Incidentally Found Midtrimester Shortened Cervical Length: Practice Patterns among American Maternal-Fetal Medicine Specialists.

OBJECTIVE: The management of incidentally found short cervical length (CL) without prior spontaneous preterm birth (PTB) can vary. While most agree on starting vaginal progesterone, management after CL shortens <10 mm varies. The purpose of this study was to elucidate current practice patterns amongst maternal-fetal medicine (MFM) specialists. STUDY DESIGN: We conducted an online survey of MFM attending physicians and fellows in the United States from May 2019 to April 2020. The primary outcome was management of varying CL based on gestational age. Variations in management were assessed descriptively. RESULTS: There were 236 respondents out of 400 eligible surveyed, with a response rate of 59.2%. Universal CL screening was reported by 93.6% (49.6% abdominal and 44.1% transvaginal). Management of short CL varied based on CL measurement, rather than gestational age at presentation. At CL <10 mm, management included cerclage (17.4-18.7%), vaginal progesterone (41.3-41.7%), or cerclage plus vaginal progesterone (43.4%). Between CL of 10 to 20 mm, the majority (77.4-91.9%) would start vaginal progesterone. At CL 21 to 25 mm, management varied between expectant management (45.5-48.5%) or vaginal progesterone (51.1-52.8%). Suture material used was ethylene terephthalate (47.4%) or polypropelene (31.2). Preoperative antibiotic use was reported by 22.3%, while 45.5% used them only if the amniotic membranes were exposed, and 32.2% reported no antibiotic use. Postoperative tocolytic use varied with 19.3% reporting no use, 32.6% using it always, 8.2% only after significant cervical manipulation, 22.7% after the patient is experiencing symptoms, and 17.6% using it only if the cervix is dilated on exam. After cerclage placement, 44.5% continued CL surveillance. CONCLUSION: Substantial differences of opinion exist among MFM physicians regarding management of incidentally found short CL in patients without history of PTB. The differences in responses obtained highlight the need for evidence-based guidelines for managing this clinical scenario. KEY POINTS: · There is lack of consensus on the management of incidentally found shortened CL.. · The purpose of this study was to elucidate current trends in CL screening and management.. · Substantial differences of opinion exist regarding management of incidentally found short CL..

What Is the Prevalence of Measles Immunity among Pregnant Women?

OBJECTIVE: This study aimed to estimate the prevalence of measles immunity in a cohort of pregnant women in New York City and determine if there is a positive correlation of measles immunity with patient demographics, rubella immunity, number of measles, mumps, and rubella vaccine (MMR) doses received, and age at last vaccination. STUDY DESIGN: This is a cross-sectional study of pregnant patients seen at a single institution from January 2019 to May 2019. Patients were classified as measles and rubella immune or nonimmune using commercial immunoglobulin G (IgG) tests. Patient characteristics were compared using t-tests, Chi-square tests, or Fisher's exact tests as appropriate. The association of age at last vaccination with immunity status was assessed using multivariable logistic regression adjusted for age at presentation. The utility of rubella IgG for distinguishing measles immunity was assessed using receiver operating characteristic curve analysis. RESULTS: Serologic immunity for measles and rubella was obtained for 1,366 patients. Of these, 1,047 (77%) were measles immune and 1,291 (95%) were rubella immune. Patients born after 1989 were less likely to be immune to measles, while multiparity and private insurance were associated with increased measles immunity. Documentation of MMR vaccination was available for 140 (10%) patients. Of these, 44 (31%) were serologically nonimmune to measles and 9 (6.4%) were nonimmune to rubella. In patients known to have received one dose of MMR, 62% (24/39) were immune to measles with an improvement to 72% (69/96) among those who received two or more doses. Age at last vaccination was not associated with measles immunity. Rubella IgG level was a poor predictor of positive measles titer (area under the curve = 0.59). CONCLUSION: Approximately one of every four pregnant patients is serologically measles nonimmune, even among women with documented MMR vaccination or documented rubella immunity. These findings raise concerns that relying on vaccination history or rubella immune status may not be sufficient to assure protection from infection with measles. If further suggests that measles serology should be added to routine prenatal laboratory testing to identify nonimmune patients that may benefit from postpartum vaccination. KEY POINTS: · Approximately one of every four pregnant patients were serologically measles nonimmune.. · Rubella immunoglobulin G was a poor predictor of measles immunity status.. · Measles serology should be added to routine prenatal laboratory testing..

Integrating Microarrays into Routine Prenatal Diagnosis: Determinants of Decision Making.

OBJECTIVES: The explosion in genetic technologies, including array comparative genomic hybridization (aCGH), has increased the complexity of genetic counseling. We now offer chorionic villus sampling (CVS) and aCGH to all first-trimester patients, as this allows the prenatal diagnosis of an additional 1% of anomalies not otherwise detectable and can detect genetic copy number variants at a much higher resolution than conventional cytogenetics. Here, we explored some of the determinants of how patients are deciding to use or not use this new technology and evaluate risk-benefit analyses for that decision. METHODS: This is a retrospective case-control study of singleton and multiples pregnancies at our center. Those having aCGH testing along with CVS were defined as 'testers' and those who declined aCGH but had the CVS were 'nontesters'. RESULTS: Demographic data of 181 educated women who chose CVS were compared. Among those carrying singletons (n = 144), older women, defined as over 35 years of age (or 'advanced maternal age'; AMA), were more likely to choose the aCGH than younger women. Further, women who had a prior history of genetic testing and who wanted to know the gender of the fetus were more likely to choose the aCGH test. In women carrying multiples (n = 37), AMA ceases to be a predictor of choice. Having had prior genetic counseling remains a strong predictor for choosing aCGH, as does wanting to know the gender of the fetus. Neither prior abortions nor having prior children were significant for women carrying singletons or multiples. CONCLUSION: Offering pregnant couples an individualized choice regarding aCGH seems an appropriate approach. There are discrete patterns associated with the choice of taking the aCGH that varied depending on whether the patient was carrying a singleton or multiples.

Amniotic fluid embolism: despite progress, challenges remain.

PURPOSE OF REVIEW: This article reviews the incidence, pathophysiology, risk factors, diagnosis, and management of amniotic fluid embolism (AFE). RECENT FINDINGS: AFE is a leading cause of maternal morbidity and mortality despite an incidence of approximately 7 to 8 per 100,000 births. Recent reevaluation of AFE suggests that the presence of fetal tissue in maternal circulation alone is not sufficient to cause the clinical syndrome, but rather an individual's response to this fetal tissue. The 'anaphylactoid reaction' associated with AFE shares many clinical and metabolic aspects of septic shock. Acute dyspnea followed by cardiovascular collapse, coagulopathy, and neurological symptoms, such as coma and seizures may all be associated with the clinical AFE syndrome. Specific biochemical markers have been described, but are of limited clinical value because of the rapid progression of the disease process. Treatment is based on an interdisciplinary approach that consists of a combination of prompt, aggressive hemodynamic resuscitation, provision of end-organ support, correction of hemostatic disorders, and delivery. SUMMARY: Although AFE cannot be prevented, early diagnosis and intervention may lead to better outcomes for both the mother and the fetus. Clinical suspicion, traditional laboratory data, or intravascular cellular debris (demonstrated only in 50% of patients) are insufficient to make a definitive diagnosis of AFE. An evolving array of novel biomarkers may help differentiate AFE from other conditions, but none of them currently provide sufficient 'early warning' ability to make real-time impact on diagnosis and/or treatment of AFE.

Fragment-based discovery of nonpeptidic BACE-1 inhibitors using tethering.

BACE-1 (beta-site amyloid precursor protein cleaving enzyme), a prominent target in Alzheimer's disease drug discovery efforts, was surveyed using Tethering technology to discover small molecule fragment ligands that bind to the enzyme active site. Screens of a library of >15000 thiol-containing fragments versus a panel of BACE-1 active site cysteine mutants under redox-controlled conditions revealed several novel amine-containing fragments that could be selectively captured by subsets of the tethering sites. For one such hit class, defined by a central aminobenzylpiperidine (ABP) moiety, X-ray crystal structures of BACE mutant-disulfide conjugates revealed that the fragment bound by engaging both catalytic aspartates with hydrogen bonds. The affinities of ABP fragments were improved by structure-guided chemistry, first for conjugation as thiol-containing fragments and then for stand-alone, noncovalent inhibition of wild-type (WT) BACE-1 activity. Crystallography confirmed that the inhibitors bound in exactly the same mode as the disulfide-conjugated fragments that were originally selected from the screen. The ABP ligands represent a new type of nonpeptidic BACE-1 inhibitor motif that has not been described in the aspartyl protease literature and may serve as a starting point for the development of BACE-1-directed Alzheimer's disease therapeutics.

The Accuracy of Group Beta Streptococcus Rectovaginal Cultures at 35 to 37 Weeks of Gestation in Predicting Colonization Intrapartum.

Objective This study aims to investigate accuracy of group beta Streptococcus (GBS) rectovaginal cultures at 35 to 37 weeks in predicting intrapartum colonization. Study Design Institutional review board (IRB) approved prospective cohort study of 302 women from October 2015 to May 2017. Patients had the following tests for GBS: first trimester urine culture, rectovaginal culture at 35 to 37 weeks, and intrapartum rectovaginal culture. Outcomes included accuracy of 35- to 37-week GBS rectovaginal culture in detecting results intrapartum, and accuracy of first trimester urine culture in comparison to intrapartum rectovaginal cultures. Results There was sufficient evidence of agreement between results at 35 to 37 weeks with intrapartum cultures ( p = 0.001). However, agreement was weak, 11 patients (3.7%) were GBS positive intrapartum but negative at 35 to 37 weeks; and 33 patients (11%) were initially GBS positive but were negative intrapartum. Sensitivity and specificity of the 35- to 37-week culture was 69% (95% confidence interval [CI]:54-84%) and 87% (95% CI: 83-91%), respectively. There was also weak agreement between first trimester urine culture and intrapartum rectovaginal culture. Specificity for this assessment was 98% (95% CI: 97-100%) and was significantly different compared with antepartum GBS culture ( p < 0.001). Accuracy between antepartum GBS rectovaginal culture and urine culture was similar (85 vs. 87%, p = 0.47). Conclusion The 35- to 37-week GBS rectovaginal culture might be a poor predictor for intrapartum colonization.

Intensive Care Unit issues in eclampsia and HELLP syndrome.

Preeclampsia, eclampsia and HELLP syndrome are life-threatening hypertensive conditions and common causes of ICU admission among obstetric patients The diagnostic criteria of preeclampsia include: 1) systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg on two occasions at least 4 hours apart and 2) proteinuria ≥300 mg/day in a woman with a gestational age of >20 weeks with previously normal blood pressures. Eclampsia is defined as a convulsive episode or altered level of consciousness occurring in the setting of preeclampsia, provided that there is no other cause of seizures. HELLP syndrome is a life-threatening condition frequently associated with severe preeclampsia-eclampsia and is characterized by three hallmark features of hemolysis, elevated liver enzymes and low platelets. Early diagnosis and management of preeclampsia, eclampsia and HELLP syndrome are critical with involvement of a multidisciplinary team that includes Obstetrics, Maternal Fetal Medicine and Critical Care. Expectant management may be acceptable before 34 weeks with close fetal and maternal surveillance and administration of corticosteroid therapy, parenteral magnesium sulfate and antihypertensive management. Worsening condition requires delivery. Complications that can be related to this spectrum of disease include disseminated Intravascular coagulation (DIC), acute respiratory distress syndrome, stroke, acute renal failure, hepatic dysfunction with hepatic rupture or liver hematoma and infection/sepsis.

Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1.

A series of novel beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to corresponding hydroxyethylene (HE) compounds. Enzymatic inhibitory values were similar for both isosteres, as were structure-activity relationships with respect to stereochemical preference and substituent variation (P2/P3, P1, and P2'); however, the AE compounds were markedly more potent in a cell-based assay for reduction of beta-secretase activity. The incorporation of preferred P2/P3, P1, and P2' substituents into the AE pharmacophore yielded compound 7, which possessed enzymatic and cell assay IC(50)s of 26 nM and 180 nM, respectively. A three-dimensional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE inhibitors. The AE isostere class represents a promising advance in the development of BACE-1 inhibitors.