Friday 31 August 2018

TREATMENT OF RECURRENT VIRUS-INDUCED WHEEZING IN YOUNG CHILDREN


Viruses are widely recognized as common triggers of early childhood wheezing both in children with recurrent wheezing with multiple triggers as well as those with episodic exacerbations whose predominant trigger of wheezing is viral infections. In fact, a viral cause was detected in 90 percent of wheezing illnesses in a birth cohort of children at increased risk of developing asthma. Early childhood wheezing encompasses many clinical phenotypes, and responses to treatment are variable. Instituting or escalating asthma therapies is effective in controlling viral-induced wheezing symptoms in some patients. However, the evidence for this approach is not definitive in controlled studies, particularly in patients with intermittent symptoms.



The optimal management for acute episodes of virus-induced wheezing in infants and preschool children has yet to be determined. Therapeutic trials in this young population are hampered by the inability to predict clinical phenotypes, such as children who will outgrow their symptoms, children who will later develop asthma, and children who have bronchiolitis, a condition for which glucocorticoids generally are not recommended. This topic reviews the treatment of young children with recurrent virus-induced wheezing, defined as a minimum of three to four wheezing exacerbations a year. Virus-induced wheezing is a heterogeneous disorder, and response to treatment may differ among individuals. Inhaled short-acting beta2-agonists are commonly used for symptomatic relief. Combination therapy with Hypertonic Saline (HS) and a bronchodilator is under investigation for treatment of acute symptoms. Inhaled and systemic glucocorticoids and Leukotriene-Receptor Antagonists (LTRAs) have been studied for the treatment and prevention of acute episodes of virus-induced wheezing in young children who require additional therapy.

 Inhaled bronchodilators are often first-line therapy for treatment of virus-induced wheezing and are an effective rescue treatment in symptomatic patients, especially in children with established asthma. However, inhaled short-acting bronchodilators have not been shown to improve clinical outcomes, decrease the rate of hospital admission, or decrease the duration of hospitalization in children with bronchiolitis. In addition, a systematic review and meta-analysis did not show benefit with the use of beta-agonists in children with acute cough or bronchitis, although the analysis was limited to two Pediatric trials.

Thursday 23 August 2018

CONGENITAL ZIKA VIRUS INFECTION: Clinical Features, Evaluation, and Management of the Neonate


Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Congenital Zika virus infection is associated with severe congenital anomalies. This topic will discuss issues related to newborns congenitally infected with Zika virus. Zika virus infection in pregnant women and other issues related to Zika virus infection, including epidemiology, travel advisories, and infection in older children and adults are reviewed separately.


Zika virus is a neurotropic virus that particularly targets neural progenitor cells. Murine and human placental studies support the hypothesis that maternal infection leads to placental infection and injury, followed by transmission of the virus to the fetal brain, where it kills neuronal progenitor cells and disrupts neuronal proliferation, migration, and differentiation, which slows brain growth and reduces viability of neural cells. Zika virus is also associated with a higher rate of fetal loss throughout pregnancy, including stillbirths. Placental insufficiency is the mechanism postulated to induce fetal loss later in pregnancy.


A series from cases described histopathological findings in tissue from two new-borns with microcephaly and severe arthrogryposis who died shortly after birth and tissue from a microcephalic infant who died at age two months. In all cases, the mothers had symptoms consistent with Zika virus infection in the first trimester. The infants were born at 36, 38, and 38 weeks of gestation. Multiple congenital malformations were noted, including a wide range of brain abnormalities, craniofacial malformations, craniosynostosis, pulmonary hypoplasia, and multiple congenital contractures, consistent with fetal akinesia deformation sequence or severe arthrogryposis. In these cases, there was immunohistochemical and molecular evidence of virus persistence in the brain. The range of neuropathology included ventriculomegaly, lissencephaly (which commonly aligns with microcephaly), and cerebellar hypoplasia, all of which have been observed in other cases studied. Brains also showed evidence of tissue destruction, including calcifications, gliosis, and necrosis. The presence of necrosis suggests ongoing cellular injury, consistent with the demonstrated continued viral presence. Thus, the patterns of injury are likely to follow from both cellular injury at the time of infection as well as subsequent damage as the brain develops. Evidence from cell culture systems places the neuronal precursor cell as a crucial target for Zika virus infection resulting in cell death. Loss of these cells early in development has been reported to substantially reduce the number of neurons generated and result in small brains without cortical gyration.


Wednesday 22 August 2018

NEURODEVELOPMENTAL OUTCOMES OF THE TINIEST BABIES


Care of preterm infants with extremely low birth weight (BW) and having intact survival is still a challenge for Neonatologists. In this issue study reported the survival rate and the outcome of preterm infants with a BW of ≤500 g in a single institute during a 10-year period. Their strategy regarding the timing of delivery of live or stillborn infants with a BW of ≤500 g is to deliver cases where continued pregnancy would compromise maternal health or where non-reassuring fetal status is identified.
The survival rate was 80% among live births, and the results of developmental assessments of 3-year-old children were 29% normal, 43% mild disability, and 29% severe disability.  All the tiniest babies were also the most immature ones, and they would die if they did not receive any resuscitation or life support after birth. The approach regarding the care of the most immature babies varies around the world.  In Japan, the limit of viability as defined in the law is 22 completed weeks of gestation. Preterm babies with a gestational age of ≥22 weeks will be resuscitated and admitted to the intensive care unit.  The differences in the approaches related to the most immature babies result in the variation of survival rates in different countries and regions.

When counselling with parents, both survival rate and long-term neurodevelopmental outcomes are important for decision-making in the management of the most immature or the tiniest babies. A systematic review and meta-analysis focusing on neurodevelopmental outcomes of the most immature babies demonstrated that the most commonly observed neurodevelopmental disability is cognitive impairment, followed by cerebral palsy.  Vision and hearing deficits occur less frequently.  In Japan, the new Kyoto Scale of Psychological Development (KSPD) test was used for neurodevelopmental evaluation. Study reported that 43% (3/7) of survived patients had mild neurodevelopmental disability. One patient was diagnosed with autism spectrum disorder with a normal DQ at the age of 3 years. In addition, 42% of the survived patients had either visual or hearing impairment. Hence, concerns remain regarding the neurodevelopmental outcomes of preterm infants with a BW of ≤500 g.

Improving the survival rate of very tiny preterm infants and preventing the adverse neurodevelopmental outcomes are of utmost importance. One of the important therapies for the tiny preterm infants is the administration of antenatal corticosteroids (ANCS). Among the live births with a BW of ≤500 g, there was only one mother who received ANCS in the study. The administration of ANCS for an impending preterm delivery before 25 weeks of gestation is a controversial issue. A recent meta-analysis study showed reduced mortality and intraventricular hemorrhage (IVH) or periventricular leukomalacia in neonates born at <25 weeks and exposed to ANCS. There was no difference in the occurrence of stage II or more of necrotizing enterocolitis (NEC), and the incidence of chronic lung disease (CLD) was higher in the group that was administered ANCS. Composite outcomes of death or major morbidities (severe IVH, NEC, or CLD) were improved after exposure to ANCS. With the improvement of perinatal care, the survival rate of the most immature and the tiniest babies has increased. Further larger and additional long-term follow-up studies as well as further research on the management of the tiniest babies are needed to guide decision-making and to prevent major morbidities and disabilities.

INTUSSUSCEPTION IN A PRETERM NEW-BORN


Intussusception, the second most common abdominal emergency in childhood, is three times more common in men, and the peak age is before 2 years. The incidence in neonates is 0.3–1.3 per 6000 cases. Most of the cases were misdiagnosed as necrotizing enterocolitis (NEC), causing a delay in treatment. Diagnosis of intussusception requires high suspicion in premature infants. Clinical symptomatology alone is not reliable. These symptoms in premature neonates when constellate with abdominal distension are very suggestive of NEC, the most common acquired gastrointestinal emergency in the NICU.

This leads to delay in treatment of patients. Most of the reported cases were diagnosed preoperatively or at autopsy. The most crucial step during the neonatal period is the timing of surgery. As time passes, the probability of developing ischemia and necrosis increases. Premature neonates are at an increased risk of developing intestinal hypo perfusion causing intestinal stasis and dysmotility, which would be a reasonable explanation for intussusceptions and rapid deterioration. The case presented here differs from those reported in the literature in not only being diagnosed preoperatively, but it is also the earliest diagnosed and the only one in which the intussusception was manually reduced.

Several patients were misdiagnosed with NEC, causing a delay in the operation. The abdominal plain film is not usually helpful in the diagnosis of neonatal intussusception. Although abdominal ultrasonography is the key modality in diagnosis, it has been mostly performed to exclude congenital anomalies, thus underutilizing its usefulness. The decision for performing an operation could be taken after severe clinical deterioration of the patient or in the presence of free air in abdominal graphs. Rectal contrast enema should not be used, despite its usefulness for the diagnosis and treatment of intussusception, due to the vulnerability of the intestines to perforation. Prompt diagnosis and shorter operation time enabled faster improvement and shorter postoperative period in contrast to its counterparts in the literature in which resection of intestines was required.  Open surgery should be the treatment of choice due to the possibility of congenital anomalies. Late diagnosis might result in extended surgery, longer hospital stays, and death, mostly due to sepsis or perforation.

NEC itself may lead to intussusception. The etiology of three patients in the literature has been reported as strictures due to NEC. However, most of the remaining was due to intestinal atresia, while some others were due to Meckel diverticula, duplication cysts, or hematomas. The patient presented here did not have any lead point. The subtle clinical and radiologic features of intussusception in premature neonates are difficult to distinguish from those of early NEC. The application of ultrasound is a feasible method in the early detection of intussusception, facilitating prompt surgical intervention and improving the outcome after surgery.

NEONATAL INTESTINAL DISEASES- EMERGING TRENDS


In the last decade, it has become increasingly clear that necrotizing enterocolitis (NEC) is neither a uniform nor a well-defined disease entity. There are many factors that are forcing this unwelcome realization upon the neonatal and Pediatric surgery communities. In the course of this manuscript we will review the acquired neonatal intestinal diseases (ANIDs), some which do lead to the common final pathology of NEC and some which do not. During the late 1970s, Necrotizing Enterocolitis (NEC) was most commonly seen in preterm infants >30 weeks of gestation an association between excessive fluid intake and the increasing incidence of NEC was noted.


Although there were a dozen or so preterm case reports of spontaneous intestinal perforation (SIP) in the literature, it was in 1988 that heralded the coming epidemic in neonatology by linking its prevalence to a case series of six very low birth weight infants. It was 10 years later, when surfactant was universally available and researchers began exploring the use of early postnatal dexamethasone as means to attenuate chronic lung disease, that SIP began to move from an infrequent complication to a regular part of the differential for every extremely low-birth-weight infant were the first to demonstrate the deleterious relationship between early postnatal steroids and SIP in a retrospective cohort. Since this initial report, many controlled trials have been stopped or altered because of an increased rate of SIP in neonates being treated with steroids. We now know that this perturbation is accentuated when steroids are given concomitantly with early indomethacin, making this the first clear example of harmful drug synergy in neonatology.

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