Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric HematologyOncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics

Justification: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. Objective: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. Process: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. Recommendations: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Primary Wilms tumor of the urinary bladder

ABSTRACT Wilms tumor (WT) can occur at various extrarenal sites; however, the urinary bladder as the primary site is occasional. A 4-year-old-female child presented with difficulty in micturition for the past month. The contrast-enhanced magnetic resonance imaging with magnetic resonance (MR) urography revealed a polypoidal, heterogeneous mass in the urinary bladder with no abnormality in the kidneys. Cystoscopy-guided biopsy was reported as an extrarenal Wilms tumor (ERWT) with triphasic components. Post-chemotherapy, a computed tomography scan revealed a residual tumor for which she underwent partial cystectomy. The diagnosis of ERWT was confirmed. She received adjuvant chemotherapy and remained well at the 9th month post completion of chemotherapy. The primary bladder WT must be considered in the differential of a small blue round cell tumor at an extrarenal site in the pediatric age group. The diagnosis is especially challenging in small biopsy material, although it has immense significance in management and prognosis.

Fibrous hamartoma of infancy with sarcomatous transformation: an unusual morphology

ABSTRACT Background Fibrous hamartoma of infancy (FHI) is a rare soft tissue lesion arising as a subcutaneous mass involving the axilla, trunk, and upper arm in infants and children <2yrs. Sarcomatous transformation in FHI is described in anecdotal cases in the literature. Case Report We describe one such example arising as a mass in the lower back in a 3-month-old infant. On histology, the tumor contained classic triphasic morphology; however, brisk mitotic activity noted at multiple foci was diagnostically challenging to categorize. The tumor was evaluated for ETV6-NTRK3 fusion to exclude other common differentials. Conclusion While FHI may be frequently encountered in infants, rare sarcomatous transformation are known to occur and merits special attention as it can be misdiagnosed. Also, a close follow-up is warranted as the lesion is known to recur locally.

Risk Factors for Microbiologically-documented Infections, Mortality and Prolonged Hospital Stay in Children with Febrile Neutropenia

Objective: To analyze the risk factors for microbiologicallydocumented infection, mortality and hospital stay more than 5days in children with febrile neutropenia.Design: Cross-sectional study (July 2013-September 2014).Setting: Government-run, tertiary-care, university hospital inChandigarh, Northern India.Participants: 414 episodes in 264 children aged <12 years, notundergoing stem-cell transplantation.Outcome measures: Predictors for ‘high-risk’ febrileneutropenia.Results: Microbiologically-documented infections wereobserved in 82 children (19.8%); bacterial 14.2%, fungal 4.3%,polymicrobial 9.7%. Complications were documented in 109(26%) children. 43 (10.3%) died: 8 due to fungal and 35 due tobacterial sepsis. Children admitted within 7 days of the lastchemotherapy (P<0.01) and having a non-upper respiratory focusof infection (P<0.02) were at risk of developing microbiologically-documented infections and death. Platelet count <20000/uL(P=0.03) was an additional predictor for microbiologically-documented infections, while albumin <2.5 g/dL (P=0.04) and C-reactive protein >90 mg/L (P=0.02) were risk factors predictingmortality. The median (IQR) duration of hospital stay was 5 (3,8)days. Hospital stay >5 days was seen in 144 (35%) children.Children with acute myeloid leukaemia (P<0.01) and admittedwithin 7 days of chemotherapy (P=0.02) were likely to have aprolonged hospital stay >5 days.Conclusions: Febrile neutropenicchildren admitted within 7days of completion of chemotherapy, those with a non-upperrespiratory focus of infection, CRP >90 mg/dL, platelet <20000/uLand albumin <2.5 g/dL need to be considered as ‘high risk’ forcomplications and mortality.

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

Objective: To evaluate the efficacy of prolonged deferiprone monotherapy in patients with ?-thalassemia major. Methods: This cross-sectional study included 40 patients (age range 9 to38 years) with thalassemia major receiving deferiprone for ?5 years. Serum ferritin, andmyocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRIwere recorded. Results: The patients were receiving deferiprone for a mean (SD) duration of12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. TheMIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3(7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severeelevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients. Conclusions: The majorityof patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load.Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

A young leukemic patient with unusual catastrophic intestinal complication.

A 14-year-old child with acute lymphoblastic leukemia who had completed induction chemotherapy presented with fever and diffuse musculoskeletal pains which was thought to be a constellation of myositis, arthralgias and arthritis. Investigations revealed initially showed normal peripheral blood counts but had pancytopenia and pre-terminally blasts were seen in the peripheral blood smear. He had bone marrow necrosis. Disseminated intravascular coagulation was suspected with a positive fungal serology. At autopsy, he had evidence of disease relapsed in lymph nodes, liver, spleen, testes and kidneys. There was extensive pseudomembranous colitis and appendicitis with changes of toxic megacolon.

Performance of Accredited Social Health Activists to Provide Home-based Newborn Care: A Situational Analysis.

Objective: To assess Accredited social health activists’ (ASHAs) ability to recognize illness in infants aged less than 2 months. Methods: Investigators observed 25 ASHAs conducting 47 visits. Results: ASHA-investigator agreement on the need to further assess infants was intermediate (kappa 0.48, P<0.001). Using IMNCI’s color codes, ASHAs misclassified 80% of infants. ASHAs did not follow home-based newborn care formats and skipped critical signs. Overall ASHA-investigator agreement on diagnosis was poor (kappa=0.23, P=0.01). Conclusion: There is a need for improved training, tools, and supportive supervision.

Serodiagnosis of celiac disease in children referred for evaluation of anemia: A pediatric hematology unit's experience.

Background: Children presenting with typical clinical features of celiac disease (CD) are diagnosed relatively easily, however, diagnosis remains challenging and is often delayed when they present with 'difficult to treat anemia' without overt gastrointestinal manifestations. Index study was undertaken to report profile of patients referred to pediatric hematology unit with 'difficult anemia' who subsequently were diagnosed with CD. Materials and Methods: The records of 83 patients (1988-2008) with CD were scrutinized retrospectively who had presented with predominant hematological manifestations. Results: CD was confirmed histologically in 31 (37%), while 52 (63%) were diagnosed by serology alone. The mean age at diagnosis was 8.0 ± 2.8 years. The mean duration of symptom-diagnosis interval was 40.9 ± 30.6 months. Eighty-one (98%) children had anemia (Hb < 11 g/dl) and 55 (66%) had received iron supplements without discernible benefit. Thirty-nine (47%) patients received a blood transfusion. Thirty-six (43%) patients did not have diarrhea. Majority of the patients had either a microcytic-hypochromic (48%) or dimorphic (43%) anemia. Twenty-four (33%) had thrombocytosis, while 5 (7%) had thrombocytopenia. Mean duration of follow-up for patients on roll in the clinic for more than six months was 17.7 ± 20.9 months. Conclusion: Pediatricians and hematologists need to be aware of the extra-intestinal manifestations of CD. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in children presenting with predominantly hematological manifestations. Investigations for CD are recommended in children presenting with iron deficiency anemia refractory to hematinics or who have coexisting growth retardation. Necessity for biopsy in overtly symptomatic cases is discussed.

Langerhans' cell histiocytosis: experience from a single center.

Clinical profile, disease-distribution and outcome of Langerhans cell histiocytosis (LCH) is presented in this retrospective analysis. There were 69 children with LCH from January 1986 to December 2004. Diagnosis was presumptive in the majority. The age ranged from 2 months to 12 years. Multisystem disease was documented in 48 (69.6%) children. Evidence of hepatic dysfunction was detected in 25 (36.2%). An elevated serum alkaline phosphatase was a prominent observation in patients with hepatic involvement. Children with localized disease received oral steroids, while cases with disseminated/multi-system disease were treated with prednisolone and, vinblastine or etoposide. 20 (54%) children with disseminated disease and organ dysfunction died. A favorable outcome was documented in all but one case with localized disease. Portal hypertension developed in 3 cases, all of whom had a fatal outcome. Twelve (17.4%) patients had diabetes insipidus. Disseminated disease with organ dysfunction was observed to be a predictor of fatal outcome.

Profile and outcome of neuroblastoma with convertional chemotherapy in children older than one year: a 15-years experience.

The clinical profile and outcome of neuroblastoma in 103 children, older than one-year is presented. 74 had Stage IV, 27 Stage III and one patient each had Stage I or II disease. Treatment included chemotherapy followed by surgical resection/debulking. Radiotherapy was administered to those with residual tumor. Chemotherapy consisted of OPEC (vincristine, cyclophosphamide, cisplatin and etoposide). The caretakers of 54 (52.4%) children either did not opt for or defaulted therapy, whilst 3 patients died before chemotherapy could be initiated. Of the remaining 46 patients, the tumor progressed during therapy in 19 (41.3%). Relapse of disease was documented in 22 (47.8%) cases. Merely 4 (8.7%) children are disease free for a period of 16.5+/-6.7 months. Majority of children presented with advanced disease and the outcome was dismal with conventional non-myloablative chemotherapy.

Attenuated form of Evans syndrome among pediatric ITP patients.

Long term follow up of adult patients with immune thrombocytopenic purpura (ITP) have shown evolvement of secondary autoimmune diseases such as SLE, Evans syndrome, autoimmune neutropenia, Graves disease etc. We studied 30 cases of pediatric ITP patients for evidence of hemolysis to assess the possibility of Evans like syndrome. Measurement of free serum haptoglobin, a sensitive indicator of red cell destruction was used after careful exclusion of micro angiopathic hemolysis, SLE or overt Evans Syndrome. Results showed abnormally low level of free serum haptoglobin in 11 of the 30 (36.7%) patients compared to that in 20 age matched controls (P < 0.001) as an evidence of hemolysis. Our data in pediatric patients is similar to that reported in adult ITP cases and support the observation of Evans made 50 years ago that there is a spectrum like relationship between primary thrombocytopenia and hemolytic anemia. Thus the concept of attenuated form of Evans syndrome could be considered, in group of patients with ITP in pediatric age group.

Hepatitis-associated aplastic anemia: successful outcome following immunosuppressive therapy.

Hepatitis-associated aplastic anemia is an uncommon variant seen in young, previously healthy individuals. The pancytopenia follows hepatitis by a few weeks and is usually severe and prolonged. Bone marrow transplantation remains the cornerstone of therapy. However, immunosuppressive therapy has been found to be effective. We report an 8-year-old girl who had non-A, B, C and E hepatitis-associated severe aplastic anemia. She became transfusion-independent and had consistent, albeit incomplete recovery after immunosuppressive therapy with antithymocyte globulin and cyclosporine.

Assessment of adrenal endocrine function in Asian thalassemics.

Adrenal endocrine function was assessed in a cohort of 20 patients, between 10 and 20 years of age, with transfusion dependent beta thalassemia. Cortisol levels were assayed before and after ACTH stimulation with 1 micrograms and 250 micrograms. Adrenal dysfunction was defined as a basal cortisol of greater than 400 nmol/L and/or peak cortisol levels of greater than 500 nmol/L. Overall, 9 patients (45 %) had in vitro evidence of adrenal dysfunction. A statistical significant correlation (r=0.4308; P < 0.05), between wasting and the basal cortisol level, was observed. Similarly, there was correlation between the number of transfusions received and growth failure (r=0.4774;P < 0.05). In comparison to the involvement of other endocrine axes in polytransfused thalassemics, the adrenal endocrine function abnormalities are minor and clinically of little consequence. The observations, albeit, in a small cohort of thalassemics, stress the need for an annual estimation of basal cortisol level, especially in patients with wasting.

An outbreak of hospital acquired diarrhea due to Aeromonas sobria.

Six children admitted in a 18 bedded hematology-oncology unit, developed acute diarrhea in a four week period between March and April 2001. Salmonella senftenberg was the additional pathogen in the stool sample of one patient who developed cola colored urine and pneumonia in the course of his illness. All the Aeromonas strains had a similar biotype and antibiogram. The diarrhea subsided spontaneously in two children whilst three responded to antimicrobial therapy. One patient sought discharge and did not return for a follow up. Aeromonas sobria with a similar profile as the isolates from the patients could be isolated from only one of several environmental sites. The outbreak could be contained by appropriate interventional measures.

Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study.

Wheat grass juice is the juice extracted from the pulp of wheat grass and has been used as a general-purpose health tonic for several years. Several of our patients in the thalassemia unit began consuming wheat grass juice after anecdotal accounts of beneficial effects on transfusion requirements. These encouraging experiences prompted us to evaluate the effect of wheat grass juice on transfusion requirements in patients with transfusion dependent beta thalassemia. Families of patients raised the wheat grass at home in kitchen garden/pots. The patients consumed about 100 mL of wheat grass juice daily. Each patient acted as his own control. Observations recorded during the period of intake of wheat grass juice were compared with one-year period preceding it. Variables recorded were the interval between transfusions, pre-transfusion hemoglobin, amount of blood transfused and the body weight. A beneficial effect of wheat grass juice was defined as decrease in the requirement of packed red cells (measured as grams/Kg body weight/year) by 25% or more. 16 cases were analyzed. Blood transfusion requirement fell by >25% in 8 (50%) patients with a decrease of >40% documented in 3 of these. No perceptible adverse effects were recognized.

Griscelli syndrome.

An eight month old male infant presented with recurrent infections and partial albinism. Initially a possibility of Chediak Higashi syndrome (CHS) was considered, but a negative investigative work up prompted us to look for an alternate diagnosis. A literature search revealed that Griscelli syndrome (GS) has overlapping symptoms and signs. The findings in skin and hair biopsies in Griscelli syndrome are distinctive.

Preoperative aspiration for anterior mediastinal cyst with respiratory distress.

We report a 5-month-old boy who presented with an anterior mediastinal cystic teratoma. Pre-operative symptoms of respiratory distress secondary to airway obstruction were markedly reduced by percutaneous aspiration. Aspiration was also beneficial in easily ventilating the baby during the surgical procedure.

Congenital dyserythropoietic anemia: clinical and hematological profile.

Congenital dyserythropoietic anemia (CDA) is a rare disorder, which manifests clinically with varying degrees of anemia and hepatosplenomegaly. These features are not pathognomic and a diagnosis of CDA is generally considered after other causes of chronic hemolytic anemia have been ruled out. The clinico-hematological profile of 10 patients with CDA is presented in this communication. Six patients had CDA type II and four had CDA type I. Age at onset of pallor ranged from birth to 9 years. Blood transfusion requirements varied from nil to monthly. This is the first report of CDA type I from India.

Melanotic neuroectodermal tumour in an infant.

Most jaw swellings in infancy are benign odontogenic cysts or tumours. The encounter with an unusual melanotic neuroectodermal tumour of the jaw in a young infant is described in this report. There has been no recurrence, after complete surgical excision, in a follow-up period of six months.