Clinical Impact of a Restrictive Labor Induction Approval Process.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact of a restrictive labor induction approval process on induction and primary cesarean delivery rates. METHODS: A retrospective cohort study was conducted at a tertiary care academic center from 2006 through 2012. The cohort of deliveries before (pre-intervention) and after (post-intervention) the process included term, singleton pregnancies with no contraindication to vaginal delivery. The primary outcome was induction of labor rates, subgrouped on the basis of whether it was medically or nonmedically indicated. Secondary outcomes included the primary cesarean rate and other maternal and neonatal outcomes. RESULTS: Of 13,753 deliveries, 6,746 met study inclusion criteria. There was a significant decrease in induction rates comparing the pre- and post-intervention periods (21.0 vs. 18.5%, p = 0.01). Nonmedically indicated induction rates also decreased significantly (2.9 vs. 0.6%, p < 0.001). No difference was observed in medically indicated induction (18.1 vs. 17.9%, p = 0.84), the primary cesarean rate (14.4 vs. 15.8%, p = 0.12), or any of the measured neonatal outcomes (p > 0.05). CONCLUSIONS: Implementation of a labor induction approval process was associated with a significant reduction in overall and non-indicated induction rates but did not affect the primary cesarean rate or neonatal outcomes.

Assessment of Chronic Wasting Disease Prion Shedding in Deer Saliva with Occupancy Modeling.

The detection of prions is difficult due to the peculiarity of the pathogen, which is a misfolded form of a normal protein. The specificity and sensitivity of detection methods are imperfect in complex samples, including in excreta. Here, we combined optimized prion amplification procedures with a statistical method that accounts for false-positive and false-negative errors to test deer saliva for chronic wasting disease (CWD) prions. This approach enabled us to discriminate the shedding of prions in saliva and the detection of prions in saliva-a distinction crucial to understanding the role of prion shedding in disease transmission and for diagnosis. We found that assay sensitivity and specificity were indeed imperfect, and we were able to draw several conclusions pertinent to CWD biology from our analyses: (i) the shedding of prions in saliva increases with time postinoculation, but is common throughout the preclinical phase of disease; (ii) the shedding propensity is influenced neither by sex nor by prion protein genotype at codon 96; and (iii) the source of prion-containing inoculum used to infect deer affects the likelihood of prion shedding in saliva; oral inoculation of deer with CWD-positive saliva resulted in 2.77 times the likelihood of prion shedding in saliva compared to that from inoculation with CWD-positive brain. These results are pertinent to horizontal CWD transmission in wild cervids. Moreover, the approach described is applicable to other diagnostic assays with imperfect detection.

Leveraging constraints and biotelemetry data to pinpoint repetitively used spatial features.

Satellite telemetry devices collect valuable information concerning the sites visited by animals, including the location of central places like dens, nests, rookeries, or haul-outs. Existing methods for estimating the location of central places from telemetry data require user-specified thresholds and ignore common nuances like measurement error. We present a fully model-based approach for locating central places from telemetry data that accounts for multiple sources of uncertainty and uses all of the available locational data. Our general framework consists of an observation model to account for large telemetry measurement error and animal movement, and a highly flexible mixture model specified using a Dirichlet process to identify the location of central places. We also quantify temporal patterns in central place use by incorporating ancillary behavioral data into the model; however, our framework is also suitable when no such behavioral data exist. We apply the model to a simulated data set as proof of concept. We then illustrate our framework by analyzing an Argos satellite telemetry data set on harbor seals (Phoca vitulina) in the Gulf of Alaska, a species that exhibits fidelity to terrestrial haul-out sites.

The basis function approach for modeling autocorrelation in ecological data.

Analyzing ecological data often requires modeling the autocorrelation created by spatial and temporal processes. Many seemingly disparate statistical methods used to account for autocorrelation can be expressed as regression models that include basis functions. Basis functions also enable ecologists to modify a wide range of existing ecological models in order to account for autocorrelation, which can improve inference and predictive accuracy. Furthermore, understanding the properties of basis functions is essential for evaluating the fit of spatial or time-series models, detecting a hidden form of collinearity, and analyzing large data sets. We present important concepts and properties related to basis functions and illustrate several tools and techniques ecologists can use when modeling autocorrelation in ecological data.

Transplacental Passage of Acetaminophen in Term Pregnancy.

Objective The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal (T1/2, 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [Vd/F], 57.5 L) and fetal compartments (T1/2, 82 minutes; Cl/F, 31.2 L/h; Vd/F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated (p < 0.0001). Conclusion Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure.

Applying to subspecialty fellowship: clarifying the confusion and conflicts!

Of graduating obstetrics and gynecology residents, 40% apply for fellowship training and this percentage is likely to increase. The fellowship interview process creates a substantial financial burden on candidates as well as significant challenges in scheduling the multiple interviews for residents, residency programs, and fellowship programs. Coverage with relatively short lead time is needed for some resident rotations, multiple residents may request time off during overlapping time periods, and applicants may not be able to interview based on conflicting interview dates or the inability to find coverage from other residents for their clinical responsibilities. To address these issues, we propose that each subspecialty fellowship within obstetrics and gynecology be allocated a specified and limited time period to schedule their interviews with minimal overlap between subspecialties. Furthermore, programs in close geographic areas should attempt to coordinate their interview dates. This will allow residents to plan their residency rotation schedules far in advance to minimize the impact on rotations that are less amenable to time away from their associated clinical duties, and decrease the numbers of residents needing time off for interviews during any one time period. In addition, a series of formal discussions should take place between subspecialties related to these issues as well as within subspecialties to facilitate coordination.

Animal movement constraints improve resource selection inference in the presence of telemetry error.

Multiple factors complicate the analysis of animal telemetry location data. Recent advancements address issues such as temporal autocorrelation and telemetry measurement error, but additional challenges remain. Difficulties introduced by complicated error structures or barriers to animal movement can weaken inference. We propose an approach for obtaining resource selection inference from animal location data that accounts for complicated error structures, movement constraints, and temporally autocorrelated observations. We specify a model for telemetry data observed with error conditional on unobserved true locations that reflects prior knowledge about constraints in the animal movement process. The observed telemetry data are modeled using a flexible distribution that accommodates extreme errors and complicated error structures. Although constraints to movement are often viewed as a nuisance, we use constraints to simultaneously estimate and account for telemetry error. We apply the model to simulated data, showing that it outperforms common ad hoc approaches used when confronted with measurement error and movement constraints. We then apply our framework to an Argos satellite telemetry data set on harbor seals (Phoca vitulina) in the Gulf of Alaska, a species that is constrained to move within the marine environment and adjacent coastlines.

Antepartum nonobstetrical surgery at ≥23 weeks' gestation and risk for preterm delivery.

OBJECTIVE: We sought to describe the influence of antepartum nonobstetrical surgical procedures performed at viable fetal gestational ages (GAs) on incidence of preterm delivery. STUDY DESIGN: This was a retrospective case series of patients requiring nonobstetrical surgery at ≥23 weeks' gestation at the Mayo Clinic during the interval 1992 through 2014. Data were abstracted for maternal demographic variables, operative procedure, anesthetic type, whether intraoperative fetal monitoring was employed, and both GA and method of delivery. RESULTS: In all, 111 patients underwent 121 operative procedures at a mean GA of 29.2 weeks (range, 23-37 weeks). The majority of procedures were completed under general anesthesia (88/121, 73%), with intraoperative fetal monitoring performed in 14 cases (14/121, 12%); fetal loss occurred during a single unmonitored procedure. Outcome data were available for the majority of patients (86/111, 78%) with preterm delivery occurring in 41% (35/86) at a mean GA of 36.9 weeks (range, 25-41 weeks). Mean interval from procedure to delivery was 7.7 weeks, with 9 patients (9/86, 10%) delivering within 1 week of surgery. Neither procedures requiring entry into the abdominal cavity (P = .65) nor GA at time of procedure (P = 1.0) statistically influenced the risk of preterm delivery. CONCLUSION: Nonobstetrical surgical procedures performed at or beyond fetal viability increased the incidence of preterm delivery regardless of surgical site or timing of procedure, however the risk of intraoperative or immediate postoperative obstetrical complications was relatively low.

Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy.

Although perimortem delivery has been recorded in the medical literature for millennia, the procedural intent has evolved to the current fetocentric approach, predicating timing of delivery following maternal cardiopulmonary arrest to optimize neonatal outcome. We suggest a call to action to reinforce the concept that if the uterus is palpable at or above the umbilicus, preparations for delivery should be made simultaneous with initiation of maternal resuscitative efforts; if maternal condition is not rapidly reversible, hysterotomy with delivery should be performed regardless of fetal viability or elapsed time since arrest. Cognizant of the difficulty in determining precise timing of arrest in clinical practice, if fetal status is already compromised further delay while attempting to assess fetal heart rate, locating optimal surgical equipment, or transporting to an operating room will result in unnecessary worsening of both maternal and fetal condition. Even if intrauterine demise has already occurred, maternal resuscitative efforts will typically be markedly improved following delivery with uterine decompression. Consequently we suggest that perimortem cesarean delivery be renamed "resuscitative hysterotomy" to reflect the mutual optimization of resuscitation efforts that would potentially provide earlier and more substantial benefit to both mother and baby.

Dexmedetomidine and Mannitol for Awake Craniotomy in a Pregnant Patient.

We describe the use of dexmedetomidine for an awake neurosurgical procedure in a pregnant patient and quantify the effect of mannitol on intrauterine volume. A 27-year-old woman underwent a craniotomy, with intraprocedural motor and speech mapping, at 20 weeks of gestation. Sedation was maintained with dexmedetomidine. Mannitol at 0.25 g/kg IV was administered to control brain volume during surgery. Internal uterine volume was estimated at 1092 cm before surgery and decreased to 770 and 953 cm at 9 and 48 hours, respectively, after baseline assessment. No adverse maternal or fetal effects were noted during the intraoperative period or up to 48 hours postoperatively.

Reduced syncytin-1 expression in choriocarcinoma BeWo cells activates the calpain1-AIF-mediated apoptosis, implication for preeclampsia.

Placentas associated with preeclampsia are characterized by extensive apoptosis in trophoblast lineages. Syncytin-1 (HERVWE1) mediates the fusion of cytotrophoblasts to form syncytiotrophoblasts, which assume the placental barrier, fetal-maternal exchange and endocrine functions. While decreased syncytin-1 expression has been observed in preeclamptic placentas, it is not clear if this alteration is involved in trophoblast apoptosis. In the current study, we found that siRNA-mediated knockdown of syncytin-1 led to apoptosis in choriocarcinoma BeWo, a cell line of trophoblastic origin. Characterization of the apoptotic pathways indicated that this effect does not rely on the activation of caspases. Rather, decreased syncytin-1 levels activated the apoptosis inducing factor (AIF) apoptotic pathway by inducing the expression, cleavage, and nuclear translocation of AIF. Moreover, calpain1, the cysteine protease capable of cleaving AIF, was upregulated by syncytin-1 knockdown. Furthermore, treatment with calpain1 inhibitor MDL28170 effectively reversed AIF cleavage, AIF nuclear translocation, and cell apoptosis triggered by syncytin-1 downregulation, verifying the specific action of calpain1-AIF pathway in trophoblast apoptosis. We confirmed that preeclamptic placentas express lower levels of syncytin-1 than normal placentas, and observed an inverse correlation between syncytin-1 and AIF/calpain1 mRNA levels, a result consistent with the in vitro findings. Immunohistochemistry analyses indicated decreased syncytin-1 and increased AIF and calpain1 protein levels in apoptotic cells of preeclamptic placentas. These findings have for the first time revealed that decreased levels of syncytin-1 can trigger the AIF-mediated apoptosis pathway in BeWo cells. This novel mechanism may contribute to the structural and functional deficiencies of syncytium frequently observed in preeclamptic placentas.

Impact of an Inexpensive Anatomy-Based Fetal Pig Simulator on Obstetric Ultrasound Training.

OBJECTIVES: The purpose of this study was to construct an inexpensive anatomy-based obstetric ultrasound task trainer and investigate whether introduction of this trainer into a hands-on obstetric ultrasound course improved course participants' ultrasound scanning skills. METHODS: The trainer was created by placing fetal pigs into preservative-filled heat-sealed polyethylene bags. Twenty-four participants in an obstetric ultrasound course at Wake Forest School of Medicine were randomized to receive hands-on scanning with pregnant women or hands-on scanning and fetal pig simulation. Biometric scans were performed before and after the course. The time to complete the scans, margin of error of biometric measurements, and number of technically adequate images per scan were compared between groups. RESULTS: Twelve participants were randomized into each group. Although a direct comparison of postcourse biometric scans demonstrated no difference between groups, participants that received simulation training showed significant improvements in the time to complete the biometric scan (P < .05) and number of technically adequate images obtained (P < .05), whereas those who did not receive simulation training did not show significant improvements. CONCLUSIONS: Addition of the fetal pig ultrasound task trainer resulted in improvements in the course participants' scanning efficiency even after very limited exposure. Incorporating the task trainer earlier and more broadly into obstetric ultrasound training may benefit trainees.

Clinical application of fetal left modified myocardial performance index in the evaluation of fetal growth restriction.

OBJECTIVE: This study aims to evaluate cardiac function in fetuses with intrauterine growth restriction (IUGR) compared with healthy fetuses, using the left modified myocardial performance index (MPI) and the association between MPI and perinatal outcome. METHODS: Pregnant women between 34 and 39 weeks of gestation, who met the criteria for IUGR and were scheduled for delivery at an Egyptian tertiary medical center, were prospectively enrolled in the study. Women in the same gestational-age group with uncomplicated pregnancies were included as a control group. MPI was measured in all fetuses. The IUGR group was analyzed based on normal and abnormal umbilical artery (UA) Doppler. Perinatal outcomes were recorded. RESULTS: The mean left MPI was significantly higher in IUGR fetuses with abnormal UA Doppler (mean 0.58±SD 0.093) compared with healthy fetuses (mean 0.45±SD 0.070) (P<0.001). IUGR fetuses with abnormal left MPI showed significantly worse perinatal outcome and increased morbidity compared with the control group. IUGR fetuses with abnormal left MPI also showed significantly worse perinatal outcome compared with IUGR fetuses with normal MPI (whether the UA Doppler was normal or abnormal). The fetal MPI was associated with the severity of fetal compromise in IUGR fetuses based on the perinatal outcome. CONCLUSION: MPI is a potentially useful tool in evaluating fetuses with suspected IUGR, which is crucial in classifying IUGR pregnancies into critical and non-critical cases and in predicting neonatal outcome.

Effect of Acetaminophen on Fetal Activity.

OBJECTIVES: The aim of this study is to determine if maternal administration of acetaminophen affects fetal activity and thereby the interpretation of clinical assessments of fetal well being. STUDY DESIGN: A longitudinal study was performed in 20 women between 30 and 34 weeks' gestation with uncomplicated pregnancies. A 1-hour ultrasound was performed and recorded to document baseline fetal breathing and body movements. All the subjects were then given a 1,000 mg dose of oral acetaminophen. One hour later, a second 1 hour ultrasound was performed to document postacetaminophen fetal breathing and body movements. The number of episodes and total duration of gross body and fetal breathing movements were then assessed by a blinded observer. The pre- and post-acetaminophen values were compared using a repeated measures t-test. RESULTS: There was no significant effect of acetaminophen on the number of episodes or time spent in fetal breathing or body movements when each activity parameter was analyzed separately. In addition, there was no effect when fetal breathing and body movements were combined into a single composite activity score. CONCLUSION: Although acetaminophen has been shown to affect fetal activity in animal models, it has little effect on humans. Thus, maternal administration of acetaminophen should not affect assessment of fetal well being.

Development of an Endometrial Ablation Model in New Zealand White Rabbits.

OBJECTIVE: To develop an animal model for radiofrequency endometrial ablation (EA) and evaluate histopathologic outcomes of EA in New Zealand White (NZW) rabbits. STUDY DESIGN: A pilot study was conducted. A radiofrequency EA device was developed and a variety of EA settings were tested on euthanized NZW rabbits. An algorithm was developed to determine target EA parameters. Bilateral radiofrequency EA was performed via laparotomy using 5.2 mm, 6.1 mm, or 7.1 mm diameter x 100 mm bipolar probes on 10 live NZW rabbits. All rabbits were screened for endometrial cancer (EC). Rabbits were euthanized 3 weeks following EA, and histopathologic analysis of postablation hysterectomy specimens was performed. RESULTS: Bilateral radiofrequency EA was successful in rabbits that were candidates for the procedure, and uterine assessment was feasible in all rabbits. One case of EC was detected. Uterine anatomy was variable among rabbits. The optimal EA setting was 4.5 W/cm2 x 20 seconds, which provided consistent thermal destruction to the endometrium and inner myometrium as verified by histology. CONCLUSION: Use of a radiofrequency EA algorithm tailored to individual NZW rabbits produces consistent thermal destruction of the endometrium and inner myometrium. This animal model can be used to study the long-term consequences of EA and the association with EC.

Mass spectrometry as a novel method for detection of podocyturia in pre-eclampsia.

BACKGROUND: Podocyturia, i.e. urinary loss of viable podocytes, may serve as a diagnostic tool for pre-eclampsia and as a marker of active renal disease. The current method to detect podocyturia is technically complex, lengthy and requires a high level of expertise for interpretation. The aim of this study was to develop a new technique for the identification of urinary podocytes, based on the detection of podocyte-specific tryptic peptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which will provide an operator-independent and highly reproducible method. METHODS AND RESULTS: The diagnosis of pre-eclampsia was confirmed in the presence of hypertension (>140/90 mmHg) and proteinuria >0.3 g/24 h urine. The diagnosis of HELLP was confirmed based on the accepted clinical criteria of hemolysis, elevated liver enzymes and low platelet count. Random urine samples within 24 h prior to delivery were collected and centrifuged. One half of the sediment was cultured for 24 h to select for viable cells and then stained with a podocin antibody, followed by a secondary fluorescein isothiocyanate-labeled antibody to identify podocytes. The second half of the pellet was solubilized, digested and analyzed by LC-MS/MS using an internal standard. We have recruited 13 patients with pre-eclampsia and 6 patients with pre-eclampsia/HELLP syndrome. The presence of podocytes was confirmed in all patients by the podocyte culture method. In the respective samples, the presence of a podocin-specific tryptic peptide was confirmed with LC-MS/MS technology. CONCLUSION: The LC-MS/MS method is a reliable technology for the identification of urinary podocytes, based on the presence of podocyte-specific proteins in the urine.

Long QT syndrome-associated mutations in intrauterine fetal death.

IMPORTANCE: Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. OBJECTIVE: To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. DESIGN, SETTING, AND PATIENTS: In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. MAIN OUTCOMES AND MEASURES: Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. RESULTS: The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2 [1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10 000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes. CONCLUSIONS AND RELEVANCE: In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth.

Low-Cost Task Trainer for In Utero Fetal Stent Placement.

INTRODUCTION: Some fetal procedures such as intrauterine fetal stent placement remain rare, and simulation is needed to help learners and specialists in attaining and maintaining technical competence. We sought to design and assess a low-cost, easily assembled yet clinically relevant task trainer for fetal stent placement. METHOD: The simulator was constructed using 2 quart-sized freezer bags filled with ultrasound gel and sealed with clear packing tape. The bags were stacked vertically in a transparent plastic container with ultrasound gel applied between the bags when ultrasound was used. This task trainer was used to deploy in utero stents with or without the use of ultrasound. It has been used at the annual meeting of the Society for Maternal-Fetal Medicine since 2015, the annual meeting of the International Society of Ultrasound in Obstetrics and Gynecology in 2015 and 2016, and at regional Maternal-Fetal Medicine Fellow simulation workshops since 2016. Participants were asked to complete a 5-point Likert scale survey regarding the model's realism and usefulness in training. RESULTS: One hundred thirty-three course participants evaluated the task trainer. The median rating for realism of the ultrasound images, haptic feel of stent deployment, and usefulness in training was 5 (interquartile range, 4-5). Seven physicians participated in the timed assessment of model assembly, stent deployment, and model reassembly. The average times required for the freezer bag task trainer were 2.3 minutes (2.20-2.35), 1.0 minutes (0.70-1.93), and 0.1 minutes (0.08-0.10), respectively. For the porcine tissue-based model tested in parallel, the average times were 6.0 minutes (5.00-7.06), 3.7 minutes (3.63-3.75), and 3.3 minutes (3.00-3.70), respectively. CONCLUSIONS: This low-cost simulator was rated highly when used to practice in utero stent deployment and allows for numerous repetitions in each training session. It could be a valuable tool in training novice providers and allow more experienced providers to maintain competence in this low-volume procedure.

The effects of heparin, aspirin, and maternal clinical factors on the rate of nonreportable cell-free DNA results: a retrospective cohort study.

BACKGROUND: Technological advances in the analysis of cell-free DNA in maternal serum have allowed expanded prenatal screening possibilities for fetal aneuploidies. The sensitivity and positive predictive value of the assay are partly dependent on the amount of cell-free DNA present in maternal circulation. Thus, it is important to know what fetal and maternal factors influence the level of cell-free DNA in maternal circulation. Maternal heparin use has been associated with an increase in nonreportable cell-free DNA results because of a low fetal fraction in some, but not all, previous studies. In addition, there are likely additional factors that affect cell-free DNA that remain uncharacterized. OBJECTIVE: This study aimed to determine whether heparins, low-dose aspirin, and maternal clinical factors affect the rate of nonreportable cell-free DNA testing results. STUDY DESIGN: A retrospective cohort study was conducted using pregnant people receiving cell-free fetal DNA testing from January 1, 2014, to June 30, 2018. Data were collected on patient demographics, medical comorbidities, medication use, and cell-free DNA test results. Univariate and multivariate analyses were performed to determine which factors were independently associated with the rate of nonreportable results. RESULTS: From an original sample of 1117 pregnant people, 743 met the inclusion criteria. Maternal weight (odds ratio, 1.02), heparin use (odds ratio, 12.06), aspirin use (odds ratio, 4.70), chronic hypertension (odds ratio, 5.26), pregestational diabetes mellitus (odds ratio, 2.46), and autoimmune disease (odds ratio, 3.59) were significantly associated with an increased rate of nonreportable results in the univariate analysis. Moreover, the association was present for maternal weight (odds ratio, 1.02), heparin use (odds ratio, 21.87),and aspirin use (odds ratio, 2.85) in the multivariate analysis. CONCLUSION: The previously seen association between maternal heparin use and an increase in nonreportable cell-free DNA results was confirmed. Furthermore, there seems to be an increase in nonreportable results in pregnant people taking low-dose aspirin. Providers should consider the effect of these medications when counseling patients on prenatal genetic screening options.

Use of land facets to design linkages for climate change.

Least-cost modeling for focal species is the most widely used method for designing conservation corridors and linkages. However, these linkages have been based on current species' distributions and land cover, both of which will change with large-scale climate change. One method to develop corridors that facilitate species' shifting distributions is to incorporate climate models into their design. But this approach is enormously complex and prone to error propagation. It also produces outputs at a grain size (km2) coarser than the grain at which conservation decisions are made. One way to avoid these problems is to design linkages for the continuity and interspersion of land facets, or recurring landscape units of relatively uniform topography and soils. This coarse-filter approach aims to conserve the arenas of biological activity rather than the temporary occupants of those arenas. In this paper, we demonstrate how land facets can be defined in a rule-based and adaptable way, and how they can be used for linkage design in the face of climate change. We used fuzzy c-means cluster analysis to define land facets with respect to four topographic variables (elevation, slope angle, solar insolation, and topographic position), and least-cost analysis to design linkages that include one corridor per land facet. To demonstrate the flexibility of our procedures, we designed linkages using land facets in three topographically diverse landscapes in Arizona, USA. Our procedures can use other variables, including soil variables, to define land facets. We advocate using land facets to complement, rather than replace, existing focal species approaches to linkage design. This approach can be used even in regions lacking land cover maps and is not affected by the bias and patchiness common in species occurrence data.