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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. (Am J Obstet Gynecol 1999;181:389-95.)

OBJECTIVE: Our goal was to compare the pregnancy outcomes of patients with intrahepatic cholestasis of pregnancy managed expectantly with antepartum testing with those of other patients who were followed up with a similar testing scheme. STUDY DESIGN: Cases of intrahepatic cholestasis of pregnancy monitored with antepartum testing at our institution over a 7-year period were reviewed. Their pregnancy outcomes were compared with those of control patients followed up with the same testing scheme for a history of stillbirth. Both groups had at least weekly nonstress tests and amniotic fluid assessment until spontaneous labor or delivery for standard obstetric indications. RESULTS: Seventy-nine patients were analyzed in each group. The two groups did not differ with respect to the mean gestational age at delivery (38.5 vs 38.8 weeks), birth weight (3216 vs 3277 gm) or incidence of preterm delivery (14% vs 7.6%). Abnormal antepartum testing prompting delivery was more common in the control group (25% vs 7.6%, p < 0.05). The risk of meconium passage was higher in the cholestasis group (44.3% vs 7.6%, p < 0.05). Two antepartum fetal deaths occurred in the cholestasis group at 36 to 37 weeks' gestation within 5 days of normal results of antepartum testing. Thick meconium and appropriate birth weight were noted in both infants. No gross anomalies were found in either infant. CONCLUSION: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcome not predicted by conventional fetal surveillance. (Am J Obstet Gynecol 1996;175:957-60.)

OBJECTIVE: Acute fatty liver of pregnancy has been associated with a syndrome of marked depression of antithrombin III and disseminated intravascular coagulation. We sought to identify the clinical importance of this accelerated coagulation. STUDY DESIGN: The medical records of patients with acute fatty liver of pregnancy identified during the period of 1982 to 1994 were retrospectively reviewed. RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were identified for an incidence of 1:6692 births. Laboratory evidence of persistent disseminated intravascular coagulation was found in all patients tested. Six patients had clinical bleeding, all associated with genital tract injury. Twenty-three of twenty-three patients tested had markedly decreased antithrombin III levels (average 11%, normal range 80% to 100%). Seven patients received antithrombin III transfusions, which was associated with a significant transient rise in the plasma level. Compared with patients not transfused, however, there was a similar clinical outcome. CONCLUSION: Profoundly depressed antithrombin III levels and laboratory evidence of disseminated intravascular coagulation were present in all cases of acute fatty liver of pregnancy but rarely influenced clinical outcome unless there was concomitant genital tract injury. Antithrombin III transfusions increased plasma levels, but no definite clinical benefit was established in this series because of the small number of cases. (AM J OBSTET GYNECOL 1996;174:211-6.)

Objective: To determine the effect of shipping blood in Streck blood collection tubes (BCT) prior to processing on cell-free DNA (cf-DNA) levels. Methods: Blood was collected in ethylenediaminetetraacetic acid (EDTA) and BCT tubes from 10 pregnant women carrying male fetuses. One set of each tube for each subject was processed to plasma immediately (standard cf-DNA protocol), whereas the other set was shipped by air courier and then processed. DNA was extracted and total and fetal DNA concentrations were measured by TaqMan multiplexed quantitative real-time PCR. Results: No significant difference was observed in total cf-DNA in plasma between immediately processed EDTA (control) and immediately processed BCT samples. Moreover, no significant change in total cf-DNA was detected in plasma of BCT samples shipped at room temperature. Significant differences in total cf-DNA leading to a significantly decreased fetal fraction were found in shipped EDTA samples and BCT samples shipped at 4°C. Discussion: BCT tubes are suitable for shipping whole blood prior to processing with respect to cf-DNA levels. However, care should be taken to ensure that samples are not exposed to extreme temperatures during shipment. This finding will benefit the development and clinical application of noninvasive methods of fetal diagnosis that utilize cf-DNA.

Background Screening tests for Trisomy 21 (T21), also known as Down syndrome, are routinely performed for the majority of pregnant women. However, current tests rely on either evaluating non-specific markers, which lead to false negative and false positive results, or on invasive tests, which while highly accurate, are expensive and carry a risk of fetal loss. We outline a novel, rapid, highly sensitive, and targeted approach to non-invasively detect fetal T21 using maternal plasma DNA. Methods and Findings Highly heterozygous tandem Single Nucleotide Polymorphism (SNP) sequences on chromosome 21 were analyzed using High-Fidelity PCR and Cycling Temperature Capillary Electrophoresis (CTCE). This approach was used to blindly analyze plasma DNA obtained from peripheral blood from 40 high risk pregnant women, in adherence to a Medical College of Wisconsin Institutional Review Board approved protocol. Tandem SNP sequences were informative when the mother was heterozygous and a third paternal haplotype was present, permitting a quantitative comparison between the maternally inherited haplotype and the paternally inherited haplotype to infer fetal chromosomal dosage by calculating a Haplotype Ratio (HR). 27 subjects were assessable; 13 subjects were not informative due to either low DNA yield or were not informative at the tandem SNP sequences examined. All results were confirmed by a procedure (amniocentesis/CVS) or at postnatal follow-up. Twenty subjects were identified as carrying a disomy 21 fetus (with two copies of chromosome 21) and seven subjects were identified as carrying a T21 fetus. The sensitivity and the specificity of the assay was 100% when HR values lying between 3/5 and 5/3 were used as a threshold for normal subjects. Conclusions In summary, a targeted approach, based on calculation of Haplotype Ratios from tandem SNP sequences combined with a sensitive and quantitative DNA measurement technology can be used to accurately detect fetal T21 in maternal plasma when sufficient fetal DNA is present in maternal plasma., Wallace H. Coulter Foundation, Medical College of Wisconsin. Biotechnology and Bioengineering Center (Inducement Grant Fund), National Science Foundation (U.S.) (PFI grant NSF#0438604), Medical College of Wisconsin. Dept. of Surgery, Tandem Diagnostics (Firm)

In 1995, the rate of cesarean delivery in the United States was 21 percent.1 The goal of Healthy People 2000, a project of the Department of Health and Human Services, is to reduce this rate to 15 ...

Infants delivered by vacuum extraction or other operative techniques may be more likely to sustain major injuries than those delivered spontaneously, but the extent of the risk is unknown.From a California data base, we identified 583,340 live-born singleton infants born to nulliparous women between 1992 and 1994 and weighing between 2500 and 4000 g. One third of the infants were delivered by operative techniques. We evaluated the relation between the mode of delivery and morbidity in the infants.Intracranial hemorrhage occurred in 1 of 860 infants delivered by vacuum extraction, 1 of 664 delivered with the use of forceps, 1 of 907 delivered by cesarean section during labor, 1 of 2750 delivered by cesarean section with no labor, and 1 of 1900 delivered spontaneously. As compared with the infants delivered spontaneously, those delivered by vacuum extraction had a significantly higher rate of subdural or cerebral hemorrhage (odds ratio, 2.7; 95 percent confidence interval, 1.9 to 3.9), as did the infants delivered with the use of forceps (odds ratio, 3.4; 95 percent confidence interval, 1.9 to 5.9) or cesarean section during labor (odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.4), but the rate of subdural or cerebral hemorrhage associated with vacuum extraction did not differ significantly from that associated with forceps use (odds ratio for the comparison with vacuum extraction, 1.2; 95 percent confidence interval, 0.7 to 2.2) or cesarean section during labor (odds ratio, 0.9; 95 percent confidence interval, 0.6 to 1.4).The rate of intracranial hemorrhage is higher among infants delivered by vacuum extraction, forceps, or cesarean section during labor than among infants delivered spontaneously, but the rate among infants delivered by cesarean section before labor is not higher, suggesting that the common risk factor for hemorrhage is abnormal labor.