Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal ...trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 × 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo point mutations in the fetal genome were detected, albeit with limited specificity. Subsampling these data and analyzing a second family trio by the same approach indicate that parental haplotype blocks of ~300 kilo-base pairs combined with shallow sequencing of maternal plasma DNA is sufficient to substantially determine the inherited complement of a fetal genome. However, ultradeep sequencing of maternal plasma DNA is necessary for the practical detection of fetal de novo mutations genome-wide. Although technical and analytical challenges remain, we anticipate that noninvasive analysis of inherited variation and de novo mutations in fetal genomes will facilitate prenatal diagnosis of both recessive and dominant Mendelian disorders.
Investigations of noninvasive prenatal screening for aneuploidy by analysis of circulating cell-free DNA (cfDNA) have shown high sensitivity and specificity in both high-risk and low-risk cohorts. ...However, the overall low incidence of aneuploidy limits the positive predictive value of these tests. Currently, the causes of false positive results are poorly understood. We investigated four pregnancies with discordant prenatal test results and found in two cases that maternal duplications on chromosome 18 were the likely cause of the discordant results. Modeling based on population-level copy-number variation supports the possibility that some false positive results of noninvasive prenatal screening may be attributable to large maternal copy-number variants. (Funded by the National Institutes of Health and others.).
Globally, each year, an estimated 13 million infants are born before 37 completed weeks of gestation. Complications from these preterm births are the leading cause of neonatal mortality. Preterm ...birth is directly responsible for an estimated one million neonatal deaths annually and is also an important contributor to child and adult morbidities. Low- and middle-income countries are disproportionately affected by preterm birth and carry a greater burden of disease attributed to preterm birth. Causes of preterm birth are multifactorial, vary by gestational age, and likely vary by geographic and ethnic contexts. Although many interventions have been evaluated, few have moderate-to high-quality evidence for decreasing preterm birth: smoking cessation and progesterone treatment in women with a high risk of preterm birth in low- and middle-income countries and cervical cerclage for those in high-income countries. Antepartum and postnatal interventions (eg, antepartum maternal steroid administration, or kangaroo mother care) to improve preterm neonatal survival after birth have been demonstrated to be effective but have not been widely implemented. Further research efforts are urgently needed to better understand context-specific pathways leading to preterm birth; to develop appropriate, efficacious prevention strategies and interventions to improve survival of neonates born prematurely; and to scale-up known efficacious interventions to improve the health of the preterm neonate.
Abstract
We found low prevalence of SARS-CoV-2 (2.7% 5/188) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted ...screening (22.2% 4/18) and universal approaches (19.1% 8/42). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative.
We found a low prevalence of severe acute respiratory syndrome coronavirus 2 among pregnant and postpartum patients after initiation of universal testing at University of Washington–affiliated hospitals using a combination of on-site rapid testing, high-throughput centralized testing, and outpatient drive-through screening prior to admission.
To describe the level of sedation for a cohort of mechanically ventilated adult intensive care unit (ICU) patients using validated subjective and objective tools.
Prospective convenience sample.
...Multidisciplinary 34-bed ICU at Maine Medical Center, a 599-bed nonuniversity, academic medical center.
Sixty-three adult ICU patients were monitored during 64 episodes of ventilatory support.
Patients were prospectively evaluated by one trained investigator using the revised Sedation-Agitation Scale (SAS) and were simultaneously monitored for 1 to 5 hrs using the Bispectral Index (BIS), a numeric scale from 0 to 100 derived from the electroencephalogram. BIS values were assigned to baseline, stimulated, and average conditions for each patient by a separate investigator blinded to SAS scores. Ventilator settings, medications, and the lung injury severity (LIS) score were also recorded. Sedation levels varied from very deep sedation (SAS score = 1, BIS score = 43) to mild agitation (SAS score = 5, BIS score = 100). Heavily sedated patients (SAS score = 1-2, n = 20) had higher FIO2 (0.52 vs. 0.42, p = .008), oxygenation index (9.4 vs. 5.4, p = .03), and LIS scores (1.3 vs. 0.7, p = .004) and lower baseline (66 vs. 78, p = .01), average (66 vs. 81, p < .001), and stimulated (89 vs. 96, p = .016) BIS scores compared with more awake patients. Patients with intermittent neuromuscular blockade use (n = 4) had higher FIO2 (0.65 vs. 0.44, p = .006), minute ventilation (14.6 vs. 9.9 L/min, p = .005), positive end-expiratory pressure (7.5 vs. 4.8 cm H2O, p = .05), oxygenation index (15.7 vs. 6.0, p < .001), and LIS scores (3.3 vs. 1.0, p = .036) and were more sedated, with higher suppression ratios (3.5 vs. 0.6, p = .05) and lower SAS scores (1.5 vs. 4, p = .035). The average BIS values correlated well with SAS (r2 = .21, p < .001).
SAS and BIS work well to describe the depth of sedation for ventilated ICU patients. Deeper sedation and intermittent neuromuscular blockade were used for patients with greater ventilatory requirements and more severe lung disease. The correlation between subjective and objective scales varied in medical, surgical, and trauma patients. Further research with SAS and BIS may facilitate the development of quantitative sedation guidelines for the ICU.
Abstract
Objective: Assess the performance of ultrasound (US) in pregnant patients presenting with acute abdominal pain concerning for appendicitis.
Methods: Descriptive analysis of pregnant patients ...who underwent an US for acute abdominal pain over a 6-year period using data from a statewide quality improvement collaborative and a single center.
Results: Statewide, 131 pregnant patients underwent an appendectomy and 85% had an US. In our single-center case series, 49 pregnant patients underwent an US for acute abdominal pain and four patients had appendicitis (8%). Of those, three were definitively diagnosed with US. The appendix was visualized by US in five patients (3 appendicitis/2 normal). Mean gestational age was 11 weeks for visualization of the appendix versus 20 weeks for non-visualization (p < 0.001). Concordance between US and pathology was similar statewide and at our institution (43%).
Conclusions: US appears to play a central role in the evaluation of appendicitis in pregnant women, especially in the first trimester, and often contributes to definitive disposition. US performed less well in excluding appendicitis; however, in certain clinical settings, providers appeared to trust US findings. From these results, we developed a multidisciplinary imaging pathway for pregnant patients who present with acute abdominal pain concerning for appendicitis.
To validate the Sedation-Agitation Scale (SAS) with the Visual Analog Scale (VAS) and Bispectral Index (BIS) in adult ICU patients after cardiac surgery.
Prospective study comparing blinded ...evaluations of the SAS, VAS and BIS.
Forty-two-bed multidisciplinary ICU.
Convenience sample of 39 adults after cardiac surgery.
Bispectral Index 3.2 was continuously recorded using the Aspect A-1000 and evaluators were blinded to this value. The bedside nurse and a trained researcher independently rated wakefulness using a 100 mm VAS upon patient arrival on the ICU, at first awakening, when ventilator weaning was started and after extubation; the researcher also evaluated patients using SAS. Upon arrival on the ICU, the median SAS score was 2 (interquartile range = 1-3), the mean VAS was 26+/-30 and the mean BIS was 70+/-16. Twenty-four patients underwent a trial of weaning from mechanical ventilation with a SAS of 4 (IQR = 4), VAS of 86+/-12 and BIS of 87+/-10. SAS correlated well with VAS performed by one researcher (r = 0.91, p < 0.001) or by 19 different bedside nurses (r = 0.43, p < 0.001) and with BIS 3.2 (r = 0.60, p < 0.001). The correlation between SAS and BIS was reduced in patients with above average electromyogram (EMG) power. As a measure of construct validity, significant differences were noted for the BIS, SAS, VAS and EMG between ICU arrival and extubation (all p < 0.001).
Sedation-Agitation Scale and BIS are valid measures of wakefulness after cardiac surgery, but EMG interference may affect the accuracy of BIS for a small percentage of patients not receiving neuromuscular blockade.
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