Can Ganciclovir and Quercetin-P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

OBJECTIVE: Determine whether combination therapy with ganciclovir (GCV) and a Quercetin-P188 solution improves hearing outcomes in a murine cytomegalovirus (CMV) model. METHODS: BALB/c mice were infected with murine CMV on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either GCV, QP188, GCV and QP188, or P188 delivery vehicle BID at 12-hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen, saline or P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV-infected groups were harvested at p10, and viral load was determined by quantitative polymerase chain reaction. RESULTS: CMV-infected mice receiving combination therapy GCV+QP188 demonstrated statistically significant lower ABR (p < 0.001) and DPOAE thresholds (p < 0.001) compared with mice treated with GCV monotherapy, QP188 monotherapy, and P188 delivery vehicle at 4, 6, and 8 weeks of age. GCV+QP188 combination therapy, GCV monotherapy, and QP188 monotherapy resulted in a nonsignificant reduction in mean viral titers compared to P188 monotherapy (p = 0.08). CONCLUSION: Combining GCV with the excipients quercetin and P188 effectively ameliorated CMV-induced sensorineural hearing loss in a murine model. This result may be partially explained by a reduction in viral titers in mouse temporal bones that correlate with in vitro studies demonstrating additive antiviral effect in cell culture. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1457-1463, 2024.

Etiology and Ontogeny of Cerebral Palsy: Implications for Practice and Research.

Cerebral palsy (CP) has been recognized as a group of neurologic disorders with varying etiologies and ontogenies. While a percentage of CP cases arises during labor, the expanded use of electronic fetal monitoring (EFM) to include prevention of CP has resulted in decades of vastly increased interventions that have not significantly reduced the incidence of CP for infants born at term in the USA. Litigation alleging that poor obstetrical practice caused CP in most of these affected children has led to contentious arguments regarding the actual etiologies of this condition and often resulted in substantial monetary awards for plaintiffs. Recent advances in genetic testing using whole exome sequencing have revealed that at least one-third of CP cases in term infants are genetic in origin and therefore not labor-related. Here, we will present and discuss previous attempts to sort out contributing etiologies and ontogenies of CP, and how these newer diagnostic techniques are rapidly improving our ability to better detect and understand such cases. In light of these developments, we present our vision for an overarching spectrum for proper categorization of CP cases into that the following groups: (1) those begun at conception from genetic causes (nonpreventable); (2) those stemming from adverse antenatal/pre-labor events (possibly preventable with heightened antepartum assessment); (3) Those arising from intrapartum events (potentially preventable by earlier interventions); (4) Those occurring shortly after birth (possibly preventable with closer neonatal monitoring); (5) Those that appear later in the postnatal period from non-labor-related causes such as untreated infections or postnatal intracranial hemorrhages.

Improving the interpretation of electronic fetal monitoring: the fetal reserve index.

Electronic fetal monitoring, particularly in the form of cardiotocography, forms the centerpiece of labor management. Initially successfully designed for stillbirth prevention, there was hope to also include prediction and prevention of fetal acidosis and its sequelae. With the routine use of electronic fetal monitoring, the cesarean delivery rate increased from <5% in the 1970s to >30% at present. Most at-risk cases produced healthy babies, resulting in part from considerable confusion as to the differences between diagnostic and screening tests. Electronic fetal monitoring is clearly a screening test. Multiple attempts have aimed at enhancing its ability to accurately distinguish babies at risk of in utero injury from those who are not and to do this in a timely manner so that appropriate intervention can be performed. Even key electronic fetal monitoring opinion leaders admit that this goal has yet to be achieved. Our group has developed a modified approach called the "Fetal Reserve Index" that contextualizes the findings of electronic fetal monitoring by formally including the presence of maternal, fetal, and obstetrical risk factors and increased uterine contraction frequencies and breaking up the tracing into 4 quantifiable components (heart rate, variability, decelerations, and accelerations). The result is a quantitative 8-point metric, with each variable being weighted equally in version 1.0. In multiple previously published refereed papers, we have shown that in head-to-head studies comparing the fetal reserve index with the American College of Obstetricians and Gynecologists' fetal heart rate categories, the fetal reserve index more accurately identifies babies born with cerebral palsy and could also reduce the rates of emergency cesarean delivery and vaginal operative deliveries. We found that the fetal reserve index scores and fetal pH and base excess actually begin to fall earlier in the first stage of labor than was commonly appreciated, and the fetal reserve index provides a good surrogate for pH and base excess values. Finally, the last fetal reserve index score before delivery combined with early analysis of neonatal heart rate and acid/base balance shows that the period of risk for neonatal neurologic impairment can continue for the first 30 minutes of life and requires much closer neonatal observation than is currently being done.

Changes in Metal-Chelating Metabolites Induced by Drought and a Root Microbiome in Wheat.

The essential metals Cu, Zn, and Fe are involved in many activities required for normal and stress responses in plants and their microbiomes. This paper focuses on how drought and microbial root colonization influence shoot and rhizosphere metabolites with metal-chelation properties. Wheat seedlings, with and without a pseudomonad microbiome, were grown with normal watering or under water-deficit conditions. At harvest, metal-chelating metabolites (amino acids, low molecular weight organic acids (LMWOAs), phenolic acids, and the wheat siderophore) were assessed in shoots and rhizosphere solutions. Shoots accumulated amino acids with drought, but metabolites changed little due to microbial colonization, whereas the active microbiome generally reduced the metabolites in the rhizosphere solutions, a possible factor in the biocontrol of pathogen growth. Geochemical modeling with the rhizosphere metabolites predicted Fe formed Fe-Ca-gluconates, Zn was mainly present as ions, and Cu was chelated with the siderophore 2'-deoxymugineic acid, LMWOAs, and amino acids. Thus, changes in shoot and rhizosphere metabolites caused by drought and microbial root colonization have potential impacts on plant vigor and metal bioavailability.

Resistance to Change.

Advances in medical technology do not follow a smooth process and are highly variable. Implementation can occasionally be rapid, but often faces varying degrees of resistance resulting at the very least in delayed implementation. Using qualitative comparative analysis, we have evaluated numerous technological advances from the perspective of how they were introduced, implemented, and opposed. Resistance varies from benign - often happening because of inertia or lack of resources to more active forms, including outright opposition using both appropriate and inappropriate methods to resist/delay changes in care. Today, even public health has become politicized, having nothing to do with the underlying science, but having catastrophic results. Two other corroding influences are marketing pressure from the private sector and vested interests in favor of one outcome or another. This also applies to governmental agencies. There are a number of ways in which papers have been buried including putting the thumb on the scale where reviewers can sabotage new ideas. Unless we learn to harness new technologies earlier in their life course and understand how to maneuver around the pillars of obstruction to their implementation, we will not be able to provide medical care at the forefront of technological capabilities.

Systematic voiding programme in adults with urinary incontinence following acute stroke: the ICONS-II RCT.

BACKGROUND: Urinary incontinence affects around half of stroke survivors in the acute phase, and it often presents as a new problem after stroke or, if pre-existing, worsens significantly, adding to the disability and helplessness caused by neurological deficits. New management programmes after stroke are needed to address urinary incontinence early and effectively. OBJECTIVE: The Identifying Continence OptioNs after Stroke (ICONS)-II trial aimed to evaluate the clinical effectiveness and cost-effectiveness of a systematic voiding programme for urinary incontinence after stroke in hospital. DESIGN: This was a pragmatic, multicentre, individual-patient-randomised (1 : 1), parallel-group trial with an internal pilot. SETTING: Eighteen NHS stroke services with stroke units took part. PARTICIPANTS: Participants were adult men and women with acute stroke and urinary incontinence, including those with cognitive impairment. INTERVENTION: Participants were randomised to the intervention, a systematic voiding programme, or to usual care. The systematic voiding programme comprised assessment, behavioural interventions (bladder training or prompted voiding) and review. The assessment included evaluation of the need for and possible removal of an indwelling urinary catheter. The intervention began within 24 hours of recruitment and continued until discharge from the stroke unit. MAIN OUTCOME MEASURES: The primary outcome measure was severity of urinary incontinence (measured using the International Consultation on Incontinence Questionnaire) at 3 months post randomisation. Secondary outcome measures were taken at 3 and 6 months after randomisation and on discharge from the stroke unit. They included severity of urinary incontinence (at discharge and at 6 months), urinary symptoms, number of urinary tract infections, number of days indwelling urinary catheter was in situ, functional independence, quality of life, falls, mortality rate and costs. The trial statistician remained blinded until clinical effectiveness analysis was complete. RESULTS: The planned sample size was 1024 participants, with 512 allocated to each of the intervention and the usual-care groups. The internal pilot did not meet the target for recruitment and was extended to March 2020, with changes made to address low recruitment. The trial was paused in March 2020 because of COVID-19, and was later stopped, at which point 157 participants had been randomised (intervention, n = 79; usual care, n = 78). There were major issues with attrition, with 45% of the primary outcome data missing: 56% of the intervention group data and 35% of the usual-care group data. In terms of the primary outcome, patients allocated to the intervention group had a lower score for severity of urinary incontinence (higher scores indicate greater severity in urinary incontinence) than those allocated to the usual-care group, with means (standard deviations) of 8.1 (7.4) and 9.1 (7.8), respectively. LIMITATIONS: The trial was unable to recruit sufficient participants and had very high attrition, which resulted in seriously underpowered results. CONCLUSIONS: The internal pilot did not meet its target for recruitment and, despite recruitment subsequently being more promising, it was concluded that the trial was not feasible owing to the combined problems of poor recruitment, poor retention and COVID-19. The intervention group had a slightly lower score for severity of urinary incontinence at 3 months post randomisation, but this result should be interpreted with caution. FUTURE WORK: Further studies to assess the effectiveness of an intervention starting in or continuing into the community are required. TRIAL REGISTRATION: This trial is registered as ISRCTN14005026. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 31. See the NIHR Journals Library website for further project information.

Urinary incontinence affects around half of stroke survivors. It causes embarrassment and distress, affecting patients' ability to take part in rehabilitation. It also has a major impact on families and may determine whether or not patients are able to return home. Finding the underlying cause and addressing it can prevent, cure or reduce problems. Doing this in a systematic way for everyone with incontinence problems as early as possible after the stroke, while they are still in hospital, may work best. We also wanted to avoid using catheters in the bladder to drain the urine away, as these are often unnecessary and can cause urinary tract infections. This study aimed to test whether or not continence problems and the use of urinary catheters could be reduced if everyone with incontinence was fully assessed and given the right management and support early after hospital admission. We also wanted to find out if the benefits outweighed the costs. We planned to involve 1024 men and women with incontinence from 18 stroke units in the study, with 512 people receiving the intervention and 512 receiving usual care. However, the trial was paused because of COVID-19, at which time only 157 participants had been recruited. When we were thinking about restarting the study and looked at its progress, we found that not enough people had agreed to take part and, of those who had agreed, many had not returned their outcome questionnaires. This indicated that the trial was not feasible and should not restart. We could not make any firm conclusions about whether or not the intervention worked, as not enough people were involved. We found that stays in hospital after stroke are shorter than they were in the past. This suggests that future studies investigating ways of treating incontinence should consider interventions with management and support for incontinence that continue after patients leave the hospital.

Fetal reduction for everyone?

Infertility treatments have benefited millions of couples to have their own children; however, the complication of multiple pregnancies with their increased morbidity and mortality has created significant problems. Fetal reduction (FR) was developed to ameliorate these issues. Over 30 years of publications show that FR has been highly successful in substantially reducing both mortality and morbidity. As with most radically new techniques, initial cases were in the "nothing to lose" category. With experience, indications liberalize, and quality of life issues increase as a proportion of cases. Overall risks for twins are not twice as those for singletons, but they are approximately 4- to 5-fold higher. In experienced hands, the combination of genetic testing by CVS followed by FR has made most multiples behave statistically as if they were originally the lower number. The use of microarray analysis to better determine fetal genetic health before deciding on which fetus(es) to keep or reduce further improves pediatric outcomes. With increasing experience and lower average starting numbers, the proportion of FRs to a singleton has increased considerably. Twins to a singleton FR now constitute an increasing proportion of cases performed. Data on such cases show improved outcomes, and we believe FR should be at least discussed and offered to all patients with a dichorionic twin pregnancy or higher. eSET is not a panacea because of the resultant monochorionic twins.

Poloxamer 188 - quercetin formulations amplify in vitro ganciclovir antiviral activity against cytomegalovirus.

Treatment of human cytomegalovirus (CMV) infection requires long-term administration of nucleoside analog antivirals such as ganciclovir (GCV), a therapy frequently limited by GCV-induced toxicity. Here, combining GCV treatment with two bioactive excipients, poloxamer 188 and quercetin, was investigated in vitro to reduce GCV dosage. Quercetin is a natural flavonoid exhibiting antiviral activity against CMV by a mechanism distinct from GCV, but is poorly soluble, limiting its use as a therapeutic. To overcome this challenge, quercetin was co-formulated with poloxamer 188 (P188, Pluronic ® F68). Quercetin-P188 (QP188) formulations yielded only modest CMV viral inhibition, with a selectivity index of 11.4, contrasted with a GCV selectivity index of 95. More significantly, when coadministered with GCV, QP188 exhibited an additive or synergistic interaction in subtherapeutic ranges of GCV. Fluorescence microscopy revealed QP188 accumulation in fibroblast mitochondria, suggesting that the excipient may modulate mitochondrial processes relevant to CMV infection. GCV antiviral therapy augmented with poloxamer-solubilized quercetin may be a viable approach to maintain CMV inhibition while lowering GCV doses, translating to reduced associated toxicity.

Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.

Background: Submicron particles (SMPs), as novel bionanomaterials, offer complementary benefits to their conventional nano-counterparts. Aim: To explore zinc oxide (ZnO) SMPs' bioimaging and anticancer potentials. Materials & methods: ZnO SMPs were synthesized into two shapes. Fluorescent spectrum and microscopy were studied for the bioimaging property. Wound healing and Live/Dead assays of glioblastoma cells were characterized for anticancer activities. Results: ZnO SMPs exhibited a high quantum yield (49%) with stable orange fluorescence emission. Both morphologies (most significant in the rod shape) showed tumor-selective properties in cytotoxicity, inhibition to cell migration and attenuating the cancer-upregulated genes. The tumor selectivity was attributed to particle degradation and surface properties on pH dependency. Conclusion: The authors propose that ZnO SMPs could be a promising anticancer drug with tunable, morphology-dependent properties for bioimaging and controlled release.

Submicron particles (SMPs) are a novel nanomaterial whose total size is microscale (around one-millionth of a meter), but at least one dimension is nanoscale (around one-billionth of a meter). Their combined micro- and nanoscale properties are complementary, which can be an improvement on their conventional nano-counterparts. The aim of this study was to explore the bioimaging and anticancer properties of zinc oxide (ZnO) SMPs. ZnO SMPs were synthesized in two shapes: rod-shaped and flower-shaped. The fluorescence spectra and microscopy images were studied to investigate their potential for imaging applications, and wound healing and viability assays of glioblastoma cells were used to characterize anticancer activity. ZnO SMPs exhibited strong and stable orange fluorescence emission. Both shapes of ZnO SMPs showed tumor-selective toxicity, inhibition to cell migration and attenuating the cancer-upregulated genes; however, these effects were more significant for the rod-shaped particles. The tumor selectivity was attributed to pH-dependent particle degradation related to surface properties. The authors therefore propose that ZnO SMPs could be a promising anticancer drug with tunable, morphology-dependent properties for bioimaging and controlled release.

Mid forceps did not cause "compromised babies" - "compromise" caused forceps: an approach toward safely lowering the cesarean delivery rate.

OBJECTIVE: Over 5 decades, Cesarean Delivery rates (CDR) have risen 6-fold while vaginal operative deliveries [VODs] decreased from >20% to ∼3%. Poor outcomes (HIE and cerebral palsy) haven't improved. Potentiating the virtual abandonment of forceps (F), particularly midforceps (Mid), were allegations about various poor neonatal outcomes. Here, we evaluate VOD and CDR outcomes controlling for prior fetal risk metrics (PR) ascertained an hour before birth. METHODS: Our 45-year-old database from a labor research unit of moderate/high risk laboring patients (288 NSVDs, 120 Lows, 30 Mids, and 32 CDs) had multiple fetal scalp samples for base excess (BE), pH, cord blood gases (CB), and umbilical artery bloods. ANOVA established relationships between birth methods and outcomes (Cord blood BE and pH and 1 and 5 min Apgar scores); correlations, and two-step multiple regression assessed PR for delivery method and neonatal outcomes. The main outcome measures were correlations of outcome measures with fetal scalp sample BE and pH up to an hour before delivery and fetal reserve index scores scored concurrently. RESULTS: NSVDs had the best immediate neonatal outcomes with significantly higher CB pH and BE as compared to forceps and CDs. However, controlling for PR revealed: (1) PR at 1 h before delivery correlated with delivery mode, i.e. the decrements in outcomes were already present before the delivery was performed; and (2) The presumed deleterious effects of interventional deliveries, per se, were significantly reduced, and (3) Fetal Reserve Index predicted neonatal outcomes better than fetal scalp sample BE, pH, or delivery mode. CONCLUSION: The historical belief that MF deliveries caused poorer outcomes than NSVDs seems mostly backwards. Appreciating PR's impact on delivery routes, and when appropriate, properly performing VODs could safely reduce CDR. If our approach lowered CDR by only ∼2%, in the United States about 80,000 CDs might be avoided, saving ∼$750 Million yearly. In the post pandemic world, safely apportioning medical expenses will be even more critical than previously.

Earlier and improved screening for impending fetal compromise.

OBJECTIVE: The use of pH and base excess (FSSPHBE) from fetal scalp sampling (FSS) was abandoned when cardiotocography (CTG) was believed to be sufficiently accurate to direct patient management. We sought to understand the fetus' tolerance to stress in the 1st stage of labor and to develop a better and earlier screening test for its risk for developing acidosis. To do so, we investigated sequential changes in fetal pH and BE obtained from FSS in the 1st stage of labor as part of a research protocol from the 1970s. We then examined the utility of multiple of the median (MoM's) conversion of BE and pH values, and the capacity of Fetal Reserve Index (FRI) scores to be a proxy for such changes. We then sought to examine the predictive capacity of 1st stage FRI and its change over the course of the first stage of labor for the subsequent development of acidosis risk in the 2nd stage of labor. METHODS: Using a retrospective research database evaluation, we evaluated FSSPHBE data from 475 high-risk parturients monitored in labor and their neonates for 1 h postpartum.We categorized specimens according to cervical dilatation (CxD) at the time of FSSPHBE and developed non-parametric, multiples of the median (MOMs) assessments. FRI scores and their change over time were used as predictors of FSSPHBE. Our main outcome measures were the changes in BE and pH at different cervical dilatations (CxD) and acidosis risk in the early 2nd stage of labor. RESULTS: FSSPHBE worsens over the course of the 1st stage. The implications of any given BE are very different depending upon CxD. At 9 cm, -8 Mmol/L is 1.1 MOM; at 3 cm, it would be 2.0 MOM. The FRI level and its trajectory provide a 1st stage screening tool for acidosis risk in the second stage. CONCLUSIONS: Fetal acid-base balance ("reserve") deteriorates beginning early in the 1st stage of labor, irrespective of whether the fetus reaches a critical threshold of concern for actual acidosis. The use of MoM's logic improves appreciation of such information. The FRI and its trajectory reasonably approximate the trajectory of the FSSPHBE and appears to be a suitable screening test for early deterioration and for earlier interventions to keep the fetus out of trouble rather than wait until high risk status develops.

Changing Perspectives of Electronic Fetal Monitoring.

The delivery of healthy babies is the primary goal of obstetric care. Many technologies have been developed to reduce both maternal and fetal risks for poor outcomes. For 50 years, electronic fetal monitoring (EFM) has been used extensively in labor attempting to prevent a large proportion of neonatal encephalopathy and cerebral palsy. However, even key opinion leaders admit that EFM has mostly failed to achieve this goal. We believe this situation emanates from a fundamental misunderstanding of differences between screening and diagnostic tests, considerable subjectivity and inter-observer variability in EFM interpretation, failure to address the pathophysiology of fetal compromise, and a tunnel vision focus. To address these suboptimal results, several iterations of increasingly sophisticated analyses have intended to improve the situation. We believe that part of the continuing problem is that the focus of EFM has been too narrow ignoring important contextual issues such as maternal, fetal, and obstetrical risk factors, and increased uterine contraction frequency. All of these can significantly impact the application of EFM to intrapartum care. We have recently developed a new clinical approach, the Fetal Reserve Index (FRI), contextualizing EFM interpretation. Our data suggest the FRI is capable of providing higher accuracy and earlier detection of emerging fetal compromise. Over time, artificial intelligence/machine learning approaches will likely improve measurements and interpretation of FHR characteristics and other relevant variables. Such future developments will allow us to develop more comprehensive models that increase the interpretability and utility of interfaces for clinical decision making during the intrapartum period.

Development of bioactive solid support for immobilized Lactobacillus casei biofilms and the production of lactic acid.

Polypropylene was modified to contain chitosan and evaluate its ability to generate Lactobacillus casei biofilms and their lactic acid production. Biofilm formation was carried out in either rich or minimal media. The chitosan-modified polypropylene harbored ~ 37% more cells than the control polypropylene. The biofilms from the chitosan-modified polypropylene grown in rich medium produced ~ 2 times more lactic acid after 72 h of incubation than the control suspended cells. There was no significant difference in the production of lactic acid after 72 h by L. casei biofilms on the chitosan-modified polypropylene grown in minimal media as compared with cells in suspension after 48 h and 72 h of incubation. Infrared spectroscopy confirmed higher deposition of nutrients and biomass on the chitosan-modified polypropylene as compared to the chitosan-free polypropylene. Electron and atomic force microscopy confirmed thicker biofilms when rich media were used to grow them as compared to minimal medium.

Fetal reduction and twins.

Infertility treatments have allowed millions of couples to have their own children, but resultant multiple pregnancies with their increased morbidity and mortality have been a significant complication. Fetal reduction was developed to ameliorate this issue. Over 30 years of publications show that fetal reduction has been highly successful in substantially reducing both mortality and morbidity related to multiple pregnancies. As with most radically new techniques, initial cases were in the "nothing to lose" category. With experience, indications liberalize, and quality of life issues gain relevance. The overall risks of twin pregnancy are not twice that of singleton pregnancy; they are about 4 to 5 times higher. In experienced hands, the combination of genetic testing by chorionic villus sampling followed by fetal reduction has made the outcomes of most multiple pregnancies statistically equivalent to those of pregnancies with lower fetal numbers. Use of microarray analysis to better determine fetal genetic health before deciding on which fetus(es) to keep or reduce further improves pediatric outcomes. With increasing experience and lower average starting numbers, the proportion of fetal reductions to a singleton has increased considerably. Twins to a singleton fetal reductions now constitute an increasing proportion of cases performed. Data on such cases show improved outcomes, and we believe fetal reduction should be at least discussed and offered to all patients with a dichorionic twin pregnancy or higher. With the increasing reliance on elective single-embryo transfers, monochorionic twins, which have much higher complication rates than dichorionic twins, have increased substantially. Furthermore, monochorionic twins cannot be readily and safely reduced, so the adverse perinatal statistics of elective single-embryo transfer are a major setback for good outcomes. Although elective single-embryo transfer is appropriate for some, we believe that for many couples, the transfer of 2 embryos is generally a more rational approach.

Uterine contraction frequency in the last hour of labor: how many contractions are too many?

OBJECTIVE: Increased frequency of uterine contractions is a component in the cluster of causal conditions that can lead to fetal hypoxia and acidosis and increase the risk for neonatal neurologic injury. For most international obstetrical societies, 5 contractions per 10 min averaged over 30 min is considered as the upper limit of normal uterine activity. We hypothesize that it might be safer to adopt an upper limit of 4 contractions per 10 min. METHODS: We reviewed our 1970's research database containing 475 patients with closely monitored and well-documented labor and neonatal assessments that included cord blood (CB) pH, base excess (BE), and continuous recording of neonatal heart rate (NHR). Using data segregated by the proportion of the last hour before delivery when uterine contraction frequency (UCF) exceeded 4 and 5 contractions per 10 min respectively, we evaluated outcomes (CB BE, pH, Apgar scores at 1 min, the status of NHR at 16 min after birth, and the proportion of births that did not the result from normal spontaneous vaginal deliveries (NSVDs). ANOVA established relationships between UCF cutoffs and these outcomes. Our sample size is sufficiently large to provide the ability of UCF, per se, to accurately detect an alpha region of .05 88% of the time with an effect size of .15. RESULTS: During the last hour prior to delivery, a UCF cutoff at 4 contractions per 10 min performed better than a UCF cutoff at 5 contractions per 10 min to enable the earlier identification of risks for abnormal outcomes. The longer UCF was increased, the worse were the outcomes that were measured, and the region >4 but ≤5 contractions identifies the beginnings of worsening conditions in a variety of measures of poor outcomes. CONCLUSION: Lowering the recommended threshold for UCF from 5 to 4 contractions per 10-minute period as averaged over 30 min facilitates earlier detection of potentially compromised fetuses and is also an important contributor to a multicomponent contextualized approach to risk assessment.

Understanding False Negative in Prenatal Testing.

A false negative can happen in many kinds of medical tests, regardless of whether they are screening or diagnostic in nature. However, it inevitably poses serious concerns especially in a prenatal setting because its sequelae can mark the birth of an affected child beyond expectation. False negatives are not a new thing because of emerging new tests in the field of reproductive, especially prenatal, genetics but has occurred throughout the evolution of prenatal screening and diagnosis programs. In this paper we aim to discuss the basic differences between screening and diagnosis, the trade-offs and the choices, and also shed light on the crucial points clinicians need to know and be aware of so that a quality service can be provided in a coherent and sensible way to patients so that vital issues related to a false negative result can be appropriately comprehended by all parties.