Clinical practice

The most important goal of introducing noninvasive ventilation (NIV) has been to decrease the need for intubation and, therefore, mechanical ventilation in newborns. As a result, this technique may reduce the incidence of bronchopulmonary dysplasia (BPD). In addition to nasal CPAP, improvements in sensors and flow delivery systems have resulted in the introduction of a variety of other types of NIV. For the optimal application of these novelties, a thorough physiological knowledge of mechanics of the respiratory system is necessary. In this overview, the modern insights of noninvasive respiratory therapy in newborns are discussed. These aspects include respiratory support in the delivery room; conventional and modern nCPAP; humidified, heated, and high-flow nasal cannula ventilation; and nasal intermittent positive pressure ventilation. Finally, an algorithm is presented describing common practice in taking care of respiratory distress in prematurely born infants.     

Clinical practice

Four patients with tyrosinemia type 1 (ages 6–32 months) were treated with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexandion (NTBC) at Cairo University Children’s Hospital, Egypt and followed up for 12–27 months. The recommended average dose of NTBC is 1 mg/kg/day. They were started on the following doses: 0.8, 0.58, 0.5, and 0.625 mg/kg/day, respectively. Two months after start of therapy, succinylacetone was undetectable in patients 1, 2, and 4, while in case 3, it was 5.4 μM. Her NTBC dose was increased from 0.5 to 0.65 mg/kg/day, and succinylacetone was undetectable 1 month later. They were kept on NTBC doses ranging from 0.55 to 0.65 mg/kg/day. These doses allowed catch up growth, normalization of synthetic liver functions, steep drop in serum alpha fetoprotein, reduction in phosphate loss in urine, normalization of serum calcium, phosphate, and alkaline phosphatase, and healing of active rickets. Succinylacetone was undetectable in urine on these doses. In conclusion: Doses of NTBC, lower than recommended, may be helpful in treatment of tyrosinemia, on condition that succinylacetone production is suppressed, and AFP is maintained normal or showing a progressive decrease. This cost-effective dose may allow treatment of affected children from economically underprivileged countries, but longer follow up periods are needed.     

Clinical practice

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids.     

Clinical practice

Both news media and entertainment fiction may lead to short-term and enduring fright reactions. Even TV programs, movies and news made for children may trigger fear. Preoperational children (3 to 7 years of age) are most afraid of fantasy characters, transformations and interpersonal violence. Operational children (8 to 11 years) are more afraid of abstract ideas and imagined implications regarding their own risk. Pediatricians must include media in their history taking and beware of ensuing fear, phobias, sleep and behavior problems. Parents can play a vital role in preventing exposure to or mediating the effects of frightening media. Hospitals must have a pediatric media exposure policy. Conclusion: Media use can have immediate and enduring fear effects that affect many children and that are far from trivial.     

Clinical practice

Proteinuria detection in children is a challenge. Five percent to 15% and 0.4–1% of school children present either transient (benign) or persistent increased amount of protein in urine, respectively. Persistent proteinuria constitutes not only a sign of overt kidney disease but may also be the first indicator of silent renal damage. Proteinuria is a marker for hyperfiltration in individuals with reduced nephron mass and one of the most important independent risk factor for renal disease progression as well. It constitutes the single most important risk factor for future loss of kidney function, preceding glomerular filtration rate reduction. Further, proteinuria itself is diagnostic of cardiovascular disease with prognostic value and target organ involvement in high-risk populations such as diabetic, obese, hypertensive children, or those with known reduced renal mass or previous renal injury. Current strategies to prevent CKD progression, a concept known as renoprotection, are focused on reducing urinary protein excretion among other factors. Reversibility of organ damage in early stages is possible; therefore, pediatricians should screen children for proteinuria or microalbuminuria, mainly in high-risk groups.     

Clinical practice

Allergen-specific immunotherapy (SIT) in its various application forms represents the main treatment approach of IgE-mediated allergic diseases in adults and children. Despite this clear recommendation, many particularities of products, patient characteristics, and product availability in different countries hamper the use of allergen-specific immunotherapy in particular in children. The frequently asked questions by parents, patients, and physicians are the backbone of this review. Thus, the potentials and limitations of allergen-specific immunotherapy in children and adolescents will be highlighted. IgE-mediated allergic diseases are affecting about 20% of the population. They manifest commonly early in life, and hence, the use of SIT should be considered also early in the course of the disease.     

Clinical practice

Childhood functional constipation has an estimated prevalence of 3% in the Western world and is probably the most common gastrointestinal complaint in children. It is characterized by infrequent painful defecation, faecal incontinence and abdominal pain. Only less than 5% of children with constipation have an underlying disease. Only recently two evidence-based guidelines (the Netherlands and Great Britain) have been developed concerning the diagnostic and therapeutic approach for childhood constipation which we both discuss in this article. At present, a thorough medical history and complete physical exam are usually sufficient to confirm the diagnosis of functional constipation. Further laboratory or radiological investigations should only be performed in case of doubt, to exclude an underlying disease. Treatment of childhood constipation consists of four steps: (1) education, (2) disimpaction, (3) prevention of re-accumulation of faeces and (4) follow-up. Surprisingly, there is only limited evidence that laxative treatment is better than placebo in children with constipation. However, according to the available evidence, the Dutch guideline recommends lactulose for children <1 year as first-choice treatment. For children below the age of older than 1 year, both lactulose and polyethylene glycol (PEG) with or without electrolytes can be used as first-choice treatment. According to the National Institute for Health and Clinical Excellence guideline, PEG plus electrolytes is the first-choice treatment for all ages. Conclusion: Children with functional constipation should be diagnosed and treated according to recently developed evidence-based guidelines.     

Clinical practice

The incidence of urolithiasis in children is increasing. Adequate knowledge of treatment modalities and surgical options is therefore essential for every pediatrician. Surgical approaches to urolithiasis in children continue to evolve with advancements in technology and sophistication of current equipment and techniques. Perhaps the most significant development in new techniques is the advent of robotic-assisted laparoscopy. This review, for the general pediatrician, summarizes the most recent pediatric data and guidelines for surgical approaches to treatment of urolithiasis.     

Clinical practice

Mucocutaneous bleeding is common in childhood and may be the result of primary hemostatic disorders such as vascular abnormalities, von Willebrand disease, thrombocytopenia, and platelet dysfunction. A detailed bleeding history and physical examination are essential to distinguish between normal and abnormal bleeding and to decide whether it is necessary to perform further laboratory evaluation. Initial laboratory tests include complete blood count, peripheral blood smear, mean platelet volume, von Willebrand factor (VWF) antigen assay, VWF ristocetin cofactor activity, and factor VIII activity. Once thrombocytopenia and von Willebrand disease have been excluded, platelet function should be tested by platelet aggregation. Additional specific diagnostic tests, such as platelet secretion tests and flow cytometry for the detection of platelet surface glycoprotein expression, are needed to confirm the raised hypothesis.     

Clinical practice

Sleep problems are very prevalent during infancy. The most common problems are those related to night wakings and sleep-disordered breathing (SDB). Most common night waking problems do not have identified physiologic etiology. Their causes appear to be behavioral or developmental by nature, and they usually respond well to behavioral interventions. SDB may result from a variety of anatomic and neurologic factors and is associated with a variety of medical and developmental disorders. Because of the high prevalence of sleep problems during infancy, their persistence, their potential adverse developmental effects, and the positive treatment outcomes, pediatricians should serve as the primary address for screening and referral to proper assessment and treatment.     

Clinical practice

An adequate early treatment of a long-lasting convulsive seizure is critical in reducing potential morbidity, and in particular, brain damage. In pre-hospital settings the use of benzodiazepines should become standard. Nowadays, rectal diazepam is used frequently, but midazoloam and lorazepam are becoming more popular, both being given either intranasally or orally. The buccal route is to be preferred because of its easy use and high efficacy. A generally accepted policy for early treatment of convulsive seizures is a crucial issue in the elaboration of an overall treatment plan for the child with epilepsy. Such a plan should include instruction and education of the parents and the caregivers surrounding the child.     

Clinical practice

Neonatal cholestasis is a serious condition which requires urgent further investigation. Delayed referral of cholestatic neonates, however, is still a significant problem. Every child presenting with jaundice beyond the age of 2 weeks should be evaluated with a fractionated bilirubin checked. In case of neonatal cholestasis, the first step should be the assessment of coagulation and urgent parenteral vitamin K administration in case of coagulopathy and the exclusion of life-threatening conditions or disorders requiring urgent specific treatment. Any child presenting with acholic stools should be referred to a paediatric hepatology unit in order to confirm or rule out biliary atresia, as prognosis after porto-enterostomy correlates with younger age at the time of surgery. Once these conditions have been excluded, a more individualised approach is used based on anamnestic, clinical and further diagnostic findings. Besides specific medical or surgical therapy for selected diseases, early supportive treatment aiming for optimal growth and development and prevention of complications is of uttermost importance.     

Clinical practice

Hyperammonemia is a life-threatening condition which can affect patients at any age. Elevations of ammonia in plasma indicate its increased production and/or decreased detoxification. The hepatic urea cycle is the main pathway to detoxify ammonia; it can be defective due to an inherited enzyme deficiency or secondary to accumulated toxic metabolites or substrate depletion. Clinical signs and symptoms in hyperammonemia are unspecific but they are mostly neurological. Thus, in any unexplained change in consciousness or in any unexplained encephalopathy, hyperammonemia must be excluded as fast as possible. Any delay in recognition and start of treatment of hyperammonemia may have deleterious consequences for the patient. Treatment largely depends on the underlying cause but is, at least in pediatric patients, mainly aimed at establishing anabolism to avoid endogenous protein breakdown and amino acid imbalances. In addition, pharmacological treatment options exist to improve urea cycle function or to remove nitrogen, but their use depend on the underlying disorder. To improve the prognosis of acute hyperammonemia, an increased awareness of this condition is probably more needed than anything else. Likewise, the immediate start of appropriate therapy is of utmost importance. This review focuses on a better understanding of factors leading to ammonia elevations and on practical aspects related to diagnosis and treatment in order to improve clinical management of hyperammonemia.     

Clinical practice

Obstructive sleep-disordered breathing in children is a relatively common problem, presenting in various ways, from primary snoring, without an apparent decrease in quality of life, to obstructive sleep apnea with cognitive, cardiac, and growth abnormalities. History, clinical examination, radiologic evaluations, sleep studies, and other diagnostic modalities are reviewed. Since application and interpretation of these methods are not consistent in studies of snoring, a consensus on optimal treatment options has not been established. Traditionally, adenotonsillectomy has long been the treatment of choice. Treatment failures or recurrences as well as the existence of causes and contributing factors other than adenotonsillar hypertrophy, like obesity, facial malformations, and Down syndrome, have changed the concept of adenotonsillectomy as the ultimate cure. Several other treatment options have been proposed on their own or in combination. Continuous positive airway pressure, anti-inflammatory medications, maxillofacial, and orthodontic treatments are reviewed suggesting the need of a multidisciplinary approach in some cases. Finally, at the end of the chapter, a diagnostic and treatment work up based on current evidence is proposed for otherwise normal children or children with specific conditions.     

Clinical practice

The haemolytic uraemic syndrome (HUS) includes the triad of haemolytic anaemia, thrombocytopenia, and acute renal failure. The classical form [D(+) HUS] is caused by infectious agents, and it is a common cause of acute renal failure in children. The enterohaemorrhagic Escherichia coli-producing Shiga toxin (Stx) is the most common infectious agent causing HUS. Other infectious agents are Shigella and Streptococcus pneumoniae. Infections by S. pneumoniae can be particularly severe and has a higher acute mortality and a higher long-term morbidity compared to HUS by Stx. Atypical HUS [D(−)Stx(−)HUS] are often used by paediatricians to indicate a presentation of HUS without preceding diarrhoea. Almost all patients with D(−)Stx(−)HUS have a defect in the alternative pathway, for example, mutations in the genes for complement factor H, factor I, and membrane co-factor protein. Mutations in the factor H gene are described more often. The majority of children with D(+) HUS develop some degree of renal insufficiency, and approximately two thirds of children with HUS will require dialysis therapy, while about one third will have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy, and the initiation of renal replacement therapy when appropriate. Specific management issues in HUS include management of the haematological complications of HUS, monitoring for extra-renal involvement, avoiding antidiarrhoeal drugs, and possibly avoiding of antibiotic therapy. In addition to the obligatory supportive treatment and tight control of hypertension, there is anecdotal evidence that plasma therapy may induce remission and, in some cases, maintain it. Fresh frozen plasma contains factor H at physiological concentrations. A new therapy for D(−)Stx(−)HUS is a humanised monoclonal antibody (Eculizumab) that blocks complement activity by cleavage of the complement protein C5. It prevents the generation of the inflammatory peptide C5a and the cytotoxic membrane–attack complex C5b-9. We have first positive results, but it is still not approved for HUS.     

Clinical practice

Static, axial, and rotational deformities of the lower extremities are very frequent in children and often a reason for clinic visits. It is important to make a difference between physiological, usually spontaneously healing conditions, and real pathology. Flatfeet and less frequently cavus feet are the main foot problems. Special attention should be paid to the cavovarus foot that often has an underlying neurological disorder. Localized foot pain has usually a very specific cause and needs further investigation. Genua valga and genua vara are typical for a given age group and correct usually spontaneously. Toeing in and toeing out are mainly cosmetic problems and can be caused by tibial or femoral rotation, very rarely by a foot deformity. Leg length discrepancy is also frequent and in most patients limited to less than 2 cm, causing no further problems. Follow-up is, however, needed because of possible increasing discrepancy during growth.     

Clinical practice

Stridor is the sound caused by abnormal air passage during breathing. The cause of stridor can be located anywhere in extrathoracic airway (nose, pharynx, larynx, and trachea) or the intrathoracic airway (tracheobronchial tree). Stridor may be acute (caused by inflammation/infection or foreign body inhalation) or chronic. It may be congenital or acquired. Stridor is a sign from which the underlying cause must be sought; it is not a diagnosis. The role of the pediatrician faced with a child or infant with noisy breathing is: (1) to determine the severity or respiratory compromise and the need for immediate intervention (to prevent respiratory failure); (2) to decide based upon history and clinical examination whether a significant lesion is suspected and, in the latter situation, to refer the child to an ENT surgeon for an upper and lower airway endoscopy; (3) to understand the consequences and management strategies of the underlying lesion and to collaborate with colleagues from related disciplines for follow-up and subsequent management of the child.     

Clinical practice

The spine in children can be affected by different bone pathologies such as trauma, infection, and tumoral processes. Most typical however are postural deformities, of which the evolution is mainly influenced by growth. An overview will be given of the most frequent problems encountered in children. Back pain is not infrequent and should always be taken seriously. In recent years, however, there has been an increase in functional complaints, mainly due to stress-related problems. Improving imaging techniques allows more and more accurate diagnoses and should be used judiciously. Postural deformities should be divided into functional and structural entities. Functional hyperkyphosis, hyperlordosis, and scoliosis should be identified by a thorough clinical evaluation and certainly not be overtreated. A structural scoliosis has the most potential of creating cardiovascular or pain problems in later life. Not all curves however have a bad prognosis. It is the task of the clinician to identify the children needing special attention, based on their knowledge of the underlying pathology as in congenital scoliosis and of the physiological age or maturity of the child, especially in the adolescent idiopathic scoliosis. Treatment should be initiated according to the prognosis regardless of the age of the child.     

Clinical practice

Renal candidiasis is an increasingly common condition affecting predominantly premature infants receiving neonatal intensive care or term infants with urogenital tract anomalies. Multiple risk factors are usually present. Although rare, some infants develop an obstructive uropathy due to fungal balls, and this requires prompt detection and intervention to preserve kidney function. The management of obstructive renal bezoars is challenging and not well summarised in the past. This is mainly due to scarce literature confined to case reports or case series only. This review clarifies various definitions used in relation to renal candidiasis and identifies infants particularly at risk of obstruction. Clinical presentation, diagnosis and the role of imaging are discussed. A summary of the recent literature is provided to outline the range of existing treatment options available with published drug dosages and mode of delivery used. No single approach is successful in all cases and clinicians need to be aware of the different options available: apart from adequate urinary drainage and use of systemic +/− local antifungal agents, additional treatment with fibrinolytic agents and/or endoscopic or open surgical removal may be required. A new simplified algorithm for use in management is proposed. We hope this review will help clinicians in their management of patients presenting with this complex and challenging diagnosis.