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Why babies die – Update on current research Dr Alexander Heazell Senior Clinical Lecturer in Obstetrics Maternal and Fetal Health Research Centre, University of Manchester, UK Definitions of Stillbirth • In the UK stillbirth is defined as an infant born without signs of life after 24 completed weeks gestation (500g) • Large international variation – 16 to 28 weeks gestation • WHO definition infant born without signs of life after 28 completed weeks’ gestation (1000g) The Scale of the Problem • WHO estimate 2.6 million stillbirths per year (2009) • 98% occur in low or middle-income countries • Only 2% of stillbirths counted through registration systems • Estimate may be as many as high as 3.79 million per annum WHO , 2011 We’re ok in HICs though? • • • • • UK stillbirth rate is 33rd out of 35 HICs UK – 5.2 per 1,000 live births Eire – 4.0 per 1,000 live births Scandinavia – 2.0-3.0 per 1,000 live births Room for improvement Flenady et al. Lancet 2011; 377: 1703–17 Changes in Stillbirth • Global reduction in stillbirth reduced by 14% from 1995-2009 • Infant mortality has reduced from 63 to 35 deaths per 1,000 births from 1990-2012 • MDG 4 – Reduce Child Mortality • In UK, stillbirths reducing by 1.1% per year • Neonatal death reducing by 2.1% per year • The ratio of stillbirth : neonatal death used to be 50%:50%, now approximately 60%:40% Changes in UK Stillbirth Rate over Time 100 7 90 80 Number of Events Number of Events 70 6 5 60 50 40 4 Stillbirth Rate Number of SBofx1000 Number Stillbirths x1000 3 Number of Live Births x 10000 Stillbirth Rate 30 2 20 10 1 0 0 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year Year ONS Data, 2013 Why do babies die? • Understanding central to reducing stillbirths • Difficult to assess, must consider: – Causation – “pathophysiologic entity initiating the chain of events that irreversibly led to death” – Association – pathophysiological entity present at and likely to have played a role in the death – Incidental finding • Obtaining information • Classification of deaths (Classification system) Stillbirth Certificates do not Reflect Cause • Analysis of Medical Certificates of Stillbirth issued in the NW region in 2009 • Compared to classification of death by panel • 229 death certificates (16 fetocides excluded) • Agreement on cause of death between certificate and panel “fair” (K=0.29) • Agreement on gestation of death between certificate and panel “almost complete agreement” (K=0.88) Cockerill et al. Paediatric Perinatal Epidemiology 2012;26(2):117-23. Differences between Certificate and Review Cockerill et al. Paediatric Perinatal Epidemiology 2012;26(2):117-23. Frequency of Errors on Stillbirth Certificates • 77.9% of stillbirth certificates had some form of error Cockerill et al. Paediatric Perinatal Epidemiology 2012;26(2):117-23. Has stillbirth changed? Primary ReCoDe 100% UNKNOWN 90% 80% 70% ABRUPTION 60% 50% 40% IUGR 30% 20% 10% ANOMALIES 0% 1986-1996 N=281 2009-2011 N=81 Heazell et al. Unpublished data Has stillbirth changed? Secondary ReCoDe 100% 90% MEDICAL 80% DISORDERS 70% 60% PLACENTAL 50% INSUFFICIENCY 40% 30% 20% 10% 0% 1986-1996 2009-2011 N=281 N=81 Heazell et al. Unpublished data Classification Systems • AttemptPurpose to group stillbirths according to cause Group Examples # Principal Intended as new INCODE, PSANZ, Codac, 8 • Understand causes, frequency, trends systems systems Recode, Tulip, Stockholm • Systematic review of classification systems New Combine the results Lawn 2005/2009, Gordijn 4 – 29 classification systems created or modified approaches of multiple systems 2004-2013 VA validity To test/improve VA – 20 pre-existing Group COD Aggarwal 2011/2013, Edmond, InterVA classification systems To assess COD in a specific group HIC datasets (4), LMIC datasets (9) 4 13 Leisher S et al. International Stillbirth Alliance Meeting, Viet Nam, 2013 Shortcomings of Classification Systems • Few are designed for / used in countries with high stillbirth rates (4 out of 10) • <20% tested for reliability, <15% for validity • 50% have 1 cause of death • 33% have 3 levels, averaging 12, 50 and 126 causes of death per level • 33% of systems are hierarchical (one cause is automatically assumed to supercede another) • In other words, little agreement, validity or comparability Leisher S et al. International Stillbirth Alliance Meeting, Viet Nam, 2013 Comparison of Classification Systems • 154 stillbirths in single institution • Used 4 different classification systems – Wigglesworth, ReCoDe, de Galan-Roosen, TULIP • Institutional protocol to determine cause – Placental histology – 77.3% – Autopsy/PM – 24.7% – Chromosomal analysis – 11.7% – Infection screen including TORCH – 18.8% Vergani et al. Am J Obstet Gynecol 2008;199(3):319.e1-4. 45.5% 14.3% 18.2% 16.2% Investigations to Determine Cause • Three investigations provide most useful information to aid classification – Autopsy / Post-mortem examination – 72.6% – Placental histology - 95.7% – Chromosomal analysis – 29.0% • Value depends upon classification system used Korteweg FJ, Erwich JJHM, Timmer A, et al. Am J Obstet Gynecol 2012;206:53.e1-12. Placental Examination • Histological examination of the placenta reduces the chance of having an “unexplained stillbirth” (OR 0.17, 95% CI 0.04-0.7) Suboptimal Care and Perinatal Audit • Need to be aware that some babies die due to suboptimal maternity care • Local review of perinatal deaths – Why did the baby die? • What conditions were present? – Were there any avoidable factors? • Major: Factor contributed significantly to the death. Different management would reasonably have been expected to alter the outcome. • Minor: Factor was a relevant contributory factor. Different management might have made a difference, but survival was unlikely in any case. • Irrelevant: Although lessons can be learned, it did not affect the eventual outcome. Confidential Enquiry / Case Review • Essential component of perinatal audit • Confidential Enquiry of 422 cases of stillbirth in 1996/7 (8th CESDI report) Confidential Enquiry of Perinatal Deaths in Cumbria • Review commissioned by NHS Cumbria • Anonymised case notes discussed by multidisplinary expert panel • 60 cases available for discussion – 63% of cases had some evidence of avoidable factors – 33% of cases had a least one major avoidable factor Confidential Enquiry – Case • Mary was in her late thirties; she had 2 children aged between 2 and 5. At the time of booking her BMI was 30, she smoked but declined the smoking cessation programme. Mary booked at 12 weeks gestation and was assessed as low risk and was booked for midwifery led care. She was seen regularly and monitored by her community midwife. • At 37+3 weeks’ gestation Mary complained of reduced fetal movements, she was seen at her local maternity unit where CTG monitoring was performed. She was discharged home a couple of hours later after a reassuring CTG. • At 39 weeks gestation Mary rang her midwife complaining of contractions and on questioning reported no fetal movements for several hours, her midwife advised her to attend the local hospital where unfortunately a fetal death in utero was identified. • Labour was induced and Mary delivered a stillborn male with a birth weight of 2.4kg. Mary declined post mortem, but agreed to have her placenta examined. Confidential Enquiry – Review Findings • Mary’s previous child was born at term and weighed 2.45 kg, which was small for gestational age. This was not picked up as a risk factor. • Mary reported reduced fetal movements: she had a CTG but not an ultrasound scan. • There was no evidence from the notes that Mary was advised about being aware of changes in her baby’s movements . Mary rang the midwife complaining of contractions, fetal movements appeared secondary to her concerns. • Placental pathology was performed but in the opinion of the perinatal histopathologist this was inadequate. Confidential Enquiry in Cumbria Importance of Understanding Why Flenady et al. Lancet 2011; 377: 1703–17 What conditions are associated with Stillbirth in Manchester? So why do babies die? • Big Three Primary Factors – Fetal Growth Restriction and Placental Failure – Infection – Lethal Congenital Abnormality • Poor at predicting and identifying FGR – Recognition and Treatment of high-risk status • Poor at communicating and engaging with BME groups (37% of SBs) Conclusions • Understanding why babies die is critical to prevention of stillbirth • Appropriate Investigation • Perinatal Audit - Identify conditions cause / associated with stillbirth – Fetal Growth Restriction – Infection • Confidential Enquiry – Ensure care optimal • Develop relevant local strategies