsy rate in the neonatal unit fell. The only
significant factor associated with consent for autopsy
was increased gestational age. Conclusions Important extra information can be
gained at neonatal autopsies. This should help parents
to make an informed decision when they are asked to
give permission for their baby to have an autopsy.
These findings are of particular relevance in view of
the recent negative publicity surrounding neonatal
autopsies and the general decline in the neonatal
autopsy rate over the decade studied. Introduction Autopsy has been important in medicine since the
15th century 1 and has contributed greatly to clinical knowledge. 24 Neonatal autopsy has a particularly valu- able role in the counselling of families after the loss of
an infant as it can help the grieving process, improve
parental understanding, and alleviate concerns over
prenatal events. 59 Genetic conditions or obstetric factors of relevance to future pregnancies may also be
identified. 10 Recently the rate and perceived importance of autopsies of adults has declined considerably. 1114 Con- versely rates of neonatal autopsy have generally
remained higher, with previous reports ranging from
59% to 81%. 3 10 1317 In 2000, however, the neonatal autopsy rate declined in Illinois. 18 Parental consent is thought to be the major limiting factor. 16 The publics exposure to the purposes and value of the autopsy is
sparse, and perceptions are often dominated by melo-
dramatic treatment in the media. 19 We measured the rate of neonatal autopsy at a ter- tiary referral centre over the past decade to investigate
the role of various factors in determining consent for autopsy. We also examined the yield of new
information in terms of discordance between diag-
noses before and after death. Methods We carried out the study in a neonatal unit in the main
tertiary neonatal referral centre for the south east of
Scotland. We included records of all deaths in the neo-
natal unit from 1 January 1990 to 31 December 1999.
The policy in the unit is that a senior clinician,
normally the relevant consultant, approaches relatives
for consent for autopsy after each death. Autopsies
were performed only after parental consent or at the
request of the procurator fiscal. Each examination was
performed by one of four consultant paediatric
pathologists using standard techniques. 20 We recorded the cause of death from the original death certificate, which was normally completed by a
consultant. We obtained maternal and infant details
from the original medical records and abstracted
autopsy findings from the concluding summary of the
pathologists report. Death certificates were not
available for 1990-2; in these cases the cause of death
was determined by a consultant neonatologist after
review of the patients records. We used a modified version of previously published schemes 11 18 to classify the concordance between autopsy findings and diagnoses before death (table 1).
We compared the proportion of events in each group
using the 2 test for discrete variables and Students t test for numerical variables. Results In over a quarter of cases new information was
obtained at autopsy (see table A on bmj.com for
further details). A single class Ia diagnosis of sigmoid
volvulus was identified along with five class Ib
diagnoses with implications for genetic advice
namely, Smith-Lemli-Opitz type II syndrome, De
Langes syndrome, ornithine carbamyltransferase defi- Three tables with
further data can be
found on bmj.com Table 1 Classification of concordance between diagnosis before death and at autopsy* Class Description IA Diagnosis that, had it been detected before death, would probably have led to change in
management that might have resulted in cure or prolonged survival IB Diagnosis with significant implications for future genetic advice II Diagnosis that, had it been detected before death, would probably not have led to change in
management or survival because:
x No appropriate therapy was available at the time x Appropriate therapy was given even though the diagnosis was unknown at the time x Patient had acute cardiopulmonary arrest that was appropriately managed, but patient did not
survive for definitive management
x Patient had do not resuscitate status III Diagnosis that may or may not have been related to main disease process and was contributory
cause of death IV Diagnosis unrelated to outcome and may or may not have affected eventual prognosis of patient V Complete concordance between diagnosis before death and findings at autopsy *Modified from Kumar et al 18 and Goldman et al. 11 Papers Editorial by Khong Royal Hospital for
Sick Children,
Edinburgh
EH9 1LW
Malcolm Brodlie
house officer in
paediatric surgery Neonatal Unit,
Simpson Memorial
Maternity Pavilion,
Edinburgh
EH3 9YW
Ian A Laing
consultant
neonatologist Department of
Paediatric
Pathology, Royal
Hospital for Sick
Children,
Edinburgh
Jean W Keeling
consultant paediatric
pathologist
Kathryn J McKenzie
consultant paediatric
pathologist Correspondence to:
Ian Laing
Ian.Laing@ed.ac.uk BMJ 2002;324:7613 761 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from ciency, DiGeorge syndrome, and GM 1 gangliosidosis. An autopsy was performed in 209 of the 314 cases
studied (see table B on bmj.com). The overall rate of
neonatal autopsy of 67% remained substantially
higher than the prevailing rate in adults. From 1994
onwards, however, the annual autopsy rates dropped
below levels earlier in the decade (figure). Gestational
age was the only factor that was found to differ signifi-
cantly between the groups who did and did not give
permission for autopsy, with means of 32 and 30
weeks respectively (table 2). Details of other factors
that we examined and that were not associated with
consent for autopsy can be found in table C on
bmj.com. Discussion Earlier studies have reported higher yields of new
information from neonatal autopsies, ranging from
34% to 48%, though classification criteria and procedures varied between publications. 10 1315 18 21 In our study a single observer classified the level of
concordance between diagnoses before death and at
autopsy. Review by a multidisciplinary team, including
a pathologist, may have resulted in a higher yield. We
abstracted clinical diagnoses from the death certificates
when they were available. The reliability of death
certificates largely depends on how accurately clini-
cians record clinical information. 22 In Edinburgh certificates were normally completed after considera-
tion of the case by the consultant in charge. Demographic features such as the sex of the infant and maternal age or marital status have never been
identified as significant determinants of consent for
neonatal autopsy. 3 16 17 VanMarter et al 17 and Manis- calco and Clarke 3 also found gestational age to be a significant factor. Possibly clinicians are less likely to
encourage parents to give consent for autopsy in
extremely preterm infants. 17 In general the strength of requests for individual autopsies is likely to vary
because clinicians will have different views as to its
importance in a specific case. The finding that in about a quarter of cases new information was gained is likely to be of use to
bereaved families when they are considering permis-
sion for an autopsy. The proportion of neonatal deaths
attributed to major genetic or congenital abnormalities
has increased. Accurate diagnosis in such cases, either
before or after death, is highly important for future
counselling. Information obtained at autopsy may not
have directly affected clinical management but is
essential for audit or educational purposes. 21 Arguably the greatest value of the neonatal autopsy is to families
during the grieving process. Such unique benefits are
far more difficult to quantify. 9 23 The apparent reduction in the neonatal autopsy rate in Edinburgh over the decade studied warrants
serious debate. There is no obvious single explanation
but possible influences include a shift in the attitude of
clinicians towards autopsies or a change in the publics
willingness to grant permission. Economic or proce-
dural considerations did not feature during the period
studied. The recent high profile disclosure concerning
organ retention in the United Kingdom 24 can only have served to harm the publics view of autopsies. A
concerted effort will be needed to promote the value
and purposes of the neonatal autopsy. We thank Gill Mitchell for her invaluable help in tracing patient
records. We are grateful to Professor Neil McIntosh for his com-
ments on the original protocol. Contributors: MB contributed to the planning of the study, collated and analysed the data, and wrote the paper. This project
began as a special study module part of the University of Edin-
burgh phase III MBChB course. IAL supervised the planning
and execution of the study, contributed to the writing of the What is already known on this topic The neonatal autopsy rate dropped in Illinois
during the 10 years from 1984 to 1993 Over recent years there has been a large amount
of negative publicity surrounding neonatal
autopsies in the United Kingdom What this study adds Over a quarter of neonatal autopsies yielded new
information; in 3% of cases this information was
crucial This finding is likely to be of use to bereaved
parents who are asked to give permission for
autopsy and provides a more positive perspective
on the utility of neonatal autopsies Table 2 Factors related to baby and mother according to whether autopsy was performed Category Autopsy performed No autopsy P value* Data not available Mean (range) SD Mean (range) SD Gestational age (weeks) 32.2 (22-42) 6.44 30.1 (23-42) 6.79 0.0066 15 Birth weight (g) 1828 (400-5250) 1179 1669 (365-5230) 1246 0.1402 7 Length of stay (days) 15.4 (1-210) 35.6 14.2 (1-240) 32.3 0.3807 6 Age at death (days) 15.8 (1-210) 35.6 15.2 (1-210) 34.8 0.4465 28 Maternal age (years) 27.3 (15-43) 5.81 28.0 (16-42) 6.16 0.1923 51 *Mean of each group compared with Students t test. Year Proportion (%) 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 40 50 60 70 80 90 Autopsy rate in neonatal unit (1990-9) Papers 762 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from paper, and will act as guarantor. JWK and KJMcK provided
advice during the study and commented on the paper. Funding: None.
Competing interests: None declared. 1 Dorsey DB. A perspective on the autopsy. Am J Clin Pathol 1977;69:217-9. 2 Landefeld CS, Chren MM, Myers A, Geller R, Robbins S, Goldman L.
Diagnostic yield of the autopsy in a university hospital and a community
hospital. N Engl J Med 1988;318:1249-54. 3 Maniscalco WM, Clarke TA. Factors influencing neonatal autopsy rate.
Am J Dis Child 1982;136:781-4. 4 Berthrong M. The autopsy as a vehicle for the lifetime education of
pathologists. Arch Pathol Lab Med 1984;108:506-9. 5 Hirsch CS. Talking to the family after an autopsy. Arch Pathol Lab Med
1984;108:513-4. 6 Reynolds RC. Autopsiesbenefits to the family. Am J Clin Pathol
1977;69:220-2. 7 Rowe J, Clyman R, Green C, Mikkelsen C, Haight J, Ataide L. Follow-up
of families who experience a perinatal death. Pediatrics 1978;62:166-70. 8 Valdes-Dapena M. The postautopsy conference with families. Arch Pathol
Lab Med 1984;108:497-8. 9 Beckwith JB. The value of the pediatric postmortem examination. Pediatr
Clin North Am 1989;36:29-35. 10 Saller DN Jr, Lesser KB, Harrel U, Rogers BB, Oyer CE. The clinical util- ity of the perinatal autopsy. JAMA 1995;273:663-5. 11 Goldman L, Sayson R, Robbins S, Cohn LH, Bettmann M, Weisberg M. The value of the autopsy in three medical eras. N Engl J Med
1983;308:1000-5. 12 Burrows S. The postmortem examination. Scientific necessity or folly? JAMA 1975;233:441-3. 13 Dhar V, Perlman M, Vilela MI, Haque KN, Kirpalani H, Cutz E. Autopsy in a neonatal intensive care unit: utilization patterns and associations of
clinicopathologic discordances. J Pediatr 1998;132:75-9. 14 Meier PR, Manchester DK, Shikes RH, Clewell WH, Stewart M. Perinatal autopsy: its clinical value. Obstet Gynecol 1986;67:349-51. 15 Craft H, Brazy JE. Autopsyhigh yield in neonatal population. Am J Dis Child 1986;140:1260-2. 16 Khong TY, Mansor FAW, Staples AJ. Are perinatal autopsy rates satisfac- tory? Med J Austr 1995;162:469-70. 17 VanMarter LJ, Taylor F, Epstein MF. Parental and physician-related deter- minants of consent for neonatal autopsy. Am J Dis Child 1987;141:149-53. 18 Kumar P, Angst DB, Taxy J, Mangurten HH. Neonatal autopsies: a 10-year experience. Arch Pediatr Adolesc Med 2000;154:38-42. 19 Brown HG. Lay perceptions of autopsy. Arch Pathol Lab Med 1984;108:446-8. 20 Keeling JW. The perinatal necropsy. In: Keeling JW, ed. Fetal and neonatal pathology. London: Springer, 1987. 21 Porter HJ, Keeling JW. Value of perinatal necropsy examination. J Clin Pathol 1987;40:180-4. 22 Kircher LT. Autopsy and mortality statistics: making a difference. JAMA 1992;267:1264-8. 23 Berger LR. Requesting the autopsy: A pediatric perspective: psycho- social and professional aspects of the autopsy in caring for the dying
child and his family. Clin Pediatr (Phila) 1978;17:445-52. 24 Hunter M. Alder Hey report condemns doctors, management, and coro- ner. BMJ 2001;322:255. (Accepted 5 November 2001) Synergism between allergens and viruses and risk of
hospital admission with asthma: case-control study Rosalind M Green, Adnan Custovic, Gwen Sanderson, Jenny Hunter, Sebastian L Johnston,
Ashley Woodcock Abstract Objective To investigate the importance of
sensitisation and exposure to allergens and viral
infection in precipitating acute asthma in adults
resulting in admission to hospital. Design Case-control study. Setting Large district general hospital. Participants 60 patients aged 17-50 admitted to
hospital over a year with acute asthma, matched with
two controls: patients with stable asthma recruited
from the outpatient department and patients
admitted to hospital with non-respiratory conditions
(inpatient controls). Main outcome measures Atopic status (skin testing
and total and specific IgE), presence of common
respiratory viruses and atypical bacteria (polymerase
chain reaction), dust samples from homes, and
exposure to allergens (enzyme linked immunosorbent
assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). Results Viruses were detected in 31 of 177 patients.
The difference in the frequency of viruses detected
between the groups was significant (admitted with
asthma 26%, stable asthma 18%, inpatient controls
9%; P = 0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised
and exposed to either mite, cat, or dog allergen than
patients with stable asthma (37%) and inpatient
controls (15%; P < 0.001). Being sensitised and
exposed to allergens was an independent associate of
the group admitted to hospital (odds ratio 2.3, 95%
confidence interval 1.0 to 5.4; P = 0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably
increased the risk of being admitted with asthma (8.4,
2.1 to 32.8; P = 0.002). Conclusions Allergens and viruses may act together
to exacerbate asthma. Introduction Asthma costs 1-2% of the total health budgets in direct
costs, with equally large indirect costs for time lost from
work and reduced productivity. 1 2 Much of these costs come from hospital admissions. Being admitted to
hospital with asthma is also an important risk factor for
death from the condition. 3 Of 450 000 adults admitted yearly with asthma to emergency departments in the United States, an
estimated 200 000 were sensitised to mite, cat, or
cockroach allergen. 4 Viral respiratory infections have been associated with most acute exacerbations of
wheeze in childhood. 5 In the early part of each school term there is an increase in hospital admissions for
asthma associated with the acquisition of new viruses. 6 An interaction has been suggested between sensitisation
and virus infection in exacerbating asthma in children. 7 Few studies have been conducted in adults, although
there is evidence that viral infections are associated with
many exacerbations of asthma. 8 In experimental studies synergistic effects have been shown between allergens
and viruses. 9 10 No studies have investigated an interaction between sensitisation, exposure to allergens,
and viral infections in real life exacerbations of asthma.
We therefore determined their relative importance in The full version of
this article appears
on bmj.com Papers North West Lung
Centre,
Wythenshawe
Hospital,
Manchester
M23 9LT
Rosalind M Green
research registrar
Adnan Custovic
National Asthma
Campaign senior
clinical research fellow
Ashley Woodcock
professor Department of
Respiratory
Medicine, National
Heart and Lung
Institute, Faculty of
Medicine, Imperial
College of Science,
Technology and
Medicine, London
W2 1PG
Gwen Sanderson
research technician
Sebastian L
Johnston
professor University
Medicine,
Southampton
General Hospital,
Southampton
SO9 6YD
Jenny Hunter
research technician Correspondence to:
A Custovic
acustovic@fs1.
with.man.ac.uk BMJ 2002;324:7636 763 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from
The web site itself may have changed. You can check the current page or check for previous versions at the Internet Archive. Yahoo! is not affiliated with the authors of this page or responsible for its content. centre: retrospective study Ten years of neonatal autopsies in tertiary referral doi:10.1136/bmj.324.7340.761 2002;324;761-763 BMJ Malcolm Brodlie, Ian A Laing, Jean W Keeling and Kathryn J McKenzie centre: retrospective study Ten years of neonatal autopsies in tertiary referral http://bmj.com/cgi/content/full/324/7340/761 Updated information and services can be found at: These include: Data supplement http://bmj.com/cgi/content/full/324/7340/761/DC1 "Tables" References http://bmj.com/cgi/content/full/324/7340/761#otherarticles 11 online articles that cite this article can be accessed at: http://bmj.com/cgi/content/full/324/7340/761#BIBL This article cites 22 articles, 11 of which can be accessed free at: Rapid responses http://bmj.com/cgi/eletter-submit/324/7340/761 You can respond to this article at: http://bmj.com/cgi/content/full/324/7340/761#responses at: 2 rapid responses have been posted to this article, which you can access for free service Email alerting the top left of the article Receive free email alerts when new articles cite this article - sign up in the box at Notes To order reprints follow the "Request Permissions" link in the navigation box http://resources.bmj.com/bmj/subscribers go to: BMJ To subscribe to on 23 July 2008 bmj.com Downloaded from Ten years of neonatal autopsies in tertiary referral centre:
retrospective study Malcolm Brodlie, Ian A Laing, Jean W Keeling, Kathryn J McKenzie Abstract Objectives To measure the neonatal autopsy rate at a
tertiary referral centre and identify trends over the
past decade. To identify factors that may influence the
likelihood of consent being given for autopsy. To
examine any discordance between diagnoses before
death and at autopsy. Design Retrospective review of patients records. Setting Tertiary neonatal referral centre affiliated to
university. Outcome measures Sex, gestational age, birth weight,
type of delivery, and length of stay in neonatal unit for
baby. Maternal age, marital status, history of previous
pregnancies, and details of who requested permission
for autopsy. Concordance between diagnoses before
death and at autopsy. Results An autopsy was performed in 209/314 (67%)
cases. New information was obtained in 50 (26%)
autopsies. In six (3%) cases this information was
crucial for future counselling. In 145 (74%) there was
complete concordance between the clinical cause of
death and the findings at autopsy. From 1994 onwards
the autopsy rate in the neonatal unit fell. The only
significant factor associated with consent for autopsy
was increased gestational age. Conclusions Important extra information can be
gained at neonatal autopsies. This should help parents
to make an informed decision when they are asked to
give permission for their baby to have an autopsy.
These findings are of particular relevance in view of
the recent negative publicity surrounding neonatal
autopsies and the general decline in the neonatal
autopsy rate over the decade studied. Introduction Autopsy has been important in medicine since the
15th century 1 and has contributed greatly to clinical knowledge. 24 Neonatal autopsy has a particularly valu- able role in the counselling of families after the loss of
an infant as it can help the grieving process, improve
parental understanding, and alleviate concerns over
prenatal events. 59 Genetic conditions or obstetric factors of relevance to future pregnancies may also be
identified. 10 Recently the rate and perceived importance of autopsies of adults has declined considerably. 1114 Con- versely rates of neonatal autopsy have generally
remained higher, with previous reports ranging from
59% to 81%. 3 10 1317 In 2000, however, the neonatal autopsy rate declined in Illinois. 18 Parental consent is thought to be the major limiting factor. 16 The publics exposure to the purposes and value of the autopsy is
sparse, and perceptions are often dominated by melo-
dramatic treatment in the media. 19 We measured the rate of neonatal autopsy at a ter- tiary referral centre over the past decade to investigate
the role of various factors in determining consent for autopsy. We also examined the yield of new
information in terms of discordance between diag-
noses before and after death. Methods We carried out the study in a neonatal unit in the main
tertiary neonatal referral centre for the south east of
Scotland. We included records of all deaths in the neo-
natal unit from 1 January 1990 to 31 December 1999.
The policy in the unit is that a senior clinician,
normally the relevant consultant, approaches relatives
for consent for autopsy after each death. Autopsies
were performed only after parental consent or at the
request of the procurator fiscal. Each examination was
performed by one of four consultant paediatric
pathologists using standard techniques. 20 We recorded the cause of death from the original death certificate, which was normally completed by a
consultant. We obtained maternal and infant details
from the original medical records and abstracted
autopsy findings from the concluding summary of the
pathologists report. Death certificates were not
available for 1990-2; in these cases the cause of death
was determined by a consultant neonatologist after
review of the patients records. We used a modified version of previously published schemes 11 18 to classify the concordance between autopsy findings and diagnoses before death (table 1).
We compared the proportion of events in each group
using the 2 test for discrete variables and Students t test for numerical variables. Results In over a quarter of cases new information was
obtained at autopsy (see table A on bmj.com for
further details). A single class Ia diagnosis of sigmoid
volvulus was identified along with five class Ib
diagnoses with implications for genetic advice
namely, Smith-Lemli-Opitz type II syndrome, De
Langes syndrome, ornithine carbamyltransferase defi- Three tables with
further data can be
found on bmj.com Table 1 Classification of concordance between diagnosis before death and at autopsy* Class Description IA Diagnosis that, had it been detected before death, would probably have led to change in
management that might have resulted in cure or prolonged survival IB Diagnosis with significant implications for future genetic advice II Diagnosis that, had it been detected before death, would probably not have led to change in
management or survival because:
x No appropriate therapy was available at the time x Appropriate therapy was given even though the diagnosis was unknown at the time x Patient had acute cardiopulmonary arrest that was appropriately managed, but patient did not
survive for definitive management
x Patient had do not resuscitate status III Diagnosis that may or may not have been related to main disease process and was contributory
cause of death IV Diagnosis unrelated to outcome and may or may not have affected eventual prognosis of patient V Complete concordance between diagnosis before death and findings at autopsy *Modified from Kumar et al 18 and Goldman et al. 11 Papers Editorial by Khong Royal Hospital for
Sick Children,
Edinburgh
EH9 1LW
Malcolm Brodlie
house officer in
paediatric surgery Neonatal Unit,
Simpson Memorial
Maternity Pavilion,
Edinburgh
EH3 9YW
Ian A Laing
consultant
neonatologist Department of
Paediatric
Pathology, Royal
Hospital for Sick
Children,
Edinburgh
Jean W Keeling
consultant paediatric
pathologist
Kathryn J McKenzie
consultant paediatric
pathologist Correspondence to:
Ian Laing
Ian.Laing@ed.ac.uk BMJ 2002;324:7613 761 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from ciency, DiGeorge syndrome, and GM 1 gangliosidosis. An autopsy was performed in 209 of the 314 cases
studied (see table B on bmj.com). The overall rate of
neonatal autopsy of 67% remained substantially
higher than the prevailing rate in adults. From 1994
onwards, however, the annual autopsy rates dropped
below levels earlier in the decade (figure). Gestational
age was the only factor that was found to differ signifi-
cantly between the groups who did and did not give
permission for autopsy, with means of 32 and 30
weeks respectively (table 2). Details of other factors
that we examined and that were not associated with
consent for autopsy can be found in table C on
bmj.com. Discussion Earlier studies have reported higher yields of new
information from neonatal autopsies, ranging from
34% to 48%, though classification criteria and procedures varied between publications. 10 1315 18 21 In our study a single observer classified the level of
concordance between diagnoses before death and at
autopsy. Review by a multidisciplinary team, including
a pathologist, may have resulted in a higher yield. We
abstracted clinical diagnoses from the death certificates
when they were available. The reliability of death
certificates largely depends on how accurately clini-
cians record clinical information. 22 In Edinburgh certificates were normally completed after considera-
tion of the case by the consultant in charge. Demographic features such as the sex of the infant and maternal age or marital status have never been
identified as significant determinants of consent for
neonatal autopsy. 3 16 17 VanMarter et al 17 and Manis- calco and Clarke 3 also found gestational age to be a significant factor. Possibly clinicians are less likely to
encourage parents to give consent for autopsy in
extremely preterm infants. 17 In general the strength of requests for individual autopsies is likely to vary
because clinicians will have different views as to its
importance in a specific case. The finding that in about a quarter of cases new information was gained is likely to be of use to
bereaved families when they are considering permis-
sion for an autopsy. The proportion of neonatal deaths
attributed to major genetic or congenital abnormalities
has increased. Accurate diagnosis in such cases, either
before or after death, is highly important for future
counselling. Information obtained at autopsy may not
have directly affected clinical management but is
essential for audit or educational purposes. 21 Arguably the greatest value of the neonatal autopsy is to families
during the grieving process. Such unique benefits are
far more difficult to quantify. 9 23 The apparent reduction in the neonatal autopsy rate in Edinburgh over the decade studied warrants
serious debate. There is no obvious single explanation
but possible influences include a shift in the attitude of
clinicians towards autopsies or a change in the publics
willingness to grant permission. Economic or proce-
dural considerations did not feature during the period
studied. The recent high profile disclosure concerning
organ retention in the United Kingdom 24 can only have served to harm the publics view of autopsies. A
concerted effort will be needed to promote the value
and purposes of the neonatal autopsy. We thank Gill Mitchell for her invaluable help in tracing patient
records. We are grateful to Professor Neil McIntosh for his com-
ments on the original protocol. Contributors: MB contributed to the planning of the study, collated and analysed the data, and wrote the paper. This project
began as a special study module part of the University of Edin-
burgh phase III MBChB course. IAL supervised the planning
and execution of the study, contributed to the writing of the What is already known on this topic The neonatal autopsy rate dropped in Illinois
during the 10 years from 1984 to 1993 Over recent years there has been a large amount
of negative publicity surrounding neonatal
autopsies in the United Kingdom What this study adds Over a quarter of neonatal autopsies yielded new
information; in 3% of cases this information was
crucial This finding is likely to be of use to bereaved
parents who are asked to give permission for
autopsy and provides a more positive perspective
on the utility of neonatal autopsies Table 2 Factors related to baby and mother according to whether autopsy was performed Category Autopsy performed No autopsy P value* Data not available Mean (range) SD Mean (range) SD Gestational age (weeks) 32.2 (22-42) 6.44 30.1 (23-42) 6.79 0.0066 15 Birth weight (g) 1828 (400-5250) 1179 1669 (365-5230) 1246 0.1402 7 Length of stay (days) 15.4 (1-210) 35.6 14.2 (1-240) 32.3 0.3807 6 Age at death (days) 15.8 (1-210) 35.6 15.2 (1-210) 34.8 0.4465 28 Maternal age (years) 27.3 (15-43) 5.81 28.0 (16-42) 6.16 0.1923 51 *Mean of each group compared with Students t test. Year Proportion (%) 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 40 50 60 70 80 90 Autopsy rate in neonatal unit (1990-9) Papers 762 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from paper, and will act as guarantor. JWK and KJMcK provided
advice during the study and commented on the paper. Funding: None.
Competing interests: None declared. 1 Dorsey DB. A perspective on the autopsy. Am J Clin Pathol 1977;69:217-9. 2 Landefeld CS, Chren MM, Myers A, Geller R, Robbins S, Goldman L.
Diagnostic yield of the autopsy in a university hospital and a community
hospital. N Engl J Med 1988;318:1249-54. 3 Maniscalco WM, Clarke TA. Factors influencing neonatal autopsy rate.
Am J Dis Child 1982;136:781-4. 4 Berthrong M. The autopsy as a vehicle for the lifetime education of
pathologists. Arch Pathol Lab Med 1984;108:506-9. 5 Hirsch CS. Talking to the family after an autopsy. Arch Pathol Lab Med
1984;108:513-4. 6 Reynolds RC. Autopsiesbenefits to the family. Am J Clin Pathol
1977;69:220-2. 7 Rowe J, Clyman R, Green C, Mikkelsen C, Haight J, Ataide L. Follow-up
of families who experience a perinatal death. Pediatrics 1978;62:166-70. 8 Valdes-Dapena M. The postautopsy conference with families. Arch Pathol
Lab Med 1984;108:497-8. 9 Beckwith JB. The value of the pediatric postmortem examination. Pediatr
Clin North Am 1989;36:29-35. 10 Saller DN Jr, Lesser KB, Harrel U, Rogers BB, Oyer CE. The clinical util- ity of the perinatal autopsy. JAMA 1995;273:663-5. 11 Goldman L, Sayson R, Robbins S, Cohn LH, Bettmann M, Weisberg M. The value of the autopsy in three medical eras. N Engl J Med
1983;308:1000-5. 12 Burrows S. The postmortem examination. Scientific necessity or folly? JAMA 1975;233:441-3. 13 Dhar V, Perlman M, Vilela MI, Haque KN, Kirpalani H, Cutz E. Autopsy in a neonatal intensive care unit: utilization patterns and associations of
clinicopathologic discordances. J Pediatr 1998;132:75-9. 14 Meier PR, Manchester DK, Shikes RH, Clewell WH, Stewart M. Perinatal autopsy: its clinical value. Obstet Gynecol 1986;67:349-51. 15 Craft H, Brazy JE. Autopsyhigh yield in neonatal population. Am J Dis Child 1986;140:1260-2. 16 Khong TY, Mansor FAW, Staples AJ. Are perinatal autopsy rates satisfac- tory? Med J Austr 1995;162:469-70. 17 VanMarter LJ, Taylor F, Epstein MF. Parental and physician-related deter- minants of consent for neonatal autopsy. Am J Dis Child 1987;141:149-53. 18 Kumar P, Angst DB, Taxy J, Mangurten HH. Neonatal autopsies: a 10-year experience. Arch Pediatr Adolesc Med 2000;154:38-42. 19 Brown HG. Lay perceptions of autopsy. Arch Pathol Lab Med 1984;108:446-8. 20 Keeling JW. The perinatal necropsy. In: Keeling JW, ed. Fetal and neonatal pathology. London: Springer, 1987. 21 Porter HJ, Keeling JW. Value of perinatal necropsy examination. J Clin Pathol 1987;40:180-4. 22 Kircher LT. Autopsy and mortality statistics: making a difference. JAMA 1992;267:1264-8. 23 Berger LR. Requesting the autopsy: A pediatric perspective: psycho- social and professional aspects of the autopsy in caring for the dying
child and his family. Clin Pediatr (Phila) 1978;17:445-52. 24 Hunter M. Alder Hey report condemns doctors, management, and coro- ner. BMJ 2001;322:255. (Accepted 5 November 2001) Synergism between allergens and viruses and risk of
hospital admission with asthma: case-control study Rosalind M Green, Adnan Custovic, Gwen Sanderson, Jenny Hunter, Sebastian L Johnston,
Ashley Woodcock Abstract Objective To investigate the importance of
sensitisation and exposure to allergens and viral
infection in precipitating acute asthma in adults
resulting in admission to hospital. Design Case-control study. Setting Large district general hospital. Participants 60 patients aged 17-50 admitted to
hospital over a year with acute asthma, matched with
two controls: patients with stable asthma recruited
from the outpatient department and patients
admitted to hospital with non-respiratory conditions
(inpatient controls). Main outcome measures Atopic status (skin testing
and total and specific IgE), presence of common
respiratory viruses and atypical bacteria (polymerase
chain reaction), dust samples from homes, and
exposure to allergens (enzyme linked immunosorbent
assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). Results Viruses were detected in 31 of 177 patients.
The difference in the frequency of viruses detected
between the groups was significant (admitted with
asthma 26%, stable asthma 18%, inpatient controls
9%; P = 0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised
and exposed to either mite, cat, or dog allergen than
patients with stable asthma (37%) and inpatient
controls (15%; P < 0.001). Being sensitised and
exposed to allergens was an independent associate of
the group admitted to hospital (odds ratio 2.3, 95%
confidence interval 1.0 to 5.4; P = 0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably
increased the risk of being admitted with asthma (8.4,
2.1 to 32.8; P = 0.002). Conclusions Allergens and viruses may act together
to exacerbate asthma. Introduction Asthma costs 1-2% of the total health budgets in direct
costs, with equally large indirect costs for time lost from
work and reduced productivity. 1 2 Much of these costs come from hospital admissions. Being admitted to
hospital with asthma is also an important risk factor for
death from the condition. 3 Of 450 000 adults admitted yearly with asthma to emergency departments in the United States, an
estimated 200 000 were sensitised to mite, cat, or
cockroach allergen. 4 Viral respiratory infections have been associated with most acute exacerbations of
wheeze in childhood. 5 In the early part of each school term there is an increase in hospital admissions for
asthma associated with the acquisition of new viruses. 6 An interaction has been suggested between sensitisation
and virus infection in exacerbating asthma in children. 7 Few studies have been conducted in adults, although
there is evidence that viral infections are associated with
many exacerbations of asthma. 8 In experimental studies synergistic effects have been shown between allergens
and viruses. 9 10 No studies have investigated an interaction between sensitisation, exposure to allergens,
and viral infections in real life exacerbations of asthma.
We therefore determined their relative importance in The full version of
this article appears
on bmj.com Papers North West Lung
Centre,
Wythenshawe
Hospital,
Manchester
M23 9LT
Rosalind M Green
research registrar
Adnan Custovic
National Asthma
Campaign senior
clinical research fellow
Ashley Woodcock
professor Department of
Respiratory
Medicine, National
Heart and Lung
Institute, Faculty of
Medicine, Imperial
College of Science,
Technology and
Medicine, London
W2 1PG
Gwen Sanderson
research technician
Sebastian L
Johnston
professor University
Medicine,
Southampton
General Hospital,
Southampton
SO9 6YD
Jenny Hunter
research technician Correspondence to:
A Custovic
acustovic@fs1.
with.man.ac.uk BMJ 2002;324:7636 763 BMJ VOLUME 324 30 MARCH 2002 bmj.com on 23 July 2008 bmj.com Downloaded from
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