1. A large, retrospective cohort study identified risk factors for amniotic fluid embolism during pregnancy, including a strong association with placental accreta.

2. Amniotic fluid embolism was associated with significant maternal morbidity.

Level of Evidence Rating: 2 (Good)

Study Rundown: Amniotic fluid embolism (AFE) is a potentially catastrophic complication of pregnancy in which a bubble of amniotic fluid or other fetal components enters the mother’s circulatory system. Although rare, the associated morbidity and mortality are significant, particularly given how challenging the diagnosis can be. Much about the pathophysiology and etiology of AFE is unknown; the present study sought to evaluate risk factors for AFE and to characterize associated maternal outcomes.

A total of 14,684,135 deliveries were performed during the study period; in this time, 880 diagnoses of AFE were identified. Therefore, the incidence rate of AFE was 6 per 100,000 pregnancies. Several demographic, maternal and fetal characteristics were identified as being associated with the incidence of AFE. The strongest associations were found with the following factors, all with an adjusted odds ratio greater than 2: grand multiparity, placental disruption or accreta, uterine rupture, intrauterine fetal demise, polyhydramnios, induction/ripening, surgical delivery. Analysis of other contributing factors to maternal mortality demonstrated a strong association between AFE and disseminated intravascular coagulation and cardiac arrest or ventricular fibrillation.

This retrospective cohort study describes several risk factors for amniotic fluid embolism, drawing from maternal, fetal and situational characteristics. The finding that placental pathologies, including placental abruption or placental accreta, are amongst the strongest risk factors for AFE is novel and clinically significant. A strength of this study is the large sample size and the multifaceted nature of the statistical analysis, which included a description of other contributors to maternal mortality. Drawbacks of this study include the inability to control for confounding variables and determine causal relationships. Future studies should seek to better understand the pathophysiology driving AFE and the associated risk factors identified here.

Click here to read this study in JAMA Network Open

Click to read an accompanying editorial in JAMA Network Open

Relevant reading: Amniotic fluid embolism: diagnosis and management

In-Depth [retrospective cohort]: A large, retrospective cohort study was conducted using population-level databases in the United States. The population of interest was patients who had delivered a baby (vaginal or cesarean routes) between 2016 and 2019. The primary database used to collect exposure and outcome data was the National Inpatient Sample (NIS) which amasses discharge data from more than 90% of the United States population. The primary outcome was the diagnosis of AFE, as identified through standard diagnostic codes. Covariates of interest included demographic data, pregnancy information, hospital information and details of the delivery.

The overall incidence of AFE was 6 per 100,000 pregnancies and increased marginally over the study period from 5.2 per 100,000 in 2016 to 6.5 per 100,000 in 2019. Several demographic factors were identified as having an association with the risk of AFE: older age (maternal age 30-35 associated with adjusted odds ratio 1.45, 95% confidence interval 1.17-1.79), Asian race (1.83, 1.44-2.31) and Black race (1.41, 1.17-1.70). Associated comorbidities included maternal asthma (1.59, 1.27-2.00), grand multiparity (2.41, 1.29-4.52), illicit substance use (1.47, 1.09-1.98) and hypertension (pregestational 1.38, 1.08-1.76).

Factors at the time of delivery associated with AFE included placental abruption (4.06, 3.17-5.21), placental accreta (10.01, 7.03-14.24) and uterine rupture (3.91, 2.07-7.36). Finally, fetal factors associated with AFE included growth restriction (1.37, 1.05-1.79), intrauterine fetal demise (3.32, 2.30-4.79), chorioamnionitis (1.64, 1.21-2.22), polyhydramnios (3.56, 2.76-4.60), and need for induction or ripening (2.19, 1.68-2.86).

The adjusted odds ratio for an association between AFE and other contributors to maternal mortality in the United States was strongest for disseminated intravascular coagulation (24.68, 19.38-31.44) and cardiac arrest/ventricular fibrillation (24.56, 17.88-33.81).

Image: PD

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