An Immunohistochemical Study of Matrix Components in Early‐Stage Vascular Canals Within Mandibular Condylar Cartilage in Midterm Human Fetuses

Matrix components of vascular canals (VCs) in human fetal mandibular condylar cartilage (15–16 weeks of gestation) were analyzed by immunohistochemistry. Prevascular canals (PVCs), consisting of spindle‐shaped cells without capillary invasion, were observed within the cartilage. Intense immunoreactivity for collagen type I, weak immunoreactivity for aggrecan and tenascin‐C, weak hyaluronan (HA) staining, and abundant argyrophilic fibers in PVCs indicated that they contain noncartilaginous fibrous connective tissues that was different from those in the perichondrium/periosteum. These structural and immunohistochemical features of PVCs are different from those of previously reported cartilage canals of the long bone. Capillaries entered the VCs from the periosteum and ascended through VCs. Following capillary invasion, loose connective tissue had formed in the lower part of VCs, and immunoreactivity for collagen types I and III, tenascin‐C, and HA staining was evident in the matrix of loose connective tissue. No chondroclasts or osteogenic cells were seen at the front of capillary invasion, although small, mononuclear tartrate‐resistant acid phosphatase (TRAP)‐positive cells were present. Meanwhile, TRAP‐positive, multinucleated chondroclasts and flattened, osteoblast‐like cells were observed in the loose connective tissue at the lower part of VCs. These results may indicate slow progress of endochondral ossification in human fetal mandibular condyle. Further, unique matrix components in PVCs/VCs, which were different from those in cartilage canals in long bone, may reflect the difference of speed of endochondral ossification in cartilage canals and human fetal mandibular condyles. Anat Rec, 298:1560–1571, 2015. © 2015 Wiley Periodicals, Inc.     

Novel application of four-dimensional sonography with B-flow imaging and spatiotemporal image correlation in the assessment of fetal congenital heart defects

Aims: To evaluate the role of four‐dimensional (4D) ultrasound with B‐flow imaging and spatiotemporal image correlation (STIC) in the evaluation of normal fetal heart and congenital heart disease during pregnancy. Methods: Volume data sets of the fetal heart were acquired with automated transverse and longitudinal sweeps of the anterior chest wall. We studied 31 normal fetuses and 28 fetuses with congenital heart disease (6 with double‐outlet right ventricle, 5 with complete transposition of great arteries, 8 with tetralogy of Fallot, 3 with right aortic arch, 2 with persistent left superior vena cava, 3 with truncus arteriosus communis, and 1 with interruption of aortic arch) at gestation ages ranging from 18 to 39 weeks using transabdominal 4D B‐flow sonography with STIC (4D BF‐STIC). Results: Four‐dimensional BF‐STIC demonstrated dynamic angiographic features in both normal and abnormal fetal hearts. Four‐dimensional BF‐STIC images could not be obtained in two normal fetuses at 18.9 and 35.6 weeks because of the high fetal heart rate and inappropriate fetal position. Of the other 29 fetuses all extracardiac vessels such as aorta, pulmonary artery, ductus arteriosus, inferior vena cava, and ductus venosus could be detected on reconstructed images. In seven normal cases, a 4D image was recorded to allow simultaneous visualization of all four pulmonary veins. In the 28 fetuses with cardiac anomalies, 4D sonography with B‐flow imaging and STIC detected the “digital casts” of the outflow tracts, great arteries, and veins draining into the heart. These results demonstrate spatial relationship among these structures which provide important anatomical information. Conclusion: Four‐dimensional BF‐STIC provides a means of real time three‐dimensional evaluation of fetal extracardiac hemodynamics in the second and third trimesters. This novel technique assists in the evaluation of fetal cardiac hemodynamics and may play an important role in future fetal cardiac research and in the identification of anatomical features of different congenital cardiac anomalies. (Echocardiography 2012;29:614‐619)     

The International society for developmental psychobiology 39th annual meeting symposium: Alcohol and development: beyond fetal alcohol syndrome

As has been repeatedly demonstrated, alcohol can exert deleterious morphological and physiological effects during early stages in development. The present review examines nonteratological links existing between alcohol and ontogeny. Human and animal studies are taken into consideration for the analysis of fetal, neonatal, infantile, adolescent, and adult responsiveness to the drug. Sensitivity to alcohol's chemosensory and postabsorptive properties, as well as learning and memory processes mediated by such properties, are examined from this developmental perspective. The studies under discussion indicate that, within each stage in development, we can trace alcohol-related experiences capable of determining or modulating alcohol seeking and intake patterns.     

The dynamic fetal brain

PURPOSE: To evaluate fetuses with normal intracranial anatomy in the second trimester that became abnormal in the third trimester. METHODS: We sonographically examined 6 fetuses with a normal second-trimester head sonogram that presented later in pregnancy with an abnormal head sonogram. RESULTS: Four categories of intracranial pathology were depicted: obstructive hydrocephalus, intraventricular intracranial hemorrhage, non-intraventricular intracranial hemorrhage, and porencephaly. CONCLUSIONS: Despite a normal midtrimester intracranial examination, evaluation of the fetal intracranial contents should be undertaken in subsequent sonographic examinations, because significant pathology can develop spontaneously.     

Airway management for neonates requiring ex utero intrapartum treatment (EXIT)

In utero congenital malformations in the fetus can occasionally lead to an obstructed airway at birth accompanied by hypoxic injury or peripartum demise, without intervention. Ex utero intrapartum treatment (EXIT) may help reduce morbidity and mortality associated with challenging airways by providing extra time on uteroplacental circulation to secure the airway. Meticulous preparation and planning are crucial for this procedure. Many different types of congenital malformations can result in a difficult airway, but there is no correlation between specific malformations and a required type of airway intervention. Based on our experience and literature review, an airway process flow diagram has been created to help assist teams in decision‐making for airway intervention in a neonate during the EXIT procedure. The management of the airway in this scenario involves additional unique considerations that accompany handling a partially delivered newborn in the uterine environment. Extensive preparation and team rehearsal are essential to the success of this procedure.     

Precocious synapses in 13.5-week fetal holoprosencephalic cortex and cyclopean retina

Background: Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20–31 weeks gestation. Materials and methods: Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, alobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears. Immunocytochemical demonstration of the synaptic vesicle protein synaptophysin was performed in the brain and retina, along with other neuronal markers. Results: Synaptophysin reactivity in the cortical plate was patchy and precocious. Radial glial fibres, demonstrated by vimentin, were oriented parallel to the cortical plate rather than perpendicular, probably because of hydrocephalus. A corpus striatum was not identified, but the poorly formed thalamus exhibited synaptophysin reactivity around many neurones. The cyclopean eye had ocular features of maturational delay including persistent hyaloid artery; ganglion cells were reduced in number, but retinal synaptophysin reactivity was paradoxically precocious. Conclusions: Holoprosencephaly exhibits abnormal patchy synapse distribution in the neocortex and retina; synaptogenesis was precocious, as we previously described in older fetuses. Too soon an onset of synapse formation may promote early epileptic circuitry, leading to severe infantile epilepsies postnatally. The visual system is the last of the special sensory systems to mature, yet in this case showed too early synapse formation. In HPE, cyclopia and in trisomy 13, total absence of external ears has not been reported; it results from faulty craniofacial induction by neural crest.     

CMV-Specific Cell-Mediated Immunity in Immunocompetent Adults with Primary CMV Infection: A Case Series and Review of the Literature

Cytomegalovirus-specific cell-mediated immunity (CMV-CMI) in actively infected healthy immunocompetent hosts has been poorly investigated. Conversely, correlates of maternal protective immunity for the fetus after primary infection in pregnancy continue to be studied. The kinetics and magnitude of CMV-specific CMI in immunocompetent primary CMV-infected adults are described. A literature review on CMV-CMI in primarily infected pregnant women and its correlation to the risk of vertical virus transmission is included. Immunological measurements after infection were performed by enzyme-linked ImmunoSPOT assay enumerating IFN-γ secreting CMV-specific T cells, at a single cell level, upon in vitro stimulation with viral antigens. Simultaneously, serological and virological profiles of infected patients were investigated. Patients displayed mild-to-moderate clinical and laboratory profiles for infection, and all showed positive EliSpot results in the early stage of infection (<20 days after onset). The virus-CMI was strong in the majority of patients (58.8%) in which the lowest CMV-DNAemia levels (<300 copies/mL) were detected. Significantly higher viral loads were observed in patients with weak CMV-CMI at the same time-point post-infection (up to 15,104 copies/mL; p < 0.001). T cell response magnitudes to IE-1 and pp65-UL83 peptides were overlapping and stable over time. In these case series, the early presence of CMV-CMI was probably pivotal in controlling viral replication and led to spontaneous viral clearance.