BMJ  2004;328:137 (17 January), doi:10.1136/bmj.37939.570104.EE (published 8 December 2003)

Paper

Autopsy after termination of pregnancy for fetal anomaly: retrospective cohort study

¹ National Perinatal Epidemiology Unit, Institute of Health Sciences, Headington, Oxford OX3 7LF, ² Dipartimento di Ginecologia, Perinatologia e Riproduzione umana, Facolta di Medicina e Chirurgia, Universita degli Studi di Firenze, Viale Morgagni 85, Firenze, ³ Division of Public Health and Primary Care, Institute of Health Sciences, University of Oxford, Headington, Oxford OX3 7LF, ⁴ Prenatal Diagnosis Unit, Women's Centre, Oxford Radcliffe NHS Trust, Oxford OX3 9DU

Abstract

Objective To study trends in termination of pregnancy for fetal anomaly over 10 years and to assess the contribution of autopsy to the final diagnosis and counselling after termination.

Design Retrospective study with cases from a congenital anomaly register and a defined unselected population.

Data sources Pregnancies resulting in termination for fetal anomaly identified from the Oxford congenital anomaly register. Details about the prenatal diagnosis and autopsy findings were retrieved from case notes.

Results Of the 57 258 deliveries, 309 (0.5%) were terminated because of prenatally diagnosed abnormality. There were 129/29 086 (0.4%) terminations for fetal anomaly carried out in 1991-5 and 180/28 172 (0.6%) in 1996-2000. The percentage of fetuses that underwent autopsy fell from 84% to 67%. Autopsy was performed in 132 cases identified by ultrasound scan, with no evidence for abnormal karyotype. In 95 (72%) the autopsy confirmed the suspected diagnosis and did not add important further information, two cases were not classified, and in 35 (27%) the autopsy added information that led to a refinement of the risk of recurrence (reduced in 17, increased in 18); in 11 of these 18 cases it was increased to a one in four risk.

Conclusions Though there has been an increase in the rate of terminations of pregnancy for fetal anomaly, there has been a decline in the autopsy rate. When a prenatal diagnosis was based on the results of a scan only, the addition of information from a autopsy by a specialist paediatric pathologist provided important information that changed the estimated risk of recurrence in 27% of cases and in 8% this was to a higher (one in four) risk.

Introduction

When a serious anomaly is suspected prenatally some parents request termination of pregnancy. This request may be based on the results of investigations that imply that the baby will almost certainly have a lethal anomaly—for example, anencephaly—or one likely to cause long term morbidity—for example, spina bifida. In other instances the implications of the investigations are less clear—for example, a fetus with mild cerebral ventriculomegaly. After termination of pregnancy the accuracy of the prenatal prediction and the implications for future pregnancies, particularly when based on ultrasound scan findings only, may be obtained from the autopsy examination.

After the adverse publicity surrounding paediatric autopsies at Alder Hey Hospital¹ it is now widely acknowledged that parents need a full explanation to make an informed decision. Currently there is little quantitative information about the likelihood of autopsy being of practical use to parents and their families by modifying the assessment of the recurrence risk.

The prenatal diagnosis unit in Oxford is a tertiary referral centre. Since 1991 anomalies suspected prenatally and those presenting postnatally have been recorded on the Oxford congenital anomaly register (OXCAR) with the outcome of each pregnancy. We used 10 years of data reported to the register^{2 3} to assess how often information from the autopsy changes the suspected prenatal diagnosis and hence the advice given to parents about risks of recurrence; to ascertain the rates of termination of pregnancy and autopsy over 10 years in cases of prenatally suspected anomalies; to report on the range of anomalies for which termination of pregnancy was carried out and their severity; and to estimate the reduction in prevalence of conditions associated with long term morbidity because of prenatal diagnosis and termination of pregnancy.

Methods

From the OXCAR register we identified all women with an OX postcode who were booked for delivery between 1 January 1991 and 31 December 2000 inclusive at the John Radcliffe or attached community hospital and in whom the outcome of pregnancy was recorded as termination. We excluded women booked into and referred from other hospitals and those with an OX postcode who would have delivered at another district hospital. The study population was therefore unselected. The total number of deliveries occurring in the same population and time period was obtained from the Oxford Maternity Data System. We reviewed autopsy reports, clinical notes, and laboratory and ultrasound reports.

We identified those cases in which a structural anomaly was diagnosed by scan, there was no evidence for abnormal karyotype, and an autopsy was carried out. Two investigators reviewed the autopsy findings to determine whether they altered the suspected prenatal diagnosis and the assessment of the risk of recurrence (table).

View this table: [in this window] [in a new window]   Contribution of autopsy in 132 cases of termination of pregnancy due to structural anomalies detected at scan with no evidence for abnormal karyotype and autopsy performed

 

Results

The figure provides an overview of the prenatal diagnosis of congenital anomalies and termination of pregnancy.

View larger version (46K): [in this window] [in a new window]   Summary chart of prenatal screening and termination of pregnancy for congenital abnormality in Oxford, 1991-2000, inclusive

 

The rate and number of terminations for suspected fetal anomaly increased during the study period, from 129 (129/29 086 (0.4%)) during 1991-5 to 180 (180/28 172 (0.6%)) during 1996-2000. In the same time periods the number of prenatal diagnoses made (with abnormality present at birth) increased from 41% to 46%.The number of terminations of pregnancy in which autopsy was carried out fell from 84% in the first five years to 67% in the second five years.

Of the 57 258 births, 309 (0.5%) were terminated because a fetal anomaly had been suspected or diagnosed prenatally. Chromosome anomalies accounted for 141 (46%) of these. Neural tube defects and other central nervous system defects were the most common structural defects, accounting for 66 (21%) cases. One hundred and fifty five (50%) fetuses were considered to have defects which probably would have proved lethal, and in 154 the defects were compatible with survival beyond a year. See bmj.com for details of the final postnatal diagnosis and their lethality.

During the 10 years of the study there were 1208 fetuses or babies with a malformation. Of these, 601 had a malformation compatible with survival with long term morbidity. The crude reduction in prevalence of congenital malformations associated with long term morbidity is 26% (that is, 154/601). The true reduction in prevalence would be lower than this because some of the pregnancies would have ended in miscarriage. See bmj.com for details of the calculation and assumptions made.

The table shows an assessment of the contribution of the autopsy findings to the final diagnosis made for the purpose of counselling after termination of pregnancy. Autopsy findings led to a refinement of the risk of recurrence (category 3) in 35 (27%) cases. In 11/18 (61%) (category 3b) of those in which the autopsy findings led to an increase in the estimated risk of recurrence this was to a probable one in four risk for subsequent pregnancies. Two cases (category 4) could not be classified; termination of pregnancy had been carried out at the parents' request before test results (subsequently normal) had been reported.²

Discussion

Autopsy rates
In an unselected population over a 10 year period there has been a decline in the number of fetal autopsies carried out despite an increase in the number of terminations of pregnancy after prenatal suspicion of fetal abnormality. Though this decline preceded the adverse publicity surrounding events at Alder Hey Hospital, it has accelerated since.¹ A fall in autopsy rates has also been reported by others.⁴

Contribution of the autopsy to estimation of recurrence risks
When parents make a difficult decision to terminate a pregnancy because of suspected fetal abnormality most want to know if the prenatal suspicions are verified and what the implications are for further pregnancies for themselves and their wider families. We have shown that when the final prenatal diagnosis was made by ultrasound scan, in 27% of cases the information from the autopsy examination led to a refinement of the risk of recurrence, and in 8% this was increased to a one in four risk. We believe that these data may be of particular value to parents, and to those counselling them. Our study of an unselected population took place at a tertiary referral centre with autopsy performed by specialist paediatric pathologists. Care should be taken in extrapolating these data to other centres, especially those without access to a specialist paediatric pathologist.

A study of neonatal autopsy found a similar proportion in which new information was revealed,⁴ although this is not directly comparable with our study of termination of pregnancy because of the influence of postnatal events and management. Another study of 300 fetal autopsies, found the autopsy examination changed the prenatal "hypothesis" in 20%, provided extensive additional information in 41%, and confirmed the prenatal hypothesis in 39%.⁵

Contribution of prenatal diagnosis to reduction in prevalence of non-lethal congenital anomalies
We have now added four more years of data to our previous report from the same population.² Recalculation of the crude reduction in prevalence of congenital anomaly associated with long term morbidity because of termination of pregnancy shows it to have increased from 20% to 26%.

Benefits of autopsy
Quantifying the value of autopsy is not easy. For example, renal cystic disease may be difficult to define on a scan because of a lack of amniotic fluid, and the differentiation between infantile polycystic kidney disease (recurrence risk 25%) and cystic renal dysplasia (recurrence risk 3%) may require histological examination.

The direct benefits of autopsy to parents are not limited to refining the risk of recurrence. Even after autopsy, sometimes a definitive diagnosis cannot be made. In such cases the storage of fetal samples for possible future genetic analysis provides the hope of an accurate diagnosis (which may have ramifications for the wider family) at a later date. In most cases in which the scan findings are confirmed parents can gain comfort that their baby had the prenatally suspected condition. The finding of additional malformations, as well as in some cases changing the diagnosis, may be helpful in targeting tests in a subsequent pregnancy. A wider importance of autopsy is in its value for quality control for prenatal diagnosis, teaching, and research.

The decline in autopsy rate has been the subject of much debate since the adverse publicity concerning autopsies and organ retention. Parents should be provided with full information and not be coerced into accepting an autopsy examination, and these discussions should be with an appropriately trained professional. Our study provides important information for parents. If a termination has been carried out because of anomalies detected by ultrasound scan, by declining an autopsy, parents will remain ignorant of information that might change the recurrence risk in one in four cases and have a one in 13 chance for missing confirmation of a high (one in four) recurrence risk.

What is already known on this topic After prenatal diagnosis of fetal anomaly some parents opt for termination of pregnancy The rate of decline in the uptake of autopsy has accelerated since adverse publicity at Alder Hey Hospital What this study adds The number of pregnancies resulting in termination after prenatal diagnosis of fetal anomaly has increased over a 10 year period When termination of pregnancy occurs after identification of structural anomalies on scan and there is no evidence for abnormal karyotype, new information from autopsy changes the estimated risk for a recurrence in more than a quarter of cases; in 8% this is increased to a one in four risk

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This is the abridged version of an article that was posted on bmj.com on 8 December 2003: http://bmj.com/cgi/doi/10.1136/bmj.37939.570104.EE

We thank CA Boyd for advice and reading the manuscript and S Gould and C Bowker (paediatric pathologists), A Roberts (specialist genetics nurse), S Hanson (data systems manager), and all the staff in the Oxford Prenatal Diagnosis Unit for help and for providing information.

Contributors: See bmj.com

Funding: No additional funding.

Competing interests: None declared.

Ethical approval: Sought but not required by local committee.

References

1. Redfern M, Keeling JW, Powell E. The Royal Liverpool Children's inquiry report. London: Stationery Office, 2001.
2. Boyd PA, Chamberlain P, Hicks NR. Six year experience of prenatal diagnosis in an unselected population in Oxford, UK. Lancet 1998;352: 1577-81.[CrossRef][Web of Science][Medline]
3. National Perinatal Epidemiology Unit. Report of the Oxford Congenital Anomaly Register 1991-2001. Oxford: National Perinatal Epidemiology Unit, 2003.
4. Brodlie M, Laing IA, Keeling JW, McKenzie KJ. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. BMJ 2002;324: 761-3.[Abstract/Free Full Text]
5. Laussel-Riera A, Devisme L, Manouvrier-Hanu S, Puech F, Robert Y, Gosselin B. Value of fetopathological examination in medical abortions: comparison of prenatal diagnosis and autopsy results of 300 fetuses. Ann Pathol 2000;20: 549-57.[Medline]

(Accepted 7 November 2003)

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