Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children

Objective To ascertain the efect of human immunodefciency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. Methods Fifty-fve children living with HIV infection (30 receiving ART for?2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo–18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. Results Mean (SD) serum MPO activity at 6 mo after ART [32.1 (±19.9) U/L] was comparable to that at disease onset [17.2 (±23.0) U/L], although it was signifcantly higher compared to that in children on ART?2 y [13.3 (±15.8) U/L] and controls [12.1 (±11.9) U/L]. Median fuorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was signifcantly higher than in the controls, as well as, children receiving ART?2 y. Stimulation index was highest in the control group [442.4 (341.9–562.9)], which was comparable to that in children on ART?2 y [304.2 (153.2–664.8)], but was signifcantly higher than the treatment-naïve cohort [266.1 (148.2–339.4)] and children on ART for 6 mo [318.8 (154.9–395.6)]. Conclusion A hyperinfammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for?2 y normalized the impaired neutrophilic phagocytic functions.

Iron Profile in Term Small for Gestational Age Infants at 10 Weeks of Age and Correlation With Maternal Iron Profile : A Prospective Cohort Study

Background: Term small for gestational age (SGA) babies are at risk for developing iron deficiency anemia. The association between maternal and infant iron stores is not clear. Objective: To assess proportion of term SGA neonates developing iron deficiency anemia by 10 weeks of age, and measure correlation between iron profile and hepcidin of babies at birth and at 10 weeks of age with maternal iron profile. Design: Prospective cohort study conducted from November, 2018 to April, 2020. Participants: 120 term SGA babies and their mothers. Intervention: Hemogram, iron profile and serum hepcidin (every fourth case) estimated in mother, cord blood and baby at 10 weeks. Babies developing anemia at 6 weeks detected by hemogram and ferritin were started on iron supplementation and excluded from the study. Outcome: Proportion of babies developing iron deficiency anemia at 10 weeks of age. Results: 35 (29.2%) of 120 term SGA babies developed anemia (hemoglobin <9 g/dL) at 6 weeks. Proportion of infants who developed iron deficiency anemia (hemoglobin <9 g/dL and serum ferritin <40 µ/dL) at 6 and 10 weeks of age was 14.2% and 23.3%, respectively. No significant correlation was found bet-ween hemoglobin, iron and hepcidin of the baby in cord blood and at 10 weeks of age with that of mothers. Serum hepcidin in babies at birth (137.5 ng/mL) were higher than maternal values (128 ng/mL). Conclusion: A significant proportion of term SGA infants developed anemia during early infancy, irrespective of maternal iron status.

Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in Hospitalized Children

Objectives: To evaluate the antibiotic resistance pattern, clinical profile and predictors for adverse outcomes in children hospitalized due to staphylococcal infection; and the frequency of nasal and axillary carrier states in these children. Methods: This descriptive study enrolled 100 symptomatic children (aged 1 month - 12 years) in whom S. aureus was isolated from cultures of blood, pus or cerebrospinal fluid. All samples were processed as per the Clinical and Laboratory Standards Institute (CLSI) standards. Antimicrobial susceptibility was tested using disc diffusion method; minimum inhibitory concentration (MIC) for vancomycin was measured using E strips. Predictors for poor recovery were determined by univariate and multivariable logistic regression analysis. Results: Skin and soft tissue infections were the most common (47%) followed by respiratory infections (37%). Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 62%, out of which 63% (39/62) were multi-drug resistant. Carrier state was present in 49% (93% MRSA); 80% were axillary carriers. High MIC (>1 µg/mL) for vancomycin was seen in 65% of patients, and was the only factor associated with poor recovery [aOR (95%CI) 5.3 (1.6,18.5); P=0.008] on multivariable logistic regression analysis. Conclusion: MRSA is the predominant strain in severe staphylococcal infections requiring hospitalization, and majority of them are multidrug resistant. High MIC to vancomycin among S. aureus is an emerging concern.

Sunlight Exposure vs Oral Vitamin D Supplementation for Prevention of Vitamin D Deficiency in Infancy: ARandomized Controlled Trial

Objective: To compare the efficacy of sunlight exposure and oral vitamin D3 supplementation to achieve vitamin D sufficiency in infants at 6 months of age. Design: Open-label randomized controlled trial. Setting: Public hospital in Northern India (28.7°N). Participant: Breastfed infants at 6-8 weeks of age. Intervention: Randomized to receive sunlight exposure (40% body surface area for a minimum of 30 minutes/week) or oral vitamin D3 supplementation (400 IU/day) till 6 months of age. Outcome: Primary - proportion of infants having vitamin D sufficiency (>20 ng/mL). Secondary - proportion of infants developing vitamin D deficiency (<12ng/mL) and rickets in both the groups at 6 months of age. Results: Eighty (40 in each group) infants with mean (SD) age 47.8 (4.5) days were enrolled. The proportion of infants with vitamin D sufficiency increased after intervention in the vitamin D group from 10.8% to 35.1% (P=0.01) but remained the same in sunlight group (13.9%) and was significant on comparison between both groups (P=0.037). The mean (SD) compliance rate was 72.9 (3.4)% and 59.7 (23.6)% in the vitamin D and sunlight group, respectively (P=0.01). The geometric mean (95% CI) serum 25(OH) D levels in the vitamin D and sunlight group were 16.23 (13.58-19.40) and 11.89 (9.93-14.23) ng/mL, respectively; (P=0.02), after adjusting baseline serum 25(OH)D with a geometric mean ratio of 1.36 (1.06-1.76). Two infants in sunlight group developed rickets. Conclusion: Oral vitamin D3 supplementation is more efficacious than sunlight in achieving vitamin D sufficiency in breastfed infants during the first 6 months of life due to better compliance.

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.

Pulmonary Dysfunction in Transfusion-Dependent Thalassemia and Response to Intensive Chelation Therapy

Objectives: To evaluate pulmonary functions in children with transfusion-dependent thalassemia, and its reversal (lung dysfunction) using intensive intravenous chelation with desferrioxamine (DFO) (4 weeks). Methods: This descriptive study enrolled 77 children with transfusion-dependent thalassemia. Pulmonary function test (PFT) and iron load (serum ferritin (SF) & T2* MRI of heart and liver) were done. PFT included spirometry, total lung capacity (TLC) by helium dilution test and diffusion capacity by carbon monoxide (DLCO). Follow-up PFT was available for 13 children with moderate to severe lung dysfunction given intravenous DFO. Results: 50 (68.8%) patients had lung dysfunction, most commonly diffusional impairment (48; 96%), and reduced TLC (11; 22%); and none had obstructive pattern. 9 (81.8%) patients with restrictive defect had moderate to severely deranged DLCO. PFT and T2* MRI values were inversely correlated with serum ferritin. Among 13 patients receiving intensive chelation for 4 weeks, significant improvement was noticed in forced expiratory volume in one minute/ forced vital capacity ratio (?FEV1/FVC) (P=0.009), ?DLCO (P=0.006) and ?SF (P=0.01). Conclusions: Pulmonary dysfunction is common in children with multi-transfused thalassemia, and routine screening by PFT needs to be part of the management guidelines.

A prospective cohort study of enteric pathogens in human immunodeficiency virus-infected Indian children and their relationship with diarrheal recurrence

Background: Opportunistic intestinal infections can increase the risk of death 11- fold in Human immunodeficiency virus (HIV) infected children presenting with diarrhea. Understanding the etiology of diarrhea and its predictors can help strategize a targeted approach to reduce child mortality due to diarrhea in this vulnerable group. Authors aim was' to compare the enteric pathogens in HIV-infected children with and without acute diarrhea, to assess the association between carriage of enteric pathogens in HIV-infected children and the occurrence of diarrhea within the next 3 months and to ascertain the relationship between enteric pathogens in HIV-infected children with their immunological and nutritional status.Methods: Stool samples were collected from HIV-infected children with acute diarrhea (n=41) and without diarrhea (n=52). All samples were subjected to microscopic examination, modified acid-fast and Trichrome staining, hanging drop examination, and bacterial culture. Serology for Cryptosporidium parvum was determined. Children who had received any antimicrobial therapy within the previous 2 weeks were excluded. Participants were followed up for three months for occurrence of diarrhea.Results: Intestinal pathogens were isolated in 48.8% and 42% of children in the diarrheal and non-diarrheal group respectively. The most common pathogens isolated in the diarrheal and non-diarrheal group were Cryptosporidium parvum and Escherichia coli (29.3% vs. 17.3%). During follow up, 8 children in each group had diarrheal occurrence. The pathogen isolated in subsequent episodes matched with the initial isolate in 3 children in each group.Conclusions: HIV-infected children without diarrhea also harbour enteric pathogens in comparable proportions to symptomatic children, which can predispose them to diarrheal occurrence in future, hence indicating need for assessing the need for preventive screening and prophylactic antibiotic regimens in this vulnerable group.

Vitamin D Supplementation for Treatment and Prevention of Pneumonia in Under-five Children: A Randomized Double-blind Placebo Controlled Trial.

Objective: To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in under-five children. Design: Randomized, double blind, placebo-controlled trial. Setting: Tertiary-care hospital. Participants: 324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL). Intervention: 100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment. Outcome variables: Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness. Results: Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1·39 (1·11, 1·76); P=0·005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22·8%); vitamin D: 39/156 (25%); RR (95% CI): 1·13 (0·67,1·90); P=0·69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention. Conclusion: There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.

Microbiome: Paediatricians’ perspective.

Millions of microorganisms inhabit the human body and affect its homeostasis in multiple ways. Alterations in this microbial community have implications for the health and survival of the human hosts. It is believed that these microorganisms should be included as part of the human genome because of their influence on human physiology hence the term “microbiome” is commonly used to refer to these microbes along with their genetic make-up and their environmental interactions. In this article we attempt to provide an insight into this recently discovered vital organ of the human body which is yet to be fully explored. We herein discuss the composition and role of microbiome in human health and disease with a special emphasis in children and culture-independent techniques employed in mapping of the microbiome. Alteration in the gut microbiome has been associated with causation of several paediatric diseases like infantile colic, necrotizing enterocolitis, asthma, atopy, obesity, type -1 diabetes, and autism. Atopic dermatitis and psoriasis have also been associated with changes in the cutaneous microbiome. Respiratory microbial imbalances during infancy have been linked with wheezing and bronchial asthma. Dysbiosis in the regional microbiome has been linked with caries, periodontitis, and chronic rhinosinusitis. The future therapeutic implications of this rapidly evolving area of research are also highlighted.

Energy Drinks: Potions of Illusion.

Energy drinks are widely consumed by adolescents as these claim to improve performance, endurance and alertness. Recent reports have shown that there are no real health benefits of these drinks. On the contrary, certain adverse effects due to energy drinks have come to the forefront, casting a big question-mark on their safety and utility. This review discusses the present status of energy drinks, their active ingredients and their safety. We conclude that energy drinks, despite having some short pleasant effects, can be harmful for the body and are best avoided.

Estimation of Gestational Age, Using Neonatal Anthropometry: A Cross-sectional Study in India.

Prematurity is a significant contributor to neonatal mortality in India. Conventionally, assessment of gestational age of newborns is based on New Ballard Technique, for which a paediatric specialist is needed. Anthropometry of the newborn, especially birthweight, has been used in the past to predict the gestational age of the neonate in peripheral health facilities where a trained paediatrician is often not available. We aimed to determine if neonatal anthropometric parameters, viz. birthweight, crown heel-length, head-circumference, mid-upper arm-circumference, lower segment-length, foot-length, umbilical nipple distance, calf-circumference, intermammary distance, and hand-length, can reliably predict the gestational age. The study also aimed to derive an equation for the same. We also assessed if these neonatal anthropometric parameters had a better prediction of gestational age when used in combination compared to individual parameters. We evaluated 1,000 newborns in a cross-sectional study conducted in Guru Teg Bahadur Hospital in Delhi. Detailed anthropometric estimation of the neonates was done within 48 hours after birth, using standard techniques. Gestational age was estimated using New Ballard Scoring. Out of 1,250 consecutive neonates, 1,000 were included in the study. Of them, 800 randomly-selected newborns were used in devising the model, and the remaining 200 newborns were used in validating the final model. Quadratic regression analysis using stepwise selection was used in building the predictive model. Birthweight (R=0.72), head-circumference (R=0.60), and mid-upper arm-circumference (R=0.67) were found highly correlated with gestation. The final equation to assess gestational age was as follows: Gestational age (weeks)=5.437×W–0.781×W2+2.815×HC–0.041×HC2+0.285×MUAC–22.745 where W=Weight, HC=Head-circumference and MUAC=Mid-upper arm-circumference; Adjusted R=0.76. On validation, the predictability of this equation is 46% (±1 week), 75.5% (+2 weeks), and 91.5% (+3 weeks). This mathematical model may be used in identifying preterm neonates.

Fate of Articles Rejected by Indian Pediatrics.

The present study was conducted to determine the fate of manuscripts rejected by Indian Pediatrics (IP), and to identify the factors facilitating publication of a rejected manuscript elsewhere. Database (PubMed, IndMed) and Google searches were performed to trace the manuscripts published elsewhere any time after rejection by Indian Pediatrics in the year 2002. Eighteen per cent of the rejected submissions (62 out of 347) were eventually (till July 2009) published elsewhere. These manuscripts subsequently appeared in 33 different journals; Indian Journal of Pediatrics published the maximum numbers (n=22). Seventy four per cent of the rejected papers were published in journals with a impact factor lesser than Indian Pediatrics. Rejection before initiating peer-review, and rejection on the grounds of overinterpretation of results or poor statistical analysis diminished the chances of subsequent publication, whereas manuscripts rejected on grounds of poor originality or poor language had greater chances of being published elsewhere. Rejection of a manuscript by IP does not preclude publication, but rejected manuscripts are published more often in non-pediatric journals or journals with a lower impact factor, although the occasional exception exists.

Burden of Congenital Rubella Syndrome (CRS) in India: A Systematic Review.

Background: Rubella, though a mild, vaccine-preventable disease, can manifest with severe teratogenic effects in the fetus labeled as congenital rubella syndrome (CRS) due to primary maternal rubella infection. Despite a reduction in disease burden of several vaccinepreventable diseases through childhood immunization, CRS continues to account for preventable severe morbidity including childhood blindness, deafness, heart disease, and mental retardation. Objective: To conduct a systematic review to describe the prevalence of CRS and its contribution to major long-term handicaps in Indian population. Another objective was to estimate the susceptibility to rubella infection in Indian adolescent girls and women of reproductive age-group. We also explored strategies to decrease CRS in India by identifying the immunogenicity of rubella containing vaccines (RCV) in Indian children and women, as well as their coverage in India. Methods: Publications reporting ‘CRS prevalence in general population as well as selected subgroups i.e., suspected intra-uterine infection, congenital ocular abnormalities, deafness, congenital heart disease, mental retardation, and congenital malformations’, ‘seroprevalence to rubella (IgG) amongst women and adolescents’, and ‘immunogenicity and coverage of RCVs’ in Indian population were retrieved through a systematic search. Primary databases employed were Medline through PubMed and IndMed, websites of the WHO, and UNICEF. No restrictions were applied in terms of study designs. The primary outcome measure was ‘congenital rubella syndrome’ (CRS) which was further categorized as ‘suspected CRS’ and ‘confirmed CRS’ as defined by World Health Organization (WHO). Results: Comprehensive evidence about the true burden of CRS in India is not available. Almost all studies have been done in institutional/hospital set-ups and community-based studies are grossly lacking. There are no studies assessing the prevalence of CRS in general population. All studies have evaluated the CRS burden in symptomatic cohorts of children. 1-15% of all infants suspected to have intra-uterine infection were found to have laboratory evidence of CRS. About 3-10% of suspected CRS cases are ultimately proven to have confirmed CRS with the aid of laboratory tests. CRS accounts for 10-15% of pediatric cataract. 10-50% of children with congenital anomalies have laboratory evidence of CRS. 10-30% of adolescent females and 12-30% of women in the reproductive age-group are susceptible to rubella infection in India. RCVs are highly immunogenic in Indian adolescents and women. The coverage data of RCVs in India is not available. However, the coverage of MMR vaccine has been reported as 42%, 30% and 5% from Delhi, Chandigarh and Goa, respectively. Conclusion: This systematic review identifies and explores factors associated with the prevalence of CRS in India. There is a need for urgent action in terms of revamping the national immunization policy and introduction of RCVs in the national immunization program. Active surveillance of rubella and CRS is needed to redress the burden of CRS in India.

Clinical and Epidemiological Profiles of Severe Malaria in Children from Delhi, India.

Plasmodium vivax is traditionally known to cause benign tertian malaria, although recent reports suggest that P. vivax can also cause severe life-threatening disease analogous to severe infection due to P. falciparum. There are limited published data on the clinical and epidemiological profiles of children suffering from ‘severe malaria’ in an urban setting of India. To assess the clinical and epidemiological profiles of children with severe malaria, a prospective study was carried out during June 2008–December 2008 in the Department of Pediatrics, Guru Teg Bahadur Hospital, a tertiary hospital located in East Delhi, India. Data on children aged ≤12 years, diagnosed with severe malaria, were analyzed for their demographic, clinical and laboratory parameters. All patients were categorized and treated as per the guidelines of the World Health Organization. In total, 1,680 children were screened for malaria at the paediatric outpatient and casualty facilities of the hospital. Thirty-eight children tested positive for malaria on peripheral smear examination (2.26% slide positivity rate). Of these, 27 (71%) were admitted and categorized as severe malaria as per the definition of the WHO while another 11 (29%) received treatment on outpatient basis. Most (24/27; 88.8%) cases of severe malaria (n=27) were infected with P. vivax. Among the cases of severe malaria caused by Plasmodium vivax (n=24), 12 (50%) presented with altered sensorium (cerebral malaria), seven (29.1%) had severe anaemia (haemoglobin <5 g/dL), and 17 (70.8%) had thrombocytopaenia, of which two had spontaneous bleeding (epistaxis). Cases of severe vivax malaria are clinically indistinguishable from severe falciparum malaria. Our study demonstrated that majority (88.8%) of severe malaria cases in children from Delhi and adjoining districts of Uttar Pradesh were due to P. vivax-associated infection. P. vivax should, thus, be regarded as an important causative agent for severe malaria in children.