Case Studies > OB/Gyn
Late-Term Pregnancy, Amniotic Fluid Draining Away -- Why?
— Early recognition and timely action were crucial
by Kate Kneisel, Contributing Writer, MedPage Today February 10, 2020
A pregnant 34-year-old woman presents to the emergency department due to loss of amniotic fluid. She explains that this is her first pregnancy, and is at 37 weeks, 2 days' gestation. She notes that for the past 4 days, she has been feeling sick to her stomach and vomiting, and has also been feeling weak and exhausted.
She has not experienced any pruritus, headache, epigastric pain, or visual impairments. Her pregnancy was monitored without intercurrences, and she has neither recently traveled nor taken drugs or medicinal herbs.
Clinicians report that on admission, the patient is jaundiced, and apyretic. Her blood pressure is 118/74 mmHg and her lower limbs are swollen.
Day 1 Laboratory Test Results
Hemoglobin 11.5 g/dL
White blood cell count of 29.60×103/μl with neutrophilia (81.2%) and lymphocytosis (13.5%)
Platelet count 146×103/μL
Serum lactate dehydrogenase 1,114 U/L
Aspartate aminotransferase (AST) 273 U/L
Alanine aminotransferase (ALT) 370 U/L
Alkaline phosphatase 419 U/L
Total bilirubin 8.21 mg/dL
Bile acids 3.3 mol
Serum creatinine 1.69 mg/dL
Urea 42 mg/dL
Albumin 24 g/L
Glucose 59 mg/dL
Prothrombin time 32.7 seconds
Activated partial thromboplastin time 59.9 seconds
Blood tests for hepatitis A, B, C, and E serology are all negative. An abdominal ultrasound reveals "liver with a slight increase of the right lobe, admitting a discrete diffuse heterogeneity with a slight increase in echogenicity, translating diffuse steatosis."
Abdominal ultrasound with diffuse hepatic steatosis.
Clinicians make a presumptive diagnosis of acute fatty liver of pregnancy (AFLP), and admit the patient to the delivery room. Because there is evidence of fetal distress, the clinicians perform an emergency cesarean section. The newborn male weighs 2,810 g and has an Apgar score of 3 in the first minute and 5 at the fifth minute, requiring resuscitation.
Postoperatively, the patient is transferred to the intensive care unit (ICU) for treatment and stabilization of acute hepatic and renal insufficiency and disseminated intravascular coagulation (DIC). She requires continuous infusion of 5% dextrose for about 10 days to maintain euglycemia.
On day 7 of hospitalization, the patient has nausea and vomiting; clinicians note elevations of amylase (260 U/L) and lipase (948 U/L), and perform an abdominal computed tomography (CT) scan, which shows "discrete globosity of the pancreatic parenchyma, with dimensions at the upper limit of normality." The patient is diagnosed with acute pancreatitis.
She recovers gradually and is progressively able to eat. Tests show progressive improvement in her hepatic function, from her day 1 values. On day 7, her prothrombin time is 16.3 seconds; activated partial thromboplastin time is 32.2, AST is 120, ALT is 126, alkaline phosphatase is 217, and total bilirubin is 4.32 mg/dL.
Case Follow-up/Discussion
The patient's DIC is managed with fresh frozen plasma, fibrinogen, and vitamin K. She improves clinically and is discharged on day 22 after the delivery of her son.
Clinicians presenting this case of AFLP note that early recognition of this pathology and timely action in a context of differentiated care is associated with decreased maternal and fetal mortality.
This rare disease remains an obstetric emergency, requiring early diagnosis and treatment, which often involves termination of pregnancy and supportive therapy. AFLP usually develops from 30 to 38 weeks of gestation, and occurs in one of every 7,000 to 15,000 pregnancies.
As in this case, the condition is more frequent in nulliparous women and those with male fetuses. Other associated factors that increase risk include a previous episode of AFLP, multiple pregnancies, body mass index less than 20, fetal long-chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD), and preeclampsia.
Development of AFLP has been linked with defects in fatty acid metabolism during pregnancy, most often affecting LCHAD, the authors note. The presence of this homozygous defect in the fetus results in accumulation of intermediate products of fatty acid metabolism, which can cause maternal liver disease.
Symptoms are nonspecific – with nausea and vomiting, epigastric pain, and jaundice identified as symptoms of a typical "AFLP-triad." The disease can progress rapidly to acute liver failure. Common complications include coagulopathy, hypoglycemia, and renal failure, and rarely, pancreatitis.
Challenging Differential Diagnosis
Diagnosis can be difficult due to the non-specific symptoms, which overlap with other high-risk liver diseases of pregnancy such as pre-eclampsia and HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet levels).
AFLP can be distinguished from HELLP syndrome and preeclampsia by hypoglycemia and jaundice, and by signs of systemic hepatic dysfunction such as mild-to-moderate elevation of transaminases, hepatic encephalopathy, and as in this patient's case, DIC. Hypoglycemia and coagulopathy have been suggested as the defining clinical features that can distinguish AFLP from HELLP syndrome.
The authors explain that given the complexity of the differential diagnosis, it has been suggested that in addition to the Swansea criteria, including antithrombin activity of less than 65% among the diagnostic criteria may help raise suspicion for AFLP and hasten diagnosis.
Other diseases to be considered in the differential diagnosis include intrahepatic cholestasis of pregnancy, viral hepatitis, and drug-induced hepatitis. In intrahepatic cholestasis of pregnancy, the predominant symptom is pruritus, with serum bilirubin less than 5 mg/dL and elevated bile acids. Viral hepatitis may be identified on blood tests, since it tends to have higher aminotransferase values.
In the absence of a gold standard for diagnosis, patients suspected to have AFLP should be assessed using the Swansea criteria as well as clinical, laboratory, and imaging findings, and a diagnosis of AFLP should be considered if at least six of these criteria are met:
Polydipsia/polyuria
Elevated bilirubin (>0.8 mg/dL or >14 μ mmol/L)
Hypoglycemia (<72 mg/dL)
Leukocytosis (>11,000 cells/μ L)
Elevated transaminases (AST or ALT) (>42 U/L)
Elevated ammonia (> 47 μmol/L)
Hyperuricemia (>5.7 mg/dL or >340 μmol/L)
Acute renal insufficiency or creatinine (>1.7 mg/dL or >150 μmol/L)
Coagulopathy or prothrombin time >14 seconds
Ascites or ultrasound with "bright" liver
Hepatic biopsy with microvesicular steatosis
The case authors report that this patient does have six of these criteria: vomiting, bilirubin over 0.8 mg/dL, hypoglycemia less than 72 mg/dL, leukocytes over 11×109/L, ALT over 42 U/L, and coagulopathy with prothrombin time over 14 seconds.
While the role of imaging tests has not been determined, they may be useful to support the diagnosis of AFLP, and a CT scan may also help identify the presence of complications such as pancreatitis, the authors note. And while this patient's ultrasound revealed diffuse hepatic steatosis, this is neither a specific result nor a diagnosis, and liver biopsy should be used only when the diagnosis is doubtful.
Treatment/Complications
Interruption of the pregnancy is the recommended treatment for AFLP, the authors note, explaining that the mode of delivery is determined based on the degree of maternal and fetal decompensation and the likelihood of successful vaginal delivery.
As occurred in this case, DIC may develop, and is one of the most frequent complications -- which may require admission to the ICU for treatments such as coagulopathy reversal, ventilation, correction of hypoglycemia, and management of renal failure. Measurement of amylase and lipase in patients with suspected AFLP may help detect pancreatitis, which is another possible complication; CT may be useful in this regard.
Improvements in maternal mortality rates in the last few decades have reduced global mortality to less than 10%, the authors state. Despite the potential to use genetic study to detect LCHAD, negative tests for the most common mutation, G1528C, do not exclude the condition. When enzymatic defect is detected, the newborn's prognosis relies mainly on clinical manifestations, and thus use of molecular diagnosis is often limited to cases of strong suspicion.
This case was diagnosed early and consequently had a good maternal and fetal prognosis. Clinicians should be alert for potential recurrence in subsequent pregnancies, although the exact risk is unknown, the authors state.
The case report authors noted having no conflicts of interest.
American Journal of Case Reports
Source Reference: de Vasconcelos Gaspar A, et al "Acute Fatty Liver of Pregnancy: Rare, but Potentially Fatal" Am J Case Rep 2020; 21: e921122.