Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing.

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood, is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound or increased genetic risk for a cytogenomic abnormality based on family history. While chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert, to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least 2 SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100% and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high resolution cytogenomic analysis demonstrates the potential of OGM to serve as a first-tier test for prenatal diagnosis.

Photoplethysmography and Heart Rate Variability for the Diagnosis of Preeclampsia.

BACKGROUND: The goal of this study was to determine a set of timing, shape, and statistical features available through noninvasive monitoring of maternal electrocardiogram and photoplethysmography that identifies preeclamptic patients. METHODS: Pregnant women admitted to Labor and Delivery were monitored with pulse oximetry and electrocardiogram for 30 minutes. Photoplethysmogram features and heart rate variability were extracted from each data set and applied to a sequential feature selection algorithm to discriminate women with preeclampsia with severe features, from normotensive and hypertensive controls. The classification boundary was chosen to minimize the expected misclassification cost. The prior probabilities of the misclassification costs were assumed to be equal. RESULTS: Thirty-seven patients with clinically diagnosed preeclampsia with severe features were compared with 43 normotensive controls; all were in early labor or beginning induction. Six variables were used in the final model. The area under the receiver operating characteristic curve was 0.907 (standard error [SE] = 0.004) (sensitivity 78.2% [SE = 0.3%], specificity 89.9% [SE = 0.1%]) with a positive predictive value of 0.883 (SE = 0.001). Twenty-eight subjects with chronic or gestational hypertension were compared with the same preeclampsia group, generating a model with 5 features with an area under the curve of 0.795 (SE = 0.007; sensitivity 79.0% [SE = 0.2%], specificity 68.7% [SE = 0.4%]), and a positive predictive value of 0.799 (SE = 0.002). CONCLUSIONS: Vascular parameters, as assessed noninvasively by photoplethysmography and heart rate variability, may have a role in screening women suspected of having preeclampsia, particularly in areas with limited resources.

Second-Trimester Uterine Model for Teaching Ultrasound-Guided Obstetric Procedures.

The declining number of ultrasound-guided obstetric procedures in clinical practice mandates a shift toward simulation-based teaching. Current uterine simulation aids are animal tissue-sourced or expensive, and improvement is needed. We describe a low-cost reusable uterine model with "fetus," cord and skin, constructed from synthetic gel and silicone rubber. Ultrasound appearance and tactile feedback approximate clinical use, and all parts of the model are portable, durable, and shelf-stable. Those made of ballistics gel can be recycled numerous times without noticeable effect. This appears to be ideal for proctored learning and independent practice within an ultrasound procedural curriculum.

Elevated midtrimester α-fetoprotein and delivery markers of inflammation in a preterm population.

OBJECTIVE: Determine whether elevated second trimester maternal serum α-fetoprotein (AFP) is associated with clinical and histopathologic markers of inflammation at preterm delivery. METHODS: 105 women <32 weeks' gestation were included. AFP levels were dichotomized at 2.0 multiples of the median (MoM). Rates of neonatal morbidities, clinical chorioamnionitis, cord blood IL-6 level, and placental inflammatory findings were compared. RESULTS: Thirteen (12.4%) had elevated AFP. Fewer women with AFP ≥ 2 MoM had histologic placental or membrane rupture site inflammation, funisitis, or placental culture positive for Mycoplasma and Ureaplasma species, compared to those with normal AFP. Neonatal death was increased in the elevated AFP group (23.1% vs. 2.27%, RR 10.6). Elevated AFP was associated with a nonsignificant increase in indicated birth (54% vs. 35%; p = 0.225). Virtually all inflammatory findings were confined to the spontaneous delivery group. CONCLUSION: Elevated midtrimester AFP conveyed significant risk of neonatal death, but was negatively associated with clinical or histopathologic inflammation in preterm infants.

Ultrasound screening for fetal aneuploidy using soft markers in the overweight and obese gravida.

OBJECTIVE: To determine the completion rate of ultrasound surveys for aneuploidy markers by maternal body mass index (BMI). METHODS: A retrospective review of ultrasounds on midtrimester singleton pregnancies was performed. Subjects were grouped as normal, overweight (BMI 25-29.9 kg/m(2)), and obese: class I (30-34.9 kg/m(2)), class II (35-39.9 kg/m(2)), and class III (>or= 40 kg/m(2)). Examinations with visualization of at least seven of eight markers were considered complete. RESULTS: Of 14 353 ultrasounds reviewed, 5690 patients were eligible: 43% normal, 29% overweight, 27% obese. Completion rates differed significantly between groups (64% normal, 64% overweight, 61% class I, 55% class II, 47% class III, p < 0.001). The screen positive rates (>or=1 marker) differed significantly overall (16% normal, 13% overweight, 15% class I, 12% class II, 10% class III, p < 0.02), but not for complete examinations (p = 0.42). CONCLUSIONS: Since completion rates for ultrasound aneuploidy screening are inversely related to maternal obesity, obese women are underscreened.