General obstetrics
DOI: 10.1111/1471-0528.13300 www.bjog.org
Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case–control study KE Fitzpatrick,a D Tuffnell,b JJ Kurinczuk,a M Knighta a National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK b Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK Correspondence: KE Fitzpatrick, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK. Email [email protected]
Accepted 7 December 2014. Published Online 12 February 2015.
Objective To describe the incidence, risk factors, management and
outcomes of amniotic-fluid embolism (AFE) over time. Design A population-based cohort and nested case–control study
using the UK Obstetric Surveillance System (UKOSS). Setting All UK hospitals with obstetrician-led maternity units. Population All women diagnosed with AFE in the UK between
February 2005 and January 2014 (n = 120) and 3839 control women. Methods Prospective case and control identification through
UKOSS monthly mailing. Main outcome measures Amniotic-fluid embolism, maternal
death or permanent neurological injury. Results The total and fatal incidence of AFE, estimated as 1.7 and 0.3 per 100 000, respectively, showed no significant temporal trend over the study period and there was no notable temporal change in risk factors for AFE. Twenty-three women died (case
fatality 19%) and seven (7%) of the surviving women had permanent neurological injury. Women who died or had permanent neurological injury were more likely to present with cardiac arrest (83% versus 33%, P < 0.001), be from ethnicminority groups (adjusted odds ratio [OR] 2.85, 95% confidence interval [95% CI] 1.02–8.00), have had a hysterectomy (unadjusted OR 2.49, 95% CI 1.02–6.06), had a shorter time interval between the AFE event and when the hysterectomy was performed (median interval 77 minutes versus 248 minutes, P = 0.0315), and were less likely to receive cryoprecipitate (unadjusted OR 0.30, 95% CI 0.11–0.80). Conclusion There is no evidence of a temporal change in the
incidence of or risk factors for AFE. Further investigation is needed to establish whether earlier treatments can reverse the cascade of deterioration leading to severe outcomes. Keywords Amniotic-fluid embolism, maternal morbidity, maternal mortality.
Please cite this paper as: Fitzpatrick KE, Tuffnell D, Kurinczuk JJ, Knight M. Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case–control study. BJOG 2016;123:100–109.
Introduction Amniotic fluid embolism (AFE) although rare, remains one of the leading causes of direct maternal mortality in high-income countries,1–3 characterised by unexplained sudden cardiovascular collapse, respiratory distress and disseminated intravascular coagulation. The rarity of AFE together with the fact that clinical diagnosis of the condition is one of exclusion makes it difficult to obtain reliable information concerning incidence, risk factors, management and outcomes. Previous reviews3,4 suggest
100
that the reported total incidence of AFE varies from 1.9 per 100 000 to 7.7 per 100 000 maternities; the reported incidence of fatal AFE cases varies from 0.4 per 100 000 to 1.7 per 100 000 and the case fatality rate due to AFE ranges from 11 to 43%; there is little consistency in the factors reported to be associated with the occurrence of AFE and very limited data are available regarding factors associated with severe maternal outcomes. The aim of this study was to extend our previous work,5 taking advantage of more recent data to not only describe the incidence, risk factors, management and outcomes of
ª 2015 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Incidence, risk factors, management and outcomes of AFE
AFE, but also to further investigate temporal trends of the condition and whether there are specific factors associated with severe maternal outcomes.
Methods A national, population-based cohort and nested case–control study was conducted using the UK Obstetric Surveillance System (UKOSS). UKOSS is a system that was set up in 2005 to investigate rare and severe complications in pregnancy and childbirth in the UK. Details of the UKOSS methodology have been described elsewhere.6 Briefly, nominated clinicians in each obstetrician-led maternity unit in the UK are sent a monthly case notification card with a list of conditions under surveillance. Women may also deliver in midwifery-led units or at home in the UK, but any woman with a severe maternal morbidity in one of these settings would be transferred to an obstetrician-led unit. Between 1 February 2005 and 31 January 2014 clinicians were asked to report cases of AFE, defined according to the criteria outlined in Box 1. On reporting a case, clinicians were sent a data collection form to complete from the woman’s medical notes to confirm the diagnosis and ascertain further information concerning potential risk factors, management and outcomes (data collection form available at www.npeu.ox.ac.uk/downloads/files/ukoss/forms/UKOSSAmniotic-Fluid-Embolism.pdf). All data requested were anonymous and up to five reminders were sent if completed forms were not returned. On receipt of data collection forms, cases were checked to confirm that they met the case definition. All cases that had postpartum haemorrhage reported as the first symptom of AFE were reviewed against the diagnostic criteria (Box 1) to determine whether AFE was the most likely diagnosis. Information on woman’s year of birth and expected date of delivery was used to identify duplicate reports. Information about maternal deaths from AFE during the study period was obtained from the Centre for Maternal and Child Enquires (CMACE) and the National Maternal, Newborn and Infant Clinical Outcome Review Programme run by MBBRACE-UK. This information was compared with maternal deaths from AFE reported through UKOSS. One additional case was identified through this route. In this instance, the relevant UKOSS reporting clinician was contacted and asked to complete a data collection form for the case. There were also four cases reported to UKOSS that were classified by the MBBRACE-UK confidential enquiry process as not AFE cases; these four cases were therefore excluded. All statistical analysis was conducted using STATA 13 software (StataCorp, College Station, TX, USA). Incidence rates for AFE with exact Poisson 95% confidence intervals (95% CIs) were calculated using the available national birth
data (2005–2012)7–10 as the denominator for the estimated number of maternities during the study period. Temporal trends in incidence rates were investigated using Poisson regression. The characteristics and management of women with AFE were described, and putative risk factors for AFE, identified from the literature, were evaluated by comparing the cases with a control group of 3839 women using unconditional logistic regression to estimate odds ratios (ORs) with 95% CIs. The control women were identified by UKOSS reporting clinicians as the two women delivering in the same hospital immediately before other UKOSS study cases,11–17 and are comparable in characteristics to the available national data on women giving birth in the UK. A full regression model was developed by including both explanatory and potential confounding factors in a core model if there was a pre-existing hypothesis or evidence to suggest that they were causally related to AFE. Addition of interaction terms to the full model and subsequent likelihood ratio testing was used to assess plausible interactions; to allow for multiple testing, a P-value of
DOI: 10.1111/1471-0528.13300 www.bjog.org
Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case–control study KE Fitzpatrick,a D Tuffnell,b JJ Kurinczuk,a M Knighta a National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK b Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK Correspondence: KE Fitzpatrick, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK. Email [email protected]
Accepted 7 December 2014. Published Online 12 February 2015.
Objective To describe the incidence, risk factors, management and
outcomes of amniotic-fluid embolism (AFE) over time. Design A population-based cohort and nested case–control study
using the UK Obstetric Surveillance System (UKOSS). Setting All UK hospitals with obstetrician-led maternity units. Population All women diagnosed with AFE in the UK between
February 2005 and January 2014 (n = 120) and 3839 control women. Methods Prospective case and control identification through
UKOSS monthly mailing. Main outcome measures Amniotic-fluid embolism, maternal
death or permanent neurological injury. Results The total and fatal incidence of AFE, estimated as 1.7 and 0.3 per 100 000, respectively, showed no significant temporal trend over the study period and there was no notable temporal change in risk factors for AFE. Twenty-three women died (case
fatality 19%) and seven (7%) of the surviving women had permanent neurological injury. Women who died or had permanent neurological injury were more likely to present with cardiac arrest (83% versus 33%, P < 0.001), be from ethnicminority groups (adjusted odds ratio [OR] 2.85, 95% confidence interval [95% CI] 1.02–8.00), have had a hysterectomy (unadjusted OR 2.49, 95% CI 1.02–6.06), had a shorter time interval between the AFE event and when the hysterectomy was performed (median interval 77 minutes versus 248 minutes, P = 0.0315), and were less likely to receive cryoprecipitate (unadjusted OR 0.30, 95% CI 0.11–0.80). Conclusion There is no evidence of a temporal change in the
incidence of or risk factors for AFE. Further investigation is needed to establish whether earlier treatments can reverse the cascade of deterioration leading to severe outcomes. Keywords Amniotic-fluid embolism, maternal morbidity, maternal mortality.
Please cite this paper as: Fitzpatrick KE, Tuffnell D, Kurinczuk JJ, Knight M. Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case–control study. BJOG 2016;123:100–109.
Introduction Amniotic fluid embolism (AFE) although rare, remains one of the leading causes of direct maternal mortality in high-income countries,1–3 characterised by unexplained sudden cardiovascular collapse, respiratory distress and disseminated intravascular coagulation. The rarity of AFE together with the fact that clinical diagnosis of the condition is one of exclusion makes it difficult to obtain reliable information concerning incidence, risk factors, management and outcomes. Previous reviews3,4 suggest
100
that the reported total incidence of AFE varies from 1.9 per 100 000 to 7.7 per 100 000 maternities; the reported incidence of fatal AFE cases varies from 0.4 per 100 000 to 1.7 per 100 000 and the case fatality rate due to AFE ranges from 11 to 43%; there is little consistency in the factors reported to be associated with the occurrence of AFE and very limited data are available regarding factors associated with severe maternal outcomes. The aim of this study was to extend our previous work,5 taking advantage of more recent data to not only describe the incidence, risk factors, management and outcomes of
ª 2015 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Incidence, risk factors, management and outcomes of AFE
AFE, but also to further investigate temporal trends of the condition and whether there are specific factors associated with severe maternal outcomes.
Methods A national, population-based cohort and nested case–control study was conducted using the UK Obstetric Surveillance System (UKOSS). UKOSS is a system that was set up in 2005 to investigate rare and severe complications in pregnancy and childbirth in the UK. Details of the UKOSS methodology have been described elsewhere.6 Briefly, nominated clinicians in each obstetrician-led maternity unit in the UK are sent a monthly case notification card with a list of conditions under surveillance. Women may also deliver in midwifery-led units or at home in the UK, but any woman with a severe maternal morbidity in one of these settings would be transferred to an obstetrician-led unit. Between 1 February 2005 and 31 January 2014 clinicians were asked to report cases of AFE, defined according to the criteria outlined in Box 1. On reporting a case, clinicians were sent a data collection form to complete from the woman’s medical notes to confirm the diagnosis and ascertain further information concerning potential risk factors, management and outcomes (data collection form available at www.npeu.ox.ac.uk/downloads/files/ukoss/forms/UKOSSAmniotic-Fluid-Embolism.pdf). All data requested were anonymous and up to five reminders were sent if completed forms were not returned. On receipt of data collection forms, cases were checked to confirm that they met the case definition. All cases that had postpartum haemorrhage reported as the first symptom of AFE were reviewed against the diagnostic criteria (Box 1) to determine whether AFE was the most likely diagnosis. Information on woman’s year of birth and expected date of delivery was used to identify duplicate reports. Information about maternal deaths from AFE during the study period was obtained from the Centre for Maternal and Child Enquires (CMACE) and the National Maternal, Newborn and Infant Clinical Outcome Review Programme run by MBBRACE-UK. This information was compared with maternal deaths from AFE reported through UKOSS. One additional case was identified through this route. In this instance, the relevant UKOSS reporting clinician was contacted and asked to complete a data collection form for the case. There were also four cases reported to UKOSS that were classified by the MBBRACE-UK confidential enquiry process as not AFE cases; these four cases were therefore excluded. All statistical analysis was conducted using STATA 13 software (StataCorp, College Station, TX, USA). Incidence rates for AFE with exact Poisson 95% confidence intervals (95% CIs) were calculated using the available national birth
data (2005–2012)7–10 as the denominator for the estimated number of maternities during the study period. Temporal trends in incidence rates were investigated using Poisson regression. The characteristics and management of women with AFE were described, and putative risk factors for AFE, identified from the literature, were evaluated by comparing the cases with a control group of 3839 women using unconditional logistic regression to estimate odds ratios (ORs) with 95% CIs. The control women were identified by UKOSS reporting clinicians as the two women delivering in the same hospital immediately before other UKOSS study cases,11–17 and are comparable in characteristics to the available national data on women giving birth in the UK. A full regression model was developed by including both explanatory and potential confounding factors in a core model if there was a pre-existing hypothesis or evidence to suggest that they were causally related to AFE. Addition of interaction terms to the full model and subsequent likelihood ratio testing was used to assess plausible interactions; to allow for multiple testing, a P-value of
