Acute fatty liver of pregnancy in 3 tertiary care centers

OBJECTIVE: The purpose of this study was to determine the demographics, clinical presentation, and maternal and neonatal outcomes in patients who were diagnosed with acute fatty liver of pregnancy over a 10-year period. STUDY DESIGN: This was a multicenter retrospective study of women with the diagnosis of acute fatty liver of pregnancy. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes. RESULTS: Sixteen cases of acute fatty liver of pregnancy were identified. Three of the 16 cases had multiple gestations (18%). Eleven of the 16 cases were diagnosed in the antepartum period, and 5 cases were diagnosed within 4 days after delivery. Nausea and vomiting were the most common symptoms (75%). There were 2 maternal deaths (12.5%) and 3 fetal deaths (15%). CONCLUSION: We recommend that patients with persistent nausea, vomiting, or epigastric pain in the third trimester receive evaluation of liver enzymes, renal function, and a complete blood count to rule out the diagnosis of acute fatty liver of pregnancy.     

Inherited long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal-maternal interaction cause maternal liver disease and other pregnancy complications.

Fetal-maternal interactions are critical determinants of maternal health during pregnancy and perinatal outcome. This review explores the causative relationship of a fetal disorder of mitochondrial fatty acid oxidation, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and the serious maternal liver diseases of pregnancy-preeclampsia, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), and acute fatty liver of pregnancy. Features of the metabolic adaptation necessitated during the fetal-neonatal transition; common phenotypes of pediatric fatty acid oxidation disorders, including neonatal hypoketotic, hypoglycemia and hepatic crisis; and clinical abnormalities of HELLP and acute fatty liver of pregnancy are presented. Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. Recommendations for molecular testing for LCHAD deficiency in families with life-threatening maternal liver disease are given.     

Acute fatty liver of pregnancy associated with pancreatitis: a life-threatening complication

OBJECTIVE: Inadequate data describe pancreatitis as a complication in women with acute fatty liver of pregnancy. Our purpose was to report our experience with this complication, which included maternal and perinatal outcomes. STUDY DESIGN: Medical records of patients with acute fatty liver of pregnancy and/or pancreatitis were reviewed over a 15-year period. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes. RESULTS: Persistent nausea and vomiting were the symptoms in 10 of 12 patients (83%). The average maternal age was 26.3 years (range, 21-37 years). There were two maternal deaths (17%); one death occurred despite liver transplantation. Maternal morbidity included encephalopathy (50%), acute respiratory distress syndrome (17%), and renal failure (33%) that resulted from acute tubular necrosis (3 cases) and acute cortical necrosis (1 case) that required renal transplantation. Of the 12 patients, 11 patients (91%) had an elevated serum lipase level, and another patient had an elevated serum amylase level (9%). Eight of 12 patients (67%) underwent radiologic studies, of which 7 patients (88%) were diagnostic for pancreatitis. Radiographic and autopsy findings noted pancreatic inflammation (3 cases), pseudocyst formation (3 cases), and hemorrhagic pancreatitis (1 case). The radiographic and serum laboratory abnormalities occurred after the onset of hepatic and renal abnormalities in all cases. CONCLUSION: Pancreatitis is a potentially lethal complication of acute fatty liver of pregnancy, and all patients with this diagnosis should undergo screening for the abnormality. Pancreatic abnormalities typically appear after hepatic and renal dysfunction.     

Recurrent acute fatty liver of pregnancy

The first reported case of recurrent acute fatty liver of pregnancy confirmed by biopsy is described. In this case a high index of suspicion led to an early diagnosis and intervention with resultant improved maternal and fetal outcome. Electron microscopic examination of a liver biopsy specimen proved more beneficial in confirmation of the diagnosis compared with routine microscopic examination.     

Use of the Kleihauer test to detect fetal erythroblasts in the maternal circulation

Non-invasive prenatal diagnosis of aneuploidies on fetal nucleated erythrocytes present in the maternal circulation is hampered by the extremely small cell number of uncertain origin (70% of erythroblasts circulating during pregnancy have a maternal origin). Therefore, a method allowing selection of the fetal cells among the maternal cells is indispensable after the erythroblast enrichment step. In the present study, after an erythroblast enrichment step on a ficoll gradient followed by a positive immuno-magnetic selection with anti-CD71 or anti-GPA antibodies, a rapid, simple and direct chemical staining method adapted from the classical Kleihauer test was developed to select fetal cells. Precise differentiation between fetal and maternal erythroblasts is based on the constitutional difference between fetal and adult haemoglobin (Hb). The fetal cells appear with an intense pink cytoplasmic staining while maternal cells with adult haemoglobin are colourless. Preservation of the cytoplasmic integrity allows one to distinguish morphological characteristics and to visualize simultaneously nuclear hybridization signal by FISH (fluorescent in situ hybridization). This approach was tested by FISH analysis using dual-colour X- and Y-specific DNA probes on blood samples from 15 pregnant women, with the results being compared to cytogenetic or sonographic sex determination. For 12 pregnancies fetal sex was determined successfully (5 XY/7 XX), in two cases in situ hybridization failed, and in one case no fetal erythroblast was observed after the Kleihauer test. The selection method was applied to a pregnancy at risk for cystic fibrosis (CF). After a Kleihauer test, fetal erythroblasts were collected by microdissection, whole genomic DNA was amplified by primer extension pre-amplification (PEP) followed by a nested CF PCR. The fetal genotype was successfully characterized and confirmed by conventional prenatal diagnosis.     

Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases.

OBJECTIVE: We sought to describe our experience with the clinical diagnosis, management, and course of patients with acute fatty liver of pregnancy. STUDY DESIGN: Twenty-eight cases of acute fatty liver of pregnancy at the Los Angeles County and University of Southern California Medical Center from 1982 to June 1997 were identified, and presenting symptoms, clinical course, laboratory values, maternal complications, and neonatal outcomes were studied. RESULTS: The incidence of acute fatty liver of pregnancy was 1 in 6659 births. There were no maternal deaths. Initial presentation was at an average of 37 weeks of gestation with a characteristic prodrome of malaise, nausea, vomiting, and abdominal pain. No patient was admitted with the diagnosis of acute fatty liver of pregnancy. The condition was diagnosed most commonly on the second hospital day after laboratory results indicated coagulopathy, renal insufficiency, and liver function abnormalities. One patient underwent liver biopsy at cesarean delivery. Radiologic studies did not aid with the diagnosis. Twenty-one patients were admitted in spontaneous labor, and 16 labors were complicated by abnormal fetal heart rate patterns or meconium. There was 1 stillbirth and 1 neonatal death as a result of perinatal asphyxia. Maternal morbidity consisted of hypoglycemia, infection, renal insufficiency, coagulopathy, encephalopathy, and wound complications. All patients had evidence of disseminated intravascular coagulopathy with profoundly decreased antithrombin levels. All patients recovered normal liver function post partum. CONCLUSIONS: Reversible peripartum liver failure may be diagnosed and managed on the basis of clinical and laboratory criteria. With adequate support, these patients may have full recovery of hepatic function.     

Overview of infection causing hepatitis other than non-A to E hepatitis virus during pregnancy

Abnormal liver function tests during pregnancy are common. While hepatic injury during pregnancy mostly has minimal adverse influence on maternal and fetal outcomes, severe maternal and fetal morbidities, and even death, sometimes occur. Here, we review the epidemiology, clinical features, diagnosis, and management of hepatitis during pregnancy caused by the less common pathogens, including Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex viruses (HSVs), dengue fever, malaria, leptospirosis, Q fever, typhoid fever, and other occasional infections, as well as the implications on breastfeeding of the infants. Hepatitis during pregnancy with fever and systemic clinical presentations, which are not attributable to the common infectious agents, should raise the suspicion of infection with above-mentioned pathogens, and appropriate laboratory tests are required. Early recognition of severe hepatitis or acute liver failure is critical in initiating appropriate and specific therapy, together with systemic supportive care, to reduce maternal and fetal mortality and long-term sequelae.     

深圳地区妊娠期急性脂肪肝的发病状况与母婴结局

目的了解深圳地区妊娠期急性脂肪肝(AFLP)的发病率、临床特点及母婴结局。 方法统计深圳地区2003年至2010年8年间分娩孕产妇数,收集符合诊断为妊娠期急性脂肪肝的病例,分析其发病率、临床特点及母婴结局。 结果8年间深圳地区分娩孕产妇982 761例次,符合妊娠期急性脂肪肝诊断标准的病例44例,发病率为1/22 335。44例妊娠合并急性脂肪肝患者中,合并妊娠期高血压疾病的有23例(52%);平均年龄(27.7±5.7)岁,发病孕周为30^＋2～40^＋3周,初产妇占33例(75%),多胎妊娠占9例(20%)。37例(84%)首发症状为不同程度的消化道症状,40例(91%)出现黄疸并进行性加重,39例(89%)病例出现凝血功能障碍,25例(57%)出现肾功能不全,9例(20%)合并肝性脑病,5例(11%)出现多器官功能障碍。孕产妇痊愈39例,死亡5例,孕产妇死亡率为11%;分娩胎儿55例,死胎9例,新生儿死亡1例,围生儿死亡率为18%。 结论深圳地区妊娠期急性脂肪肝以晚孕期消化道症状为首发症状,同时伴有黄疸、肝酶升高、凝血功能障碍,并出现早发肾功能不全为主要临床特点。早期诊断,及时终止妊娠可改善母婴结局。     

Acute myocardial infarction in pregnancy and the puerperium: a population-based study

OBJECTIVE: To estimate the population-based incidence and pregnancy outcomes of acute myocardial infarction (MI) in pregnancy. METHODS: Maternal and newborn hospital discharge records were linked to birth/death certificates for the 10-year period January 1, 1991, to December 30, 2000, for the majority (98%) of deliveries in California. This database was searched for the diagnosis of acute MI, demographic characteristics, and pregnancy outcomes. Patients were divided into 4 groups: antenatal diagnosis, intrapartum diagnosis, up to 6-week postpartum diagnosis, and those without the diagnosis of acute MI. All groups were compared by Student t test or chi(2) or both, where appropriate. RESULTS: A total of 151 women had an acute MI during the antepartum (38%), intrapartum (21%), or 6-week postpartum (41%) period, giving an incidence rate of 1 in 35,700 deliveries. The incidence rate increased over the study period. The maternal mortality rate was 7.3%, and maternal death only occurred in women with an acute MI before or at delivery (P < .01). Compared with women who did not have an acute MI, those with one were more likely to be older (30% were older than 35 years compared with 10%), multiparous (78% compared with 61%), non-Hispanic white (40% compared with 35%) or African Americans (15% compared with 7%). All measures of maternal and neonatal morbidity were increased in the acute MI group compared with those without an acute MI. Multivariate analysis identified chronic hypertension, diabetes, advancing maternal age, eclampsia, and severe preeclampsia as independent risk factors for acute MI. CONCLUSION: Acute MI during pregnancy remains a rare event, with significant maternal, fetal, and neonatal morbidity and mortality and maternal mortality limited to the antepartum and intrapartum period.     

Fatty liver in pregnancy. A report of two cases and medical literature review

Acute fatty liver of pregnancy is an uncommon and potentially fatal disorder usually found in the third trimester of pregnancy and the early days postpartum. It is characterized by a micro vesicular stheatosis of the liver, which is reversible with complete regression of the disease. We present two clinical cases, in the first one the patient developed encephalopathy and hypoglycemia in her third day post cesarean section; the patient underwent surgical exploration because of a subaponeurotic hematoma and the diagnosis was confirmed by liver biopsy. The patient presented spontaneous resolution of the disease and was discharged home on her 21st day after delivery. The second case was a patient on her 37th week of pregnancy that arrived to the emergency room complaining of malaise, nausea and vomit, her laboratory analyses were remarkable hypoglycemia and hyperbilirubinemia. She underwent elective pregnancy termination with a favorable maternal and fetal outcome towards spontaneous resolution. It is critical to diagnose and treat this disease in a expedite manner in order to have a favorable maternal and fetal outcome. The mortality rate has decreased dramatically from 80% in 1965 to 100% survival in 1999 according to the latest reviews. This regression of the symptoms and signs along with normalization of the laboratory values has driven some authors to call this disease as the "reversible peripartum liver failure".     

Fetal genotypes and pregnancy outcomes in 35 families with mitochondrial trifunctional protein mutations

OBJECTIVE: The purpose of this study was to evaluate the effects of fetal genotype on maternal and fetal outcomes in families with mitochondrial trifunctional protein mutations in the United States. Trifunctional protein has 3 enzymatic activities that include long-chain 3-hydroxyacyl-CoA dehydrogenase, which catalyzes long-chain fatty acid beta-oxidation. STUDY DESIGN: We analyzed pregnancy history and offspring genotypes in 35 families with heterogeneous mutations. The fetal genotype was determined in utero in 11 pregnancies and after birth in 50 pregnancies. RESULTS: Forty-nine percent of the women who carried affected fetuses had acute fatty liver of pregnancy. Another 11% of the women had the syndrome of hemolysis, elevated liver enzymes, and low platelets, or preeclampsia. All women who had the maternal illness carried fetuses with isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Sixty-eight percent and 43% of the affected pregnancies also were associated with premature delivery and intrauterine growth retardation, respectively. No maternal or fetal complications were associated with heterozygous or wild-type fetal genotypes. CONCLUSION: Fetal mitochondrial trifunctional protein defects should be considered a cause for maternal liver disease, preterm labor, and intrauterine growth retardation.     

Isolation of epsilon-haemoglobin-chain positive fetal cells with micromanipulation for prenatal diagnosis

OBJECTIVES: The isolation and analysis of fetal cells in maternal blood during pregnancy is under investigation as a means of noninvasive prenatal diagnosis. The aim of our study was to detect fetal gender from maternal peripherial blood samples during pregnancy with the detection and analysis of epsilon-haemoglobin-chain positive fetal nucleated red blood cells (NRBCs) collected by a micromanipulator. Here we report our first results. DESIGN AND METHODS: We obtained maternal blood from 14 singleton pregnancies. After a double density gradient separation, magnetic activated cell sorting was performed by positive selection for nucleated red blood cells with anti-CD71. With the help of this enrichment step, followed by immunophenotyping with an anti-haemoglobin-epsilon monoclonal antibody, the isolation of the epsilon haemoglobin chain positive cells with micromanipulation could be done. We performed single cell fluorescent PCR analysis of these cells; we used primers for the amelogenin gene to detect fetal gender. We compared our findings with the results of amniocentesis. RESULTS: Fetal gender was successfully determined in 11 out of 14 cases; among them, in 2 cases with Klinefelter syndrome (47,XXY). CONCLUSION: The results of our study suggest that micromanipulation and QF-PCR analysis of anti-haemoglobin-epsilon fluorescent antibody stained fetal cells from maternal blood can be useful in prenatal diagnosis to detect fetal gender and promising to be improved to detect chromosomal abnormalities.     

妊娠急性脂肪肝患者的妊娠结局和随访分析

目的回顾性分析妊娠急性脂肪肝（acute fatty liver of pregnancy,AFLP）的临床特点,探讨早期诊断和治疗与妊娠结局及产后随访结局的关系。方法对5年内收治的6例AFLP患者的临床资料进行回顾性分析,并进行了1~5年的随访。结果临床表现有厌食、喜冷饮、恶心、呕吐、上腹不适、乏力及进行性加重的黄疸等。实验室检查肝转氨酶和血清胆红素升高、纤维蛋白原下降、凝血酶原时间延长。B超和CT显示脂肪肝影像。孕产妇并发症有低蛋白血症、肾功能损害、肝性脑病、低血糖等。发病至终止妊娠时间超过10d2例,其围产儿死亡,孕产妇病情危重。无孕产妇死亡病例发生。随访1～5年,产妇和存活的婴儿均健康,2例再次妊娠无再发病。结论掌握该病的临床特点,早期诊断、尽快终止妊娠及支持治疗,是提高母婴预后的关键,治愈后无远期不良结局。     

Acute fatty liver of pregnancy: a rare pathology of the third trimester

Acute fatty liver of pregnancy is a rare clinical syndrome of pregnancy that occurs during the third trimester. Clinicians must have a high index of suspicion for this condition when a woman has nausea or vomiting during the last trimester. Early diagnosis and prompt delivery improve foetal and maternal prognosis. We report a case of a previously healthy 23-year-old woman who presented an acute fatty liver of pregnancy with intrauterine fetal death. Based on this experience as well as on medical literature, characteristics of this uncommon pathology are discussed.     

Maternal medical compromise during pregnancy and pregnancy outcomes

Objective: To examine the outcomes of pregnancy and newborn following an event of maternal medical compromise during pregnancy.

Methods: A retrospective study was performed on all patients hospitalized following an event of medical compromise during pregnancy. Medical compromise was divided to acute or chronic bleeding, major or complicated operations, and admission to intensive care unit (ICU). Data collected included maternal, fetal, neonatal and child’s follow-up.

Results: The study included 51 pregnant patients and 58 fetuses. The study group had increased risk of preterm deliveries (35.0 versus 6.5%, p?p?p?=?0.002). Patients with acute bleeding had higher rates of cesarean sections, preterm deliveries, admissions to neonatal ICU and neonatal mortality. Two cases of fetal abnormalities included brain abnormalities and pericardial effusion. Three terminations of pregnancies were performed: two in patients in ICU due to severe maternal medical condition and one in the fetus with brain abnormalities.

Conclusions: Maternal medical compromise during pregnancy increases the risk for preterm deliveries, cesarean delivery and low Apgar scores. Acute bleeding was the main cause of medical compromised and with the higher rates of adverse outcomes.     

双胎输血综合征合并镜像综合征引产一例

镜像综合征又称巴兰坦综合征,主要表现为胎儿、胎盘水肿和继发性母体不同程度的水肿及血液稀释的临床特点。镜像综合征发病率极低,病情进展快,国内外报道例数较少,目前其病因大多与诱发胎儿水肿的因素相关,其中双胎输血综合征是胎儿非免疫性水肿病因之一。回顾南京医科大学附属第一医院2019年2月收治的双胎输血综合征合并镜像综合征的病例,分析患者的一般情况,并予以合理治疗干预,分析预后情况。该患者在入院保守治疗的情况下病情加重,最终选择终止妊娠,妊娠终止后病情较前明显好转,予以出院门诊随访。现对其诊断、鉴别诊断和治疗方式进行讨论。     

Drug-induced liver injury in pregnancy

Drug intake in pregnant women is common, including prescribed and over-the-counter medications, and herbal medicine and supplements. Drug-induced liver injury (DILI) has become the leading cause of acute liver failure in Western countries, and pregnancy is thought to be a risk factor, but only few anecdotal reports concerning pregnant women are found. These involved antihypertensive, antithyroid, antiretroviral, and antituberculosis medications, and antibiotics. Presentation was usually in the first 20 weeks of gestation following a latency of several weeks, because these drugs were usually prescribed before or in early pregnancy due to their fetal safety. The hepatotoxicity is usually of the idiosyncratic form, and most would resolve spontaneously although occasional liver transplantation and maternal death were reported. The scanty reports could have been related to under-reporting and missed diagnosis due to spontaneous resolution in most cases. DILI should remain one of the differential diagnoses in pregnant women with hepatitis.     

21年糖尿病合并妊娠88例母儿结局的临床分析

目的：研究糖尿病患者孕期血糖控制对妊娠结局的影响。方法：回顾性分析1981－2001年间88例糖尿病孕妇孕期血糖水平与妊娠结局的关系。88例患者中2例行中期引产，1例行人工流产，将其余85例分为两组：孕期血糖控制满意者42例（A组），血糖控制不满意或未控制者43例（B组）。结果：B组胎死宫内5例，其中3例发生在围产期，A组无一例发生胎死宫内（P值为0．069）。B组妊高征及早产发生率分别为44．2％和30．2％，显著高于A组的21．4％和9．2％（P值分别为0．026和0．017）；B组新生儿窒息发生率为24．4％，显著高于A组的4．8％（P值为0．011）；新生儿畸形9例（10．2％）。结论：加强糖尿病患者孕前及孕期血糖控制和监测，可明显地减少孕产妇合并症、围产儿病率及死亡率，改善母儿结局。     

Review of Twin Pregnancies with Single Fetal Death: Management,Maternal and Fetal Outcome

Aim

To study management and maternal and fetal outcome in single fetal death in twin pregnancies.

Materials and Methods

We studied 64 (1.37 %) twin deliveries out of a total of 4,655 deliveries in GMC, Haldwani (Uttrakhand). Out of them, 5 (7.81 %) were complicated with single fetal death in the second or third trimester. These cases were managed conservatively with regular monitoring of maternal coagulation profile along with intensive fetal surveillance for the surviving twin. The cases were studied for antenatal complications and placental chorionicity with placental histopathology and postmortem of the dead fetus. Neonatal and maternal outcome in the postpartum period was also studied.

Results

No antenatal complications were present in four out of five cases with one having PIH. Three out of five pregnancies could be extended to term and had no maternal complications. The other fetus could be salvaged in three and all of them had a normal neonatal period. One pregnancy ended in preterm labor with delivery of a preterm baby which could not be saved. One resulted in death of the other fetus also where pregnancy was remote from term.

Conclusions

Although our study was small, it indicates that in case of twin pregnancy with single fetal death with good surveillance, the live fetus can be salvaged.     

妊娠期急性阑尾炎66例诊疗分析

目的：探讨妊娠期急性阑尾炎的诊断及治疗方法。方法：回顾性分析66例妊娠期急性阑尾炎的临床资料,29例患者不同意手术而接受保守治疗,其中12例感染不能控制,改手术治疗,另37例入院急诊外科手术治疗。结果：66例患者顺利出院;8例患者出院后要求行人工流产术;2例患者术后流产,1例患者术后10 d早产;无胎儿宫内窘迫、死胎及妊娠妇女死亡等严重并发症。结论：妊娠期急性阑尾炎的及时诊断和手术治疗,是保证临床效果及母婴安全的重要手段。但对感染症状轻、局部腹膜炎不明显、不同意手术的患者,可先予保守治疗,密切观察,治疗效果不明显时应立即手术。