Unique prenatal manifestations of biallelic NDUFAF5 variants: expansion of phenotype.

OBJECTIVE: Mitochondrial complex-I deficiency, nuclear type 16, is a rare autosomal recessive disorder caused by biallelic pathogenic variants in NDUFAF5 (C20orf7) (OMIM 618238). The aim of this study was to describe a severe early prenatal manifestation of this disorder, which was previously considered to occur only postnatally. METHODS: This was a multicenter retrospective case series including five fetuses from three non-related families, which shared common sonographic abnormalities, including brain cysts, corpus callosal malformations, non-immune hydrops fetalis and growth restriction. Genetic evaluation included chromosomal microarray analysis and exome sequencing. Two fetuses from the same family were also available for pathology examination, including electron microscopy. RESULTS: Chromosomal microarray analysis revealed no chromosomal abnormality in any of the tested cases. Trio exome sequencing demonstrated that three affected fetuses from three unrelated families were compound heterozygous or homozygous for likely pathogenic variants in NDUFAF5. No other causative variants were detected. The association between NDUFAF5 variants and fetal malformations was further confirmed by segregation analysis. Histological evaluation of fetal tissues and electron microscopy of the skeletal muscle, liver, proximal tubules and heart demonstrated changes that resembled postmortem findings in patients with mitochondrial depletion disorders as well as previously undescribed findings. CONCLUSIONS: Mitochondrial complex-I deficiency and specifically biallelic mutations in NDUFAF5 have a role in abnormal fetal development, presenting with severe congenital malformations. Mitochondrial complex-I disorders should be considered in the differential diagnosis of corpus callosal malformations and brain cysts, especially when associated with extracranial abnormalities, such as fetal growth restriction and non-immune hydrops fetalis. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Afferent venous perfusion of fetal liver: umbilical and portal blood-flow volumes in fetuses born small-for-gestational age.

OBJECTIVE: To quantify the dynamic changes in the afferent venous flow volume of the liver in low-risk pregnancies with fetuses born small-for-gestational age. METHODS: This was a prospective study of low-risk singleton pregnancies with estimated fetal weight (EFW) and birth weight ≤ 10th centile attending for a routine second- or third-trimester ultrasound examination. Their umbilical and portal blood-flow volumes were compared with those of a control group of fetuses born appropriate-for-gestational age from which normal reference ranges were constructed. Absolute and Z-score differences between the groups were assessed. RESULTS: In total, 133 fetuses were included in the study group and 362 in the control group. The mean umbilical blood-flow volume in the study group, both absolute and normalized per kg of EFW, was below that of the appropriate-for-gestational-age fetuses for most of the period of pregnancy studied (overall mean Z-score, -0.82 and -0.84, respectively). In contrast, the mean portal blood-flow volume, per kg of EFW, showed the opposite trend (overall mean Z-score, +0.86), reaching its maximum level (+1.43) in the late third trimester. This resulted in a steep decrease in the mean placental-to-portal-blood-flow volume ratio, from 14.4 at 24 weeks of gestation (above the 60th centile) to 4.7 at 38 weeks of gestation (15th centile), corresponding to Z-scores of +0.4 and -1.02, respectively. CONCLUSION: In fetuses born small-for-gestational age, the ratio of blood-flow volume in the umbilical vein to that in the portal vein decreases consistently during pregnancy, and to a greater extent compared with those born appropriate-for-gestational age, reaching a lower nadir in the third trimester. This additional redistribution of liver perfusion affects negatively fetal growth even in low-risk pregnancy, and should be taken into account when planning delivery. We suggest considering liver venous perfusion as an ancillary tool for monitoring small-for-gestational-age pregnancies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Whole campus wastewater surveillance of SARS-CoV-2 for COVID-19 outbreak management.

In this long-term study (eight months), a wastewater-based epidemiology program was initiated as a decision support tool for the detection and containment of COVID-19 spread in the Technion campus. The on-campus students' accommodations (∼3,300 residents) were divided into housing clusters and monitored through wastewater SARS-CoV-2 surveillance in 10 manholes. Results were used to create a 'traffic-light' scheme allowing the Technion's COVID-19 task force to track COVID-19 spatiotemporal spread on the campus, and consequently, contain it before high morbidity levels develop. Of the 523 sewage samples analysed, 87.4% were negative for SARS-CoV-2 while 11.5% were positive, corroborating morbidity information the COVID-19 task force had. For 7.6% of the SARS-CoV-2 positive samples, the task force had no information about positive resident/s. In these events, new cases were identified after the relevant residents were clinically surge tested for COVID-19. Hence, in these instances, wastewater surveillance provided early warning helping to secure the health of the campus residents by minimising COVID-19 spread. The inflammation biomarker ferritin levels in SARS-CoV-2 positive sewage samples were significantly higher than in negative ones. This may indicate that in the future, ferritin (and other biomarkers) concentrations in wastewater could serve as indicators of infectious and inflammatory disease outbreaks.

Visual biofeedback using transperineal ultrasound in second stage of labor.

OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor. METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives. RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P = 0.01), as indicated by a significantly lower delta AoP before (mean, 22.2° (95% CI, 13.9-31.7°)) compared with after (mean, 35.2° (95% CI, 25.9-45.3°)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P = 0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P = 0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups. CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Can Ultrasound Performed in Prolonged Second Stage of Labor Predict the Difficulty and Success Rates of Operative Vaginal Delivery?

OBJECTIVE: To evaluate different sonographic methods for the prediction of the difficulty and the success of operative vaginal delivery (OPD). MATERIALS AND METHODS: A prospective study was performed on 45 term singleton uncomplicated pregnancies with prolonged 2nd stage of delivery with cephalic presentation. Measurements of the fetal head, relations between the fetal head and maternal pelvic parameters during rest and during maternal pushing were taken using translabial ultrasound. RESULTS: 29 cases of OPD were successful and 4 cases failed ending in cesarean section. The passage of the biparietal diameter (BPD) of the infrapubic line (IPL) was statistically correlated with the success of OPD. Head station, passage of the BPD of the IPL, percentage of head after the IPL, circumference of head after IPL were all correlated with the difficulty of OPD. When the distance between the widest diameter of the head and the IPL is < 1.2 cm, there is a 90 % probability of success of OPD. When that distance is > 3.3 cm, there is 90 % probability of cesarean section. When the percentage of head beyond the IPL was > 54 %, there was 90 % probability of successful OPD. DISCUSSION: Translabial ultrasound is useful in the prediction of the difficulty and the success of OPD. The higher the extent of head that passed the IPL, the less difficult the OPD and the greater the success rate of the OPD.

Prenatal Brain Imaging in Isolated vs. Complicated Club Foot: A Cohort Study.

Purpose: Talipes equinovarus (TEV) is a common birth defect. Differentiation between isolated and complex TEV is fundamental due to its effect on prognosis. Association between TEV and poor neurological outcome is more prominent in complex cases and highlights the significance of brain evaluation. The aim of the current study was to evaluate the contribution of fetal brain MRI to sonographic evaluation. Materials and Methods: In this retrospective study we evaluated charts of all pregnant patients referred for fetal brain MRI due to fetal TEV between 1/1/2011 and 12/31/14 in a single tertiary referral center. Isolated and complex TEV were differentiated according to associated anomalies. Brain US and MRI results were compared. Results: 28 pregnant patients were included with an average gestation and parity of 2.5 and 1.5, respectively. Both isolated and complicated TEV groups included 14 fetuses after initial TEV diagnosis on anatomical survey. Brain sonography and MRI were normal among 12/14 patients with isolated TEV while two patients were later diagnosed with mild ventriculomegaly. US brain evaluation has revealed pathologic findings in 4 (28.6 %) cases in the complicated TEV group, while MRI demonstrated abnormal findings in 8 (57.1 %) fetuses with notable severity diversity. In 6 cases, MRI diagnosed additional pathologies which were not demonstrated by US. Conclusion: Brain fetal MRI is an efficient tool during antenatal evaluation of complicated TEV with a high percentage of additional findings not demonstrated songraphically while its efficacy in isolated cases is in doubt. The current study expands the relevance of fetal brain MRI in cases of non-CNS anomalies.

A continuous active monitoring approach to identify cross-connections between potable water and effluent distribution systems.

A continuous active monitoring approach was developed for identification of cross-connections between potable water supply systems and treated wastewater effluent reuse distribution systems. The approach is based on monitoring the oxidation reduction potential (ORP) at the potable water system while injecting sulfite (a reducing agent) into the effluent line. A sharp decrease in the ORP of the potable water would indicate a cross-connection event. The approach was tested in batch experiments on treated municipal wastewater effluent of varying degree of treatment, and at dilution ratios of up to 1:100 (effluent/potable). The approach was then examined under continuous flow conditions, which simulated cross-connection events at various dilution ratios (up to 1:100). In the continuous runs, differences between the potable water ORP and the effluent-potable water mixture (containing sulfite as sodium bisulfite (SBS)) ORP were 450-630 mV. This suggests high potential for identifying a cross-connection event. Implementation of the approach includes adding sulfite to effluent used for agricultural irrigation; hence, possible effects on soil and on crops were studied in soil columns and pots planted with basil (Ocimum basilicum) as a model plant. No negative effects of sulfite addition to the irrigation effluent were observed in the irrigated soils and plants, and therefore, it could be safely implemented also in agricultural applications.

Head progression distance in prolonged second stage of labor: relationship with mode of delivery and fetal head station.

OBJECTIVE: To evaluate the clinical significance of fetal head progression distance (HPD), measured by transperineal ultrasound, during prolonged second stage of labor. METHODS: In this prospective study, a single operator, who was blinded to the results of the digital examination, assessed using transperineal ultrasound women at ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Patients had an empty urinary bladder and the examination was performed during maternal pushing. HPD was defined as the length of the line perpendicular to the infrapubic line that would connect it to the lowest part of the fetal bony skull. We analyzed associations between HPD and digital examination of fetal head station, fetomaternal characteristics, mode of delivery and perinatal outcome. RESULTS: Sixty-five patients in prolonged second stage of labor participated in the study. The overall mean HPD was 6.50 (± 1.35; 95% CI, 6.16-6.83) cm. No correlation was found between HPD and head position or mode of delivery, but HPD was positively correlated with fetal head station and neonatal head circumference measured after delivery. Logistic regression and receiver-operating characteristics curve analysis demonstrated no significant predictive value of HPD with respect to mode of delivery. CONCLUSION: Although HPD in prolonged second stage of labor could not predict mode of delivery, it may have a role as an ancillary tool for fetal head station assessment.

Pubic arch angle in prolonged second stage of labor: clinical significance.

OBJECTIVE: To evaluate the clinical significance of the pubic arch angle (PAA) measured by transperineal ultrasound during prolonged second stage of labor. METHODS: We evaluated prospectively 62 women ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Transperineal ultrasound (transverse plane) was used to measure the pubic arch angle. Correlations with fetomaternal characteristics, mode of delivery and perinatal outcome were evaluated. RESULTS: The mean PAA was 101.1° (± 13.1°; range, 80°-135°). We found a negative correlation with maternal age. Patients with an occipitotransverse fetal position had a significantly smaller angle compared with those with occipitoanterior positions (94.3° ± 5.5° vs. 103.2° ± 14.8°, P < 0.05), as did those with operative deliveries compared with those with spontaneous vaginal delivery (97.1° ± 11.5° vs. 110.1° ± 14.0°, P < 0.05). The prediction of operative delivery in prolonged second stage of labor by receiver-operating characteristics curve using PAA alone yielded an area under the curve of 0.75. The predicted probability for operative delivery increased as PAA decreased, with an odds ratio of 0.933 for each decrease in angle of 1°. CONCLUSION: Our study suggests a correlation between the PAA and mode of delivery in prolonged second stage of labor. This may be used as an adjunctive parameter when considering delivery mode.

Fetal tricuspid annular plane systolic excursion (f-TAPSE): evaluation of fetal right heart systolic function with conventional M-mode ultrasound and spatiotemporal image correlation (STIC) M-mode.

OBJECTIVES: Fetal tricuspid annular plane systolic excursion (f-TAPSE) is a modified method to measure the vertical movement of the tricuspid valve annulus by M-mode ultrasound, in order to assess the fetal right heart. Evaluation of right heart function is well-recognized in pediatric and adult cardiology, but has not been studied widely in the fetus. We aimed to study f-TAPSE in the second half of gestation in normal fetuses, to establish reference ranges for this measure, to evaluate the usefulness of spatiotemporal image correlation (STIC) M-mode in obtaining it, and to compare conventional M-mode and STIC M-mode-based measures of f-TAPSE. METHODS: We recruited gravidae presenting to our centers from 20 to 38 weeks for targeted organ scans, fetal echocardiography or third-trimester fetal surveillance, with structurally normal singleton fetuses and verified gestational age (GA). Because of the small number of subjects at the lower limit, fetuses at 20 and those at 21 weeks were combined into a single group ('21 weeks'). During the booked scan, in addition to standard biometry, M-mode was applied to the tricuspid annulus, parallel to the ventricular septum, and the amplitude of the resulting wave was measured. To allow comparison with STIC M-mode, a STIC volume was acquired and saved. In post-processing, the volume was rotated to show an apical four-chamber view, and f-TAPSE was investigated in a similar fashion to that used for conventional M-mode. Two to three measures of TAPSE were taken and the results averaged. In thirty women, measurements were performed by two observers and inter- and intraobserver variation were calculated. RESULTS: We examined 341 fetuses at GA 20-39 weeks. Conventional M-mode f-TAPSE values ranged from a mean of 3.6 (± 1.1) mm at 21 weeks to a mean of 8.6 (± 1.5) mm at 39 weeks. In 45 cases we were unable to perform conventional M-mode ultrasound because of fetal lie; in eight cases STIC volumes were found in post-processing to be unsuitable for analysis. STIC f-TAPSE values ranged from a mean of 4.2 (± 1.4) mm at 21 weeks to a mean of 8.3 (± 1.5) mm at 39 weeks. Scatterplots of f-TAPSE measures obtained with conventional M-mode and with STIC M-mode were created vs GA and estimated fetal weight (EFW). For both modalities, f-TAPSE increased linearly with GA and with EFW. Good correlation was found between the two methods (Pearson's R(2) = 0.904). No significant difference was found in mean or variance of the distributions or slopes of the regression equations. Inter- and intraobserver variation (intraclass correlation coefficient) in conventional M-mode and STIC M-mode f-TAPSE measures were 0.94 and 0.97, respectively. CONCLUSION: F-TAPSE in normal fetuses increases over the course of gestation and correlates to EFW. F-TAPSE measurement is easy to perform and available on all ultrasound machines; STIC f-TAPSE is possible on machines with STIC capability and produces similar measures with a greater success rate. We suggest the addition of f-TAPSE measurement to fetal right cardiac function evaluation.

Umbilical vein anomaly in fetuses with Down syndrome.

OBJECTIVE: To describe the prevalence of abnormal umbilical vein (UV) anatomy in fetuses with Down syndrome. METHODS: This was a retrospective survey covering a 24-month period of fetuses with a genetic diagnosis of Down syndrome following a routine early second-trimester (12-16-week) detailed fetal anomaly scan at a single academic tertiary referral center. In our unit this exam includes fetal umbilicoportal venous system evaluation. RESULTS: During the study period, 37 fetuses were diagnosed with Down syndrome and had a detailed early anatomy scan. In four (11%) the detailed early anomaly scan revealed that the UV was connected to the hepatic portion of the inferior vena cava (IVC) at a position lower than its usual site. Their average gestational age at diagnosis was 13 + 6 (range, 11 + 6 to 15 + 2) weeks. Three of the four fetuses had a nuchal translucency thickness of 3-4 mm. In one fetus there was an additional finding of significant tricuspid regurgitation and the one with normal nuchal translucency thickness had an atrioventricular septal defect (atrioventricular canal) and umbilical cord hernia. During the same period three of 2500 (0.12%) fetuses with normal karyotype demonstrated similar anomalous insertion of the UV into the IVC, creating a portocaval shunt which had normal ductus venosus-like Doppler flow in all three cases. The odds ratio for abnormal umbilicoportal venous system in fetuses with Down syndrome compared with the normal population was 107.4 (95% CI, 19.2-637.1). CONCLUSIONS: Fetuses with Down syndrome demonstrate an increased prevalence of abnormal connection of the UV to the IVC.

Spontaneous regression of congenital cutaneous hemangiomas in a calf.

Congenital vascular tumors of the skin have been described in people and a few animals, but unlike infantile hemangiomas in children, spontaneous regression has not been described in animals. A 2-day-old male Belgian Blue cross calf was presented for multiple congenital cutaneous masses that were soft, alopecic, and hyperemic; the calf had no other apparent abnormalities. Two weeks later, one mass had regressed. Surgical excision of one of the remaining masses was performed; histopathologic and immunohistochemical findings were considered diagnostic for epithelioid hemangioma. Eight months following initial presentation, all the masses had regressed spontaneously. This constitutes the first account in the veterinary literature of spontaneous regression in a congenital vascular tumor.

Three and four dimensional ultrasound: a novel method for evaluating fetal cardiac anomalies.

OBJECTIVE: To evaluate the role of various new models of 3- and 4-dimensional (3D and 4D) ultrasound (US) applications in prenatal assessment of fetal cardiac anomalies. METHODS: Volume data sets of 81 fetuses with fetal cardiac anomalies, as previously diagnosed by 2D US, were acquired by 3D and cine 4D using spatiotemporal image correlation (STIC) software. Various additional rendering tools were applied. Color, power, high definition Doppler and B-flow were added to the volumes acquired. A retrospective offline analysis of the cardiac defects was performed. RESULTS: The mean gestational age at diagnosis was 24 weeks (range 13-38); 128 anomalies were detected and were classified into the following categories: I, Situs anomalies in 8 cases; II, abnormal four-chamber view in 63 cases; III, outflows tract anomalies in 27 cases; IV, arches anomalies in 21 cases; and V, veins anomalies in 9 cases. Rendering tools differed in each groups of anomalies. CONCLUSIONS: Fetal cardiac anomalies can be evaluated adequately by the information gained by 3D and 4D volumes obtained by STIC. Since no single module is sufficiently accurate for the diagnosis of all cardiac anomalies, each of the cardiac anomaly categories requires different and appropriate module of visualization.

Carcinoid tumor of the appendix: ultrasound findings in early pregnancy.

Ultrasound examination of a woman in early pregnancy with right lower quadrant abdominal pain demonstrated an edematous appendix with amorphous fluid surrounding the appendix. At laparotomy, these findings were confirmed. On pathological evaluation following surgical removal of the appendix a rare case of carcinoid tumor of the appendix was diagnosed. This is the first description of the transvaginal ultrasound features of a carcinoid tumor of the appendix.

Prenatal ultrasonographic diagnosis of persistent hyperplastic primary vitreous.

Persistent hyperplastic primary vitreous (PHPV) is a rare developmental malformation of the eye characterized by the presence of a vascular membrane located behind the lens. We report, for the first time in the literature, the identification on ultrasound examination of bilateral cataract and thickened hyaloid artery-lens junction, leading to a diagnosis of bilateral PHPV, in a fetus at 23 weeks' gestation. Histological examination at postmortem confirmed the prenatal diagnosis of bilateral PHPV and cataract. A thorough ultrasound examination of the fetal eye in cases with cataract is recommended.

Secondary cytomegalovirus infection can cause severe fetal sequelae despite maternal preconceptional immunity.

OBJECTIVES: To describe our experience in cases with sonographic signs of fetal infection and with maternal serological 'immunity' to cytomegalovirus (CMV) infection. METHODS: This was a bicenter study of six pregnant women referred for evaluation of suspected fetal infection. All cases had confirmed maternal serology for past exposure to CMV but no evidence of recent secondary CMV infection. All underwent sonographic evaluation as well as complete investigation for CMV infection. RESULTS: The mean age of the women was 29 (range, 23-35) years and the mean gestational age at diagnosis was 23.5 weeks (range, 20-31) weeks. Sonographic findings included microcephaly, ventriculomegaly, periventricular calcifications and cystic lesions, echogenic bowel, hydrops and hepatosplenomegaly. Amniocentesis was performed in all cases for fetal karyotyping and viral assessment, and all were found by polymerase chain reaction to be positive for CMV infection. Four pregnancies were terminated following the parents' request. One pregnancy continued until intrauterine fetal death occurred 2 weeks after diagnosis. Postmortem was denied in all cases but one. One infant was delivered with evidence of severe cerebral palsy. CONCLUSION: In the presence of sonographic findings suggestive of fetal CMV infection, prompt investigation of amniotic fluid should follow even if maternal serology does not support recent maternal seroconversion.