Acute Fatty Liver of Pregnancy: Neonatal Implications

A 34-year-old Gravida 3, para 0020 woman at 37 weeks and 4 days’ gestation presented to the Labor and Delivery floor with 1 week of progressive fatigue, nausea, and vomiting. The day before admission, she was unable to tolerate anything by mouth and developed new right-sided upper quadrant discomfort. Additionally, she perceived no fetal movement in the 12 hours before presentation. Her pregnancy was otherwise uncomplicated.On arrival, she was placed on the monitor, and vitals were obtained. Her blood pressure was mildly elevated. She was noted to be slightly jaundiced, slow to respond to verbal questions, and had occasional slurred speech with normal gross motor coordination. The fetal heart tracing showed a baseline of 150 bpm, absent variability, and recurrent late decelerations (Figure 1).Following verbal consent, an emergent cesarean under general anesthesia was performed given the category III tracing. Her laboratory results from admission resulted when the patient was in the operating room and were notable for hemolysis with significant elevations in her bilirubin, creatinine, and transaminase levels and a coagulopathy, with an increased International Normalized Ratio and low fibrinogen level. Her serum glucose level was low. The findings of hemolysis, hypoglycemia, synthetic liver dysfunction, and coagulopathy were most consistent with acute fatty liver of pregnancy (AFLP), particularly when combined with her physical presentation and symptoms. The differential diagnosis included HELLP (ie, Hemolysis, Elevated Liver Enzymes, Low Platelets) syndrome and preeclampsia with severe features. She remained hemodynamically stable, but an additional intravenous line was placed preemptively for access. Magnesium sulfate was started empirically because preeclampsia could not be excluded. Subsequently, she was admitted directly to the intensive care unit (ICU) for close monitoring and supportive care, as well as the need for multiple product transfusion to correct her coagulopathy.A male early-term neonate was delivered and had decreased respiratory effort prompting positive pressure ventilation. He had an Apgar score of 3, 6, and 7 at 1, 5, and 10 minutes, respectively. Umbilical cord gases revealed a metabolic acidosis (arterial pH of 6.81 and a base excess of 23.1 mEq/L).He was admitted to the neonatal ICU (NICU), and his birth weight was 2675 g (17%). He required intubation for respiratory failure, treatment of acidosis, and therapeutic hypothermia owing to neonatal encephalopathy. During rewarming, seizures were noted on electroencephalography, and phenobarbital was initiated. Magnetic resonance imaging demonstrated acute infarctions in the left middle cerebral artery distribution. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) testing yielded a negative result. He was discharged home on phenobarbital with neurology and occupational therapy follow-up.The mother’s immediate postoperative course was unremarkable on postoperative day 1 (POD1). Her mental status improved spontaneously. The magnesium sulfate infusion continued until 24-hours postpartum. However, on POD2, she appeared more jaundiced, and serial laboratory tests demonstrated progressive acidosis and deterioration of her liver synthetic function. Her ammonia, bilirubin, and lactate levels increased, which raised concern for progression of her AFLP. Her coagulopathy persisted. Hepatology was consulted given her worsening hepatic function and potential need for hepatic transplant.On POD4, she had an acute change in her clinical status, became obtunded, and was intubated for airway protection. She also required hemodynamic support with 3 vasopressors for distributive shock, attributed to the vasodilatory effects of liver failure. Continuous veno-venous hemodialysis and single-pass albumin dialysis were initiated. In the following days, her condition improved. Her coagulopathy and liver failure resolved. She was transferred out of the ICU and discharged home on POD8.On POD15, she developed bleeding from her cesarean incision. Her hemoglobin was found to be 6.9 g/dL, and computed tomography imaging of her abdomen and pelvis showed a 17-cm hematoma in the subcutaneous tissue inferior to her skin incision (Figure 2). She was taken to the operating room for evacuation of the hematoma. A blood clot was evacuated, and the surrounding tissue and skin appeared healthy without necrosis or infection. The incision was closed with staples, and she was discharged the following day. There was no coagulopathy, and her liver function tests were normal.AFLP is a rare and potentially catastrophic obstetric condition that typically occurs in the third trimester and can lead to liver failure, renal failure, disseminated intravascular coagulopathy, hypoglycemia, encephalopathy, stillbirth, and maternal death. The condition is diagnosed in in 1 in 7000 to 1 in 20 000 pregnancies and can mimic preeclampsia and HELLP syndrome (Table 1).1,2The diagnosis is typically made when a patient meets 6 or more of the Swansea criteria, which consists of clinical and laboratory findings.2 There is no single laboratory test that confirms the diagnosis. A diagnosis using the Swansea criteria has a reported positive predictive value of 85% and a negative predictive value of 100%.3 The gold standard for diagnosis is liver biopsy. However, given the potential risks of liver biopsy and the strong predictive value of the Swansea criteria, biopsy is infrequently performed unless the diagnosis is in question and the patient is being evaluated for liver transplant.3 Our patient met 11 of the Swansea criteria. Symptoms and signs of severe hepatic insufficiency and synthetic liver failure include hypoglycemia, hyperbilirubinemia, encephalopathy, ascites, and coagulopathy, which are more consistent with a diagnosis of AFLP than HELLP or preeclampsia with severe features. Microangiopathic hemolytic anemia caused by destruction of erythrocytes in small blood vessels is more common in HELLP syndrome but may still occur in AFLP (Table 1).4When AFLP is recognized in a pregnant patient, prompt delivery is required, regardless of gestational age, along with supportive care and directed blood product transfusion to correct any coagulopathy (Table 2). Transfer to a center with liver transplant capabilities may be required. Recent literature has described cesarean delivery in approximately 65% of cases,5 with mortality of the pregnant patient being less than 10% with early recognition and management.6 Patients with AFLP have a high risk of developing disseminated intravascular coagulopathy and severe postpartum hemorrhage; therefore, close monitoring for coagulopathy and directed blood product transfusion is important. In most cases, patients return to normal liver function in 7 to 10 days, and, generally, coagulopathies resolve within the first few days after delivery.5 In patients who recover from the acute episode, fortunately nearly all patients have no lifelong liver injury.7,8 Transplant is reserved for cases in which recovery is not seen following delivery. In less than 2% of cases, intrahepatic rupture or hepatic hemorrhage can occur.9AFLP is associated with increased perinatal morbidity and mortality, although this is thought to be because of prematurity or maternal decompensation causing placental malperfusion rather than the disease itself.2,5 Because the maintenance treatment of AFLP is delivery, once diagnosed, an expedited delivery plan should be made regardless of gestational age.10 This management differs from cases of preeclampsia, when expectant management may be reasonable in a clinically stable pregnant patient at less than 34 weeks’ gestation. The diagnosis of AFLP is most often made between 30 and 38 weeks’ gestation, with a median gestational age at diagnosis of 36 weeks’ gestation.1Induction of labor rather than cesarean delivery can be considered if the well-being of the fetus and pregnant patient are reassuring. Any concern for decompensation in the fetus or pregnant person is reason to proceed to cesarean, provided corrective treatment of any coagulopathy is being administered.2 In the pregnant patient at a preterm gestational age, routine guidelines for betamethasone and magnesium sulfate can be followed. Delivery should not be delayed for completion of the betamethasone course given the risk of clinical status deterioration in the fetus and pregnant patient with a diagnosis of AFLP.A strong association exists between recessively inherited fetal LCHAD deficiency and the development of AFLP in the pregnant patient.11 Among pregnancies affected by fetal LCHAD deficiency, liver disease in the pregnant individual, including AFLP, occurs in approximately 20% to 70% of cases, representing an estimated 50-fold increased risk compared with unaffected pregnancies.12 The underlying pathophysiology frequently involves a defect in fetal mitochondrial fatty acid β-oxidation resulting in accumulation of toxic long-chain 3-hydroxy fatty acid metabolites. These metabolites cross from the fetal–placental circulation into the maternal bloodstream, resulting in hepatocellular injury and microvesicular steatosis and culminating in AFLP.11,12 Many affected pregnancies occur in patients who are heterozygous carriers of an LCHAD mutation and are carrying a fetus homozygous for the defect; however, not all cases of AFLP are associated with aberrant fatty acid metabolism in the fetus.11,12 Newborns of mothers with AFLP should be screened for LCHAD deficiency because of the risk of severe neonatal metabolic decompensation11,12; this can be accomplished via blood for acylcarnitines (available on some newborn state screens) and confirmed with genetic testing to sequence known genes associated with LCHAD deficiency. Genetic counseling is recommended for affected families.5In this case presentation, AFLP resulted in significant maternal and neonatal morbidity in the early-term period. Without an alternative treatment, astute recognition by clinicians combined with patient education of possible signs and symptoms of AFLP syndrome are important to help optimize outcomes for this rare obstetrical emergency.