Autopsy after termination of pregnancy for fetal anomaly: retrospective cohort study
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《英国医生杂志》
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, Florence, 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
Correspondence to: P Boyd Patricia.boyd@orh.nhs.uk
Abstract
The Abortion Act 1967 allows termination of pregnancy if there is substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously disabled. During the past decade new screening and diagnostic tests have been introduced that allow earlier and more accurate diagnosis of fetal anomaly.1-3
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 termination of pregnancy may be requested when the implications of the investigations are less clear—for example, a fetus with mild cerebral ventriculomegaly. After termination of pregnancy most parents will want to know if the prenatal prediction was accurate and what the implications are for future pregnancies. This is particularly true when the prenatal diagnosis is based on ultrasound scan findings only. Such information may be obtained from the autopsy examination.
After the adverse publicity surrounding paediatric autopsies at Alder Hey Hospital4 there is widespread recognition that parents need a full explanation to make an informed decision. This information should not only be about the autopsy technique but also about the potential benefits. 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 risk of recurrence.
The prenatal diagnosis unit in Oxford is a tertiary referral centre in a teaching hospital. Since 1991 all anomalies (with the exception of those on the Office for National Statistics exclusion list5) 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 register6 7 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
Figure 1 provides an overview of the prenatal diagnosis of congenital anomalies and termination of pregnancy for fetal anomaly in local deliveries in Oxford during the 10 years 1991-2000 inclusive. Of the 57 258 deliveries (live births, neonatal deaths, stillbirths over 20 weeks, and all pregnancies terminated at any gestation for fetal anomaly), 1208 (2.1%) resulted in a fetus or baby with an abnormality.
Fig 1 Summary chart of prenatal screening and termination of pregnancy for congenital abnormality in Oxford, 1991-2000, inclusive
Of the 57 258 births, 309 (0.5%) were terminated pregnancies because a fetal anomaly had been suspected or diagnosed prenatally. The rate and number of terminations for suspected fetal anomaly increased during the study period, from 129 (129/29 086 (0.4%)) in 1991-5 to 180 (180/28 172 (0.6%)) in 1996-2000. In the same time periods the number of prenatal diagnoses made (with abnormality present at birth) increased from 41% to 46%.7 The investigation that led to the final diagnosis being made was ultrasound scan (that is, structural anomaly, no evidence for chromosome anomaly) in 152 (49%) cases, abnormal karyotype (by chorionic villus sampling, amniocentesis, or fetal blood sampling) in 141 (46%), and molecular testing of DNA in 16 (5%).
Figure 2 shows that 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.
Fig 2 Number of pregnancies terminated because of fetal anomaly by year (n=309), number of autopsies, and number terminated before 13 weeks' gestation (autopsy not possible before 14 weeks)
Table 1 gives the final postnatal diagnosis for those fetuses from terminated pregnancies grouped by the body system involved and by lethality as previously described.6 Chromosome anomalies accounted for 141 (46%) of the 309 cases. Neural tube defects and other central nervous system defects were the most common structural defects, accounting for a further 66 (21%) cases. One hundred and thirty three (43%) fetuses were considered to have defects which would have proved lethal, and 44 (14%) defects were possibly lethal. In 132 (43%) the defects were compatible with survival beyond a year.
Table 1 Number of pregnancies terminated broadly categorised by defect and lethality
In this population 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. If we assume that half of those 44 fetuses with defects classified as possibly lethal (for example, diaphragmatic hernia) did survive (that is, 154 survivors in all), the reduction in prevalence of congenital malformations associated with long term morbidity due to termination of pregnancy would be 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 (for example, 43% of Down's syndrome cases diagnosed between the time of chorionic villus sampling and term or 23% between the time of amniocentesis and term8).
Table 2 shows an assessment of the contribution of the autopsy findings to the final diagnosis made for the purpose of counselling after termination of pregnancy for the 132 cases with structural anomalies and no evidence for abnormal karyotype. 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 of the 132 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 as described previously.6
Discussion
Royal College of Obstetricians and Gynaecologists. Ultrasound screening for fetal abnormalities: report of the RCOG working party. London: RCOG, 1997.
Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down's syndrome. A review. Health Technol Assess 1998;2: 1-112.
Bricker L, Garcia J, Henderson J, Mugford M, Neilson J, Roberts T, et al. Ultrasound screening in pregnancy: a systematic review of the clinical effectiveness, cost-effectiveness and women's views. Health Technol Assess 2000;4: 1-193.
Redfern M, Keeling JW, Powell E. The Royal Liverpool Children's inquiry report. London: Stationery Office, 2001.
Congenital malformation statistical notifications 1994. London: HMSO, 1997. (Series MB3 No 10.)
Boyd PA, Chamberlain P, Hicks NR. Six year experience of prenatal diagnosis in an unselected population in Oxford, UK. Lancet 1998;352: 1577-81.
National Perinatal Epidemiology Unit. Report of the Oxford Congenital Anomaly Register 1991-2001. Oxford: National Perinatal Epidemiology Unit, 2003.
Morris JK, Wald NJ, Watt HC. Fetal loss in Down syndrome pregnancies. Prenat Diagn 1999;19: 142-5.
Brodlie M, Laing IA, Keeling JW, McKenzie KJ. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. BMJ 2002;324: 761-3.
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.
Gaffney G, Manning N, Gould S, Boyd PA, Chamberlain P. An ultrasonographic assessment of skeletal dysplasias—a report of the diagnostic and prognostic accuracy in 35 cases. Prenat Diagn 1998;18: 357-62.
Khong TY. Falling neonatal autopsy rates BMJ 2002;324: 749-50.
Hunter M. Alder Hey report condemns doctors, management, and coroner. BMJ 2000;322: 255.
Anonymous. Families need more information about postmortem examinations. BMJ 2002;325: 1121.
Bauchner H, Vinci R. What have we learnt from the Alder Hey affair? BMJ 2001;322: 309-10.
((P A Boyd, senior clinical)
Correspondence to: P Boyd Patricia.boyd@orh.nhs.uk
Abstract
The Abortion Act 1967 allows termination of pregnancy if there is substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously disabled. During the past decade new screening and diagnostic tests have been introduced that allow earlier and more accurate diagnosis of fetal anomaly.1-3
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 termination of pregnancy may be requested when the implications of the investigations are less clear—for example, a fetus with mild cerebral ventriculomegaly. After termination of pregnancy most parents will want to know if the prenatal prediction was accurate and what the implications are for future pregnancies. This is particularly true when the prenatal diagnosis is based on ultrasound scan findings only. Such information may be obtained from the autopsy examination.
After the adverse publicity surrounding paediatric autopsies at Alder Hey Hospital4 there is widespread recognition that parents need a full explanation to make an informed decision. This information should not only be about the autopsy technique but also about the potential benefits. 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 risk of recurrence.
The prenatal diagnosis unit in Oxford is a tertiary referral centre in a teaching hospital. Since 1991 all anomalies (with the exception of those on the Office for National Statistics exclusion list5) 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 register6 7 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
Figure 1 provides an overview of the prenatal diagnosis of congenital anomalies and termination of pregnancy for fetal anomaly in local deliveries in Oxford during the 10 years 1991-2000 inclusive. Of the 57 258 deliveries (live births, neonatal deaths, stillbirths over 20 weeks, and all pregnancies terminated at any gestation for fetal anomaly), 1208 (2.1%) resulted in a fetus or baby with an abnormality.
Fig 1 Summary chart of prenatal screening and termination of pregnancy for congenital abnormality in Oxford, 1991-2000, inclusive
Of the 57 258 births, 309 (0.5%) were terminated pregnancies because a fetal anomaly had been suspected or diagnosed prenatally. The rate and number of terminations for suspected fetal anomaly increased during the study period, from 129 (129/29 086 (0.4%)) in 1991-5 to 180 (180/28 172 (0.6%)) in 1996-2000. In the same time periods the number of prenatal diagnoses made (with abnormality present at birth) increased from 41% to 46%.7 The investigation that led to the final diagnosis being made was ultrasound scan (that is, structural anomaly, no evidence for chromosome anomaly) in 152 (49%) cases, abnormal karyotype (by chorionic villus sampling, amniocentesis, or fetal blood sampling) in 141 (46%), and molecular testing of DNA in 16 (5%).
Figure 2 shows that 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.
Fig 2 Number of pregnancies terminated because of fetal anomaly by year (n=309), number of autopsies, and number terminated before 13 weeks' gestation (autopsy not possible before 14 weeks)
Table 1 gives the final postnatal diagnosis for those fetuses from terminated pregnancies grouped by the body system involved and by lethality as previously described.6 Chromosome anomalies accounted for 141 (46%) of the 309 cases. Neural tube defects and other central nervous system defects were the most common structural defects, accounting for a further 66 (21%) cases. One hundred and thirty three (43%) fetuses were considered to have defects which would have proved lethal, and 44 (14%) defects were possibly lethal. In 132 (43%) the defects were compatible with survival beyond a year.
Table 1 Number of pregnancies terminated broadly categorised by defect and lethality
In this population 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. If we assume that half of those 44 fetuses with defects classified as possibly lethal (for example, diaphragmatic hernia) did survive (that is, 154 survivors in all), the reduction in prevalence of congenital malformations associated with long term morbidity due to termination of pregnancy would be 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 (for example, 43% of Down's syndrome cases diagnosed between the time of chorionic villus sampling and term or 23% between the time of amniocentesis and term8).
Table 2 shows an assessment of the contribution of the autopsy findings to the final diagnosis made for the purpose of counselling after termination of pregnancy for the 132 cases with structural anomalies and no evidence for abnormal karyotype. 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 of the 132 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 as described previously.6
Discussion
Royal College of Obstetricians and Gynaecologists. Ultrasound screening for fetal abnormalities: report of the RCOG working party. London: RCOG, 1997.
Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down's syndrome. A review. Health Technol Assess 1998;2: 1-112.
Bricker L, Garcia J, Henderson J, Mugford M, Neilson J, Roberts T, et al. Ultrasound screening in pregnancy: a systematic review of the clinical effectiveness, cost-effectiveness and women's views. Health Technol Assess 2000;4: 1-193.
Redfern M, Keeling JW, Powell E. The Royal Liverpool Children's inquiry report. London: Stationery Office, 2001.
Congenital malformation statistical notifications 1994. London: HMSO, 1997. (Series MB3 No 10.)
Boyd PA, Chamberlain P, Hicks NR. Six year experience of prenatal diagnosis in an unselected population in Oxford, UK. Lancet 1998;352: 1577-81.
National Perinatal Epidemiology Unit. Report of the Oxford Congenital Anomaly Register 1991-2001. Oxford: National Perinatal Epidemiology Unit, 2003.
Morris JK, Wald NJ, Watt HC. Fetal loss in Down syndrome pregnancies. Prenat Diagn 1999;19: 142-5.
Brodlie M, Laing IA, Keeling JW, McKenzie KJ. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. BMJ 2002;324: 761-3.
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.
Gaffney G, Manning N, Gould S, Boyd PA, Chamberlain P. An ultrasonographic assessment of skeletal dysplasias—a report of the diagnostic and prognostic accuracy in 35 cases. Prenat Diagn 1998;18: 357-62.
Khong TY. Falling neonatal autopsy rates BMJ 2002;324: 749-50.
Hunter M. Alder Hey report condemns doctors, management, and coroner. BMJ 2000;322: 255.
Anonymous. Families need more information about postmortem examinations. BMJ 2002;325: 1121.
Bauchner H, Vinci R. What have we learnt from the Alder Hey affair? BMJ 2001;322: 309-10.
((P A Boyd, senior clinical)