Dataset Information

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

ABSTRACT:

Background

Amniotic fluid embolism (AFE) remains one of the principal reported causes of direct maternal mortality in high-income countries. However, obtaining robust information about the condition is challenging because of its rarity and its difficulty to diagnose. This study aimed to pool data from multiple countries in order to describe risk factors, management, and outcomes of AFE and to explore the impact on the findings of considering United Kingdom, international, and United States AFE case definitions.

Methods and findings

A population-based cohort and nested case-control study was conducted using the International Network of Obstetric Survey Systems (INOSS). Secondary data on women with AFE (n = 99-218, depending on case definition) collected prospectively in population-based studies conducted in Australia, France, the Netherlands, Slovakia, and the UK were pooled along with secondary data on a sample of control women (n = 4,938) collected in Australia and the UK. Risk factors for AFE were investigated by comparing the women with AFE in Australia and the UK with the control women identified in these countries using logistic regression. Factors associated with poor maternal outcomes (fatality and composite of fatality or permanent neurological injury) amongst women with AFE from each of the countries were investigated using logistic regression or Wilcoxon rank-sum test. The estimated incidence of AFE ranged from 0.8-1.8 per 100,000 maternities, and the proportion of women with AFE who died or had permanent neurological injury ranged from 30%-41%, depending on the case definition. However, applying different case definitions did not materially alter findings regarding risk factors for AFE and factors associated with poor maternal outcomes amongst women with AFE. Using the most liberal case definition (UK) and adjusting for the severity of presentation when appropriate, women who died were more likely than those who survived to present with cardiac arrest (89% versus 40%, adjusted odds ratio [aOR] 10.58, 95% confidence interval [CI] 3.93-28.48, p < 0.001) and less likely to have a source of concentrated fibrinogen (40% versus 56%, aOR 0.44, 95% CI 0.21-0.92, p = 0.029) or platelets given (24% versus 49%, aOR 0.23, 95% CI 0.10-0.52, p < 0.001). They also had a lower dose of tranexamic acid (median dose 0.7 g versus 2 g, p = 0.035) and were less likely to have had an obstetrician and/or anaesthetist present at the time of the AFE (61% versus 75%, aOR 0.38, 95% CI 0.16-0.90, p = 0.027). Limitations of the study include limited statistical power to examine factors associated with poor maternal outcome and the potential for residual confounding or confounding by indication.

Conclusions

The findings of our study suggest that when an AFE is suspected, initial supportive obstetric care is important, but having an obstetrician and/or anaesthetist present at the time of the AFE event and use of interventions to correct coagulopathy, including the administration of an adequate dose of tranexamic acid, may be important to improve maternal outcome. Future research should focus on early detection of the coagulation deficiencies seen in AFE alongside the role of tranexamic acid and other coagulopathy management strategies.

SUBMITTER: Fitzpatrick KE

PROVIDER: S-EPMC6850527 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

Fitzpatrick Kathryn E KE van den Akker Thomas T Bloemenkamp Kitty W M KWM Deneux-Tharaux Catherine C Kristufkova Alexandra A Li Zhuoyang Z Schaap Timme P TP Sullivan Elizabeth A EA Tuffnell Derek D Knight Marian M

PLoS medicine 20191112 11

<h4>Background</h4>Amniotic fluid embolism (AFE) remains one of the principal reported causes of direct maternal mortality in high-income countries. However, obtaining robust information about the condition is challenging because of its rarity and its difficulty to diagnose. This study aimed to pool data from multiple countries in order to describe risk factors, management, and outcomes of AFE and to explore the impact on the findings of considering United Kingdom, international, and United Stat ...[more]

PMID: 31714909

Similar Datasets

Project description:Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. SUMMARY:Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.

Project description:ImportanceAmniotic fluid embolism (AFE) is an uncommon pregnancy complication but is associated with high maternal mortality. Because of the rarity of AFE, associated risks factors and maternal outcomes have been relatively understudied.ObjectiveTo examine the clinical, pregnancy, and delivery characteristics and the maternal outcomes related to AFE in a recent period in the US.Design, setting, and participantsThis retrospective cohort study examined hospital deliveries from January 1, 2016, to December 31, 2019, from the Healthcare Cost and Utilization Project's National Inpatient Sample.Main outcomes and measuresThe primary outcome was clinical, pregnancy, and delivery characteristics of AFE, assessed with a multivariable binary logistic regression model. The coprimary outcome was failure to rescue, defined as maternal mortality after AFE. Associations with other severe maternal morbidity indicators and failure to rescue per clinical and pregnancy characteristics were also assessed.ResultsA total of 14 684 135 deliveries were examined, with AFE diagnosed in 880 women, corresponding to an incidence rate of 6.0 per 100 000 deliveries. The cohort-level median patient age was 29 years (IQR, 25-33 years). In a multivariable analysis, (1) patient factors of older age, Asian and Black race, Western US region, pregestational hypertension, asthma, illicit substance use, and grand multiparity; (2) pregnancy factors of placental accreta spectrum (PAS), placental abruption, uterine rupture, polyhydramnios, chorioamnionitis, preeclampsia, fetal growth restriction, and fetal demise; and (3) delivery factors of early gestational age, cervical ripening, cesarean delivery, operative delivery, and manual removal were associated with AFE. Among these characteristics, PAS had the largest association with AFE (adjusted odds ratio [aOR], 10.01; 95% CI, 7.03-14.24). When stratified by the PAS subtypes, more severe forms of PAS had a greater association with AFE (aOR for increta and percreta, 17.35; 95% CI, 10.21-28.48; and aOR for accreta, 7.62; 95% CI, 4.83-12.01). Patients who had AFE were more likely to have coagulopathy (aOR, 24.68; 95% CI, 19.38-31.44), cardiac arrest (aOR, 24.56; 95% CI, 17.84-33.81), and adult respiratory distress syndrome (aOR, 10.72; 95% CI, 8.09-14.20). The failure-to-rescue rate after AFE was 17.0% overall. However, the failure-to-rescue rate exceeded 30% when AFE co-occurred with other severe maternal morbidity indicators: 45.8% for AFE, cardiac arrest, and coagulopathy; 43.2% for AFE, shock, and cardiac rhythm conversion; and 38.6% for AFE, cardiac arrest, coagulopathy, and shock. The failure-to-rescue rate after AFE also exceeded 30% when AFE occurred in the setting of placental pathology: 42.9% for AFE and PAS and 31.3% for AFE and placental abruption.Conclusions and relevanceThis contemporaneous, national-level analysis validated previously known risk factors for AFE and confirmed the dismal outcomes of pregnancy complicated by AFE. The association between PAS and AFE, which was not previously reported, warrants further investigation.

Project description:BackgroundEvidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk.MethodsIn this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance.ResultsPFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p?=?0.042; FDR q value?=?0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR?=?0.100; 95% CI 0.016, 0.630; p?=?0.014; FDR q value?=?0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR?=?1.002; 95% CI 1.000, 1.004; p?=?0.05). However, after multiple comparison correction, the association was not significant (FDR q value?=?0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity.ConclusionsThe presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD.

Dataset Information

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

Background

Methods and findings

Conclusions

Publications

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets