DNA sequencing versus standard prenatal aneuploidy screening.

BACKGROUND: In high-risk pregnant women, noninvasive prenatal testing with the use of massively parallel sequencing of maternal plasma cell-free DNA (cfDNA testing) accurately detects fetal autosomal aneuploidy. Its performance in low-risk women is unclear. METHODS: At 21 centers in the United States, we collected blood samples from women with singleton pregnancies who were undergoing standard aneuploidy screening (serum biochemical assays with or without nuchal translucency measurement). We performed massively parallel sequencing in a blinded fashion to determine the chromosome dosage for each sample. The primary end point was a comparison of the false positive rates of detection of fetal trisomies 21 and 18 with the use of standard screening and cfDNA testing. Birth outcomes or karyotypes were the reference standard. RESULTS: The primary series included 1914 women (mean age, 29.6 years) with an eligible sample, a singleton fetus without aneuploidy, results from cfDNA testing, and a risk classification based on standard screening. For trisomies 21 and 18, the false positive rates with cfDNA testing were significantly lower than those with standard screening (0.3% vs. 3.6% for trisomy 21, P<0.001; and 0.2% vs. 0.6% for trisomy 18, P=0.03). The use of cfDNA testing detected all cases of aneuploidy (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13; negative predictive value, 100% [95% confidence interval, 99.8 to 100]). The positive predictive values for cfDNA testing versus standard screening were 45.5% versus 4.2% for trisomy 21 and 40.0% versus 8.3% for trisomy 18. CONCLUSIONS: In a general obstetrical population, prenatal testing with the use of cfDNA had significantly lower false positive rates and higher positive predictive values for detection of trisomies 21 and 18 than standard screening. (Funded by Illumina; ClinicalTrials.gov number, NCT01663350.).

An effective pressure pack for severe pelvic hemorrhage.

OBJECTIVE: To evaluate our experience with the "pelvic pressure pack," a surgical technique for controlling posthysterectomy bleeding. METHODS: This is an observational descriptive report of cases collected by the authors during the years 1968-2006. Packs were constructed of various materials (eg, pillow cases, gauze sheets, plastic X-ray cassette drapes, or orthopedic stockings) filled with gauze rolls introduced abdominally and exiting the vagina. RESULTS: We report 11 new cases (10 obstetric and one gynecologic). Massive red blood cell transfusion and coagulopathy occurred in all cases. The pelvic pressure pack successfully controlled bleeding in 82% (9 of 11) of cases. Postoperative febrile morbidity occurred in most cases. There were no maternal deaths. CONCLUSION: In the contemporary management of posthysterectomy bleeding, the pelvic pressure pack appears to be a valuable surgical option, affording correction of coagulopathy and further stabilization. Given near-universal postoperative febrile morbidity in our series, prophylactic broad-spectrum antibiotic therapy should be strongly considered. We believe all obstetrician-gynecologists should be familiar with this simple, potentially life-saving technique. LEVEL OF EVIDENCE: III.

Fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia for pain management following gynecological surgery: a meta-analysis of randomized, controlled trials.

AIM: To compare the efficacy and safety of patient-controlled fentanyl iontophoretic transdermal system (ITS) with morphine intravenous (i.v.) patient-controlled analgesia (PCA) for pain management following gynecological surgery. METHODS: Two-open-label, multicenter, randomized, active-controlled, parallel-group studies (n = 1142) were conducted that compared fentanyl ITS with morphine iv. PCA for postoperative pain. The subgroup of gynecological surgery patients from each trial was utilized for this meta-analysis (n = 604). Of these patients, 295 received fentanyl ITS (40 µg/dose) and 309 received morphine i.v. PCA (1 mg/dose) for up to 72 h. Efficacy measures included the patient global assessment (PGA) and the investigator global assessment (IGA) of the method of pain control. RESULTS: Gynecological surgery patients (n = 604) included in this meta-analysis had a mean age of 45 years, were predominantly Caucasian (65%) and had a mean body mass index of 29 mg/kg2. There were statistically significantly more patients treated with fentanyl ITS and more investigators who rated their pain control method as 'excellent' on the PGA at 24 h (49.3 vs 37.4%, respectively; p = 0.0029) and IGA at the last assessment (59.5 vs. 38.0%, respectively; p < 0.0001), respectively, compared with morphine iv. PCA at the last assessment. CONCLUSION: Following gynecological surgery, patients and investigators were more satisfied (had a higher percent of an 'excellent' rating on the PGA and IGA, respectively) with fentanyl ITS than morphine iv. PCA as a method of pain control.

Determination of placental growth factor (PlGF) levels in healthy pregnant women without signs or symptoms of preeclampsia.

OBJECTIVE: To identify a reference range for placental growth factor (PlGF) in normotensive women without symptoms or signs of preeclampsia. STUDY DESIGN: Comprising the study cohort were 247 term pregnancies without preeclampsia or adverse neonatal outcomes from 16 sites in the US and Canada. Serial plasma samples were collected in 6 gestational age (GA) intervals between 20+0 and 40+0weeks. Non-parametric percentiles of the distribution of PlGF were estimated in each GA interval and a parametric model was developed to describe the distribution of PlGF as a continuous smooth function of GA (from 20 to 40weeks) in normal healthy pregnancy. Demographic and clinical factors influencing PlGF levels were also examined. RESULTS: There were 1366 evaluable samples collected from 247 subjects (242, 238, 226, 223, 222, and 215 samples in each GA interval, 20-24, 24-29, 29-32, 32-35, 35-37, and 37-40weeks, respectively). The 5th percentile of PlGF was 76.4, 141.1, 139.3, 65.5, 31.7, and 23.4pg/mL in each respective GA interval. The distribution of PlGF is approximately log normal with parameters that vary continuously as a function of GA. PlGF distribution is weakly dependent on maternal age, race/ethnicity, parity, and maximum systolic blood pressure (taken between weeks 20 and 24). Although statistically significant, these factors did not modify PlGF levels by more than ±15%. CONCLUSION: These data provide a valid reference range for PlGF in normal pregnancy.