COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction.

COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ10 levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ10 (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

Soft-tissue dystocia due to paradoxical contraction of the levator ani as a cause of prolonged second stage: concept, diagnosis, and potential treatment.

Smaller pelvic floor dimensions seem to have been an evolutionary need to provide adequate support for the pelvic organs and the fetal head. Pelvic floor dimension and shape contributed to the complexity of human birth. Maternal pushing associated with pelvic floor muscle relaxation is key to vaginal birth. Using transperineal ultrasound, pelvic floor dimensions can be objectively measured in both static and dynamic conditions, such as pelvic floor muscle contraction and pushing. Several studies have evaluated the role of the pelvic floor in labor outcomes. Smaller levator hiatal dimensions seem to be associated with a longer duration of the second stage of labor and a higher risk of cesarean and operative deliveries. Furthermore, smaller levator hiatal dimensions are associated with a higher fetal head station at term of pregnancy, as assessed by transperineal ultrasound. With maternal pushing, most women can relax their pelvic floor, thus increasing their pelvic floor dimensions. Some women contract rather than relax their pelvic floor muscles under pushing, which is associated with a reduction in the anteroposterior diameter of the levator hiatus. This phenomenon is called levator ani muscle coactivation. Coactivation in nulliparous women at term of pregnancy before the onset of labor is associated with a higher fetal head station at term of pregnancy and a longer duration of the second stage of labor. In addition, levator ani muscle coactivation in nulliparous women undergoing induction of labor is associated with a longer duration of the active second stage of labor. Whether we can improve maternal pelvic floor relaxation with consequent improvement in labor outcomes remains a matter of debate. Maternal education, physiotherapy, and visual feedback are promising interventions. In particular, ultrasound visual feedback before the onset of labor can help women increase their levator hiatal dimensions and correct levator ani muscle coactivation in some cases. Ultrasound visual feedback in the second stage of labor was found to help women push more efficiently, thus obtaining a lower fetal head station at ultrasound and a shorter duration of the second stage of labor. The available evidence on the role of any intervention aimed to aid women to better relax their pelvic floor remains limited, and more studies are needed before considering its routine clinical application.

When time is brain: a systematic review about Wernicke encephalopathy as a dramatic consequence of thiamin deficiency in hyperemesis gravidarum.

Nausea and vomiting affect up to 80% of all pregnancies, sometimes so severely that the condition of hyperemesis gravidarum (HG) is established. HG may in addition be a predisposing factor for Wernicke encephalopathy (WE), a severe and life-threatening condition due to vitamin B1 (thiamin) deficiency. If untreated, WE may progress to Korsakoff's syndrome, an irreversible cognitive disorder. We reported a case that recently occurred at our clinic and performed a systematic review of the literature to investigate the clinical presentation, maternal and perinatal outcomes and treatment of WE in women with HG. METHODS: We performed a systematic review of case series and case reports searching the Medline database on Pubmed from inception until December 2021. We used as search terms (Wernicke encephalopathy) OR (Wernicke-Korsakoff syndrome) AND (hyperemesis gravidarum) AND (pregnancy) AND (thiamin deficiency). Articles were considered eligible for inclusion in our review if they described at least one case of WE due to thiamin deficiency in relation to HG. An overall of 82 cases of WE due to HG in pregnancy from 66 manuscripts, including our own, were selected. RESULTS: The maternal mean age was 26.38 ± 5.23 years, while mean gestational week at hospitalization was 14.57 ± 4.12 after a mean of 6.6 ± 3.14 weeks of vomiting duration. WE manifestation occurred at a mean gestational age of 16.54 ± 3.06 weeks. Regarding clinical presentation, ocular signs and symptoms were reported by 77/82 (93.9%) women, 61/82 (74.4%) presented with ataxia and 63/82 (76.8%) with confusion. Dysarthria affected 15/82 women (18,3%), while muscular weakness was present in 36/82 (43.9%) and impaired reflexes in 42/82 (51.2%). Memory impairment involved 25/82 (30.5%) of the study population. Almost all cases reported a thiamin administration treatment, however data regarding the clinical course of the neurological condition and the perinatal outcomes were often missing and showed a great heterogeneity when reported. CONCLUSION: WE is a challenging diagnosis, as its clinical presentation is nonspecific. A high clinical suspicion and the awareness of its possible predisposing conditions such as HG may help clinicians to get a prompt diagnosis and starting treatment, which are vital to prevent possible life-impairing neurological sequelae.

Increased nuchal translucency can be ascertained using transverse planes.

BACKGROUND: The detection of increased nuchal translucency is crucial for the assessment risk of aneuploidies and other fetal anomalies. OBJECTIVE: This study aimed to investigate the ability of a transverse view of the fetal head to detect increased fetal nuchal translucency at 11 to 13 weeks of gestation. STUDY DESIGN: This was a prospective study enrolling a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for combined screening and were examined by operators certified by the Fetal Medicine Foundation. In each patient, nuchal translucency measurements were obtained both from a median sagittal view and from a transverse view. A second sonologist blinded to the results of the first examination obtained another measurement to assess intermethod and interobsever reproducibility. RESULTS: A total of 1023 women were enrolled. An excellent correlation was found between sagittal and transverse nuchal translucency measurements, with a mean difference of 0.01 mm (95% confidence interval, -0.01 to 0.02). No systematic difference was found between the 2 techniques. The inter-rater reliability (intraclass correlation coefficient, 0.957; 95% confidence interval, 0.892-0.983) and intrarater reliability (intraclass correlation coefficient, 0.976; 95% confidence interval, 0.941-0.990) of axial measurements were almost perfect. Transverse measurements of 3.0 mm identified all cases with sagittal measurements of ≥3.0 with a specificity of 99.7%; transverse measurements of >3.2 mm identified all cases with sagittal measurements of 3.5 mm with a specificity of 99.7%. The time required to obtain transverse nuchal translucency measurements was considerably shorter than for sagittal measurements, particularly when the fetus had an unfavorable position. CONCLUSION: When the sonogram is performed by an expert sonologist, the difference in nuchal translucency measurement obtained with a transverse or sagittal plane is minimal. Increased nuchal translucency can be reliably identified by using transverse views, and in some cases, this may technically be advantageous.

Sonography of fetal holoprosencephaly: a guide to recognize the lesser varieties.

BACKGROUND: Alobar holoprosencephaly (HPE) is easily detected during a first-trimester screening examination, conversely, recognizing the lesser varieties may be difficult even in the second trimester. OBJECTIVES: To describe the imaging findings of a cohort of fetuses with holoprosencephaly (HPE) and to elucidate the appearances of the different anatomical varieties. MATERIALS AND METHODS: We reviewed medical records and stored images of pregnant women referred to our clinic because of a diagnosis or the suspicion of various forms of HPE. We reported the imaging characteristics, the presence of other associated anomalies, magnetic resonance findings, karyotype and autoptic examinations when available. RESULTS: Alobar forms show great distortion of normal brain anatomy, with a single ventricle detectable during the first trimester of pregnancy. Extracerebral, face and karyotype abnormalities are often associated. In semilobar and lobar forms the septum pellucidum is typically absent in axial planes, with fused frontal horns, while posterior fossa is often normal. At multiplanar neurosonogram, anomalies involving corpus callosum and cortex development can be detected. Face abnormalities are mild in lobar forms: receding forehead, various degrees of hypotelorism and the presence of a single central maxillary incisor are reported. CONCLUSIONS: The alobar forms are detectable since the first trimester, with a peculiar single ventricle and extremely frequent extracerebral and karyotype abnormalities. The semilobar and lobar forms are more challenging and the diagnosis is easily missed in a mid-trimester screening exam unless a careful evaluation of both cavum septi pellucidi and frontal horns as well is conducted.

The correlation between levator ani co-activation and fetal head regression on maternal pushing at term.

OBJECTIVE: To assess the correlation between fetal head regression and levator ani muscle (LAM) co-activation under Valsalva maneuver. STUDY DESIGN: This study was a secondary analysis of a prospective cohort study on the association between the angle of progression (AoP) and labor outcome. We scanned a group of nulliparous women at term before the onset of labor at rest and under maximum Valsalva maneuver. In addition to the previously calculated AoP, in the present study, we measured the anteroposterior diameter of LAM hiatus (APD) on each ultrasound image. LAM co-activation was defined as APD at Valsalva less than that at rest, whereas fetal head regression was defined as AoP at Valsalva less than that at rest. We calculated the correlation between the two phenomena. Finally, we examined various labor outcomes according to the presence, absence, or co-existence of these two phenomena. RESULTS: We included 469 women. A total of 129 (27.5%) women presented LAM co-activation while 50 (10.7%) showed head regression. Only 15 (3.2%) women showed simultaneous head regression and LAM co-activation. Women with coexisting LAM co-activation and head regression had the narrowest AoP at Valsalva in comparison with other study groups (p < .001). In addition, they had the highest risk of Cesarean delivery (40%) and longest first, second, and active second stage durations, although none of these reached statistical significance. CONCLUSION: In nulliparous women at term before the onset of labor fetal head regression and LAM co-activation at Valsalva are two distinct phenomena that uncommonly coexist.

The maternal pelvic floor and labor outcome.

Vaginal birth is the major cause of pelvic floor damage. The development of transperineal ultrasound has improved our understanding of the relationship between vaginal birth and pelvic floor dysfunction. The female pelvic floor dimensions and function can be assessed reliably in pregnant women. Maternal pushing associated with pelvic floor muscle relaxation is the central requirement of vaginal birth. Many studies have evaluated the role of the pelvic floor on labor outcomes. Smaller levator hiatal dimensions and incomplete or absent levator ani muscle relaxation seem to be associated with a longer duration of the second stage of labor and a higher risk of cesarean and operative deliveries. Here, we presented an overview of the current knowledge of the correlation between female pelvic floor dimension and function, as assessed by transperineal ultrasound, and labor outcome.

The correlation between transperineal ultrasound assessment of the levator ani muscle and postpartum urinary incontinence.

AIMS: The primary aim of the present study was to assess the association between levator ani muscle (LAM) integrity and function on the one hand, and the risk of urinary incontinence (UI) on the other. A secondary objective was to assess the association between fundal pressure in the second stage of labor (Kristeller maneuver) and the risk of postpartum UI. METHODS: In this prospective cohort study, women underwent a clinical and transperineal ultrasound examination at rest, at pelvic floor muscle contraction (PFMC), and at Valsalva maneuver 3-6 months after their first vaginal delivery. LAM avulsion and levator hiatal area (LHA) were evaluated. In addition, women were interviewed about the presence of UI, whether stress (SUI) or urgency (UUI). RESULTS: Overall, data of 244 women were analyzed. SUI was reported in 50 (20.5%), while UUI was reported in 19 (7.8%) women. Women who reported SUI had a higher prevalence of LAM avulsion and less proportional reduction in LHA from rest to a maximum contraction in comparison to women with no SUI. Women who reported UUI had a greater LHA at rest, during contraction, and during maximal Valsalva in comparison to women without UUI. No significant association was found between the Kristeller maneuver and the incidence of any UI. CONCLUSION: Levator ani avulsion and less proportional reduction of LHA with PFMC appear to be associated with a higher risk of postpartum urinary stress incontinence.

Predicting cesarean delivery for failure to progress as an outcome of labor induction in term singleton pregnancy.

BACKGROUND: Induction of labor is one of the most common interventions in modern obstetrics, and its frequency is expected to continue to increase. There is inconsistency as to how failed induction of labor is defined; however, the majority of studies define success as the achievement of vaginal delivery. Induction of labor in nulliparous women poses an additional challenge with a 15% to 20% incidence of failure, ending in emergency operative deliveries. The Bishop score has been traditionally used before decisions for induction of labor. Nonetheless, it is subjective and prone to marked interobserver variation. Several studies have been conducted to find alternative predictors, yet a reliable, objective method still remains to be introduced and validated. Hence, there is still a need for the development of new predictive tools to facilitate informed decision making, optimization of resources, and minimization of potential risks of failure. Furthermore, a peripartum transperineal ultrasound scan has been proven to provide objective, noninvasive assessment of labor. OBJECTIVE: This study aimed to assess the feasibility of developing and validating an objective and reproducible model for the prediction of cesarean delivery for failure to progress as an outcome of labor induction in term singleton pregnancies. STUDY DESIGN: This was a prospective observational cohort study conducted in Cairo University Hospitals and University of Bologna Hospitals between November 2018 and November 2019. We recruited 382 primigravidae with singleton term pregnancies in cephalic presentation. All patients had baseline Bishop scoring together with various transabdominal and transperineal ultrasound assessments of the fetus, maternal cervix, and pelvic floor. The managing obstetricians were blinded to the ultrasound scan findings. The method and indication of induction of labor, the total duration of stages of labor, mode of birth, and neonatal outcomes were all recorded. Women who had operative delivery for fetal distress or indications other than failure to progress in labor were excluded from the final analysis, leaving a total of 344 participants who were randomly divided into 243 and 101 pregnancies that constituted the model development and cross-validation groups, respectively. RESULTS: It was possible to perform transabdominal and transperineal scans and assess all the required parameters on all study participants. Univariate and multivariate analyses were used for selection of potential predictors and model fitting. The independent predictive variables for cesarean delivery included maternal age (odds ratio, 1.12; P=.003), cervical length (odds ratio, 1.08; P=.04), angle of progression at rest (odds ratio, 0.9; P=.001), and occiput posterior position (odds ratio, 5.7; P=.006). We tested the performance of the prediction model on our cross-validation group. The calculated areas under the curve for the ability of the model to predict cesarean delivery were 0.7969 (95% confidence interval, 0.71-0.87) and 0.88 (95% confidence interval, 0.79-0.97) for the developed and validated models, respectively. CONCLUSION: Maternal age and sonographic fetal occiput position, angle of progression at rest, and cervical length before labor induction are very good predictors of induction outcome in nulliparous women at term.

The role of the angle of progression in the prediction of the outcome of occiput posterior position in the second stage of labor.

BACKGROUND: Occiput posterior position is the most frequent cephalic malposition, and its persistence at delivery is associated with a higher risk of maternal and perinatal morbidity. Diagnosis and management of occiput posterior position remain a clinical challenge. This is partly caused by our inability to predict fetuses who will spontaneously rotate into occiput anterior from those who will have persistent occiput posterior position. The angle of progression, measured with transperineal ultrasound, represents a reliable tool for the evaluation of fetal head station during labor. The relationship between the persistence of occiput posterior position and fetal head station in the second stage of labor has not been previously assessed. OBJECTIVE: This study aimed to evaluate the role of fetal head station, as measured by the angle of progression, in the prediction of persistent occiput posterior position and the mode of delivery in the second stage of labor. STUDY DESIGN: We recruited a nonconsecutive series of women with posterior occiput position diagnosed by transabdominal ultrasound in the second stage of labor. For each woman, a transperineal ultrasound was performed to measure the angle of progression at rest. We compared the angle of progression between women who delivered fetuses in occiput anterior position and those with persistent occiput posterior position at delivery. Receiver operating characteristics curves were performed to evaluate the accuracy of the angle of progression in the prediction of persistent occiput posterior position. Finally, we performed a multivariate logistic regression to determine independent predictors of persistent occiput posterior position. RESULTS: Overall, 63 women were included in the analysis. Among these, 39 women (62%) delivered in occiput anterior position, whereas 24 (38%) delivered in occiput posterior position (persistent occiput posterior position). The angle of progression was significantly narrower in the persistent occiput posterior position group than in women who delivered fetuses in occiput anterior position (118.3°±12.2° vs 127.5°±10.5°; P=.003). The area under the receiver operating characteristics curve was 0.731 (95% confidence interval, 0.594-0.869) with an estimated best cutoff range of 121.5° (sensitivity of 72% and specificity of 67%). On logistic regression analysis, the angle of progression was found to be independently associated with persistence of occiput posterior position (odds ratio, 0.942; 95% confidence interval, 0.889-0.998; P=.04). Finally, women who underwent cesarean delivery had significantly narrower angle of progression than women who had a vaginal delivery (113.5°±8.1 vs 128.0°±10.7; P<.001). The area under the receiver operating characteristics curve for the prediction of cesarean delivery was 0.866 (95% confidence interval, 0.761-0.972). At multivariable logistic regression analysis including the angle of progression, parity, and gestational age at delivery, the angle of progression was found to be the only independent predictor associated with cesarean delivery (odds ratio, 0.849; 95% confidence interval, 0.775-0.0930; P<.001). CONCLUSION: In fetuses with occiput posterior at the beginning of the second stage of labor, narrower values of the angle of progression are associated with higher rates of persistent occiput posterior position at delivery and a higher risk of cesarean delivery.

Reliability of transperineal ultrasound for the assessment of the angle of progression in labor using parasagittal approach versus midsagittal approach.

OBJECTIVE: To assess the inter-method agreement between midsagittal (msAoP) and parasagittal (psAoP) measurements of the angle of progression (AoP) during labor. In addition, we aimed to evaluate the correlation between AoP measurements by both midsagittal and parasagittal approaches with the mode of delivery. METHODS: We recruited a nonconsecutive series of women in active labor with a singleton uncomplicated term pregnancy with fetuses in vertex presentation. Women underwent transperineal ultrasound in the absence of uterine contractions or maternal pushing to measure both msAoP and psAoP. The inter-method agreement between the two acquisitions was then assessed. Lastly, both measurements were compared between women who had a vaginal delivery versus those who underwent cesarean section (CS). RESULTS: Overall, 151 women were included in the study. We found an excellent agreement between msAoP and psAoP (ICC 0.935; 95% CI 0.912-0.953, p < .001). On the other hand, psAoP overestimated the measurements in comparison with msAoP (101.2 ± 15.6 versus 98.2 ± 16.0, p < .001). There was a significant correlation between both methods of AoP assessment and duration of the active second stage of labor and AoP measured by either method was significantly wider in patients who delivered vaginally compared to those who had a CS. CONCLUSIONS: Our data showed a significant difference in the measured angle between the psAoP and the originally described msAoP. The automated measurements of AoP that have been introduced are designed using the parasagittal visualization of the more echogenic pubic arch, rather than the hypoechogenic pubic symphysis. We think that in the light of our data, care should be taken before applying data from midsagittal measurement in centers using the parasagittal automated approach.

The use of lung ultrasound during the COVID-19 pandemic: A narrative review with specific focus on its role in pregnancy.

The novel coronavirus disease (COVID-19) is a challenge to every health system. Unfortunately, it is unlikely that this pandemic will disappear soon. No health system, with its present resources and workflow, is capable enough to deal with a full-blown wave of this pandemic. Acquisition of specific new skills may be fundamental in delivering appropriate health care for our patients. The gold standard for diagnosis of the COVID-19 infection is real-time reverse transcription polymerase chain reaction. Radiological investigations (chest X-ray or high-resolution computerized tomography [CT]) can be helpful both for diagnosis and management, but they have many limitations. Ultrasound has been suggested as a reliable and accurate tool for assessing the lungs in COVID-19 patients. Lung ultrasound (LUS) can show specific signs of interstitial pneumonia, which is characteristic of COVID-19 pulmonary infection. In addition, nonradiologist specialists with experience in ultrasound can be trained on LUS with a relatively rapid learning curve. In pregnancy, LUS can be particularly useful due to the avoidance of exposure to ionizing radiation. In this review, we present the advantages, techniques, and limitations of the use of LUS during the COVID-19 pandemic, with specific focus on pregnancy.

The dynamic change of the anteroposterior diameter of the levator hiatus under Valsalva maneuver at term and labor outcome.

AIM: The aim of the present study was to evaluate the correlation between the proportional change of anteroposterior diameter (APD) of levator hiatus from rest to maximum Valsalva maneuver in nulliparous women at term and labor outcome. METHODS: We prospectively recruited nulliparous women at term before the onset of labor. Women underwent a two-dimensional transperineal ultrasound, measuring the APD of the levator hiatus at rest and under maximum Valsalva's maneuver. APD change from rest to maximum Valsalva was described both in terms of absolute figures and proportional change. Correlation of APD change with the mode of delivery and with labor durations was assessed. RESULTS: Overall, 486 women were included in the analysis. No significant association between change in APD and the mode of delivery. We found a significant negative correlation between change of APD from rest to Valsalva and the duration of active second stage both in terms of absolute change (Pearson's r = -0.138, P = .009) and in terms of proportional change (Pearson's r = -0.154, P = .004). Survival outcomes based on Cox-regression model showed that APD was independently associated with the duration of active second stage of labor after adjusting for epidural analgesia, maternal age and body mass index (hazard ratio, 1.008; 95% confidence interval, 1.001-1.016; P = .04) CONCLUSION: Women with higher increase of the anteroposterior diameter of the levator hiatus from rest to Valsalva have a shorter active second stage of labor.

Risk of adverse pregnancy outcomes by pre-pregnancy Body Mass Index among Italian population: a retrospective population-based cohort study on 27,807 deliveries.

PURPOSE: To estimate the impact of increasing pre-pregnancy Body Mass Index (BMI) on the risk of adverse maternal and perinatal outcomes, in patients who delivered in an Italian tertiary care Obstetric department. METHODS: Data, related to women who delivered at Sant'Anna Hospital, Turin, between 2011 and 2015, were collected retrospectively from the hospital database. According to BMI, women were considered as normal weight, overweight, and class 1, 2 and 3 obese (WHO criteria). Logistic regression analysis studied the impact of BMI on maternal and neonatal outcomes, adjusting results for maternal age and parity. Adjusted absolute risks of each outcome were reported according to incremental values in pre-pregnancy BMI. RESULTS: A total of 27,807 women were included. 75.8% of pregnancies occurred among normal-weight women, whereas 16.7% were overweight, and 7.5% obese women (5.4% class 1, 1.7% class 2 and 0.4% class 3). A 10% decrease in pre-pregnancy BMI was associated with a reduction of at least 15% of Gestational diabetes mellitus (GDM), preeclampsia, maternal admission to intensive care unit (ICU), macrosomia, APGAR 5' < 6 and neonatal admission to ICU. GDM and preeclampsia resulted in the highest reduction being almost 30%. Larger differences in BMI (20-25%) corresponded to at least a 10% in reduction of risk of preterm and very preterm delivery and emergency cesarean section. Differences in maternal pre-pregnancy BMI had no impact on the frequency of shoulder dystocia and stillbirth. CONCLUSIONS: This study offers a quantitative estimation of negative impact of pre-pregnancy obesity on the most common pregnancy and perinatal complications.