Intrafamilial Variability of the R694C Variant in BICD2 Presenting with Lethal Severe Arthrogryposis

Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition comprising congenital multiple joint contractures, and it is secondary to decreased fetal mobility following environmental/genetic abnormalities. BICD2 pathogenic variants have been associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). We report the case of a newborn with decreased fetal movements and ventriculomegaly diagnosed in utero, born with severe AMC, multiple bone fractures, congenital hip dislocation, and respiratory insufficiency that led to neonatal death. His mother had AMC diagnosis without established etiology. Her phenotype characterization was key to guide the genetic investigation. A BICD 2 heterozygous variant (NM_001003800.1; c.2080C > T; p. [Arg694Cys]) was detected both in the mother and the newborn. This variant had previously been reported in 3 cases, all having de novo severe SMALED-type 2B (MIM#618291) phenotype. This is the first report of this variant (p. [Arg694Cys]) presenting with an inherited, severe, and lethal phenotype associated to intrafamilial variability, suggesting a more complex phenotype-genotype correlation than previously stated.

Prenatal Abdominal Electrocardiogram Monitoring System using IoT in Cloud Environment: A MIMO approach

<p>The application of Internet of Things (IoT) for acquiring, analyzing and transmission of medical data is increasing in recent years. Especially in abdominal ECG processing the need is more. Since the fetal movements are random in the abdomen, a single electrode can’t be able to acquire the fetal ECG. So multi-electrodes are used to record the same. At the same time all electrodes will not provide continuous ECG signal due to the fetal movements. The temperature, pressure and heart rate of the mother also monitored for effective diagnosis. This options makes the design a multi-input structure. In existing methods, Multi-input multi-output options are not available. In addition to that the complexity increases if number of input increases. In conventional methods, the complete machine is available in the patient room. But here in this work the product is divided into three units, bedside unit, doctors unit and main server. The bedside unit is an ECG acquisition device developed using a multi-lead heart rate monitor, sensors and microcontroller. Zigbee is used to transmit the information from the patient bedside to doctors unit which makes it wireless. During the movement of the patient also the data can be viewed. The Multi-output data corresponds to fetal ECG, maternal ECG, heart rate, temperature, pressure. The IoT using raspberry pi module connects the doctors unit with the main server. The machine learning algorithms analyze the ECG data of all electrodes and sensor outputs. The multi-outputs are viewed in a Graphical User Interface (GUI). The integration of the system is conducted to construct a complete IoT-based ECG monitoring system and diagnosis in Cloud environment. </p>

Prenatal Abdominal Electrocardiogram Monitoring System using IoT in Cloud Environment: A MIMO approach

<p>The application of Internet of Things (IoT) for acquiring, analyzing and transmission of medical data is increasing in recent years. Especially in abdominal ECG processing the need is more. Since the fetal movements are random in the abdomen, a single electrode can’t be able to acquire the fetal ECG. So multi-electrodes are used to record the same. At the same time all electrodes will not provide continuous ECG signal due to the fetal movements. The temperature, pressure and heart rate of the mother also monitored for effective diagnosis. This options makes the design a multi-input structure. In existing methods, Multi-input multi-output options are not available. In addition to that the complexity increases if number of input increases. In conventional methods, the complete machine is available in the patient room. But here in this work the product is divided into three units, bedside unit, doctors unit and main server. The bedside unit is an ECG acquisition device developed using a multi-lead heart rate monitor, sensors and microcontroller. Zigbee is used to transmit the information from the patient bedside to doctors unit which makes it wireless. During the movement of the patient also the data can be viewed. The Multi-output data corresponds to fetal ECG, maternal ECG, heart rate, temperature, pressure. The IoT using raspberry pi module connects the doctors unit with the main server. The machine learning algorithms analyze the ECG data of all electrodes and sensor outputs. The multi-outputs are viewed in a Graphical User Interface (GUI). The integration of the system is conducted to construct a complete IoT-based ECG monitoring system and diagnosis in Cloud environment. </p>

Intrauterine Fetal Demise After Uncomplicated COVID-19: What Can We Learn from the Case?

Background: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. Case study: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillous fibrinoid, lympho-histiocytic infiltration, scant neutrophils, clumping of villi, and extant infarctions. Immunohistochemistry identified focal SARS-CoV-2 nucleocapsid and spike protein in the syncytiotrophoblast and isolated in situ hybridization of the virus’ RNA. Low ACE2 and TMPRSS2 contrasted with strong basigin/CD147 and PDL-1 positivity in the trophoblast. An autopsy of the fetus showed no morphological abnormalities except for lung interstitial infiltrate, with prevalent CD8-positive T-lymphocytes and B-lymphocytes. Immunohistochemistry and in situ hybridization proved the presence of countless dispersed SARS-CoV-2-infected epithelial and endothelial cells in the lung tissue. The potential virus-receptor protein ACE2, TMPRSS2, and CD147 expression was too low to be detected. Conclusion: Over three weeks’ persistence of trophoblast viral infection lead to extensive intervillous fibrinoid depositions and placental infarctions. High CD147 expression might serve as the dominant receptor for the virus, and PDL-1 could limit maternal immunity in placental tissue virus clearance. The presented case indicates that the SARS-CoV-2 infection-induced changes in the placenta lead to ischemia and consecutive demise of the fetus. The infection of the fetus was without significant impact on its death. This rare complication of pregnancy can appear independently to the severity of COVID-19’s clinical course in the pregnant mother.

Decreased Fetal Movements: A Sign of Placental SARS-CoV-2 Infection with Perinatal Brain Injury

Neonatal COVID-19 is rare and mainly results from postnatal transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, can infect the placenta and compromise its function. We present two cases of decreased fetal movements and abnormal fetal heart rhythm 5 days after mild maternal COVID-19, requiring emergency caesarean section at 29 + 3 and 32 + 1 weeks of gestation, and leading to brain injury. Placental examination revealed extensive and multifocal chronic intervillositis, with intense cytoplasmic positivity for SARS-CoV-2 spike antibody and SARS-CoV-2 detection by RT-qPCR. Vertical transmission was confirmed in one case, and both neonates developed extensive cystic peri-ventricular leukomalacia.

Development of a core outcome set (COS) for studies relating to awareness and clinical management of reduced fetal movement: study protocol

Background Concerns regarding reduced fetal movements (RFM) are reported in 5–15% of pregnancies, and RFM are associated with adverse pregnancy outcomes including fetal growth restriction and stillbirth. Studies have aimed to improve pregnancy outcomes by evaluating interventions to raise awareness of RFM in pregnancy, such as kick counting, evaluating interventions for the clinical management of RFM, or both. However, there is not currently a core outcome set (COS) for studies of RFM. This study aims to create a COS for use in research studies that aim to raise awareness of RFM and/or evaluate interventions for the clinical management of RFM. Methods A systematic review will be conducted, to identify outcomes used in randomised and non-randomised studies with control groups that aimed to raise awareness of RFM (for example by using mindfulness techniques, fetal movement counting, or other tools such as leaflets or mobile phone applications) and/or that evaluated the clinical management of RFM. An international Delphi consensus will then be used whereby stakeholders will rate the importance of the outcomes identified in the systematic review in (i) awareness and (ii) clinical management studies. The preliminary lists of outcomes will be discussed at a consensus meeting where one final COS for awareness and management, or two discrete COS (one for awareness and one for management), will be agreed upon. Discussion A well-developed COS will provide researchers with the minimum set of outcomes that should be measured and reported in studies that aim to quantify the effects of interventions.

Severe Neonatal Anemia Due to Spontaneous Massive Fetomaternal Hemorrhage at Term: An Illustrative Case with Suspected Antenatal Diagnosis and Brief Review of Current Knowledge

Fetomaternal hemorrhage is defined as transfer of fetal blood into placental circulation and therefore into maternal circulation during pregnancy, and represents an important contributor to intrauterine fetal demise and neonatal death. The condition is rarely diagnosed prenatally because clinical findings are often nonspecific, and it is unpredictable. In this paper we present an illustrative case of massive spontaneous fetomaternal hemorrhage where the diagnosis was highly suspected antenatally based on maternal reported reduced fetal movements, abnormal suggestive cardiotocographic trace, and increased peak systolic velocity in the fetal middle cerebral artery. We discuss obstetrical and neonatal management and review the current knowledge in the literature. Maintaining a high index of suspicion for this condition allows the obstetrician to plan for adequate diagnostic tests, arrange intrauterine treatment or delivery, and prepare the neonatal team.