Current Pediatric Reviews - Volume 1, Issue 3, 2005

Twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. According to recent studies, different pathophysiological mechanisms may play a role. Diagnosis of TTTS is no longer based on neonatal criteria such as birth weight discordance and hemoglobin difference, but on strict prenatal ultrasound criteria. A significant evolution in prenatal care strategies and management options for patients with TTTS has occurred during the last decade. Endoscopical laser ablation of communicating placental vessels is a new treatment modality that has led to an increase in survival rates. In perinatology, a decrease in mortality rates may be associated with an increase in morbidity rates. Follow-up studies in infants with TTTS are shedding more light on the wide range of morbidity associated with TTTS, such as neurological, cardiac and renal sequelae. This review analyzes the possible pathophysiological mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS.

Varicella belongs to serious infections during pregnancy. After introduction of prevention by vaccination in several countries, there is a particular interest to learn more about the consequences of maternal varicella for the infant. Pregnant women who contract varicella are at risk of severe pneumonia and death. At any stage during pregnancy, chickenpox may cause intrauterine infection by placental transmission of the virus. The consequences for the infant depend on the time of maternal disease. During the first two trimesters, maternal varicella may cause the congenital varicella syndrome which has been reported in about 2%. Maternal infection near term is associated with a substantial risk of neonatal varicella. Serious disseminated infections with visceral involvement may occur in the infant. Aside from epidemiology and clinical consequences, the present paper reviews the current possibilities of diagnosis, prevention and therapy of varicella-zoster virus infections during pregnancy.

Human preterm infants are at risk to develop cerebral palsy, cognitive or behavioural impairments. The most recognized underlying brain lesion in preterms is periventricular white matter damage (WMD) which can be focal, multifocal or diffuse. Periventricular leukomalacia is the best described type of periventricular WMD. Clinical, epidemiological and experimental studies have allowed demonstrating the multifactorial origin of these WMD in preterms, generating more than one potential target for neuroprotection. These studies have permitted to unravel some key factors such as inflammation and excess production of cytokines, oxidative stress, hypoxic-ischemic insults, excess release of glutamate and the excitotoxic cascade. Animal models have also revealed that pre-oligodendrocytes, macrophages-microglia and sub-plate neurons are key cells in the pathophysiology of periventricular WMD. One key safety issue for potential neuroprotective strategies in premature newborns is the demonstration of the lack of interference with normal brain development. Several neuroprotective approaches are currently tested in animal models of WMD, including drugs targeting glutamate receptors, drugs targeting inflammation, cytokines or macrophage activation, antioxidant molecules, and strategies such as growth factors and cell replacement aiming at improving post-lesional plasticity and tissue repair. Finally, some clinical trials using magnesium sulfate in preterms have been completed or are in progress.

In recent years, the application of molecular techniques in the evaluation of patients with CH has made it possible to define the molecular basis in a number of cases. A prerequisite for molecular studies is the distinction between primary and secondary or central CH. In primary CH (disordered organogenesis of the thyroid gland or defective thyroxine synthesis), the genetic defects, thus far identified, include those of genes encoding the transcription factors TTF1, TTF2 and PAX8 or the TSHR, NIS, TG and TPO. In some of these molecular abnormalities (TTF2), CH may be associated with various morphogenetic defects. In central CH, the defect lies in the hypothalamic-pituitary axis: TRH synthesis, TRH receptor, synthesis of the TSH β subunit. The biochemical localization of the defect in such cases can be accomplished by a TRH test. Genetic defects in transcription factors involved in pituitary ontogenesis (HESX1, LHX3, Prop1, Pit1) can also result in CH. In such cases, low TSH occurs in association with other pituitary hormone deficiencies. It must be underlined that, in patients with CH, as in other genetically determined disorders, the localization of the molecular defect is very important for genetic counseling, antenatal diagnosis and delineation of prognosis.

In the last few years much attention has been devoted to neonatal analgesia, and in particular nonpharmacological analgesia. We know the effectiveness of oral sucrose administration and non-nutritional sucking and some papers exist on these topics. However, there has not been any review of applications of non-pharmacological analgesia. Here we examine the above two methods and other strategies described in the literature, among which: oral glucose, fructose milk or sweeteners; breastfeeding; cuddling; music; vestibular stimulation; kangaroo care, Newborn Individualized Developmental Care and Assessment Program (NIDCAP); sensorial saturation, springloaded lances, supine position, swaddling and facilitated tucking. Seventy-seven studies assessing the efficacy of non-pharmacologic procedures for relieving pain in neonates were identified. It emerges from this review that certain strategies can be combined with oral sucrose and non-nutritional sucking to provide effective and almost complete analgesia for acute pain in neonates.

Hypoplastic Left Heart Syndrome (HLHS) is a devastating congenital cardiac defect affecting approximately one thousand newborns annually in the United States. Without surgery, this condition is universally fatal. Currently, there are three management options for children born with HLHS: the Norwood palliative surgical procedure, neonatal cardiac transplantation, and comfort care without surgery. In the following review, I will first briefly describe the anatomy and embryology of HLHS. I will then describe the three management options, including published survival statistics, neurodevelopmental outcomes, and other considerations for infants receiving each of the treatment options. I will also describe new developments that may improve outcomes in the near future. Published data of parental choices in the care of infants born with HLHS, as well as published data on physician attitudes towards the three treatment options will be presented. Finally, I will offer guidelines for physician-parent discussions drawing from the informed consent literature and case law.

Although lumbar puncture is generally safe, bleeding into the cerebrospinal fluid (CSF), may occur as a result of trauma during the procedure. As a consequence bacteria (in patients with sepsis) or leukemic cells (in patients with leukemia) circulating in blood may be introduced into the CSF as a result of TLP. Therefore paediatric preventive measures must be taken when performing diagnostic LP procedures in pediatric patients suspected of having leukaemia or bacteremia, including the use of deep sedation or general anaesthesia, collection of the initial diagnostic CSF by a very skilled practitioner, and platelets transfusion for ALL patients with thrombocytopenia and circulating leukaemic cells.

A wide spectrum of disorders may cause chronic diarrhea in children and most of the times, it is not very easy to establish a specific diagnosis by pediatricians. In this review, some simple clues regarding history, physical examination, and laboratory tests are given to pediatricians in order to help their approach to the infant/child/adolescent with chronic diarrhea. Among the causes, post-enteritis syndrome, a still common but under-recognized entity especially in under-developed or developing countries, is also discussed.

Liver transplantation has become the accepted method of treatment for children with end-stage liver disease. Combining new methods of immunosuppression, modifications in surgical technique, improved anesthetic management, organ availability, and identification and treatment of postoperative complications, survival rates have reached 80% to 90% in many centers performing pediatric liver transplants. With the improvement in survival rates, indications for liver transplantation in children have broadened; however, the availability of organs suitable for children is still extremely limited. Although pediatric cases only represent approximately 10% of the total patients on the waiting list, the number of deaths on the waiting list increased from 196 in 1988 to 1753 in 1999. The recent development of surgical procedures that enable the use of cut down "reduced" livers, split liver grafts (splitting a cadaveric liver for 2 different recipients), and living related donors, are creating new options for the long list of children waiting for hepatic transplants. In light of the increasing incidence of liver disease and continuing shortage of donor organs, cell-based therapies are getting attention as promising treatments for liver failure. These include: isolated cell transplantation, tissue engineering of implantable constructs, transgenic xenotransplantation, and extracorporeal bioartificial liver devices. Hepatocyte transplantation aims to correct inborn errors or acquired liver function defects by supplying metabolically active cells to the diseased liver. Experimentally, hepatocytes can be successfully isolated by collagenase digestion of the liver. Cells can then be transplanted in the spleen or the liver via the portal vein or hepatic artery. In both sites, cells engraft and become metabolically active, can synthesize albumin, or correct inborn errors of metabolism. They have been shown to prolong survival in models of fulminant liver failure, and so far have been shown to bring partial metabolic control in Crigler-Najjar disease type I and Refsum disease. Extracorporeal support for patients with liver failure has been attempted for over 40 years. Various nonbiological approaches have met with limited success, presumably because of the role of synthetic and metabolic functions of the liver that are inadequately replaced in these systems. Bioartificial devices typically incorporate isolated cells into bioreactors to simultaneously promote cell survival and function as well as provide for the level of transport seen in vivo. While the safety of bioartificial liver devices has been established, there are no uniform standards of efficacy that may vary with the etiology of the liver failure. Consensus is needed in clinical trial design, including choice of the end points, use of controls, and indications for enrollment. Also, a better understanding of the interplay between liver regeneration and bioartificial liver support therapy will be critical to optimizing the implementation of this modality. Pediatric liver transplantation is a challenging and rewarding field with continued improvement in patient and graft survival. A multidisciplinary team approach coupled with improvement in organ availability, immunosuppression, and peri-operative management has had a dramatic impact on survival. The increasing incidence of liver disease and continuing shortage of donor organs has led to the development of new therapies using cell-based therapies as an alternative to transplantation. The procedure is less radical, less invasive, potentially less expensive, and fully reversible. It may, to a certain extent, alleviate the problem of organ shortage. Despite these advances, transplantation remains a costly procedure and patients still require lifelong immunosuppressive therapy subjecting them to potential side effects and infections. In some children with liver disease, transplantation is the only alternative, whereas in others the risks and benefits must be considered relative to other treatment options.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) is an immunological mediated hypersensitivity reaction to a variety of inhaled allergens that may cause an acute and subacute interstitial pneumonitis and may lead to a chronic end-stage lung disease. Though more common in adults, hypersensitivity pneumonitis needs to be considered in the differential diagnosis of interstitial pneumonitis in children. In children, the most common antigens are from residential exposure to birds, humidifiers and indoor molds. Clinical features are dependent upon stage of disease, and can include fevers, chills, cough, dyspnea, fatigue and weight loss. Physical examination often reveals rales, and dyspnea and hypoxemia are usually present. Routine laboratory testing demonstrates a moderately elevated erythrocyte sedimentation rate, leukocyte count, total IgG level and a positive rheumatoid factor. Though serum IgG antibodies are elevated to the inhaled antigen(s) in hypersensitivity pneumonitis, they may be present in asymptomatic exposed individuals. The immunopathogenesis involves cellular immunity to inhaled allergens, especially CD8+ cytotoxic T cells, multinucleated giant cells, and ultimately granulomas. The role of antigen-specific IgG antibodies is unclear, but may be involved in antibody-dependent-cellular-cytotoxicity (ADCC) and/or interaction with FcRg on dendritic cells and monocytes that enhance a Th1 response. Pulmonary function studies demonstrate a restrictive pattern with a diffusion defect resulting in hypoxemia. Radiographic changes vary according to the stage of the disease and are best evaluated by high resolution computerized tomography. Bronchoalveolar lavage demonstrates a lymphocytosis with characteristic increase of CD8+ T cells and NK cells. However, recent literature suggests that the CD4+/CD8+ ratio may not be decreased in children as found in adults. Treatment of hypersensitivity pneumonitis is antigen avoidance and systemic corticosteroids, and prognosis depends on early recognition of the disease.

Cough is the most common presenting symptom to medical practitioners to the USA and Australia. Worldwide, the desire to reduce the impact of the symptom of cough is reflected in the billions of dollars spent on over the counter cough medications. Easy to apply and clinically relevant definitions of cough are necessary for effective communication and to progress clinical research. Based on current data, pediatric cough definitions have been formulated on timeframe (acute and chronic), clinical cough characteristics (dry vs wet/productive and classical recognizable cough sounds) and suggestive broad underlying etiology categories (expected cough, specific cough, non-specific cough and protracted bronchitis). These definitions are distinct from adult definitions, as many of adult-type aspects of cough cannot be applied to young children. With the lack of pediatric data, adult data is often inappropriately extrapolated to children. In the second part of this paper, the evidence for and against the use of the various pharmaceuticals (such as OTC medications, antimicrobials, treatment for gastroesophageal reflux and asthma) for cough in children are reviewed. The utility of 'time to response' is important in the management of cough in children to minimize possible associated morbidity of the therapies for non-specific cough.