Current Pediatric Reviews (v.10, #3)

Thrombotic Complications of Neonates and Children with Congenital Nephrotic Syndrome by Keith K. Lau, Howard H. Chan, Patti Massicotte, Anthony K. Chan (169-176).
Congenital nephrotic syndrome (CNS) refers to a disease presenting with massive proteinuria in associationwith hypoalbuminemia, hyperlipidemia, and edema at birth or within the first three months of life. In the past, most childrenwith CNS had extremely poor prognosis and succumbed to various complications, usually within the first 6 months.Recent advancements in protein supplementation and nutritional support, renal replacement therapy and renal transplantationin infancy, render these patients to have much better outcomes [1-5]. However, there are still many hurdles in themanagement of this disease. Thromboembolism is an uncommon, yet important complication which the healthcare giversmust be aware of. This article reviews the challenges in the management of the thrombotic complications with specialemphasis on the unique characteristics of the newborn hemostasis system and anti-thrombin (AT) depletion in nephroticsyndrome. Due to the relatively low incidence of CNS in children and scarce information in the literature on the optimalmanagement of the thromboembolic complications, most of the recommendations are based on the authors' experience.

Iron deficiency remains the most common nutritional deficiency worldwide despite the fact that global preventionis a high priority. Recent guidelines suggest intake of red meat both in infants and toddlers to prevent iron deficiency.However frequent consumption of red and processed meat may be associated with an increased risk for cancer, cardiovasculardisease and diabetes. Evidence also suggests that even in vegetarian diets or diets with little consumption of white orred meat, iron status may not be adversely affected. The Eastern Orthodox Christian Church dietary recommendationswhich is a type of periodic vegetarian diet, has proved beneficial for the prevention of iron deficiency and avoidance ofexcess iron intake. This paper aims to provide examples of meals for children and adolescents that may be sufficient tomeet age specific iron requirements without consumption of red meat beyond the recommended consumption which isonce or twice per month.

The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionalsfor long and often lack of child specific dosage forms and the associated events that follow with it have been consideredto be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over theyears to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), PediatricResearch Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceuticalindustry towards development of child friendly dosage forms. Initiatives taken in past by organisations likeWorld Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of childfriendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV)and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersibleplatforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage formsfor children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimentaleffects of additional factors such as parents understanding of label instructions and complexities involved in executingpediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parentsand healthcare providers to work for better treatment outcomes in children.

Chvostek's Sign in Paediatric Practice by Zeeshaan U. Hasan, Rania Absamara, Mas Ahmed (194-197).
Chvostek's Sign was first described in 1876, as a clinical clue associated with patients who suffered from latenttetany, and is induced by percussion of the angle of the jaw. However, over the years many clinicians have called intoquestion the strength of the association with latent tetany, particularly in paediatric practice. This review examines thevariation in techniques used to elicit the sign in studies conducted on this phenomenon in children as well as how differencesin the classification of a positive Chvostek's sign have lead to varied reports on the strength of the association. Furthermore,an appraisal of the literature regarding the proposed mechanism of Chvostek's sign is reported alongside analysingother diseases which have been associated with Chvostek's sign to uncover any unifying mechanism for the presenceof this clinical sign in children.

Rhinosinusitis in the Pediatric Patient with Cystic Fibrosis by Christopher Fundakowski, Rosemary Ojo, Ramzi Younis (198-201).
Cystic fibrosis (CF) is a common autosomal recessive genetic disorder where a deletion mutation and subsequentdownstream alteration in transmembrane regulator proteins results in increased mucus viscosity. CF manifests clinicallywith chronic multisystem inflammation and recurrent infections. Nearly all children with CF have chronic sinusitis,and a large majority will have concurrent sinonasal polyposis. Chronic sinusitis and sinonasal polyposis in pediatric patientswith CF can be managed conservatively initially, though most will fail medical management and require surgicalintervention. Unfortunately, symptom resolution is marginal and polyp recurrence rates are high. Currently, no cure existsfor CF and the mainstay of treatment is to provide symptomatic relief, and minimize disease morbidity.

The Role of Oxidative Stress on Necrotizing Enterocolitis in Very Low Birth Weight Infants by Serafina Perrone, Maria Luisa Tataranno, Antonino Santacroce, Simona Negro, Giuseppe Buonocore (202-207).
Necrotizing enterocolitis (NEC) is a devastating and common disease of very low birth weight (VLBW) infantswith a mortality rate of 10% to 50% and a significant cause of morbidity in survivors. The incidence of NEC has increasedfrom 5% to 7% in the last decades and this rate is likely to rise because of the increased survival of infants born at24 weeks gestation, which are at high risk of developing NEC. NEC etiology is multifactorial: ischemia, infections, cytokines,enteral feeding and reactive oxygen species or free radicals (FRs) may contribute to the disruption of the immaturegut barrier. In particular, ischemia, hypoxia-reperfusion, infection and inflammation are mechanisms capable of producinghigh levels of FRs, perturbing the normal redox balance and shifting cells to a state of oxidative stress (OS).;Despite advances in neonatal medicine, the early diagnosis of NEC remains a major challenge. Early clinical signs are nonspecific and the laboratory findings are not fully reliable. Therefore, its delayed occurrence after birth, its rapid onset, thehighly fulminant nature, and its severe morbidity, as well as the possibility of progression to death, strongly require theidentification of new prospective biomarkers specific for high NEC risk. There is evidences that OS biomarkers in cordblood allow the early identification of infants at risk for NEC and thereby can be used to develop novel therapies for thisdevastating disease which predominantly occurs in premature infants.

The experience of early adversity can increase one's risk of psychopathology later in life. Extremely low birthweight (ELBW) provides a unique model of early adversity that affords us the opportunity to understand how prenatal andearly postnatal stressors can affect the development of emotional, biological, and behavioural systems. Since the neuroendocrinesystem and emotion regulation can both be negatively affected by exposure to early adversity, and dysregulationin these regulatory systems has been linked to various forms of psychopathology, it is possible that these systems couldmediate and/or moderate associations between early adversity, specifically ELBW, and later internalizing disorders. Inthis review, we discuss evidence of an early programming hypothesis underlying psychopathology and the identificationof neuroendocrine markers of early adversity that may mediate/moderate the development of psychopathology.

Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandinE2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renalarterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesisclose PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations.;Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacintreatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants.Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants withPDA.;Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January2013 was the cutoff point.;Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. Foribuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infantsincluded in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate withthe gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinineconcentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and theclearance is reduced in preterm infants as compared with fullterm infants.;Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases therisk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 islengthened in prematures as compared with term infants.

A Review of the Management of Lymphangiomas by Jennifer Ha, Yu-Ching Yu, Francis Lannigan (238-248).
Introduction: Lymphangioma is a rare benign cyst caused by congenital malformation of the lymphatic systemsthat often occurs in the cervicofacial region. There is no consensus on its management: Observation, aspiration, injection,cryotherapy, electrocautery, radiation, laser, ligation and excision.;Methods: We performed a literature search with the keywords “cystic hygroma”, “lymphangioma”, “management”, “OK432” and “picibanil” from Medline, Embase and PubMed databases.;Results: We present a review of the history, signs and symptoms, diagnosis, histology, classification and management optionsof cystic hygroma.;Conclusion: There is no consensus on the treatment options. It should be individualised depending on the size of the lesion,anatomic localisation and complications.