Coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center: Application to Early Management of Infants With Cleft Lip and Palate.

Background/purpose: The primary objective of this study is to describe the authors' experience at the Children's National Health System with the coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center. This collaboration highlights the accuracy and completeness of prenatal diagnosis of cleft abnormalities with expedient postnatal management.

Methods: With Institutional Review Board approval, the authors retrospectively reviewed 74 patients referred for potential orofacial cleft and 44 met the inclusion criteria.

Whole-exome sequencing for diagnosis of Peters-plus syndrome after prenatal diagnosis of recurrent low PAPP-A and multiple fetal anomalies in two consecutive pregnancies.

 We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings.

Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis.

Purpose: Emerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted.

Methods: A total of 1023 women undergoing prenatal diagnosis were enrolled.

Identifying an optimal epoch length for spectral analysis of heart rate of critically-ill infants.

Background And Objective: To identify the optimal epoch length for power spectral analysis of cardiac beat-to-beat intervals (BBi) in critically ill newborns.

Materials And Method: BBi of 49 term newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy with well-defined outcomes (good outcome (n = 28): no or mild brain injury and adverse outcome (n = 21): moderate or severe brain injury or death) served as test population. A power spectrum of BBi was calculated with an autoregressive model in three different epoch lengths: 2 min, 5 min, and 10 min.

Fetal lung interstitial tumor: Prenatal presentation of a rare fetal malignancy.

Fetal lung interstitial tumor (FLIT) is a rare fetal malignancy that is typically diagnosed in the postnatal period, or, if recognized prenatally can mimic a benign lesion such as congenital pulmonary airway malformation. We present the earliest case of a FLIT tumor described by ultrasound and MRI at 26 weeks of gestation. Our case highlights features suggestive of FLIT including presentation later in gestation in combination with findings on fetal MRI such as a solid appearance with radiating curved bands of high signal within and along the periphery of the lesion (not as intensely high signal as the typical CPAM), possibly detailing a radiographic signature for these tumors.

The effects of perineal disinfection on infant's oral microflora after transvaginal examination during delivery.

Background: Early life microflora is an important determinant of immune and metabolic development and may have lasting consequences. However, the mode of delivery and the effect of povidone iodine disinfection on neonatal oral microflora colonization are still unclear. The objective of the study was to understand the effects of the use of polyvidone iodine on infant's oral microflora after transvaginal examination during delivery, provided data support for the establishment of neonatal oral microflora health.

Whole-exome sequencing for diagnosis of Peters-plus syndrome after prenatal diagnosis of recurrent low PAPP-A and multiple fetal anomalies in two consecutive pregnancies.

 We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings.

Comparison of Frequency- and Time-Domain Autoregulation and Vasoreactivity Indices in a Piglet Model of Hypoxia-Ischemia and Hypothermia.

Introduction: The optimal method to detect impairments in cerebrovascular pressure autoregulation in neonates with hypoxic-ischemic encephalopathy (HIE) is unclear. Improving autoregulation monitoring methods would significantly advance neonatal neurocritical care.

Methods: We tested several mathematical algorithms from the frequency and time domains in a piglet model of HIE, hypothermia, and hypotension.

SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration.

Rho GTPase-activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small GTP-binding protein RhoA (GTP-RhoA) to its inactive GDP-bound form and is a putative tumor suppressor gene associated with cell growth and migration. Here, the involvement of ARHGAP26 in ovarian cancer cell proliferation and migration was investigated. In this study, low ARHGAP26 expression was observed in ovarian cancer tissues and was associated with a poor overall survival and higher β-catenin expression in patients with ovarian cancer.

Early proton magnetic resonance spectroscopy during and after therapeutic hypothermia in perinatal hypoxic-ischemic encephalopathy.

Background: Hypoxic-ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment despite treatment with therapeutic hypothermia. Magnetic resonance H-spectroscopy measures concentrations of cerebral metabolites to detect derangements in aerobic metabolism.

Objective: We assessed MR spectroscopy in neonates with HIE within 18-24 h of initiating therapeutic hypothermia and at 5-6 days post therapeutic hypothermia.

Epidemiologic features of enterovirus associated with hand, foot and mouth disease in 2013 and 2014 in Shenzhen, China.

Hand, foot and mouth disease (HFMD) is responsible for a heavy economic and social burden in the Asia-Pacific region. Previous studies have shown that coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) have become the predominant agents of HFMD in mainland China in recent years, replacing enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), although it is unclear if this is consistent throughout China. In this study, samples from 253 HFMD cases were collected in Shenzhen, China, from May 2013 through April 2014 to identify the etiological agent of HFMD.

Impaired Interneuron Development in a Novel Model of Neonatal Brain Injury.

Prematurity is associated with significantly increased risk of neurobehavioral pathologies, including autism and schizophrenia. A common feature of these psychiatric disorders is prefrontal cortex (PFC) inhibitory circuit disruption due to GABAergic interneuron alteration. Cortical interneurons are generated and migrate throughout late gestation and early infancy, making them highly susceptible to perinatal insults such as preterm birth.

The effect of unilateral stroke on autonomic function in the term newborn.

Background: The mature cerebral cortex has a topographically organized influence on reflex autonomic centers of the brainstem and diencephalon and sympathetic activation coming primarily from the right hemisphere and parasympathetic activation from the left. In the term newborn, the maturational status of this central autonomic system remains poorly understood.

Methods: Sixteen term newborns admitted to Children's National with unilateral middle cerebral artery (MCA) strokes (n = 8 left, n = 8 right) had archived continuous electrocardiograph (EKG) signals available.

Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy.

Objective: To investigate whether the early glycemic profile in infants with hypoxic ischemic encephalopathy is associated with distinct patterns of brain injury on magnetic resonance imaging (MRI).

Study Design: We performed a secondary analysis of 178 prospectively enrolled infants who received therapeutic hypothermia for hypoxic ischemic encephalopathy. Glycemic profiles were identified by glucose concentrations within 24 hours after birth: normoglycemia (all glucose concentrations of >47 to ≤150 mg/dL; n = 62); hypoglycemia (≥1 concentration ≤47 mg/dL; n = 17); hyperglycemia (≥1 concentration >150 mg/dL; n = 76); and labile glucose (both hypoglycemia and hyperglycemia; n = 23).

An experimental study of ovarian cancer imaging and therapy by paclitaxel-loaded phase-transformation lipid nanoparticles combined with low-intensity focused ultrasound.

Drug-loaded phase-transformation lipid nanoparticles (NPs) combined with low-intensity focused ultrasound (LIFU) for ultrasound molecular imaging and therapy, which is a very promising drug carrier and can provide both physical and chemical therapeutics, simultaneously. We successfully prepared the paclitaxel (PTX) loaded anti-LHRHR targeted phase-transformation lipid nanoparticles (PTX-anti-LHRHR-PTNPs) for ovarian cancer in this study combined with LIFU has the following characteristics: On the one hand, it showed smaller size and greater stability than blood cells, which significantly prolonged its half-life in the body, and can actively target ovarian cancer OVCAR-3 cells, and smoothly penetrate the endothelial gap into the tumor site for specifically killing the ovarian cancer cells. Thereby, the special drug carrier improved the therapeutic effect and reduced toxic and side effects, maximized the protection of normal tissues and minimized adverse reactions.

Autonomic nervous system depression at term in neurologically normal premature infants.

Background: Premature infants are vulnerable to destructive brain injury and disturbed neurological development. Prematurity may alter maturation of the central autonomic nervous system (ANS).

Aims: To compare ANS function (using heart rate variability; HRV) between preterm infants with normal neuroimaging at term equivalent age and low-risk term controls.

Team counseling in prenatal evaluation: the partnership of the radiologist and genetic counselor.

Fetal medicine programs within children's hospitals have been developed to ensure access to pediatric specialists across multiple disciplines. The cases that present to these programs are usually complex and require involvement of a multidisciplinary care team. Although some providers on the team limit their focus to their pediatric specialty when counseling patients, the radiologist and genetic counselor have a distinct perspective allowing them to take the larger picture into account in the evaluation of the fetus.

Autonomic Dysfunction in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia Impairs Physiological Responses to Routine Care Events.

Objective: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury.

Study Design: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia. Videos between 16 and 24 hours of age identified 99 distinct care events, including stimulating events (diaper changes, painful procedures), and vagal stimuli (endotracheal tube manipulations, pupil examinations).

Understanding the Influence of Flow Velocity, Wall Motion Filter, Pulse Repetition Frequency, and Aliasing on Power Doppler Image Quantification.

Objectives: Although power Doppler imaging has been used to quantify tissue and organ vascularity, many studies showed that limitations in defining adequate ultrasound machine settings and attenuation make such measurements complex to be achieved. However, most of these studies were conducted by using the output of proprietary software, such as Virtual Organ computer-aided analysis (GE Healthcare, Kretz, Zipf, Austria); therefore, many conclusions may not be generalizable because of unknown settings and parameters used by the software. To overcome this limitation, our goal was to evaluate the impact of the flow velocity, pulse repetition frequency (PRF), and wall motion filter (WMF) on power Doppler image quantification using beam-formed ultrasonic radiofrequency data.

Identification of QRS complex in non-stationary electrocardiogram of sick infants.

Background: Due to the high-frequency of routine interventions in an intensive care setting, electrocardiogram (ECG) recordings from sick infants are highly non-stationary, with recurrent changes in the baseline, alterations in the morphology of the waveform, and attenuations of the signal strength. Current methods lack reliability in identifying QRS complexes (a marker of individual cardiac cycles) in the non-stationary ECG. In the current study we address this problem by proposing a novel approach to QRS complex identification.

Treatment of heterotopic caesarean scar pregnancy complicated with post termination increase in size of residual mass and morbidly adherent placenta.

We report a case of a secundipara with heterotopic cesarean scar pregnancy (HCSP) treated with potassium chloride injection into the ectopic embryo followed by sac aspiration. The remaining "mass" increased in size threefold and was surrounded by a rich vascular network. An arteriovenous malformation was suspected; however, appropriate treatment was precluded because of the viability of the ectopic gestation.

Differential neuronal susceptibility and apoptosis in congenital Zika virus infection.

To characterize the mechanism of Zika virus (ZIKV)-associated microcephaly, we performed immunolabeling on brain tissue from a 20-week fetus with intrauterine ZIKV infection. Although ZIKV demonstrated a wide range of neuronal and non-neuronal tropism, the infection rate was highest in intermediate progenitor cells and immature neurons. Apoptosis was observed in both infected and uninfected bystander cortical neurons, suggesting a role for paracrine factors in induction of neuronal apoptosis.

Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy.

Objective: To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE).

Study Design: The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1β, TNF-α, IFN-λ) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21).

Cerebral modulation of the autonomic nervous system in term infants.

Objective: Central topography of autonomic nervous system (ANS) function has yet to be fully deciphered. In adults it has been shown to lateralize sympathetic and parasympathetic influence predominantly to the right and left cerebral hemispheres, respectively. We examined functional topography of central ANS in newborn subjects utilizing spectral analysis of heart rate variability (HRV), an established measure of ANS function.