- Email: [email protected]
Cardiotocography and ST analysis for intrapartum fetal monitoring
Correspondence
We declare that we have no conflicts of interest.
*Fulvio A Scorza, Ricardo M Arida, Esper A Cavalheiro [email protected] Disciplina de Neurologia Experimental, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, SP 04023-900, Brazil (FAS, EAC); and Departamento de Fisiologia, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, SP, Brazil (RMA).
www.thelancet.com Vol 378 September 24, 2011
1
2
3
4
5
Schmidt MI, Duncan BB, Azevedo e Silva G, et al. Chronic non-communicable diseases in Brazil: burden and current challenges. Lancet 2011; 377: 1949–61. de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav 2008; 12: 540–46. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: current knowledge and future directions. Lancet Neurol 2008; 7: 1021–31. Scorza FA, Arida RM, Terra VC, et al. What can be done to reduce the risk of SUDEP? Epilepsy Behav 2010; 18: 137–38. Hirsch LJ, Donner EJ, So EL, et al. Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy. Neurology 2011; 76: 1932–38.
Inequities in suicide prevention in Brazil The paper by Michael Reichenheim and colleagues (June 4, p 1962)1 covers mortality related to homicides and accidents, but not suicide—the third external cause of death in Brazil, on which serious inequities can be found. Suicide is responsible for 6·8% of deaths due to external causes, despite its under-reporting.2 In fact, nearly 20% of deaths due to external causes in Brazil are recorded only as to mechanism, not intent (ie, falls and drowning 10·9%; undetermined intention 8·7%), making it impossible to ascertain how many are accidents or suicides. Whichever overall rate it might be, it does not immediately reveal the inequities found across regions (4·7 per 100 000 in the north vs 9·4 per 100 000 in the southeast), across towns of different population sizes (eg, 4 per 100 000 in populations of >200 000 vs 13 per 100 000 in populations of <20 000), and across age and sex: in the past 25 years, overall suicide rates have increased by 29·5% in Brazil; however, for men aged 15–24 years it increased by 1900% (from 0·3 to 6·0 per 100 000) and for women by 300% (from 0·5 to 2·0 per 10 000).3 The 2006 announcement of a national strategy for suicide prevention was not followed by the expected action. The success in
bringing health equity to the centre of national politics, evident in other areas, unfortunately has not happened in relation to suicide prevention. In the absence of an effectively implemented policy for its prevention, inequities related to suicide mortality will continue at unacceptable levels. In the worst case scenario, they will increase.
Science Photo Library
It knows no geographic, social, or racial boundaries, occurring in men and women and affecting people of all ages.2 People with epilepsy are more likely to die prematurely than are those without epilepsy, and the most common epilepsy-related cause is sudden unexpected death in epilepsy (SUDEP).3 Risk factors include refractory epilepsy, generalised tonicclonic seizures, polytherapy, duration of seizure disorder, early onset of epilepsy, and young age.3 Improved seizure control by treatment (pharmacological or surgical) seems to be one of the most important measures to prevent SUDEP, and promising strategies include reduction of stress, physical activity, dietary management (eg, omega 3 supplementation), supervision at night, and family members’ knowledge of cardiopulmonary resuscitation and defibrillator use.4 Our research group has organised annual Latin-American Summer Schools on Epilepsy since 2007. SUDEP has been intensively discussed at these events, and it has become clear to us that this issue needs to be addressed by short-term and longterm strategies at the individual, institutional, and global levels. The US National Institute of Neurological Disorders and Stroke has also sponsored a 3-day multidisciplinary workshop to advance research into SUDEP and its prevention.5 We fully agree with the SUDEP Coalition established there—ie, that with the expansion of clinical, genetic, and basic science research, there is reasonable hope of advancing our understanding of SUDEP and ultimately our ability to prevent it.5
We declare that we have no conflicts of interest.
*J M Bertolote, N Botega, D de Leo [email protected] Griffith University, Brisbane, QLD, Australia (JMB, DdL); *Faculdade de Medicina de Botucatu, UNESP, Botucatu, SP 18607-142, Brazil (JMB); and Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brazil (NB) 1
2
3
Reichenheim ME, de Souza ER, Moraes CL, de Mello Jorge MHP, da Silva CMFP, de Souza Minayo MC. Violence and injuries in Brazil: the effect, progress made, and challenges ahead. Lancet 2011; 377: 1962–75. Marin-Leon L, Barros MB. Mortes por suicidio: diferencas de genero e nivel socioeconomico Rev Saude Publica 2003; 37: 357–63. Mello-Santos C, Bertolote JM, Wang YP. Epidemiology of suicide in Brazil (1980–2000). Rev Bras Psiquiat 2005; 27: 131–34.
Cardiotocography and ST analysis for intrapartum fetal monitoring The 2001 paper by Isis Amer-Wåhlin and colleagues,1 describing a randomised trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring, has been subject to inquiries by the Swedish Research Council, which criticised the principal investigator, Karel Maršál, and the monitor for not having sufficiently guaranteed the data quality. Eight cases of metabolic acidosis have been the subject of concern. However, there are other concerns regarding the quality control. Maršál, in private correspondence with The Lancet dated Aug 2, 2010, presented a reanalysis and comment on the report by the Swedish Research Council. He defended the exclusion of some of these eight cases owing to the 1137
Science Photo Library
Correspondence
See Online for webappendix
applied quality control. The specified criteria were “According to the study protocol, blood samples from both the cord artery and cord vein were required (minimum difference in pH 0·03 and in pCO2 1·0 kPa)“. Those criteria are not mentioned in the original article. In the reanalysis, Maršál does not consider that, if the same criteria are applied for the originally included 46 cases of metabolic acidosis, another ten patients do not comply with the inclusion criteria. In the reanalysis, now published,2 there is a completely new and quite different definition of valid data. Implementation of those two different criteria will give large differences in participants with valid data in the total study. I and another reviewer have earlier recommended a complete reanalysis of the data. Such a control was not done by the Swedish Research Council. I hope that Maršál will take the responsibility, and, according to the decision of the Vice-Chancellor of Lund University, present a reanalysis based on validated data according to the prespecified criteria. Finally, inconsistent application of prespecified rules is a major concern. I declare that I have no conflicts of interest.
Ulf Hanson [email protected] Department of Obstetrics and Gynecology, Uppsala University, 75643 Uppsala, Sweden 1
2
Amer-Wåhlin I, Hellsten C, Norén H, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet 2001; 358: 534–38. Amer-Wåhlin I, Kjellmer I, Maršál K, Olofsson P, Rosén KG. Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal ECG revisited: analysis of data according to standard versus modified intention-to-treat principle. Acta Obstet Gynecol Scand 2011; 90: 990–96.
Author’s reply To improve the identification of fetuses at risk of asphyxia in labour, an automatic analyser of the ST waveform of the fetal electrocardiogram (STAN) for use in combination with cardiotocography (CTG) was 1138
introduced in the 1990s. During 1998–2000, we did a randomised controlled trial to compare CTG only with CTG+ST in 4966 labouring women at three Swedish labour wards.1 The rate of metabolic acidosis in the umbilical arterial blood was found to be significantly lower in the CTG+ST group than in the CTG group (see webappendix). Subsequently, the STAN method became commercially available and used in clinical practice around Europe. From Sweden, some cases of adverse neonatal outcome were reported when using ST waveform analysis. This initiated a debate regarding the validity of data on metabolic acidosis in our trial. Three subsequent investigations of the study were undertaken by external experts: one initiated by the research group and two by Lund University. In September, 2010, the Vice-Chancellor of Lund University concluded that there were errors in a few cases, but that no misconduct in research had taken place.2 The original data have been scrutinised by the STAN research group and two cases of misclassification were identified (one case of erroneous rounding of the third decimal of a pH value and one with acid-base data missing in the study database). Furthermore, six cases of metabolic acidosis in the CTG group and four in the CTG+ST group should not have been considered since too small an arteriovenous gradient in pH or pCO2 made the acid-base data invalid. The statistical analysis after corrections showed slightly changed relative risks and 95% CIs; however, the level of significance remained unchanged in favour of the CTG+ST group (webappendix). Thus, the results of renewed analysis did not change the conclusion of the original study that intrapartum monitoring with CTG+ST waveform analysis resulted in an improved perinatal outcome as reflected in a decreased rate of metabolic acidosis at birth. The
details of the reanalysis and discussion of various types of data analysis when assessing medical devices in a randomised controlled trial have been published elsewhere.3 During the past decade, substantial experience in the use of the STAN method in labour has been gained, confirming its clinical usefulness,4 and international guidelines for users have been developed.5 I declare that I have no conflicts of interest.
Karel Maršál, on behalf of all authors [email protected] Department of Obstetrics and Gynecology, Skåne University Hospital Lund, 22185 Lund, Sweden 1
2
3
4
5
Amer-Wåhlin I, Hellsten C, Norén H, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet 2001; 358: 534–38. Lunds Universitet. Utredning av forskningsoredlighet— fosterövervakningstekniken STAN. http:// www.med.lu.se/nyheter/utredning_av_ forskningsoredlighet (accessed May 24, 2011). Amer-Wåhlin I, Kjellmer I, Maršál K, Olofsson P, Rosén KG. Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal ECG revisited: analysis of data according to standard versus modified intention-to-treat principle. Acta Obstet Gynecol Scand 2011; 90: 990–96. Norén H, Carlsson A. Reduced prevalence of metabolic acidosis at birth: an analysis of established STAN usage in the total population of deliveries in a Swedish district hospital. Am J Obstet Gynecol 2010; 202: 546.e1–7. Amer-Wåhlin I, Arulkumaran SS, Hagberg H, Maršál K, Visser GHA. Fetal electrocardiogram: ST waveform analysis in intrapartum surveillance. BJOG 2007; 114: 1191–93.
www.thelancet.com Vol 378 September 24, 2011
We declare that we have no conflicts of interest.
*Fulvio A Scorza, Ricardo M Arida, Esper A Cavalheiro [email protected] Disciplina de Neurologia Experimental, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, SP 04023-900, Brazil (FAS, EAC); and Departamento de Fisiologia, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, SP, Brazil (RMA).
www.thelancet.com Vol 378 September 24, 2011
1
2
3
4
5
Schmidt MI, Duncan BB, Azevedo e Silva G, et al. Chronic non-communicable diseases in Brazil: burden and current challenges. Lancet 2011; 377: 1949–61. de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav 2008; 12: 540–46. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: current knowledge and future directions. Lancet Neurol 2008; 7: 1021–31. Scorza FA, Arida RM, Terra VC, et al. What can be done to reduce the risk of SUDEP? Epilepsy Behav 2010; 18: 137–38. Hirsch LJ, Donner EJ, So EL, et al. Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy. Neurology 2011; 76: 1932–38.
Inequities in suicide prevention in Brazil The paper by Michael Reichenheim and colleagues (June 4, p 1962)1 covers mortality related to homicides and accidents, but not suicide—the third external cause of death in Brazil, on which serious inequities can be found. Suicide is responsible for 6·8% of deaths due to external causes, despite its under-reporting.2 In fact, nearly 20% of deaths due to external causes in Brazil are recorded only as to mechanism, not intent (ie, falls and drowning 10·9%; undetermined intention 8·7%), making it impossible to ascertain how many are accidents or suicides. Whichever overall rate it might be, it does not immediately reveal the inequities found across regions (4·7 per 100 000 in the north vs 9·4 per 100 000 in the southeast), across towns of different population sizes (eg, 4 per 100 000 in populations of >200 000 vs 13 per 100 000 in populations of <20 000), and across age and sex: in the past 25 years, overall suicide rates have increased by 29·5% in Brazil; however, for men aged 15–24 years it increased by 1900% (from 0·3 to 6·0 per 100 000) and for women by 300% (from 0·5 to 2·0 per 10 000).3 The 2006 announcement of a national strategy for suicide prevention was not followed by the expected action. The success in
bringing health equity to the centre of national politics, evident in other areas, unfortunately has not happened in relation to suicide prevention. In the absence of an effectively implemented policy for its prevention, inequities related to suicide mortality will continue at unacceptable levels. In the worst case scenario, they will increase.
Science Photo Library
It knows no geographic, social, or racial boundaries, occurring in men and women and affecting people of all ages.2 People with epilepsy are more likely to die prematurely than are those without epilepsy, and the most common epilepsy-related cause is sudden unexpected death in epilepsy (SUDEP).3 Risk factors include refractory epilepsy, generalised tonicclonic seizures, polytherapy, duration of seizure disorder, early onset of epilepsy, and young age.3 Improved seizure control by treatment (pharmacological or surgical) seems to be one of the most important measures to prevent SUDEP, and promising strategies include reduction of stress, physical activity, dietary management (eg, omega 3 supplementation), supervision at night, and family members’ knowledge of cardiopulmonary resuscitation and defibrillator use.4 Our research group has organised annual Latin-American Summer Schools on Epilepsy since 2007. SUDEP has been intensively discussed at these events, and it has become clear to us that this issue needs to be addressed by short-term and longterm strategies at the individual, institutional, and global levels. The US National Institute of Neurological Disorders and Stroke has also sponsored a 3-day multidisciplinary workshop to advance research into SUDEP and its prevention.5 We fully agree with the SUDEP Coalition established there—ie, that with the expansion of clinical, genetic, and basic science research, there is reasonable hope of advancing our understanding of SUDEP and ultimately our ability to prevent it.5
We declare that we have no conflicts of interest.
*J M Bertolote, N Botega, D de Leo [email protected] Griffith University, Brisbane, QLD, Australia (JMB, DdL); *Faculdade de Medicina de Botucatu, UNESP, Botucatu, SP 18607-142, Brazil (JMB); and Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brazil (NB) 1
2
3
Reichenheim ME, de Souza ER, Moraes CL, de Mello Jorge MHP, da Silva CMFP, de Souza Minayo MC. Violence and injuries in Brazil: the effect, progress made, and challenges ahead. Lancet 2011; 377: 1962–75. Marin-Leon L, Barros MB. Mortes por suicidio: diferencas de genero e nivel socioeconomico Rev Saude Publica 2003; 37: 357–63. Mello-Santos C, Bertolote JM, Wang YP. Epidemiology of suicide in Brazil (1980–2000). Rev Bras Psiquiat 2005; 27: 131–34.
Cardiotocography and ST analysis for intrapartum fetal monitoring The 2001 paper by Isis Amer-Wåhlin and colleagues,1 describing a randomised trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring, has been subject to inquiries by the Swedish Research Council, which criticised the principal investigator, Karel Maršál, and the monitor for not having sufficiently guaranteed the data quality. Eight cases of metabolic acidosis have been the subject of concern. However, there are other concerns regarding the quality control. Maršál, in private correspondence with The Lancet dated Aug 2, 2010, presented a reanalysis and comment on the report by the Swedish Research Council. He defended the exclusion of some of these eight cases owing to the 1137
Science Photo Library
Correspondence
See Online for webappendix
applied quality control. The specified criteria were “According to the study protocol, blood samples from both the cord artery and cord vein were required (minimum difference in pH 0·03 and in pCO2 1·0 kPa)“. Those criteria are not mentioned in the original article. In the reanalysis, Maršál does not consider that, if the same criteria are applied for the originally included 46 cases of metabolic acidosis, another ten patients do not comply with the inclusion criteria. In the reanalysis, now published,2 there is a completely new and quite different definition of valid data. Implementation of those two different criteria will give large differences in participants with valid data in the total study. I and another reviewer have earlier recommended a complete reanalysis of the data. Such a control was not done by the Swedish Research Council. I hope that Maršál will take the responsibility, and, according to the decision of the Vice-Chancellor of Lund University, present a reanalysis based on validated data according to the prespecified criteria. Finally, inconsistent application of prespecified rules is a major concern. I declare that I have no conflicts of interest.
Ulf Hanson [email protected] Department of Obstetrics and Gynecology, Uppsala University, 75643 Uppsala, Sweden 1
2
Amer-Wåhlin I, Hellsten C, Norén H, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet 2001; 358: 534–38. Amer-Wåhlin I, Kjellmer I, Maršál K, Olofsson P, Rosén KG. Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal ECG revisited: analysis of data according to standard versus modified intention-to-treat principle. Acta Obstet Gynecol Scand 2011; 90: 990–96.
Author’s reply To improve the identification of fetuses at risk of asphyxia in labour, an automatic analyser of the ST waveform of the fetal electrocardiogram (STAN) for use in combination with cardiotocography (CTG) was 1138
introduced in the 1990s. During 1998–2000, we did a randomised controlled trial to compare CTG only with CTG+ST in 4966 labouring women at three Swedish labour wards.1 The rate of metabolic acidosis in the umbilical arterial blood was found to be significantly lower in the CTG+ST group than in the CTG group (see webappendix). Subsequently, the STAN method became commercially available and used in clinical practice around Europe. From Sweden, some cases of adverse neonatal outcome were reported when using ST waveform analysis. This initiated a debate regarding the validity of data on metabolic acidosis in our trial. Three subsequent investigations of the study were undertaken by external experts: one initiated by the research group and two by Lund University. In September, 2010, the Vice-Chancellor of Lund University concluded that there were errors in a few cases, but that no misconduct in research had taken place.2 The original data have been scrutinised by the STAN research group and two cases of misclassification were identified (one case of erroneous rounding of the third decimal of a pH value and one with acid-base data missing in the study database). Furthermore, six cases of metabolic acidosis in the CTG group and four in the CTG+ST group should not have been considered since too small an arteriovenous gradient in pH or pCO2 made the acid-base data invalid. The statistical analysis after corrections showed slightly changed relative risks and 95% CIs; however, the level of significance remained unchanged in favour of the CTG+ST group (webappendix). Thus, the results of renewed analysis did not change the conclusion of the original study that intrapartum monitoring with CTG+ST waveform analysis resulted in an improved perinatal outcome as reflected in a decreased rate of metabolic acidosis at birth. The
details of the reanalysis and discussion of various types of data analysis when assessing medical devices in a randomised controlled trial have been published elsewhere.3 During the past decade, substantial experience in the use of the STAN method in labour has been gained, confirming its clinical usefulness,4 and international guidelines for users have been developed.5 I declare that I have no conflicts of interest.
Karel Maršál, on behalf of all authors [email protected] Department of Obstetrics and Gynecology, Skåne University Hospital Lund, 22185 Lund, Sweden 1
2
3
4
5
Amer-Wåhlin I, Hellsten C, Norén H, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet 2001; 358: 534–38. Lunds Universitet. Utredning av forskningsoredlighet— fosterövervakningstekniken STAN. http:// www.med.lu.se/nyheter/utredning_av_ forskningsoredlighet (accessed May 24, 2011). Amer-Wåhlin I, Kjellmer I, Maršál K, Olofsson P, Rosén KG. Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal ECG revisited: analysis of data according to standard versus modified intention-to-treat principle. Acta Obstet Gynecol Scand 2011; 90: 990–96. Norén H, Carlsson A. Reduced prevalence of metabolic acidosis at birth: an analysis of established STAN usage in the total population of deliveries in a Swedish district hospital. Am J Obstet Gynecol 2010; 202: 546.e1–7. Amer-Wåhlin I, Arulkumaran SS, Hagberg H, Maršál K, Visser GHA. Fetal electrocardiogram: ST waveform analysis in intrapartum surveillance. BJOG 2007; 114: 1191–93.
www.thelancet.com Vol 378 September 24, 2011