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Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (2): 159-165    DOI: 10.31083/j.ceog.2020.02.5176
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Amniotic fluid embolism: the pathophysiology, diagnostic clue, and blood biomarkers indicator for disease prediction
R. Suvannasarn1, T. Tongsong1, P. Jatavan1, *()
1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Chiang Mai University, Chiang Mai, Thailand
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Abstract  Objective: This article aims to review and provide more understanding of current knowledge of amniotic fluid embolism regarding pathophysiology, diagnostic criteria, risk factors, indicating biomarkers, treatment strategies and outcomes of some case reports. Study design: A systematic literature review was performed using the PubMed database, restricted to articles published in English from 1992 to 2018. Original research, case reports, guideline recommendations, and review articles were reviewed in this study. Summary: Amniotic fluid embolism (AFE) is a rare catastrophic obstetric condition defined by clinical manifestations of pregnancy with sudden onset of cardiopulmonary arrest, consumptive coagulopathy or neurological deficits without other explainable illnesses. The incidence varies from 1.7-14.8 cases per 100,000 worldwide. The current understanding of AFE pathophysiology includes fetal components obstructing maternal microvessels with subsequent anaphylactoid reaction. Maternal pulmonary vasospasm and hematologic activation occur later, followed by heart failure and sudden cardiovascular collapse. Some of the possible risk factors for AFE include; 1) Maternal risk: age over 35 years, hypertensive disorder and diabetes mellitus; 2) Fetal risk: polyhydramnios, multiparity, non-vertex at delivery, fetal distress and fetal macrosomia; 3) Obstetric risks: amniocentesis, artificial amniotic fluid injection, oxytocin infusion, and placental abruption. Some of the useful biomarkers have been proposed including zinc coproporphyrin-1, squamous cell carcinoma antigen, carcinoembryonic antigen, cancer antigen 125, Siatyl Tn, monoclonal antibody TKH-2, C3, C4, tryptase, insulin-like growth factor binding protein-1, C1 esterase inhibitor. Management of AFE requires immediate basic life support and advanced cardiac life support. Adequate oxygenation, ventilation, coagulopathy correction, and appropriate vasopressors are recommended. However, the outcome prediction of AFE remains challenging.
Key words:  Amniotic fluid embolism      Pathophysiology      Biomarker      Diagnosis      Cases     
Published:  15 April 2020     
Fund: Chiang Mai University Fund
*Corresponding Author(s):  P. Jatavan     E-mail:

Cite this article: 

R. Suvannasarn, T. Tongsong, P. Jatavan. Amniotic fluid embolism: the pathophysiology, diagnostic clue, and blood biomarkers indicator for disease prediction. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 159-165.

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Figure 1.  — Diagnostic criteria of AFE in different countries.

Figure 2.  — Mechanism of AFE.

Table 1  — Risk factors for AFE.
Maternal Risk Fetal Risk Obstetric Risk
- Age over 35 years - Polyhydramnios - Amniocentesis
- Hypertensive disorder - Multiparity - Artificial amniotic fluid injection
- Pre-eclampsia or eclampsia - Non-vertex at delivery - Oxytocin infusion
- Diabetes - Male fetus - Cesarean section
- Fetal distress - Forceps or vacuum-assisted delivery
- Fetal macrosomia - Uterine rupture or laceration
- Intrauterine death - Placenta previa
- Placental abruption
- Cervical laceration
Table 2  — Biomarkers and tests proposed for AFE diagnosis.
Author, Year Marker Abnormal finding AFE cases Non-AFE cases Sensitivity Specificity
Kanayama N, 1992 [20] Zinc Coproporphyrin-1 Serum level > 35 nmol/L 4 50 100% 98%
Sarandakou A, 1992 [31] CEA Serum level, Umbilical 0 56 - -
cord blood, Amniotic

fluid level > 5 ng/ml
Serum level, Umbilical




cord blood, Amniotic

Squamous cell car-
fluid level > 35 U/ml
Serum level, Umbilical




cinoma antigen cord blood, Amniotic

Kobayashi H, 1993 [19]

Siatyl Tn
fluid level > 2.5 ng/ml
Serum level > 50 U/mL




Kobayashi H, 1997 [29] Monoclonal anti- Positive staining 4 4 100% 100%
body TKH-2
Benson M, 2001 [14] C3 Serum level < 70
6 22 87.50% 100%
C4 Serum level < 16
6 22 100% 100%
Tryptase Serum level > 2 SD 9 22 0% -
Sialyl Tn 22 77.80% -
Iwai K, 2011 [21] Sialyl-Tn Serum level > 47 U/ml 127 74 25.80% 97.30%
Serum level > 1.6
127 74 45.90% 73%
Legrand M, 2012 [23] Insulin-like growth
factor binding
Serum level > 104.5
25 94 92% 97.80%
Tanura N, 2014 [25] C1 Esterase in- Serum activity level 106 88 - -
hibitor 25%
Koike N, 2017 [22] Squamous cell carcinoma antigen Serum level > 7.15 ng/mL 20 74 60.00% 89.20%
Table 3  — Cases reports of AFE and outcomes.
Author, Year Age GA (week) Route of delivery Onset Cardiac arrest Outcome Remark
MahshidN, 2009 [34] 27 35 Cesarean section Following placental delivery Yes Dead
Lee JH, 2010 [35] 33 40+6 Cesarean section 5 minutes after spinal block Yes Dead
Hosoya Y, 2013 [36] 40 36 Cesarean section - Yes Resolved
Campanharo FF 2015 [27] 33 Cesarean section Rapidly after anesthetic block No Resolved Maternal underlying of systemic lupus erythematous
Mita K, 2017 [37] 29 37 Cesarean section After placental delivery Yes Resolved Complicated with pheochromocytoma crisis
Drukker L, 2017 [15]
36 24 - Rapidly after amnio-centesis No Resolved Maternal underlying of portal hypertension, portal vein thrombosis, esophageal varices, factor V Leiden homozygosity, hypothyroidism
Tincres F, 2017 [38] 35 39 Cesarean section 4 hours after epidural analgesia Yes Resolved Successfully treated by veno-arterial extracorporeal membrane oxygenation
Lynch W, 2017 [39] 28 41 Vaginal delivery with vacuum extraction After labor epidural catheter was placed Yes Resolved Lipid emulsion infusion was applied for rescue
Chen W, 2018 [40] 28 39 Vaginal delivery with forceps extraction 20 minutes after artificial rupture of membrane Yes Dead Complicated with maternal hepatic rupture
Maack KH, 2018 [41] 40 40+2 Cesarean section Immediately after spontaneous rupture of membrane Yes Resolved Complicated with maternal right heart mass
Seong GM, 2018 [10] 32 39+1 Vaginal delivery After entirely opened cervix Yes Resolved Successfully treated by veno-arterial extracorporeal membrane oxygenation
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