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Confidential enquiries into hypoxic ischaemic encephalopathy
Best Practice & Research Clinical Obstetrics and Gynaecology 23 (2009) 357–368
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Confidential enquiries into hypoxic ischaemic encephalopathy Eckhart J. Buchmann, MBBCh, MSc(Med), FCOG(SA), PhD, Associate Professor and Head a, *, Sithembiso C. Velaphi, MBChB, MMed, FCPaed(SA), Associate Professor and Head b a
Department of Obstetrics and Gynaecology, Chris Hani Baragwanath Hospital and University of the Witwatersrand, P.O. Bertsham, 2013 Johannesburg, South Africa b Division of Neonatology, Department of Paediatrics and Child Health, Chris Hani Baragwanath Hospital and University of the Witwatersrand, P.O. Bertsham, 2013 Johannesburg, South Africa
Keywords: asphyxia neonatorum confidential enquiry clinical audit hypoxic ischaemic encephalopathy perinatal mortality
Hypoxic ischaemic encephalopathy (HIE) may be regarded as a near miss marker for perinatal death resulting from intrapartum hypoxia. Considering the serious long-term consequences of HIE and issues of blame and liability for clinicians, regional or national audit of HIE might best be done using confidential enquiries. These are conducted by independent multidisciplinary panels, and should identify weaknesses in delivery of health care. A confidential enquiry into HIE may determine intrapartum factors that could have caused the poor outcome. It should also consider the role of associated preconceptual and antepartum factors, which may predispose the fetus to intrapartum damage. The enquiry should also assess avoidable factors and suboptimal care. These may involve patient- and family-related problems, administrationrelated suboptimal care, and health worker-related suboptimal care. The dissemination of the results of confidential enquiries should result in an improvement in quality of health care, including better allocation of health resources and health worker education. Ó 2009 Elsevier Ltd. All rights reserved.
Globally, over 900 000 newborns die each year from labour-related causes.1 This makes intrapartum hypoxia or asphyxia the third most common cause of newborn death (23%) after infections (36%) and preterm birth (28%).2 Another 1.1 million babies die during labour and are stillborn. Intrapartum hypoxia is the most frequent mechanism of damage, with the majority of deaths being at term in * Corresponding author. Tel.: þ27 119338156; Fax: þ27 119381534. E-mail address: [email protected] (E.J. Buchmann). 1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2008.12.004
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otherwise uncomplicated pregnancies.3 Not surprisingly, a large proportion of these events are considered avoidable4,5, and audit of such perinatal deaths therefore seems essential.3,6 Not all babies that suffer intrapartum hypoxia die. Some survive with residual brain damage. Therefore, near miss audit may have a place in analysis of poor perinatal outcomes related to intrapartum hypoxia. This suggests that audit of survivors of significant hypoxic episodes during labour may provide similar information to that obtained from audit into deaths resulting from intrapartum hypoxia. Such audit may determine clinical causes for these events, and identify associated suboptimal care or avoidable factors. This has relevance especially in developing countries, where intrapartum-related perinatal death is eight times more frequent than in developed countries.2 It also has application for risk management in industrialised nations, where substantial claims are made for child disability alleged to have been caused by intrapartum hypoxia.7 Defining a near miss outcome for death from intrapartum hypoxia Near miss audit should look for individuals who suffered an insult that almost resulted in death or very poor outcome. For example, a near miss for a maternal death is a woman who almost died. This has been defined as a pregnant or recently pregnant woman that suffered organ system failure or required extraordinary health care interventions.8 For a newborn near miss resulting from intrapartum hypoxia, one is looking for a similar survivor. There should be clinical markers that identify such an individual. To understand the selection of such markers, it is necessary to review briefly the pathology of intrapartum hypoxic ischaemic injury, also termed ‘‘intrapartum asphyxia’’. Pathology of hypoxic ischaemic injury A fetus may become hypoxic during labour because of umbilical cord compression or insufficient uteroplacental circulation, as seen with excessively strong uterine contractions or placental separation. After an initial compensatory response, there is decompensation with organ damage and dysfunction. Compensatory responses include a reduction in heart rate, reduction in oxygen utilisation such as cessation of body movements, redistribution of blood flow to vital organs including the brain, and a switch to anaerobic metabolism.9 Further hypoxia and anaerobic metabolism results in metabolic acidosis and cardiovascular decompensation. There is peripheral vasodilatation and a drop in cardiac output, resulting in profound hypotension and reduced cerebral perfusion. This sets the stage for cerebral damage.10 The process of brain cellular death is complex, involving not only hypoxic ischemic necrosis, but also apoptosis induced by membrane depolarisation and inflammation.11 Indicators of intrapartum hypoxic ischaemic injury The first indication of intrapartum hypoxia may be fetal heart rate abnormality during labour. The most frequent source of such information is the cardiotocograph (CTG). In most infants who have suffered intrapartum hypoxic damage, significant abnormalities of the CTG will be evident, typically fetal tachycardia with reduced baseline variability and late decelerations.12 The problem with the CTG is that it is only a non-specific indicator of intrapartum hypoxia, with a poor positive predictive value.13,14 A case control study of infants with neonatal encephalopathy compared with normal infants found that over 50% of controls had abnormal CTGs.15 This suggests that the CTG has little value as an indicator of severe hypoxic fetal injury during labour. More convincing evidence of preceding intrapartum hypoxia is found in umbilical cord arterial blood. Severe metabolic acidaemia at or shortly after birth presents reasonably good evidence of an hypoxic insult during labour.10 It has been shown that brain injury becomes likely in the presence of a pH 7.0 and/or a base deficit of 12 mmol/l.16,17 However, the majority of infants with metabolic acidaemia of this degree appear clinically well and do not go on to show any evidence of neurological deficit.13,17 Most of such newborns do not have their blood analysed, as their healthy condition does not warrant investigation. At birth, the survivor of a significant intrapartum hypoxic insult may present with respiratory depression, cyanosis, poor responsiveness, hypotonia and bradycardia (low Apgar score).18 When
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neonatal resuscitation results in rapid clinical improvement, brain injury is likely to be minimal and reversible. However, when resuscitation does not result in improvement of a low Apgar score, it becomes likely that severe and irreversible brain injury has occurred.19,20 For example, an Apgar score 3 at 10 minutes is associated with a subsequent cerebral palsy risk of 17%. This risk increases to 57% with an Apgar score 3 at 20 minutes.21 It should, however, be noted that a low Apgar score may result from antepartum or intrapartum hypoxia, or a combination of the two. Also, the Apgar score on its own is not a specific indicator of antecedent hypoxia.20 There are other causes for a low Apgar score, such as prematurity, maternal sedative drugs, congenital abnormality, and intrauterine infection. Some evidence for intrapartum hypoxia as the cause of a low Apgar score can be provided by the finding of fetal distress in labour and metabolic acidaemia after birth. Following initial resuscitation, the newborn with hypoxic ischaemic injury may develop signs of encephalopathy. This may be mild (stage 1), moderate (stage 2), or severe (stage 3).22 This classification has relevance for prognosis, with mild encephalopathy typically associated with an excellent outcome, and severe encephalopathy frequently resulting in disability or death (Table 1).16,23,24 Long-term prognosis is likely to be significantly worse in developing nations. A Nepalese study with follow-up to one year of age showed that encephalopathy stages 1, 2 and 3 were associated with subsequent death or disability rates of 21, 71 and 97%, respectively.25 While the initial description of neonatal encephalopathy was based on the study of infants suffering from ‘‘perinatal asphyxia’’, the condition is not restricted to newborns who have suffered an intrapartum hypoxic ischaemic insult. A number of well controlled studies have shown that a large proportion of infants with neonatal encephalopathy have no evidence of such insult, and that their pathology can be traced to antepartum rather than intrapartum problems.26,27 In many cases, a combination of antepartum and intrapartum factors is found to be responsible.
Hypoxic ischaemic encephalopathy as a near miss outcome It should be evident from the above discussion that, on their own, low Apgar scores, ‘‘fetal distress’’ during labour, metabolic acidosis at birth, and neonatal encephalopathy, do not provide convincing evidence of severe intrapartum hypoxia. Such evidence needs to come from a combination of these markers. The severity of the injury is established by the presence of encephalopathy developing in the first 24 hours after birth, which can be termed ‘‘hypoxic ischaemic’’ if there is metabolic acidaemia, associated with evidence of fetal distress and a low Apgar score. Indeed, as suggested in a recent review, the term ‘‘hypoxic ischaemic encephalopathy’’ (HIE) should be reserved for instances where the clinical and laboratory picture fits with that description.28 HIE, correctly defined, provides the near miss outcome that best identifies surviving neonates that almost died as a result of intrapartum hypoxia, with or without an antepartum predisposing cause. A definition of HIE that identifies labour as
Table 1 Stages of neonatal encephalopathy22, with subsequent long-term prognosis.16,23,24
Stage 1 – Mild encephalopathy
Stage 2 – Moderate encephalopathy
Stage 3 – Severe encephalopathy
Clinical signs
Likelihood of subsequent associated disability or infant death
Hyperalertness Uninhibited primitive reflexes Symphathetic effects Obtundation Mild hypotonia Distal flexion Seizures Stupor or coma Flaccidity Suppressed brain stem and autonomic functions
Almost zero
20–27%
50–72%
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a significant contributor to the hypoxic ischaemic event is shown in Table 2. This definition is made as a consensus suggestion based on a number of reviews and studies on HIE.16,17,22,27 Confidential enquiries The near miss definition (HIE) for death from intrapartum hypoxia will include some infants who have a good long-term outcome and others who later show evidence of residual cerebral damage. Generally, the concept of near miss implies that no harm was done, only that there was almost harm. However, if there is residual damage following HIE, this indicates harm, and the infant ceases to be a true near miss. HIE may therefore not be an ideal near miss outcome. Yet, as discussed above, using only ‘‘soft’’ markers such as fetal distress and Apgar scores will include too many infants who did not suffer intrapartum hypoxia. The difficulty then with using HIE as a near miss outcome is that audit and discussion of such newborns becomes fraught with issues of blame and even medicolegal liability. This may hinder the audit process, which is intended to be educational and part of quality improvement. Staff that have been involved in clinical management that preceded HIE may be deliberately defensive and may avoid open disclosure of events. For this reason, confidentiality needs to be introduced into the process. Therefore, a confidential enquiry process might provide the best mechanism for disclosure in a non-accusatory and non-punitive atmosphere. Purpose of confidential enquiries The United Kingdom’s Confidential Enquiry into Maternal and Child Health (CEMACH) states that ‘‘the primary purpose of a confidential enquiry is to review deaths and other adverse outcomes, seeking to identify avoidable factors and to derive lessons for wider policy and practice’’. The stated aim of CEMACH is ‘‘to improve the health of mothers, babies and children by carrying out confidential enquiries. and widely disseminating (their) findings and recommendations’’.29 There is consensus in the literature that the function of confidential enquiries should be to identify weaknesses in health care services, and that the information gained may inform reorganisation or improvements.30,31 Conduct of confidential enquiries By its nature, a confidential enquiry has to pass judgment on a health care service. The judgment call is based on the clinical audit principle that the care delivered should meet certain predetermined standards.32 However, this call may still be subjective and different experts may not agree. For this reason, a confidential enquiry should use a multidisciplinary panel. For example, a confidential enquiry into neonatal encephalopathy done in the United Kingdom employed an obstetrician, a midwife, a neonatologist, a neonatal nurse and an epidemiologist.33 Furthermore, to avoid conflicts of interest, panels should be made up of independent persons who are not on the staff of the institutions where the poor outcomes occurred. Notification of a poor outcome to a confidential enquiry requires clear definition of the outcome. There is little difficulty if the outcome is death, but for cases of near miss, there must be a simple but
Table 2 Criteria for assigning a diagnosis of hypoxic-ischaemic encephalopathy, where intrapartum hypoxia is the likely cause.
1. 2. 3. 4. 5.
Neonatal encephalopathy grade 1, 2 or 3. Umbilical artery pH <7.0 or base deficit 12 mmol/la Five-minute Apgar score <7 Gestational age at birth 37 weeksb Absence of any evidence of infection, congenital defect, or inborn error of metabolism
a Institutions that cannot perform blood gas testing may have to rely on the Apgar score and/or evidence of intrapartum fetal distress on CTG. b Inclusion of infants of gestational age 34 weeks may be acceptable.
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precise definition of the outcome. Therefore, the criteria to make a diagnosis of neonatal encephalopathy secondary to intrapartum hypoxia must be clearly defined as shown in Table 2. Efficient processes need to be set up for confidential enquiries. Examples of successful confidential enquiries include the South African and United Kingdom Maternal Deaths enquiries.31,34 These are permanently constituted. Ad hoc confidential enquiries may also be set up to answer specific questions about health care.33,35 A national or regional committee takes responsibility for the process, and secretariats at regional or local level manage the enquiries by nominating panel members, calling meetings, and handling submissions of cases from institutions. Participating institutions should allocate staff to identify cases that qualify for enquiry. Copies of case notes are sent to the secretariat within a prescribed time limit from the date of the poor clinical outcome. The secretariat sends copies of the case notes to panelists for assessment. Ideally, all named references to patients, clinicians and institutions should be removed from the notes to ensure confidentiality. The panelists meet regularly to discuss cases they have considered, and decide on causes and avoidable factors. At prescribed intervals, the findings of the enquiries are published and circulated, with recommendations made for improvements. Are confidential enquiries effective? Principles of evidence-based practice dictate that expensive and potentially harmful interventions should be introduced only after there is good evidence of effectiveness. The Cochrane Library has reviewed controlled trials of audit and feedback, and noted improvements in professional practice after clinical audit exercises combined with feedback to involved health care workers.36 However, a Cochrane review on critical incident audit of maternal and perinatal morbidity and mortality could find no trials to show improved outcomes associated with such audit.37 The review makes specific mention of confidential enquiries. The reviewers state that the necessity of collecting data is not in question. Their concern is whether the recording of suboptimal care makes any difference, and whether feedback of critical incident audit is provided adequately to health workers and planners. This question could be answered by designing a controlled trial using regions where confidential enquiries are done and comparing outcomes in these areas with regions where enquiries are not done. The Cochrane reviewers conclude, for now, that confidential enquiries should continue. In short, as stated in relation to the French confidential enquiries into maternal deaths, such reports provide essential information for reorganising current health care practices.30 Limitations of confidential enquiries If properly done, confidential enquiries provide robust and valuable information about outcomes and practice. They should, however, not be used as epidemiological tools, as they are primarily quality improvement projects. For example, the South African confidential enquiries into maternal deaths are not structured to collect information on deaths that occur outside health institutions.34 Therefore, maternal mortality ratios cannot be computed from the data collected by those enquiries. An important limitation of confidential enquiries relates to feedback of reviews to clinicians involved in the care of submitted cases. The clinical information gathered during an enquiry may show serious deficiencies in individual clinicians’ care or in certain institutions. Participants in the enquiry may feel that focused corrective action is then needed. This was well illustrated in a qualitative interview study on panelists from the United Kingdom maternal death confidential enquiries. One panelist, relating her experience of one enquiry, said that ‘‘something needed to be done about it. In other words, a practice that was unacceptable.and they needed to understand that their practice had to change’’.38 The understandable wish to provide such feedback unfortunately undermines confidentiality, and would in the long term reduce the value of clinical information submitted. Honesty and full disclosure of events could be compromised. It is important to understand that confidential enquiries give feedback at a general level, and offer recommendations to improve the health care delivery system, based on deficiencies identified at individual institutions. The institutions should be discussing their own critical incidents, such as perinatal deaths and cases of HIE, at closed audit meetings, where involved clinicians are present. This is part of standard audit practice.
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Factors for review during confidential enquiries into HIE Infants with HIE as defined above are selected for confidential enquiry. This should aim to determine factors that were associated with, or caused the HIE. The definition presented in Table 2 places the focus on cases with an intrapartum aetiology for encephalopathy. Yet, underlying preconceptual and antepartum risk factors will frequently be found. A brief review of studies and audits of neonatal encephalopathy, HIE, and perinatal deaths related to intrapartum hypoxia will reveal important risk factors and causes for HIE. Data that should be included, as suggested by this review, are listed in Table 3.
Table 3 Preconceptual, antepartum and intrapartum factors that may be associated with HIE and could be included in a check-list for a confidential enquiry. Preconceptual factors Maternal age Parity Previous caesarean section Race Socio-economic status Marital status Maternal epilepsy Maternal hypothyroidism Maternal HIV status Antepartum factors Pre-eclampsia Maternal anaemia Maternal viral illness Maternal febrile illness Smoking during pregnancy Hospital admission during pregnancy Intrauterine growth restriction/small for gestational age at birth Postterm pregnancy Macrosomia/large for gestational age at birth Multiple pregnancy Male fetus Placental histopathology report Intrapartum factors Place of birth – home, rural or urban, level of care Induction of labour Duration of first stage of labour Occipitoposterior position Duration of rupture of membranes Chorio-amnionitis Fever during labour Oxytocin augmentation used Analgesia used – opiates, epidural Cardiotocograph or fetal heart rate findings Grade of meconium staining of amniotic fluid Antepartum haemorrhage or abruptio placentae Uterine rupture Umbilical cord prolapse Mode of delivery – normal vaginal, instrumental, caesarean section Fetal presentation at birth Duration of second stage of labour Difficult breech delivery Difficult vaginal twin delivery Difficult instrumental vaginal delivery
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Preconceptual factors There may be an association between perinatal death from intrapartum hypoxia and extremes of maternal age.3,27 Also, both nulliparity 27,39 and multiparity 40,41 have shown associations. Poor socioeconomic conditions have been shown in several studies to predispose to intrapartum hypoxia3,26,39,42, as has single motherhood.43 An Australian study of antepartum risk factors for neonatal encephalopathy found an independent association between maternal epilepsy and newborn neurological deficit, including convulsions.26 Maternal hypothyroidism was associated with subsequent neonatal encephalopathy in the same study and in a report from Nepal.27 Recently, a significant association was found in South Africa between maternal HIV seropositivity and perinatal death from intrapartum hypoxia.44 Previous caesarean section emerged as a significant risk in one study.45 All of these factors need to be recorded in a confidential enquiry into HIE. Antepartum factors A number of underlying pregnancy conditions may put fetuses at risk for hypoxia during labour. Significant associations have been found with pre-eclampsia26,46–49, small for dates baby3,26,39,42,48, postterm pregnancy47,50, febrile illness26,48, male fetus40,42,50, multiple pregnancy27, expected birth weight 4.5 kg39, antepartum hospital admission48, and maternal smoking.39 The damaging effect of pre-eclampsia is thought to be more complex than simple fetal hypoxia associated with a compromised uteroplacental circulation. There is possibly an inflammatory component that may contribute to cerebral vasoconstriction in the fetus, perhaps the result of oxidative stress.46 Maternal anaemia is a frequent association in developing countries (Malawi, Uganda, Nepal).27,45,48 Where possible, placental histopatholocal examination may be a useful tool to identify underlying antepartum pathology, for example, vascular lesions or infections.51,52 Intrapartum factors As expected, intrapartum complications are frequently found in association with or as causes of HIE. These include acute events such as cord prolapse3,27,35,43,50,53, vaginal breech delivery3,27,35,45,47,49,53, uterine rupture3,35,43, shoulder dystocia35,53,54, and CTG evidence of fetal distress in labour.35,43,47,53 There is a strong association with emergency caesarean section39,43,47–49,53, and instrumental vaginal delivery.27,35,43,47,48,50 Operative delivery is, however, a final choice of management in complicated labour rather than a cause of intrapartum hypoxia. Indeed, prolonged first stage 40,41 and prolonged second stage of labour 27,35,41,49 have shown associations with intrapartum hypoxia, as has induction or augmentation with oxytocin.27,40,43,49 Other risk factors include meconium-stained amniotic fluid43,48, abruptio placentae39,43,48,49, prolonged rupture of membranes27,48, persistent occipitoposterior position55, chorioamnionitis55,56, epidural analgesia40, rural place of birth5, and possibly home birth.57 An interesting and probably important risk factor for fetal neurological damage is intrapartum fever.39,40,55 The studies demonstrating this relationship found it to be independent of prolonged labour or clinically evident infection. This has received some attention in recent literature, with the suggestion that an associated inflammatory process may mediate cerebral damage.28,40,56 Elements of suboptimal care for reporting in confidental enquiries into HIE A confidential enquiry, as discussed earlier, is constituted to identify weaknesses in a health service. In this clinical context, it should therefore identify avoidable factors for HIE. A good subdivision is provided by South Africa’s Perinatal Problem Identification Programme (PPIP) audits.5 This follows the principle that avoidable factors may arise as a result of patients or families not making use of health care facilities, or they may be associated with suboptimal care in the health service. The latter may be of an ‘‘administrative’’ nature, where the service does not deliver facilities according to accepted norms, for example, failure to provide working neonatal resuscitation equipment. This may also be ‘‘health worker’’-related, where nurses, midwives or doctors do not deliver care according to prescribed protocols, for example, inadequate efforts at neonatal resuscitation in the presence of working
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equipment. To label care as suboptimal, there has to be knowledge of norms and standards regarding facilities, and there should be awareness of local clinical management protocols. For example, to determine if CTG monitoring was adequate, a Scottish audit consulted the Royal College of Obstetricians and Gynaecology guideline (now the National Institute for Clinical Excellence guideline).53 Each confidential enquiry must determine to what degree the HIE was associated with suboptimal care. Studies differ on how suboptimal care should be graded. In a Swedish study of infants with moderate neonatal encephalopathy, obstetric care was ‘‘suboptimal’’ in 33% of cases and ‘‘questionable’’ in 21%.47 A South African study of perinatal deaths related to intrapartum hypoxia found that about one-third of deaths were ‘‘probably’’ preventable.5 The Scottish audit of intrapartum critical events reported that there was ‘‘major’’ suboptimal care in 30% of cases, ‘‘minor’’ suboptimal care in 10% and ‘‘incidental’’ suboptimal care in 5%.53 This meaningful classification is similar to the CESDI (Confidential Enquiry into Stillbirths and Deaths in Infancy) grading, where grade 0 represents no suboptimal care, and grade 3 represents suboptimal care such that the death could have been avoided, as shown in Table 4.7 A brief review of studies, audits and confidential enquiries that have investigated intrapartum hypoxia will identify suboptimal care and avoidable factors associated with HIE. Checklists of such factors may be used for confidential enquiries (Table 5). Patient- and family-related avoidable factors Several studies have mentioned lack of, or inappropriate, antenatal care as a risk factor for intrapartum hypoxia.26,27,50 More detail on patient-related avoidable factors is provided in the PPIP report from South Africa.5 This audit found a number of intrapartum-related deaths to be associated with delay in seeking help during labour. Administrative-related suboptimal care The South African PPIP audit provides instructive information.5 Deaths from intrapartum-related asphyxia were associated with lack of transport, inadequate neonatal care facilities, insufficiently trained staff, shortage of midwives, shortage of doctors, and lack of obstetric operating room facilities. A confidential enquiry into cases of neonatal encephalopathy in the United Kingdom found associations with administrative problems (lack of human resources, lack of equipment) but specifics of these deficiencies were not given.33 A staffing problem may arise after working hours, and care may not be at its best at night and on weekends.58 It may be of value, in an investigation of suboptimal care, to state the rank of the most senior person on duty in the labour ward.7 Health worker-related suboptimal care An English audit found frequent failure to recognise, and act, on abnormal CTG tracings.7 CTG interpretation and action features in a number of studies33,53,59, and where CTGs are not always available, the term ‘‘fetal monitoring inadequate’’ has been used.5 Two audits investigated whether fetal scalp blood sampling was done if indicated53,59, and one investigated the time interval from first evidence of pathological CTG to delivery.59 Failure of communication by midwives or doctors is Table 4 Grades of suboptimal care (avoidable factors) used in the United Kingdom’s Confidential Enquiry into Stillbirths and Deaths in Infancy.7
Grade 0: No suboptimal care Grade 1: Suboptimal care but different management would have made no difference to the outcome (incidental suboptimal care - no avoidable factor) Grade 2: Suboptimal care where different management might have made a difference to the outcome (possibly avoidable poor outcome) Grade 3: Suboptimal care where different management would reasonably be expected to have made a difference to the outcome (probably avoidable poor outcome)
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Table 5 Elements of suboptimal care that may be included in a check-list for a confidential enquiry into HIE. Patient and family related avoidable factors No antenatal care Inappropriate antenatal care attendance Delay in seeking help during labour or in an emergency Administrative related suboptimal care Lack of emergency vehicle transport Staff insufficiently trained Shortage of doctors Shortage of midwives Inadequate operating room facilities Inadequate neonatal resuscitation facilities Inadequate neonatal surveillance facilities Time of birth Day of birth – weekday or weekend Rank of most senior person on duty Health worker related suboptimal care Failure to recognize evidence of fetal distress Failure to act on evidence of fetal distress Time interval from evidence of fetal distress to delivery Fetal scalp blood sampling not done - if indicated and possible Senior help not called during labour or for delivery Mother not referred to higher level of care during labour Senior person did not come when called, or arrived too late Inappropriate use of oxytocin Non-use of labour graph Breech presentation not detected Improperly performed breech delivery Improperly performed vaginal twin delivery Improperly performed instrumental vaginal delivery Decision to delivery interval - for emergency caesarean section Neonatal doctor not called to a difficult delivery Inadequate neonatal resuscitation Inadequate neonatal surveillance after resuscitation Senior help not called at neonatal resuscitation
frequently a problem5,7,33,59, for example, not calling more senior staff, delay with referral, or not calling a paediatrician to a difficult delivery. At times, doctors do not come when called, or arrive late.59 Other areas of suboptimal obstetric care include inappropriate use of oxytocin33,59, failure to use a labour graph5, failure to detect breech presentation5, prolonged second stage of labour without intervention5, improperly performed breech, twin or instrumental delivery59, and excessively long interval between decision to deliver and delivery.53,59 Health worker-related suboptimal care of the newborn mostly involves inadequate or incorrect resuscitation5,33,53, and insufficient neonatal surveillance after resuscitation.33 Doctors or paediatricians may also not respond to calls for help with neonatal resuscitation.5 Examples of confidential enquiries into HIE Only one example of a confidential enquiry into neonatal encephalopathy could be found in the English language literature.33 This enquiry did not specify an intrapartum aetiology, hence its use of the term ‘‘neonatal encephalopathy’’. The enquiry included infants with neonatal encephalopathy stage 2 or stage 3 born at 35 weeks’ gestation, without any infection or congenital abnormalities, who survived for 28 days. An independent panel assessed each case for suboptimal care by CESDI grading. Of 49 cases assessed, 64% were associated with suboptimal care grade 2 or 3. A peripartum insult alone was responsible for 45% of the 49 cases, and combined antepartum and peripartum insults were found
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in another 43%. Suboptimal care included delay in communication (41%), failure to recognise an abnormal CTG or meconium (25%), uterine stimulation despite evidence of fetal distress (6%), inadequate neonatal resuscitation (25%), and inadequate neonatal surveillance (25%). The enquiry was found to provide similar information to CESDI. The authors’ conclusion was: ‘‘we have demonstrated that it is possible.to apply the CESDI method to specific important ‘‘near miss’’ cases of morbidity’’. Prospects for quality improvement Serial data suggest that perinatal care can be improved in association with audit of perinatal deaths or neonatal depression.6,7 Identification of weaknesses in perinatal health care services should be able to highlight areas for improvement. Shortages in staff and facilities can be addressed based on data from confidential enquiries. General and specific educational opportunities may also emerge. Examples include improvements in practice following introduction of training in CTG interpretation7, obstetric emergencies60, and neonatal resuscitation.61,62 Conclusion There has been a general decline in rates of intrapartum hypoxia and its consequences, especially in developed countries.42,63 However, a large proportion of these incidents remain avoidable. Audit and especially confidential enquiry may be an important vehicle for providing information to help prevent HIE and intrapartum-related perinatal death. Summary Perinatal deaths of term infants as a result of intrapartum hypoxia are always tragic, and are frequently preventable. Audit of such deaths may provide information that can improve perinatal care and prevent future deaths. Some infants do not die but are damaged by intrapartum hypoxia and develop hypoxic ischaemic encephalopathy (HIE). They may go on to develop disability and be the subject of substantial monetary claims by their families. Staff involved in the perinatal care of such infants may have legitimate medicolegal concerns about being subjected to audit. Therefore, audit of HIE for quality improvement may best be done using confidential enquiries. Such enquiries should be co-ordinated regionally and conducted by independent multidisciplinary panels. This process provides the potential for improvements, and the prevention of unnecessary intrapartum-related death or brain damage. While confidential enquiries are considered by many to be useful exercises, no controlled trials have been done to show whether they are effective in improving health care delivery systems. It is also not known if confidential enquiries into perinatal deaths, as are now conducted in the UK, need to be augmented by confidential enquiries into near misses (for example, HIE). This question could be answered by a well designed controlled trial using regions where HIE audit is done and comparing outcomes there with areas where HIE audit is not done. Practice points Selection of cases for confidential enquiries must adhere strictly to chosen definitions. A designated clinician at each institution must identify and submit all eligible cases for confidential enquiry. The institution should send case notes to a regional secretariat for review. Names of patients, clinicians and institutions are removed from the notes. An independent multidisciplinary panel reviews each case. The panel prepares reports at regular intervals and identifies areas of weakness in health care delivery. The reports must be widely disseminated and discussed so that perinatal care may be improved in the region.
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Research agenda What is the best near miss outcome for perinatal death resulting from intrapartum hypoxia? Does audit of near miss perinatal outcomes offer any advantage over audit of perinatal deaths? Do confidential enquiries into poor perinatal outcomes offer any advantage over conventional perinatal audit?
References *1. Lawn J, Shibuya K & Stein C. No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bull WHO 2005; 83: 409–417. 2. Lawn JE, Cousens S, Zupan J & for the Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: When? Where? Why? Lancet 2005; 365: 891–900. 3. Confidential Enquiry into Maternal and Child Health (CEMACH). Perinatal Mortality 2006: England, Wales and Northern Ireland. London: CEMACH, 2008. 4. Buchmann EJ, Pattinson RC & Nyathikazi N. Intrapartum-related birth asphyxia in South Africa – lessons from the first national perinatal care survey. S Afr Med J 2002; 92: 897–901. *5. Velaphi S & Pattinson R. Avoidable factors and causes of neonatal deaths from perinatal asphyxia-hypoxia in South Africa: national perinatal survey. Ann Trop Paediatr 2007; 27: 99–106. 6. Ward HR, Howarth GR, Jennings OJ et al. Audit incorporating avoidability and appropriate intervention can significantly decrease perinatal mortality. S Afr Med J 1995; 85: 147–150. *7. Young P, Hamilton R, Hodgett S et al. Reducing risk by improving standards of intrapartum fetal care. J R Soc Med 2001; 94: 226–231. 8. Mantel GD, Buchmann E, Rees H et al. Severe acute maternal morbidity: a pilot study of a definition for a near-miss. Br J Obstet Gynaecol 1998; 105: 985–990. 9. Fahey J & King TL. Intrauterine asphyxia: clinical implications for providers of intrapartum care. J Midwifery Womens Health 2005; 50: 498–506. *10. Low JA. Determining the contribution of asphyxia to brain damage in the neonate. J Obstet Gynaecol Res 2004; 30: 276–286. 11. Calvert JW & Zhang JH. Pathophysiology of an hypoxic-ischemic insult during the perinatal period. Neurol Res 2005; 27: 246–260. 12. Schifrin BS & Ater S. Fetal hypoxic and ischemic injuries. Curr Opin Obstet Gynecol 2006; 18: 112–122. 13. Larma JD, Silva AM, Holcroft CJ et al. Intrapartum electronic fetal heart rate monitoring and the identification of metabolic acidosis and hypoxic-ischemic encephalopathy. Am J Obstet Gynecol 2007; 197: 301. e1-301.e8. 14. Greene MF. Obstetricians still await a Deus ex Machina. N Engl J Med 2006; 355: 2247–2248. 15. Spencer JAD, Badawi N, Burton P et al. The intrapartum CTG prior to neonatal encephalopathy at term: a case-control study. Br J Obstet Gynaecol 1997; 104: 25–28. *16. Low JA. Intrapartum fetal asphyxia: definition, diagnosis and classification. Am J Obstet Gynecol 1997; 176: 957–959. 17. Perlman JM. Intrapartum hypoxic-ischemic cerebral injury and subsequent cerebral palsy: medicolegal issues. Pediatrics 1997; 99: 851–859. 18. Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953; 32: 260–267. 19. American Academy of Pediatrics. Use and abuse of the Apgar score. Pediatrics 1996; 98: 141–142. 20. Freeman JM & Nelson KB. Intrapartum asphyxia and cerebral palsy. Pediatrics 1988; 82: 240–249. 21. Nelson KB & Ellenberg JH. Apgar scores as predictors of chronic neurological disability. Pediatrics 1981; 68: 36–44. *22. Sarnat HB & Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33: 696–705. 23. Low JA, Galbraith RS, Muir DW et al. The relationship between perinatal hypoxia and newborn encephalopathy. Am J Obstet Gynecol 1985; 152: 256–260. 24. Dixon G, Badawi N, Kurinczuk JJ et al. Early developmental outcomes after newborn encephalopathy. Pediatrics 2002; 109: 26–33. 25. Ellis M, Manandhar N, Shrestha PS et al. Outcome at 1 year of neonatal encephalopathy in Kathmandu, Nepal. Dev Med Child Neurol 1999; 41: 689–695. 26. Badawi N, Kurinczuk JJ, Keogh JM et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998; 317: 1549–1553. *27. Ellis M, Manandhar N, Manandhar DS et al. Risk factors for neonatal encephalopathy in Kathmandu, Nepal, a developing country: unmatched case-control study. BMJ 2000; 320: 1229–1236. 28. Nelson KB. Is it HIE? And why that matters. Acta Paediatr 2007; 96: 1113–1114. 29. Pearson GA (ed.). Why children die: a pilot study 2006; England (South West, North East and West Midlands), Wales and Northern Ireland. London: CEMACH, 2008. 30. Bouvier-Colle MH. Confidential enquiries and medical expert committees: a method for evaluating health care [Article in French]. Rev Epidemiol Sante´ Publique 2002; 50: 203–217. 31. Papworth S & Cartlidge P. Learning from adverse events – the role of confidential enquiries. Semin Fetal Neonatal Med 2005; 10: 39–43. 32. Maresh MJA. What is audit? In Maresh MJA (ed.). Audit in obstetrics and gynaecology. Oxford: Blackwell, 1994, pp. 3–17.
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*33. Draper ES, Kurinczuk JJ, Lamming CR et al. A confidential enquiry into cases of neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 2002; 87: F176–F180. 34. Department of Health. Saving Mothers. Third report on confidential enquiries into maternal deaths in South Africa 2002–2004. Pretoria: Department of Health, 2006. 35. Buchmann EJ & Pattinson RC. Babies who die from labour-related intrapartum hypoxia: a confidential enquiry in South African public hospitals. Trop Doct 2006; 36: 8–10. 36. Jamtvedt G, Young JM, Kristoffersen DT et al. Audit and feedback: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2006; (Issue 2). Art. No.: CD000259. 37. Pattinson RC, Say L, Makin JD et al. Critical incident audit and feedback to improve perinatal and maternal mortality and morbidity. Cochrane Database Syst Rev 2005; (Issue 4). Art. No.: CD002961. 38. Rankin J, Bush J, Bell R et al. Impacts of participating in confidential enquiry panels: a qualitative study. BJOG 2006; 113: 387–392. 39. Baskett TF, Allen VM, O’Connell CM et al. Predictors of respiratory depression at birth in the term infant. BJOG 2006; 113: 769–774. 40. Impey LWM, Greenwood CEL, Black RS et al. The relationship between intrapartum maternal fever and neonatal acidosis as risk factors for neonatal encephalopathy. Am J Obstet Gynecol 2008; 198: 49. e1-49.e6. 41. Hall DR, Smith M & Smith J. Maternal factors contributing to asphyxia neonatorum. J Trop Paediatr 1996; 42: 192–195. 42. Wu YW, Backstrand KH, Zhao S et al. Declining diagnosis of birth asphyxia in California: 1991–2000. Pediatrics 2004; 114: 1584–1590. 43. Milsom I, Ladfors L, Thiringer K et al. Influence of maternal, obstetric and fetal risk factors on the prevalence of birth asphyxia at term in a Swedish urban population. Acta Obstet Gynecol Scand 2002; 81: 909–917. 44. Van Hoorick L & Pattinson RC. The effect of maternal HIV infection on perinatal deaths in southwest Tshwane. In Pattinson RC (ed.). Saving Babies 2003–2005: fifth perinatal care survey of South Africa. Pretoria: University of Pretoria, MRC, CDC, 2007. 45. Kulmala T, Vaahtera M, Rannikko J et al. The relationship between antenatal risk characteristics, place of delivery and adverse delivery outcome in rural Malawi. Acta Obstet Gynecol Scand 2000; 79: 984–990. 46. Impey L, Greenwood C, Sheil O et al. The relationship between pre-eclampsia at term and neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 2001; 85: F170–F172. 47. Lindstro¨m K, Hallberg B, Blennow M et al. Moderate neonatal encephalopathy: pre- and perinatal risk factors and longterm outcome. Acta Obstet Gynecol Scand 2008; 87: 503–509. 48. Kaye D. Antenatal and intrapartum risk factors for birth asphyxia among emergency obstetric referrals in Mulago Hospital, Kampala, Uganda. East Afr Med J 2003; 80: 140–143. 49. Chandra S, Ramji S & Thirupuram S. Perinatal asphyxia: multivariate analysis of risk factors in hospital births. Indian Pediatr 1997; 34: 206–212. 50. Futrakul S, Praisuwanna P & Thaitumyanon P. Risk factors for hypoxic-ischemic encephalopathy in asphyxiated newborn infants. J Med Assoc Thai 2006; 89: 322–328. 51. Redline RW. Severe fetal placental vascular lesions in term infants with neurologic impairment. Am J Obstet Gynecol 2005; 192: 452–457. 52. Pacora P, Chaiworapongsa T, Maymon E et al. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2002; 11: 18–25. *53. Kernaghan D, Penney G & Adamson L. Scotland-wide learning from intrapartum critical events. Final report covering events in 2005. Aberdeen: Scotland Programme for Clinical Effectiveness in Reproductive Health, 2006. 54. MacKenzie IZ, Shah M, Lean K et al. Management of shoulder dystocia. Trends in incidence and maternal and neonatal morbidity. Obstet Gynecol 2007; 110: 1059–1068. 55. Badawi N, Kurinczuk JJ, Keogh JM et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998; 317: 1554–1558. 56. Shalak LF & Perlman JM. Infection markers and early signs of neonatal encephalopathy in the term infant. Ment Retard Dev Disabil Res Rev 2002; 8: 14–19. 57. Mori R, Dougherty M & Whittle M. An estimation of intrapartum-related perinatal mortality rates for booked home births in England and Wales between 1994 and 2003. BJOG 2008; 115: 554–559. 58. Stewart J, Andrews J & Cartlidge PHT. Number of deaths related to intrapartum asphyxia and timing of birth in all Wales perinatal survey 1993–5. BMJ 1995; 316: 657–660. *59. Berglund S, Grunewald C, Pettersson H et al. Severe asphyxia due to delivery-related malpractice in Sweden 1990–2005. BJOG 2008; 115: 316–323. 60. Draycott T, Sibanda T, Owen L et al. Does training in obstetric emergencies improve neonatal outcome? BJOG 2006; 113: 177–182. ¨ et al. The impact of Neonatal Resuscitation Program courses on mortality and morbidity 61. Duran R, Aladag˘ N, Vatansever U of newborn infants with perinatal asphyxia. Brain Dev 2008; 30: 43–46. 62. Patel D, Piotrowski ZH, Nelson MR et al. Effect of a statwide neonatal resuscitation training program on Apgar scores among high-risk neonates in Illinois. Pediatrics 2001; 107: 648–655. 63. Becher J, Stenson B & Lyon A. Is intrapartum asphyxia preventable? BJOG 2007; 114: 1442–1444.
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7
Confidential enquiries into hypoxic ischaemic encephalopathy Eckhart J. Buchmann, MBBCh, MSc(Med), FCOG(SA), PhD, Associate Professor and Head a, *, Sithembiso C. Velaphi, MBChB, MMed, FCPaed(SA), Associate Professor and Head b a
Department of Obstetrics and Gynaecology, Chris Hani Baragwanath Hospital and University of the Witwatersrand, P.O. Bertsham, 2013 Johannesburg, South Africa b Division of Neonatology, Department of Paediatrics and Child Health, Chris Hani Baragwanath Hospital and University of the Witwatersrand, P.O. Bertsham, 2013 Johannesburg, South Africa
Keywords: asphyxia neonatorum confidential enquiry clinical audit hypoxic ischaemic encephalopathy perinatal mortality
Hypoxic ischaemic encephalopathy (HIE) may be regarded as a near miss marker for perinatal death resulting from intrapartum hypoxia. Considering the serious long-term consequences of HIE and issues of blame and liability for clinicians, regional or national audit of HIE might best be done using confidential enquiries. These are conducted by independent multidisciplinary panels, and should identify weaknesses in delivery of health care. A confidential enquiry into HIE may determine intrapartum factors that could have caused the poor outcome. It should also consider the role of associated preconceptual and antepartum factors, which may predispose the fetus to intrapartum damage. The enquiry should also assess avoidable factors and suboptimal care. These may involve patient- and family-related problems, administrationrelated suboptimal care, and health worker-related suboptimal care. The dissemination of the results of confidential enquiries should result in an improvement in quality of health care, including better allocation of health resources and health worker education. Ó 2009 Elsevier Ltd. All rights reserved.
Globally, over 900 000 newborns die each year from labour-related causes.1 This makes intrapartum hypoxia or asphyxia the third most common cause of newborn death (23%) after infections (36%) and preterm birth (28%).2 Another 1.1 million babies die during labour and are stillborn. Intrapartum hypoxia is the most frequent mechanism of damage, with the majority of deaths being at term in * Corresponding author. Tel.: þ27 119338156; Fax: þ27 119381534. E-mail address: [email protected] (E.J. Buchmann). 1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2008.12.004
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otherwise uncomplicated pregnancies.3 Not surprisingly, a large proportion of these events are considered avoidable4,5, and audit of such perinatal deaths therefore seems essential.3,6 Not all babies that suffer intrapartum hypoxia die. Some survive with residual brain damage. Therefore, near miss audit may have a place in analysis of poor perinatal outcomes related to intrapartum hypoxia. This suggests that audit of survivors of significant hypoxic episodes during labour may provide similar information to that obtained from audit into deaths resulting from intrapartum hypoxia. Such audit may determine clinical causes for these events, and identify associated suboptimal care or avoidable factors. This has relevance especially in developing countries, where intrapartum-related perinatal death is eight times more frequent than in developed countries.2 It also has application for risk management in industrialised nations, where substantial claims are made for child disability alleged to have been caused by intrapartum hypoxia.7 Defining a near miss outcome for death from intrapartum hypoxia Near miss audit should look for individuals who suffered an insult that almost resulted in death or very poor outcome. For example, a near miss for a maternal death is a woman who almost died. This has been defined as a pregnant or recently pregnant woman that suffered organ system failure or required extraordinary health care interventions.8 For a newborn near miss resulting from intrapartum hypoxia, one is looking for a similar survivor. There should be clinical markers that identify such an individual. To understand the selection of such markers, it is necessary to review briefly the pathology of intrapartum hypoxic ischaemic injury, also termed ‘‘intrapartum asphyxia’’. Pathology of hypoxic ischaemic injury A fetus may become hypoxic during labour because of umbilical cord compression or insufficient uteroplacental circulation, as seen with excessively strong uterine contractions or placental separation. After an initial compensatory response, there is decompensation with organ damage and dysfunction. Compensatory responses include a reduction in heart rate, reduction in oxygen utilisation such as cessation of body movements, redistribution of blood flow to vital organs including the brain, and a switch to anaerobic metabolism.9 Further hypoxia and anaerobic metabolism results in metabolic acidosis and cardiovascular decompensation. There is peripheral vasodilatation and a drop in cardiac output, resulting in profound hypotension and reduced cerebral perfusion. This sets the stage for cerebral damage.10 The process of brain cellular death is complex, involving not only hypoxic ischemic necrosis, but also apoptosis induced by membrane depolarisation and inflammation.11 Indicators of intrapartum hypoxic ischaemic injury The first indication of intrapartum hypoxia may be fetal heart rate abnormality during labour. The most frequent source of such information is the cardiotocograph (CTG). In most infants who have suffered intrapartum hypoxic damage, significant abnormalities of the CTG will be evident, typically fetal tachycardia with reduced baseline variability and late decelerations.12 The problem with the CTG is that it is only a non-specific indicator of intrapartum hypoxia, with a poor positive predictive value.13,14 A case control study of infants with neonatal encephalopathy compared with normal infants found that over 50% of controls had abnormal CTGs.15 This suggests that the CTG has little value as an indicator of severe hypoxic fetal injury during labour. More convincing evidence of preceding intrapartum hypoxia is found in umbilical cord arterial blood. Severe metabolic acidaemia at or shortly after birth presents reasonably good evidence of an hypoxic insult during labour.10 It has been shown that brain injury becomes likely in the presence of a pH 7.0 and/or a base deficit of 12 mmol/l.16,17 However, the majority of infants with metabolic acidaemia of this degree appear clinically well and do not go on to show any evidence of neurological deficit.13,17 Most of such newborns do not have their blood analysed, as their healthy condition does not warrant investigation. At birth, the survivor of a significant intrapartum hypoxic insult may present with respiratory depression, cyanosis, poor responsiveness, hypotonia and bradycardia (low Apgar score).18 When
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neonatal resuscitation results in rapid clinical improvement, brain injury is likely to be minimal and reversible. However, when resuscitation does not result in improvement of a low Apgar score, it becomes likely that severe and irreversible brain injury has occurred.19,20 For example, an Apgar score 3 at 10 minutes is associated with a subsequent cerebral palsy risk of 17%. This risk increases to 57% with an Apgar score 3 at 20 minutes.21 It should, however, be noted that a low Apgar score may result from antepartum or intrapartum hypoxia, or a combination of the two. Also, the Apgar score on its own is not a specific indicator of antecedent hypoxia.20 There are other causes for a low Apgar score, such as prematurity, maternal sedative drugs, congenital abnormality, and intrauterine infection. Some evidence for intrapartum hypoxia as the cause of a low Apgar score can be provided by the finding of fetal distress in labour and metabolic acidaemia after birth. Following initial resuscitation, the newborn with hypoxic ischaemic injury may develop signs of encephalopathy. This may be mild (stage 1), moderate (stage 2), or severe (stage 3).22 This classification has relevance for prognosis, with mild encephalopathy typically associated with an excellent outcome, and severe encephalopathy frequently resulting in disability or death (Table 1).16,23,24 Long-term prognosis is likely to be significantly worse in developing nations. A Nepalese study with follow-up to one year of age showed that encephalopathy stages 1, 2 and 3 were associated with subsequent death or disability rates of 21, 71 and 97%, respectively.25 While the initial description of neonatal encephalopathy was based on the study of infants suffering from ‘‘perinatal asphyxia’’, the condition is not restricted to newborns who have suffered an intrapartum hypoxic ischaemic insult. A number of well controlled studies have shown that a large proportion of infants with neonatal encephalopathy have no evidence of such insult, and that their pathology can be traced to antepartum rather than intrapartum problems.26,27 In many cases, a combination of antepartum and intrapartum factors is found to be responsible.
Hypoxic ischaemic encephalopathy as a near miss outcome It should be evident from the above discussion that, on their own, low Apgar scores, ‘‘fetal distress’’ during labour, metabolic acidosis at birth, and neonatal encephalopathy, do not provide convincing evidence of severe intrapartum hypoxia. Such evidence needs to come from a combination of these markers. The severity of the injury is established by the presence of encephalopathy developing in the first 24 hours after birth, which can be termed ‘‘hypoxic ischaemic’’ if there is metabolic acidaemia, associated with evidence of fetal distress and a low Apgar score. Indeed, as suggested in a recent review, the term ‘‘hypoxic ischaemic encephalopathy’’ (HIE) should be reserved for instances where the clinical and laboratory picture fits with that description.28 HIE, correctly defined, provides the near miss outcome that best identifies surviving neonates that almost died as a result of intrapartum hypoxia, with or without an antepartum predisposing cause. A definition of HIE that identifies labour as
Table 1 Stages of neonatal encephalopathy22, with subsequent long-term prognosis.16,23,24
Stage 1 – Mild encephalopathy
Stage 2 – Moderate encephalopathy
Stage 3 – Severe encephalopathy
Clinical signs
Likelihood of subsequent associated disability or infant death
Hyperalertness Uninhibited primitive reflexes Symphathetic effects Obtundation Mild hypotonia Distal flexion Seizures Stupor or coma Flaccidity Suppressed brain stem and autonomic functions
Almost zero
20–27%
50–72%
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a significant contributor to the hypoxic ischaemic event is shown in Table 2. This definition is made as a consensus suggestion based on a number of reviews and studies on HIE.16,17,22,27 Confidential enquiries The near miss definition (HIE) for death from intrapartum hypoxia will include some infants who have a good long-term outcome and others who later show evidence of residual cerebral damage. Generally, the concept of near miss implies that no harm was done, only that there was almost harm. However, if there is residual damage following HIE, this indicates harm, and the infant ceases to be a true near miss. HIE may therefore not be an ideal near miss outcome. Yet, as discussed above, using only ‘‘soft’’ markers such as fetal distress and Apgar scores will include too many infants who did not suffer intrapartum hypoxia. The difficulty then with using HIE as a near miss outcome is that audit and discussion of such newborns becomes fraught with issues of blame and even medicolegal liability. This may hinder the audit process, which is intended to be educational and part of quality improvement. Staff that have been involved in clinical management that preceded HIE may be deliberately defensive and may avoid open disclosure of events. For this reason, confidentiality needs to be introduced into the process. Therefore, a confidential enquiry process might provide the best mechanism for disclosure in a non-accusatory and non-punitive atmosphere. Purpose of confidential enquiries The United Kingdom’s Confidential Enquiry into Maternal and Child Health (CEMACH) states that ‘‘the primary purpose of a confidential enquiry is to review deaths and other adverse outcomes, seeking to identify avoidable factors and to derive lessons for wider policy and practice’’. The stated aim of CEMACH is ‘‘to improve the health of mothers, babies and children by carrying out confidential enquiries. and widely disseminating (their) findings and recommendations’’.29 There is consensus in the literature that the function of confidential enquiries should be to identify weaknesses in health care services, and that the information gained may inform reorganisation or improvements.30,31 Conduct of confidential enquiries By its nature, a confidential enquiry has to pass judgment on a health care service. The judgment call is based on the clinical audit principle that the care delivered should meet certain predetermined standards.32 However, this call may still be subjective and different experts may not agree. For this reason, a confidential enquiry should use a multidisciplinary panel. For example, a confidential enquiry into neonatal encephalopathy done in the United Kingdom employed an obstetrician, a midwife, a neonatologist, a neonatal nurse and an epidemiologist.33 Furthermore, to avoid conflicts of interest, panels should be made up of independent persons who are not on the staff of the institutions where the poor outcomes occurred. Notification of a poor outcome to a confidential enquiry requires clear definition of the outcome. There is little difficulty if the outcome is death, but for cases of near miss, there must be a simple but
Table 2 Criteria for assigning a diagnosis of hypoxic-ischaemic encephalopathy, where intrapartum hypoxia is the likely cause.
1. 2. 3. 4. 5.
Neonatal encephalopathy grade 1, 2 or 3. Umbilical artery pH <7.0 or base deficit 12 mmol/la Five-minute Apgar score <7 Gestational age at birth 37 weeksb Absence of any evidence of infection, congenital defect, or inborn error of metabolism
a Institutions that cannot perform blood gas testing may have to rely on the Apgar score and/or evidence of intrapartum fetal distress on CTG. b Inclusion of infants of gestational age 34 weeks may be acceptable.
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precise definition of the outcome. Therefore, the criteria to make a diagnosis of neonatal encephalopathy secondary to intrapartum hypoxia must be clearly defined as shown in Table 2. Efficient processes need to be set up for confidential enquiries. Examples of successful confidential enquiries include the South African and United Kingdom Maternal Deaths enquiries.31,34 These are permanently constituted. Ad hoc confidential enquiries may also be set up to answer specific questions about health care.33,35 A national or regional committee takes responsibility for the process, and secretariats at regional or local level manage the enquiries by nominating panel members, calling meetings, and handling submissions of cases from institutions. Participating institutions should allocate staff to identify cases that qualify for enquiry. Copies of case notes are sent to the secretariat within a prescribed time limit from the date of the poor clinical outcome. The secretariat sends copies of the case notes to panelists for assessment. Ideally, all named references to patients, clinicians and institutions should be removed from the notes to ensure confidentiality. The panelists meet regularly to discuss cases they have considered, and decide on causes and avoidable factors. At prescribed intervals, the findings of the enquiries are published and circulated, with recommendations made for improvements. Are confidential enquiries effective? Principles of evidence-based practice dictate that expensive and potentially harmful interventions should be introduced only after there is good evidence of effectiveness. The Cochrane Library has reviewed controlled trials of audit and feedback, and noted improvements in professional practice after clinical audit exercises combined with feedback to involved health care workers.36 However, a Cochrane review on critical incident audit of maternal and perinatal morbidity and mortality could find no trials to show improved outcomes associated with such audit.37 The review makes specific mention of confidential enquiries. The reviewers state that the necessity of collecting data is not in question. Their concern is whether the recording of suboptimal care makes any difference, and whether feedback of critical incident audit is provided adequately to health workers and planners. This question could be answered by designing a controlled trial using regions where confidential enquiries are done and comparing outcomes in these areas with regions where enquiries are not done. The Cochrane reviewers conclude, for now, that confidential enquiries should continue. In short, as stated in relation to the French confidential enquiries into maternal deaths, such reports provide essential information for reorganising current health care practices.30 Limitations of confidential enquiries If properly done, confidential enquiries provide robust and valuable information about outcomes and practice. They should, however, not be used as epidemiological tools, as they are primarily quality improvement projects. For example, the South African confidential enquiries into maternal deaths are not structured to collect information on deaths that occur outside health institutions.34 Therefore, maternal mortality ratios cannot be computed from the data collected by those enquiries. An important limitation of confidential enquiries relates to feedback of reviews to clinicians involved in the care of submitted cases. The clinical information gathered during an enquiry may show serious deficiencies in individual clinicians’ care or in certain institutions. Participants in the enquiry may feel that focused corrective action is then needed. This was well illustrated in a qualitative interview study on panelists from the United Kingdom maternal death confidential enquiries. One panelist, relating her experience of one enquiry, said that ‘‘something needed to be done about it. In other words, a practice that was unacceptable.and they needed to understand that their practice had to change’’.38 The understandable wish to provide such feedback unfortunately undermines confidentiality, and would in the long term reduce the value of clinical information submitted. Honesty and full disclosure of events could be compromised. It is important to understand that confidential enquiries give feedback at a general level, and offer recommendations to improve the health care delivery system, based on deficiencies identified at individual institutions. The institutions should be discussing their own critical incidents, such as perinatal deaths and cases of HIE, at closed audit meetings, where involved clinicians are present. This is part of standard audit practice.
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Factors for review during confidential enquiries into HIE Infants with HIE as defined above are selected for confidential enquiry. This should aim to determine factors that were associated with, or caused the HIE. The definition presented in Table 2 places the focus on cases with an intrapartum aetiology for encephalopathy. Yet, underlying preconceptual and antepartum risk factors will frequently be found. A brief review of studies and audits of neonatal encephalopathy, HIE, and perinatal deaths related to intrapartum hypoxia will reveal important risk factors and causes for HIE. Data that should be included, as suggested by this review, are listed in Table 3.
Table 3 Preconceptual, antepartum and intrapartum factors that may be associated with HIE and could be included in a check-list for a confidential enquiry. Preconceptual factors Maternal age Parity Previous caesarean section Race Socio-economic status Marital status Maternal epilepsy Maternal hypothyroidism Maternal HIV status Antepartum factors Pre-eclampsia Maternal anaemia Maternal viral illness Maternal febrile illness Smoking during pregnancy Hospital admission during pregnancy Intrauterine growth restriction/small for gestational age at birth Postterm pregnancy Macrosomia/large for gestational age at birth Multiple pregnancy Male fetus Placental histopathology report Intrapartum factors Place of birth – home, rural or urban, level of care Induction of labour Duration of first stage of labour Occipitoposterior position Duration of rupture of membranes Chorio-amnionitis Fever during labour Oxytocin augmentation used Analgesia used – opiates, epidural Cardiotocograph or fetal heart rate findings Grade of meconium staining of amniotic fluid Antepartum haemorrhage or abruptio placentae Uterine rupture Umbilical cord prolapse Mode of delivery – normal vaginal, instrumental, caesarean section Fetal presentation at birth Duration of second stage of labour Difficult breech delivery Difficult vaginal twin delivery Difficult instrumental vaginal delivery
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Preconceptual factors There may be an association between perinatal death from intrapartum hypoxia and extremes of maternal age.3,27 Also, both nulliparity 27,39 and multiparity 40,41 have shown associations. Poor socioeconomic conditions have been shown in several studies to predispose to intrapartum hypoxia3,26,39,42, as has single motherhood.43 An Australian study of antepartum risk factors for neonatal encephalopathy found an independent association between maternal epilepsy and newborn neurological deficit, including convulsions.26 Maternal hypothyroidism was associated with subsequent neonatal encephalopathy in the same study and in a report from Nepal.27 Recently, a significant association was found in South Africa between maternal HIV seropositivity and perinatal death from intrapartum hypoxia.44 Previous caesarean section emerged as a significant risk in one study.45 All of these factors need to be recorded in a confidential enquiry into HIE. Antepartum factors A number of underlying pregnancy conditions may put fetuses at risk for hypoxia during labour. Significant associations have been found with pre-eclampsia26,46–49, small for dates baby3,26,39,42,48, postterm pregnancy47,50, febrile illness26,48, male fetus40,42,50, multiple pregnancy27, expected birth weight 4.5 kg39, antepartum hospital admission48, and maternal smoking.39 The damaging effect of pre-eclampsia is thought to be more complex than simple fetal hypoxia associated with a compromised uteroplacental circulation. There is possibly an inflammatory component that may contribute to cerebral vasoconstriction in the fetus, perhaps the result of oxidative stress.46 Maternal anaemia is a frequent association in developing countries (Malawi, Uganda, Nepal).27,45,48 Where possible, placental histopatholocal examination may be a useful tool to identify underlying antepartum pathology, for example, vascular lesions or infections.51,52 Intrapartum factors As expected, intrapartum complications are frequently found in association with or as causes of HIE. These include acute events such as cord prolapse3,27,35,43,50,53, vaginal breech delivery3,27,35,45,47,49,53, uterine rupture3,35,43, shoulder dystocia35,53,54, and CTG evidence of fetal distress in labour.35,43,47,53 There is a strong association with emergency caesarean section39,43,47–49,53, and instrumental vaginal delivery.27,35,43,47,48,50 Operative delivery is, however, a final choice of management in complicated labour rather than a cause of intrapartum hypoxia. Indeed, prolonged first stage 40,41 and prolonged second stage of labour 27,35,41,49 have shown associations with intrapartum hypoxia, as has induction or augmentation with oxytocin.27,40,43,49 Other risk factors include meconium-stained amniotic fluid43,48, abruptio placentae39,43,48,49, prolonged rupture of membranes27,48, persistent occipitoposterior position55, chorioamnionitis55,56, epidural analgesia40, rural place of birth5, and possibly home birth.57 An interesting and probably important risk factor for fetal neurological damage is intrapartum fever.39,40,55 The studies demonstrating this relationship found it to be independent of prolonged labour or clinically evident infection. This has received some attention in recent literature, with the suggestion that an associated inflammatory process may mediate cerebral damage.28,40,56 Elements of suboptimal care for reporting in confidental enquiries into HIE A confidential enquiry, as discussed earlier, is constituted to identify weaknesses in a health service. In this clinical context, it should therefore identify avoidable factors for HIE. A good subdivision is provided by South Africa’s Perinatal Problem Identification Programme (PPIP) audits.5 This follows the principle that avoidable factors may arise as a result of patients or families not making use of health care facilities, or they may be associated with suboptimal care in the health service. The latter may be of an ‘‘administrative’’ nature, where the service does not deliver facilities according to accepted norms, for example, failure to provide working neonatal resuscitation equipment. This may also be ‘‘health worker’’-related, where nurses, midwives or doctors do not deliver care according to prescribed protocols, for example, inadequate efforts at neonatal resuscitation in the presence of working
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equipment. To label care as suboptimal, there has to be knowledge of norms and standards regarding facilities, and there should be awareness of local clinical management protocols. For example, to determine if CTG monitoring was adequate, a Scottish audit consulted the Royal College of Obstetricians and Gynaecology guideline (now the National Institute for Clinical Excellence guideline).53 Each confidential enquiry must determine to what degree the HIE was associated with suboptimal care. Studies differ on how suboptimal care should be graded. In a Swedish study of infants with moderate neonatal encephalopathy, obstetric care was ‘‘suboptimal’’ in 33% of cases and ‘‘questionable’’ in 21%.47 A South African study of perinatal deaths related to intrapartum hypoxia found that about one-third of deaths were ‘‘probably’’ preventable.5 The Scottish audit of intrapartum critical events reported that there was ‘‘major’’ suboptimal care in 30% of cases, ‘‘minor’’ suboptimal care in 10% and ‘‘incidental’’ suboptimal care in 5%.53 This meaningful classification is similar to the CESDI (Confidential Enquiry into Stillbirths and Deaths in Infancy) grading, where grade 0 represents no suboptimal care, and grade 3 represents suboptimal care such that the death could have been avoided, as shown in Table 4.7 A brief review of studies, audits and confidential enquiries that have investigated intrapartum hypoxia will identify suboptimal care and avoidable factors associated with HIE. Checklists of such factors may be used for confidential enquiries (Table 5). Patient- and family-related avoidable factors Several studies have mentioned lack of, or inappropriate, antenatal care as a risk factor for intrapartum hypoxia.26,27,50 More detail on patient-related avoidable factors is provided in the PPIP report from South Africa.5 This audit found a number of intrapartum-related deaths to be associated with delay in seeking help during labour. Administrative-related suboptimal care The South African PPIP audit provides instructive information.5 Deaths from intrapartum-related asphyxia were associated with lack of transport, inadequate neonatal care facilities, insufficiently trained staff, shortage of midwives, shortage of doctors, and lack of obstetric operating room facilities. A confidential enquiry into cases of neonatal encephalopathy in the United Kingdom found associations with administrative problems (lack of human resources, lack of equipment) but specifics of these deficiencies were not given.33 A staffing problem may arise after working hours, and care may not be at its best at night and on weekends.58 It may be of value, in an investigation of suboptimal care, to state the rank of the most senior person on duty in the labour ward.7 Health worker-related suboptimal care An English audit found frequent failure to recognise, and act, on abnormal CTG tracings.7 CTG interpretation and action features in a number of studies33,53,59, and where CTGs are not always available, the term ‘‘fetal monitoring inadequate’’ has been used.5 Two audits investigated whether fetal scalp blood sampling was done if indicated53,59, and one investigated the time interval from first evidence of pathological CTG to delivery.59 Failure of communication by midwives or doctors is Table 4 Grades of suboptimal care (avoidable factors) used in the United Kingdom’s Confidential Enquiry into Stillbirths and Deaths in Infancy.7
Grade 0: No suboptimal care Grade 1: Suboptimal care but different management would have made no difference to the outcome (incidental suboptimal care - no avoidable factor) Grade 2: Suboptimal care where different management might have made a difference to the outcome (possibly avoidable poor outcome) Grade 3: Suboptimal care where different management would reasonably be expected to have made a difference to the outcome (probably avoidable poor outcome)
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Table 5 Elements of suboptimal care that may be included in a check-list for a confidential enquiry into HIE. Patient and family related avoidable factors No antenatal care Inappropriate antenatal care attendance Delay in seeking help during labour or in an emergency Administrative related suboptimal care Lack of emergency vehicle transport Staff insufficiently trained Shortage of doctors Shortage of midwives Inadequate operating room facilities Inadequate neonatal resuscitation facilities Inadequate neonatal surveillance facilities Time of birth Day of birth – weekday or weekend Rank of most senior person on duty Health worker related suboptimal care Failure to recognize evidence of fetal distress Failure to act on evidence of fetal distress Time interval from evidence of fetal distress to delivery Fetal scalp blood sampling not done - if indicated and possible Senior help not called during labour or for delivery Mother not referred to higher level of care during labour Senior person did not come when called, or arrived too late Inappropriate use of oxytocin Non-use of labour graph Breech presentation not detected Improperly performed breech delivery Improperly performed vaginal twin delivery Improperly performed instrumental vaginal delivery Decision to delivery interval - for emergency caesarean section Neonatal doctor not called to a difficult delivery Inadequate neonatal resuscitation Inadequate neonatal surveillance after resuscitation Senior help not called at neonatal resuscitation
frequently a problem5,7,33,59, for example, not calling more senior staff, delay with referral, or not calling a paediatrician to a difficult delivery. At times, doctors do not come when called, or arrive late.59 Other areas of suboptimal obstetric care include inappropriate use of oxytocin33,59, failure to use a labour graph5, failure to detect breech presentation5, prolonged second stage of labour without intervention5, improperly performed breech, twin or instrumental delivery59, and excessively long interval between decision to deliver and delivery.53,59 Health worker-related suboptimal care of the newborn mostly involves inadequate or incorrect resuscitation5,33,53, and insufficient neonatal surveillance after resuscitation.33 Doctors or paediatricians may also not respond to calls for help with neonatal resuscitation.5 Examples of confidential enquiries into HIE Only one example of a confidential enquiry into neonatal encephalopathy could be found in the English language literature.33 This enquiry did not specify an intrapartum aetiology, hence its use of the term ‘‘neonatal encephalopathy’’. The enquiry included infants with neonatal encephalopathy stage 2 or stage 3 born at 35 weeks’ gestation, without any infection or congenital abnormalities, who survived for 28 days. An independent panel assessed each case for suboptimal care by CESDI grading. Of 49 cases assessed, 64% were associated with suboptimal care grade 2 or 3. A peripartum insult alone was responsible for 45% of the 49 cases, and combined antepartum and peripartum insults were found
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in another 43%. Suboptimal care included delay in communication (41%), failure to recognise an abnormal CTG or meconium (25%), uterine stimulation despite evidence of fetal distress (6%), inadequate neonatal resuscitation (25%), and inadequate neonatal surveillance (25%). The enquiry was found to provide similar information to CESDI. The authors’ conclusion was: ‘‘we have demonstrated that it is possible.to apply the CESDI method to specific important ‘‘near miss’’ cases of morbidity’’. Prospects for quality improvement Serial data suggest that perinatal care can be improved in association with audit of perinatal deaths or neonatal depression.6,7 Identification of weaknesses in perinatal health care services should be able to highlight areas for improvement. Shortages in staff and facilities can be addressed based on data from confidential enquiries. General and specific educational opportunities may also emerge. Examples include improvements in practice following introduction of training in CTG interpretation7, obstetric emergencies60, and neonatal resuscitation.61,62 Conclusion There has been a general decline in rates of intrapartum hypoxia and its consequences, especially in developed countries.42,63 However, a large proportion of these incidents remain avoidable. Audit and especially confidential enquiry may be an important vehicle for providing information to help prevent HIE and intrapartum-related perinatal death. Summary Perinatal deaths of term infants as a result of intrapartum hypoxia are always tragic, and are frequently preventable. Audit of such deaths may provide information that can improve perinatal care and prevent future deaths. Some infants do not die but are damaged by intrapartum hypoxia and develop hypoxic ischaemic encephalopathy (HIE). They may go on to develop disability and be the subject of substantial monetary claims by their families. Staff involved in the perinatal care of such infants may have legitimate medicolegal concerns about being subjected to audit. Therefore, audit of HIE for quality improvement may best be done using confidential enquiries. Such enquiries should be co-ordinated regionally and conducted by independent multidisciplinary panels. This process provides the potential for improvements, and the prevention of unnecessary intrapartum-related death or brain damage. While confidential enquiries are considered by many to be useful exercises, no controlled trials have been done to show whether they are effective in improving health care delivery systems. It is also not known if confidential enquiries into perinatal deaths, as are now conducted in the UK, need to be augmented by confidential enquiries into near misses (for example, HIE). This question could be answered by a well designed controlled trial using regions where HIE audit is done and comparing outcomes there with areas where HIE audit is not done. Practice points Selection of cases for confidential enquiries must adhere strictly to chosen definitions. A designated clinician at each institution must identify and submit all eligible cases for confidential enquiry. The institution should send case notes to a regional secretariat for review. Names of patients, clinicians and institutions are removed from the notes. An independent multidisciplinary panel reviews each case. The panel prepares reports at regular intervals and identifies areas of weakness in health care delivery. The reports must be widely disseminated and discussed so that perinatal care may be improved in the region.
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Research agenda What is the best near miss outcome for perinatal death resulting from intrapartum hypoxia? Does audit of near miss perinatal outcomes offer any advantage over audit of perinatal deaths? Do confidential enquiries into poor perinatal outcomes offer any advantage over conventional perinatal audit?
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