A patient with mosaic USP9X gene variant.

The finding of USP9X variants in females has been associated with female-restricted X-linked mental retardation (MRXS99F), a rare syndrome featured by developmental delay and distinct congenital anomalies. Here, we report a female fetus with MRXS99F due to a novel frameshift variant, c.6679_6685delAAATTATinsTCCTG (p.Lys2227SerfsTer2) in USP9X, which was present in a mosaic state in the amniocytes and in the peripheral blood after birth (14% and 30%, respectively). The X methylation status analysis displayed a partially skewed X-inactivation with 80% of inactive paternal X. The first signs of the MRXS99F were prenatally detected at 20 weeks, with an enlarged posterior cranial fossa, an upward rotation of the cerebellar vermis and partial corpus callosum agenesis, together with a cardiac septal defect and a single umbilical artery. After birth and during postnatal follow-up the anal anteriorization and the presence of a bilateral membranous choanal atresia were noted, whereas the MRI revealed the hypo/aplasia of the olfactory bulbs, a widening of the subarachnoid spaces and a delay in the myelinisation. During the 18-months follow-up a severe growth and global developmental delay, together with a bilateral moderate deafness with a threshold at 40 dB, dental enamel erosions and an initial scoliosis were observed. We report the prenatal and postnatal features of a classical MRXS99F phenotype and a mosaic USP9X frameshift variant with a partially skewed X inactivation and discuss genotype/phenotype correlations in view of the published studies so far.

Three-Dimensional Sonographic Evaluation of the Position of the Fetal Conus Medullaris at First Trimester.

OBJECTIVE: The objective of this study was to assess the position of the conus medullaris (CM) at the first trimester 3D ultrasound in a cohort of structurally normal fetuses. METHODS: This was a multicenter prospective study involving a consecutive series of structurally normal fetuses between 11 and 13 weeks of gestation (CRL between 45 and 84 mm). All fetuses were submitted to 3D transvaginal ultrasound using a sagittal view of the spine as the starting plane of acquisition. At offline analysis, the position of the CM was evaluated by 2 independent operators with a quantitative and a qualitative method: (1) the distance between the most caudal part of the CM and the distal end of the coccyx (CMCd) was measured; (2) a line perpendicular to the fetal spine joining the tip of the CM to the anterior abdominal wall was traced to determine the level of this line in relation to the umbilical cord insertion (conus to abdomen line, CAL). Interobserver agreement for the CCMd was evaluated. Linear regression analysis was used to determine the association between the CMCd and CRL, and a normal range was computed based on the best-fit model. The absence of congenital anomalies was confirmed in all cases after birth. RESULTS: In the study period between December 2019 and March 2020, 143 fetuses were recruited. In 130 fetuses (90.9%), the visualization of the CM was feasible. The mean value of the CMCd was 1.09 ± 0.16 cm. The 95% limits of agreement for the interobserver variability in measurement of the CMCd were 0.24 and 0.26 cm. The interobserver variability based on the intra-class correlation coefficient (ICC) for the CCMd was good (ICC = 0.81). We found a positive linear relationship between the CCMd and CRL. In all these fetuses, the CAL encountered the abdominal wall at or above the level of the cord insertion. CONCLUSION: In normal fetuses, the assessment of the CM position is feasible at the first trimester 3D ultrasound with a good interobserver agreement. The CM level was never found below the fetal umbilical cord insertion, while the CMCd was noted to increase according to the gestational age, confirming the "ascension" of the CM during fetal life.

Intrapartum sonographic assessment of the fetal head flexion in protracted active phase of labor and association with labor outcome: a multicenter, prospective study.

BACKGROUND: To date, no research has focused on the sonographic quantification of the degree of flexion of the fetal head in relation to the labor outcome in women with protracted active phase of labor. OBJECTIVE: This study aimed to assess the relationship between the transabdominal sonographic indices of fetal head flexion and the mode of delivery in women with protracted active phase of labor. STUDY DESIGN: Prospective evaluation of women with protracted active phase of labor recruited across 3 tertiary maternity units. Eligible cases were submitted to transabdominal ultrasound for the evaluation of the fetal head position and flexion, which was measured by means of the occiput-spine angle in fetuses in nonocciput posterior position and by means of the chin-to-chest angle in fetuses in occiput posterior position. The occiput-spine angle and the chin-to-chest angle were compared between women who had vaginal delivery and those who had cesarean delivery. Cases where obstetrical intervention was performed solely based on suspected fetal distress were excluded. RESULTS: A total of 129 women were included, of whom 43 (33.3%) had occiput posterior position. Spontaneous vaginal delivery, instrumental delivery, and cesarean delivery were recorded in 66 (51.2%), 17 (13.1%), and 46 (35.7%) cases, respectively. A wider occiput-spine angle was measured in women who had vaginal delivery compared with those submitted to cesarean delivery owing to labor dystocia (126±14 vs 115±24; P<.01). At the receiver operating characteristic curve, the area under the curve was 0.675 (95% confidence interval, 0.538-0.812; P<.01), and the optimal occiput-spine angle cutoff value discriminating between cases of vaginal delivery and those delivered by cesarean delivery was 109°. A narrower chin-to-chest angle was measured in cases who had vaginal delivery compared with those undergoing cesarean delivery (27±33 vs 56±28 degrees; P<.01). The area under the curve of the chin-to-chest angle in relation to the mode of delivery was 0.758 (95% confidence interval, 0.612-0.904; P<.01), and the optimal cutoff value discriminating between vaginal delivery and cesarean delivery was 33.0°. CONCLUSION: In women with protracted active phase of labor, the sonographic demonstration of fetal head deflexion in occiput posterior and in nonocciput posterior fetuses is associated with an increased incidence of cesarean delivery owing to labor dystocia. Such findings suggest that intrapartum ultrasound may contribute in the categorization of the etiology of labor dystocia.

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes. CONCLUSION: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Prediction of spontaneous vaginal delivery in nulliparous women with a prolonged second stage of labor: the value of intrapartum ultrasound.

BACKGROUND: A limited number of studies have addressed the role of intrapartum ultrasound in the prediction of the mode of delivery in women with prolonged second stage of labor. OBJECTIVE: The objective of the study was to evaluate the role of transabdominal and transperineal sonographic findings in the prediction of spontaneous vaginal delivery among nulliparous women with prolonged second stage of labor. STUDY DESIGN: This was a 2-center prospective study conducted at 2 tertiary maternity units. Nulliparous women with a prolonged active second stage of labor, as defined by active pushing lasting more than 120 minutes, were eligible for inclusion. Transabdominal ultrasound to evaluate the fetal head position and transperineal ultrasound for the measurement of the midline angle, the head-perineum distance, and the head-symphysis distance were performed in between uterine contractions and maternal pushes. At transperineal ultrasound the angle of progression was measured at rest and at the peak of maternal pushing effort. The delta angle of progression was defined as the difference between the angle of progression measured during active pushing at the peak of maternal effort and the angle of progression at rest. The sonographic findings of women who had spontaneous vaginal delivery vs those who required obstetric intervention, either vacuum extraction or cesarean delivery, were evaluated and compared. RESULTS: Overall, 109 were women included. Spontaneous vaginal delivery and obstetric intervention were recorded in 40 (36.7%) and 69 (63.3%) patients, respectively. Spontaneous vaginal delivery was associated with a higher rate of occiput anterior position (90% vs 53.2%, P < .0001), lower head-perineum distance and head-symphysis distance (33.2 ± 7.8 mm vs 40.1 ± 9.5 mm, P = .001, and 13.1 ± 4.6 mm vs 19.5 ± 8.4 mm, P < .001, respectively), narrower midline angle (29.6° ± 15.3° vs 54.2° ± 23.6°, P < .001) and wider angle of progression at the acme of the pushing effort (153.3° ± 19.8° vs 141.8° ± 25.7°, P = .02) and delta-angle of progression (17.3° ± 12.9° vs 12.5° ± 11.0°, P = .04). At logistic regression analysis, only the midline angle and the head-symphysis distance proved to be independent predictors of spontaneous vaginal delivery. More specifically, the area under the curve for the prediction of spontaneous vaginal delivery was 0.80, 95% confidence interval (0.69-0.92), P < .001, and 0.74, 95% confidence interval (0.65-0.83), P = .002, for the midline angle and for the head-symphysis distance, respectively. CONCLUSION: Transabdominal and transperineal intrapartum ultrasound parameters can predict the likelihood of spontaneous vaginal delivery in nulliparous women with prolonged second stage of labor.

Impact of fetal brain ultrasound tutor smartphone application on normal anatomy learning.

OBJECTIVE: The "Fetal Brain Tutor 4us" (FBTApp) is a recently developed application for interactive multiplanar navigation through the normal fetal brain. The purpose of this work was to assess its impact on normal anatomy learning. METHODS: A multiple-choice quiz (MCQ) was administered to first-year resident doctors in Obstetrics and Gynecology in two separate sessions, before and 2 weeks after downloading the FBTApp. For each MCQ, the junior trainee was asked to use one out of five items to label a specific cerebral structure on an ultrasound image of a normal midtrimester fetal brain. Six sonographic images of the fetal brain on each of the three scanning planes (axial, sagittal, and coronal) were shown to the participants at either session. The results of the two sessions were analysed and compared. RESULTS: Overall, 216 questions were administered to the trainees in the 2-week study, 108 before and 108 after the use of the FBTApp. From the first to the second sessions, a significant increase of correct answers was noted (from 47/108 or 43% to 77/108 or 71%, P < 0.01). Particularly, a better improvement was obtained in the correct labelling of cerebral structures on the nonaxial (from 32% to 67%, +35%) vs axial (from 67% to 81%, +14%) view planes of the brain (P < 0.01). CONCLUSION: The use of FBTApp seems capable to improve the knowledge of the normal fetal brain anatomy in subjects naive to dedicated prenatal ultrasound. This improvement seems greater on nonaxial planes.