Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Unexplained stilbirths
- Sandra F Robinson (22 October 2005)
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Stillbirths - classification is not explanation
- Edwin P Kirk (11 November 2005)
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Classification of stillbirth by relevant condition at death
- Neil J Sebire (11 November 2005)
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The fetal growth charts are the main issue
- mark sillender (14 November 2005)
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Classification of stillbirth: cause, condition or mechanism?
- Jan Jaap HM Erwich, Jozien P Holm, Fleurisca J Korteweg, and Albertus Timmer (16 November 2005)
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Classification of stillbirths
- Jason Gardosi (17 November 2005)
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Customised growth charts and ReCoDe system
- Pensee Wu, Chris P. Spencer, Consultant Obstetrician and Gynaecologist, St John's Hospital, Chelmsford, Essex, CM2 9BG (25 November 2005)
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Re: Customised growth charts and ReCoDe system
- Jason Gardosi (1 December 2005)
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Classification and Growth Restriction in Stillbirths
- Steve J Gould, Michael Weindling. (2 December 2005)
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Sandra F Robinson, Medical Sales MK45 1JY
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Interesting report. My first child was stillborn at 37 weeks. He weighed 6lbs 2 oz. Despite a full post-mortem, no cause was found. I was assured that subsequent pregnancies would be normal as "lightning never strikes twice". My second son was born this year, weighing 7lbs 15 oz. He seemed OK, but had some blistering on his skin. We were devastated to learn that he had a fatal genetic condition called Herlitz junctional epidermolysis bullosa. He died aged 4 months. What angers me the most is that the skin blistering was noticed at the post mortem but not investigated further; all that was needed was a biopsy. I was mis-informed and my poor baby son had to suffer unimaginable pain. I'm not the only one. More needs to be done to investigate "unexplained" stillbirths. Yours sincerely A grieving mum. Competing interests: None declared |
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Edwin P Kirk, Staff Specialist Dept of Medical Genetics, Sydney Children's Hospital, High St, Randwick NSW 2031, Australia
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Gardosi et al congratulate themselves that under the ReCoDe classification "only 15.2% of stillbirths remained unexplained". But if the most common "condition" was fetal growth restriction, and 43% fell into this category, then at least 58% are still unexplained under this system. To classify something falls well short of explaining its cause. There are many different known causes for fetal growth restriction, and doubtless many unknown or at least unidentifiable ones. Some of these may not even contribute to a risk of stillbirth when present. The goal should be a clear understanding of the UNDERLYING cause of every stillbirth. The fetal postmortem examination, despite its lack of effect on classification in this study, remains a vital part of this effort, and has repeatedly been shown to have an important impact on counselling to parents about recurrence risks. Competing interests: None declared |
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Neil J Sebire, Consultant in Paediatric Pathology Great Ormond Street Hospital, London WC1N 3JH
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The recent publication by Gardozi et al1 raises several issues requiring further discussion. First, it is somewhat surprising that in a study based on classification of stillbirth using previous pathological classifications, no perinatal pathologist was involved in this study. Second, and most importantly, many might take issue with the underlying premise of this study. The authors state that any classification system that results in a high proportion of cases being defined as unexplained is not fulfilling its purpose. Surely the purpose of a classification system is to the accurate so as to improve understanding of the underlying disease processes. If it is true that the mechanism or cause leading to death in an individual case cannot be determined with more than speculative certainty, it is entirely correct to classify the case as unexplained rather than to assign a potentially erroneous or artificial cause of death in order to create the impression of knowledge. It is unclear why the term ‘relevant condition at death’ was introduced, rather than ‘cause of death’, which is used in all other settings of death investigation, since the term ‘relevant’ presumably means ‘relevant to the cause of death’ as opposed to any other possible relevance. In particular, the main finding of this study is the reclassification of numerous apparently previously unexplained cases, as fetal growth restriction (FGR), such classification being on the basis of an estimated customised weight for gestation below the 10th percentile. The clinical relevance of growth restriction according to these criteria remain controversial in ongoing pregnancies, and to therefore attribute the cause of death to FGR in the absence of other specific findings may well be incorrect. It is, of course, entirely possible that growth restriction is an important contributory factor to stillbirth. However, the issue in these cases is primarily to try to understand why a minority of fetuses with mild growth restriction should die in-utero, whilst 10% of the entire obstetric population will demonstrate a similar degree of FGR but will result in livebirth. It is agreed that current antenatal management only detects a small proportion of intrauterine FGR, and that improved detection methods may be associated with improved outcomes. Nevertheless, the suggestions of this study have the potential to lead to both misleading interpretations of the cause of death in future cases of stillbirth, and to a falsely inflated sense of understanding of the underlying mechanisms leading to such intrauterine death in the absence of an apparent pathophysiological basis. Although it is entirely appropriate to highlight that severe FGR can lead to intrauterine death, to suggest that the mere presence of biometric markers suggesting a mild degree of growth restriction similar to that of a large proportion of the population of living fetuses ‘causes’ death, does not in anyway improve our understanding or certainty of underlying disease processes in these cases and is inappropriate for introduction into clinical practice on the basis of currently available evidence. Yours Sincerely Dr NJ Sebire
1. Gardosi J, Kady SM, McGeown P, Francis P, Tonks A. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. Br Med J 2005; ,331: 1113-7. Competing interests: None declared |
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mark sillender, obstetrician & gynaecologist Chelsea & Westminster Hospital, SW10 9NH
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Gardosi et al's (1) recent report seems to lack focus on the main issue. Definition of a new classification for stillbirth may be slightly useful, but shouldn't be used retrospectively to justify the utility of individually customised fetal growth charts. The authors' method of using customised charts to improve detection of pathologically small babies seems logical, and may prove to be a significant advance in antenatal care. However, it may also expose women & babies to iatrogenic harm if delivery is brought forward for no or little benefit. I look forward to the authors producing a prospective randomised controlled trial which would hopefully validate their charts. Hopefully this trial will have a cute acronym too. References 1. Gardosi J, Kady SM, McGeown P, Francis P, Tonks A. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. Br Med J 2005; ,331: 1113-7. Competing interests: None declared |
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Jan Jaap HM Erwich, Staff specialist fetal maternal medicine University Medical Centre Groningen 9700 RB Groningen The Netherlands, Jozien P Holm, Fleurisca J Korteweg, and Albertus Timmer
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Editor- The paper of Gardosi et al1 is important to illustrate the inadequacy of current classification systems and to stress the preponderance of fetal growth restriction which, presumably, is not diagnosed before the death occurs. Although definition of relevant conditions at death may mute the debate about its cause, the distinction between conditions, causes or mechanisms of death is still not clear in this paper. Clear definitions or guidelines are not provided. Asphyxia is a non-specific final common pathway of death not a cause nor a condition. The authors intend to identify as many conditions as possible for a case. This would be a powerful tool to stop debates about the cause where conditions overlap or where several entities coexist, like fetal growth restriction, pre-eclampsia, placental insufficiency and oligohydramnios. However, the paper describes one condition as primary (cause?) and one as secondary. Interestingly, in the primary group of fetal growth restriction only 53/1129 (4.7%) have placental insufficiency as a secondary condition. This unexpected low number illustrates the loss of insight into the pathway to death. The issue of using a hierarchy is motivated to “reflect clinical relevance”. Although it seems preferable, a classification system for perinatal mortality cannot be strictly hierarchical because of the cognitive process of how doctors make a diagnosis2. Any system restricted to stillbirths neglects the issue of iatrogenous preterm delivery with neonatal death in cases with the same relevant conditions. We welcome any suggestion for better classification of perinatal mortality, since this is essential for both patient care and prevention. The value of ReCoDe needs to be proven. 1. Gardosi J, Kady SM, McGeown P, Francis A, Tonks A. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. BMJ, doi:10.1136/bmj.38629.587639.7C (19 October 2005). 2. Elstein AS, Schwarz A. Clinical problem solving and diagnostic decision making: selective review of the cognitive literature. BMJ 2002; 324(7339):729-732. Competing interests: No competing financial interests. Authors are developing a classification system themselves. |
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Jason Gardosi, Director Perinatal Institute, Birmingham B15 3QE
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Editor - on behalf of my co-authors, I would like to thank your correspondents for their interest in our paper. Ms Robinson’s sad outcome of her first pregnancy reminds us that often no cause of stillbirth is found, despite a postmortem. An overt emphasis on ‘cause’, and the frequent inability to find one, is difficult for bereaved parents who are seeking to understand what has happened. A causal classification system often also fails to do justice to the pathologist’s efforts, when an ‘unexplained’ category results despite a high quality postmortem. We found that with ReCoDe, postmortem findings could be fed very easily into the classification system. We therefore agree with Dr Kirk on the need to emphasise the importance of postmortems, and believe that they are more informative when coupled with a more relevant classification system. We were very careful in our paper not to present the ReCoDe classification as a way to identify causes of death. Yet Dr Sebire's letter still refers to ‘causes’ over half a dozen times. For example, fetal growth restriction should not be seen as a cause of death, but a relevant condition which is known to increase the risk of stillbirth 5 fold for fetuses below the 10th customised centile, and over 10 fold for fetuses below the 3rd customised centile [1]. Of course not all growth restricted fetuses die; but nor do most fetuses with conditions representing any of the old perinatal mortality categories. Dr Sebire also takes issue with the fact that no pathologist was listed as co-author. This is explained by the BMJ’s strict rules on authorship. The Perinatal Institute in fact enjoys a very active collaboration with the regional perinatal pathology team led by Dr Phil Cox. They have not only commented favourably on our new classification, but already initiated studies on stillbirth and postmortem assessment of fetal growth restriction. Theirs is a good indication that ReCoDe, which deals with conditions, will stimulate further research into causes. Clearly, identifying causes has been a formidable challenge over the years. Using the conventional system, the proportion of stillbirths classified as ‘unexplained’ has in fact been getting larger [2]. In addition, overall stillbirth rates have been on the increase [3]. While everyone hopes that more of the underlying causes of stillbirths will be determined one day, the main stakeholders require more immediately to have a better insight into the relevant conditions. They include the bereaved parents, who have to come to terms with the loss; the clinicians who will want to focus on better methods to recognise fetal growth problems as major risk factors of in-utero death; and those who are tasked with planning health services, and who will need to allocate the necessary resources for improved strategies for prevention. Finally, Dr Sillender is correct to state that an RCT of antenatal growth assessment would be welcome. For sufficient power to demontrate a reduction in stillbirths, the size of such a trial would need to be formidable, and attempts to obtain funding have not been successful in the past. Perhaps this lack of interest was linked to the fact that most stillbirths, to date, have been classified as ‘unexplained’… 1. Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus population-based birthweight standards. Br J Obstet Gynaecol 2001;108:830-4. 2. Maternal and Child Health Consortium. CESDI 4th Annual Report: Confidential Enquiry of Stillbirths and Deaths in Infancy, 1997 3. Confidential Enquiry into Maternal and Child Health. Stillbirth, Neonatal and Post-neonatal Mortality 2000–2003, England, Wales and Northern Ireland. London:RCOG Press; 2005 Competing interests: None declared |
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Pensee Wu, Specialist Registrar in Obstetrics and Gynaecology St John's Hospital, Chelmsford, Essex, CM2 9BG, Chris P. Spencer, Consultant Obstetrician and Gynaecologist, St John's Hospital, Chelmsford, Essex, CM2 9BG
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Editor - The findings of Gardosi et al [1] relies heavily on their customised antenatal growth charts as the ReCoDe system has reclassified most of the unknown stillbirths as associated with fetal growth restriction. It is questionable how these charts could account for the growth velocity of fetuses from varying ethnicity, maternal weight and parity, as population based studies would be required to obtain background data for calculation. In addition, in order to determine that a fetus has not achived its full growth potential, at least two serial assessments of growth are needed. Furthermore, in Asian populations, where fetal size is generally smaller than Caucasian counterparts, a reclassification of small for dates babies would actually suggest that these babies are normally small and are not associated with intrauterine growth restriction. Consequently, this would increase the number of unexplained stillbirths. Certain occult conditions, such as undiagnosed gestational diabetes could also explain a significant number of stillbirths but is very difficult to diagnose as glucose tolerance returns to normal so rapidly after placental delivery. In its attempt to be comprehensive, the ReCoDe system has become overly complicated with confusing primary and secondary classifications. In order for a classification system to be widely accepted, it should be simple to understand with clearly defined categories that help reduce interpersonal errors in classification. We look forward to a modified version of ReCoDe in the future. Pensee Wu, Specialist Registrar in Obstetrics and Gynaecology, St John's Hospital, Chelmsford, Essex, CM2 9BG Chris P. Spencer, Consultant Obstetrician and Gynaecologist, St John's Hospital, Chelmsford, Essex, CM2 9BG 1. Gardosi J, Kady SM, McGeown P, Francis P, Tonks A. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. Br Med J 2005; 331: 1113-7. Competing interests: None declared |
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Jason Gardosi, Director Perinatal Institute, Birmingham B6 5RQ
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Editor: Our response to Erwich and colleagues is available on http://bmj.bmjjournals.com/cgi/content/full/331/7527/1270 Wu and Spencer question the ability of customised charts to define growth restriction in our study of stillbirths. In fact we used customised birthweight percentiles (www.gestation.net/centiles) to calculate which baby was growth restricted. In the majority of cases where a baby is small for gestational age at birth, either alive or dead, the fact that it was small was not recognised as such antenatally. If there was no suspicion, it is likely that there were no ‘growth scans’, as in most units these are not done routinely. However if they were done, and growth restriction was recognised, then it is possible that delivery was expedited once the baby was considered to be mature enough. Thus relying on serial growth scans to explain growth restriction as a relevant condition for stillbirth is likely to be of limited use. Customised centiles are indeed based on coefficients from heterogeneous populations, and adjust – within normal limits – for physiological variables such as maternal height, weight, ethnic group and parity as well as the sex of the baby. A low customised birth weight percentile is a good indicator of pathological smallness [1]. A summary of the evidence is available from www.perinatal.nhs.uk/growth/. Wu and Spencer consider that the detail of primary and secondary conditions in our paper makes ReCoDe too complicated. The analysis was undertaken to test the coding in our new classification and to shed new light on conditions associated with stillbirth. However we agree that categories can be reported in a more simplified way. We have done this in a recent regional report [2], where we summarised stillbirths in 9 major ReCoDe groups: congenital anomaly; infection; fetal growth restriction; umbilical cord; placenta; maternal conditions; intrapartum asphyxia; miscellaneous; and unclassified/unknown. 1. Gardosi J. Customised Fetal Growth Standards: Rationale and Clinical Application. Seminars in Perinatology 2004;28(1):33-40. 2. Gardosi J and Francis A. Perinatal Mortality and Social Deprivation. In: Key Health Data for the West Midlands, University of Birmingham, 2005 (Chapter 5), www.perinatal.nhs.uk/pnm/Keyheathdatachapter5.pdf Competing interests: None declared |
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Steve J Gould, Consultant Paediatric Pathologist OX39DU, Michael Weindling.
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We were very interested to read the paper on the Classification of Stillbirth by Gardosi et al (1) and agree that current UK classification systems require reassessment. The Confidential Enquiry into Maternal and Child Health (CEMACH) is concerned that the decline in infant mortality rate has distracted attention from an apparent deterioration in the stillbirth rate. Confidential enquiry data (to be published) show a small but significant increase in the stillbirth rate over the last ten years from 5.37 per 1000 livebirths in 1994 to 5.69 in 2004, a trend also suggested by Office of National Statistics data. Over 60% of stillbirths reported to CEMACH are classified as ‘unexplained’. This is unacceptable if it is therefore inferred that no relevant factors exist or that these deaths are inevitable. We agree that many ‘unexplained’ stillbirths show evidence of growth restriction. A CESDI study of antepartum term stillbirths showed a simple reclassification reduced the proportion of ‘unexplained’ deaths from approximately 77% to 31% (2). In Liverpool, a review of 177 stillbirths found that only 27% of deaths remained unexplained following full clinico- pathological correlation which took into account growth restriction (3). Clearly, growth restriction is not, in itself, a cause of death: although its presence implies impaired fetal nutrition probably from reduced utero- placental blood flow in many cases. Although there is a shortage of pathologists with appropriate expertise, autopsy remains helpful in diagnosing growth restriction by providing evidence of nutritional deprivation not available to the obstetrician. CEMACH believes that a national programme should be developed with the ultimate aim of reducing the stillbirth rate and is in a position to assist in this process. Whether ReCoDe is the optimal solution is as yet unclear, but with the current limitations in knowledge, a better and informative classification system would be a major step forward. References 1 Gardosi J, Kady, SM, McGeown P, Francis A, Tonks A. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. BMJ 2005; 331: 1113 - 1117 2 Study of Antepartum Term Stillbirths. Confidential Enquiry into Stillbirths and Deaths in Infancy. 5th Annual Report. pp 41 – 50, 1998. 3 Weindling AM, Shukla R, Ashworth M, Kokai G, Fleming K. Perinatal deaths in the UK: A better classification system needed? Archives of Disease in Childhood 2005; 90, supplement II, A64. Competing interests: None declared |
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