Dysmorphism in non-syndromic autism: <Emphasis Type="Italic">A cross-sectional study</Emphasis>

Objectives

To determine the effect of association of dysembryogenesis (manifested by presence of dysmorphic markers) on the developmental profile of autistic children.

Methods

26 autistic children were classified into complex autism (if they had specific dysmorphic markers) or essential autism (in the absence of dysmorphic markers) using the Miles Autism Dysmorphology Measure (ADM). The developmental abilities (Griffith’s Mental Development Scales) and the clinical severity (Childhood Autism Rating Scale) of both groups were compared. The prevalence of dysmorphic markers was also determined in 140 non-autistic controls.

Results

Children with complex autism had poorer development (General Quotient 29.4 vs 34.0, P=0.06) and earlier onset of autistic symptoms (18 vs 24 mo, P=0.05). Dysmorphic markers were significantly more in autistic children compared to normal children (27% vs 10%, P=0.002).

Conclusions

Dysembryogenesis may contribute to the clinical heterogeneity of autistic children.

     

Relationship between immune parameters and non-alcoholic fatty liver disease in obese children

Objective

To investigate the relationship between immune parameters and non-alcoholic fatty liver disease (NAFLD) in obese children.

Design

Cross-sectional study

Setting

Hospital-based study in Zhejiang Province, China between July to September 2015.

Participants

A total of 117 obese children and 209 healthy nonobese children were studied as the obese and control groups. Depending on the severity of NAFLD, the obese group was divided into subgroups 1 (without NAFLD), 2 (with simple fatty liver) and 3 (with steatohepatitis).

Outcome Measures

Glucose metabolism, lipid metabolism and immune parameters.

Results

In the obese group, body mass index (BMI), waist-and hip-circumferences, fasting insulin, Homeostasis model of assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo)B/ApoA1, alanine aminotransferase, uric acid, white blood cells, neutrophils percentage, platelet and interleukin (IL)-6 were significantly higher than those in the controls (P<0.05), while lower high density lipoprotein cholesterol and lymphocyte percentage were noted (P<0.05). IL-10 in the subgroup 3 was higher than those in the control group, subgroup 1 and 2 (P<0.05). Logistic regression analysis showed that BMI, LDL-C, HOMA-IR and IL-10 were independent factors of NAFLD (P<0.05).

Conclusions

These results support a low-grade chronic inflammation in obese children. Moreover, obesity, dyslipidaemia and IR are risk factors while IL-10 may be a protective factor for NAFLD.

     

Double dose <Emphasis Type="Italic">versus</Emphasis> standard dose hepatitis B vaccine in HIV-infected children: <Emphasis Type="Italic">A randomized controlled trial</Emphasis>

Objective

To compare the efficacy of double dose (20 μg) with standard dose (10 μg) of hepatitis B vaccine in HIV-infected children.

Methods

Unvaccinated HIV-infected children were randomized to receive 3 doses of double dose (N=27) or standard dose (N=28) of recombinant Hepatitis B vaccine. Anti-HBs antibody titres were measured 3 mo after the last dose. An antibody titre ≥10 mIU/mL 12 weaks after the third dose was considered as serporotection.

Result

Seroprotection was achieved by 17 (60.7%) children in standard dose group against 20 (74%) in the double dose group [RR (95%CI) 0.8 (0.17-1.7); P=0.29]. CD4 count < 500 cells/mm3 was significantly associated with lower rates of seroprotection.

Conclusion

Double dose of hepatitis B vaccine does not seem to provide any advantage when compared to standard dose in HIV-infected children.

     

Carbapenem-resistant <Emphasis Type="Italic">Enterobacteriaceae</Emphasis> in pediatric bloodstream infections in rural Southern India

Objective

To measure the frequency of antimicrobial resistance in pediatric blood culture isolates of Escherichia coli and Klebsiella spp. with focus on carbapenem resistance.

Methods

Over a period of three years, pediatric blood culture isolates were tested for antimicrobial susceptibility, including molecular investigations for carbapenem resistance.

Results

Amikacin, carbapenems, colistin and tigecycline had an antimicrobial efficacy of >70% (n=140). 7 of the 15 randomly selected isolates were positive for carbapenemase gene; among them, five were New Delhi Metallo β-lactamase (NDM).

Conclusion

There was a high prevalence of Klebsiella spp. in pediatric bacteremia and dissemination of NDMmediated carbapenem resistance in pediatric wards.

     

Nasal Continuous Positive Airway Pressure in Bronchiolitis: <Emphasis Type="Italic">A Randomized Controlled Trial</Emphasis>

Objective

To evaluate the efficacy of nasal continuous positive airway pressure (nCPAP) in decreasing respiratory distress in bronchiolitis.

Design

Randomized controlled trial.

Setting

Tertiary-care hospital in New Delhi, India.

Participants

72 infants (age < 1y) hospitalized with a clinical diagnosis of bronchiolitis were randomized to receive standard care, or nCPAP in addition to standard care, in the first hour after admission. 23 parents refused to give consent for participation. 2 infants did not tolerate nCPAP.

Intervention

The outcome was assessed after 60 minutes. If nCPAP was not tolerated or the distress increased, the infant was switched to standard care. Analysis was done on intention-to-treat basis.

Main outcome measures

Change in respiratory rate, Silverman-Anderson score and a Modified Pediatric Society of New Zealand Severity Score.

Results

14 out of 32 in nCPAP group and 5 out of 35 in standard care group had change in respiratory rate ≥10 (P=0.008). The mean (SD) change in respiratory rate[8.0 (5.8) vs 5.1 (4.0), P=0.02] in Silverman-Anderson score [0.78 (0.87) vs 0.39 (0.73), P=0.029] and in Modified Pediatric Society of New Zealand Severity Score [2.5 (3.01) vs. 1.08 (1.3), P=0.012] were significantly different in the nCPAP and standard care groups, respectively.

Conclusion

nCPAP helped reduce respiratory distress significantly compared to standard care.

     

Second Dose of Scorpion Antivenom in Children with Indian Red Scorpion (<Emphasis Type="Italic">Mesobuthus tamulus</Emphasis>) Sting Envenomation

Objective

To study the effect of the second dose of scorpion antivenom in children with nonresolving or worsening scorpion sting envenomation.

Methods

72 children aged ≤12 years with scorpion sting envenomation grade 2 and above were enrolled. 61 received the first dose of three vials of antivenom at admission (group A). Children with persistent/worsening envenomation within 6 hours received the second dose (group B). The time required for resolution of autonomic symptoms, myocardial dysfunction, predictors of the second dose and side effects were studied.

Results

The mean time taken for resolution of autonomic symptoms were comparable in Group A and B (4.1 vs. 5.3 h, P=0.4), and of myocardial dysfunction was shorter in Group A (10.8 vs. 37.6 h, P=0.02). On regression analysis, abnormal echocardiography at admission was found to be a significant predictor of the second dose (OR=27.6, 95% CI, 4.7–162.5; P=<0.001).

Conclusion

Children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of scorpion antivenom.

Trial registration

CTRI/2015/03/005652.

     

Laparoscopic <Emphasis Type="Italic">versus</Emphasis> open appendectomy for acute appendicitis in children

Objective

To compare the efficacy and safety of laparoscopic appendectomy and open appendectomy for acute appendicitis in children.

Methods

This study was conducted as a retrospective comparison of hospital records for postoperative complications, duration of operation, and postoperative length of stay between children (aged <18y) who underwent laparoscopic (n=190) or open (n=199) appendectomy over a six-year period. Quality of life was evaluated immediately and 1 month postoperatively.

Results

The major complication rate after surgery in laparoscopic group was significantly lower than that of open appendectomy group (13% vs 27%, P<0.05). The mean (SD) postoperative hospital stay was also shorter in laparoscopic group (2.4 (0.6) days vs 3.7 (1.1) days, P<0.05). The postoperative minor complication rate and hospital expenses were not significantly different between the two groups. The duration of surgery was longer in laparoscopic group (P<0.05). Children in laparoscopic group had less postoperative pain and higher quality of life after one month than those in open appendectomy group.

Conclusions

Laparoscopic technique seems to be safer than open appendectomy for acute appendicitis in children.

     

Clinical presentation and cardiovascular outcome in complete <Emphasis Type="Italic">versus</Emphasis> incomplete Kawasaki disease

Objective

To compare the demographic, clinical, and laboratory features of incomplete and complete presentations of Kawasaki disease.

Methods

A retrospective review of the electronic case records between January 2000 and December 2015 in a tertiary care referral center of Sohar, Oman.

Results

31 out of 64 children (48.4%) had incomplete presentation. Children with incomplete presentation had higher incidence of skin rash, lymphadenopathy and conjunctivitis. They took a longer time to show clinical response to intravenous immunoglobulin [mean (SD) 52.6 (17.4) h vs 40.1 (16.4) h, P=0.005], and had prolonged hospitalization [mean (SD) 6.2 (2.5) d vs 4.6 (1.7) d, P=0.009].

Conclusions

Children with incomplete presentation of Kawasaki disease tend to have prolonged hospitalization but short- and long-term coronary outcomes appear to be similar.

     

Hotspots in <Emphasis Type="Italic">PTPN11</Emphasis> gene among Indian children with Noonan syndrome

Objectives

To test for PTPN11 mutations in clinically diagnosed cases of Noonan syndrome.

Methods

17 individuals with clinical diagnosis of Noonan syndrome were included in the study. Sanger sequencing of all the 15 exons of PTPN11 was done. A genotype-phenotype correlation was attempted.

Results

Mutation in PTPN11 was detected in 11 out of 17 (64.7 %) patients with Noonan syndrome; 72% had mutation in exon 3 and 27 % had mutation in exon 13.

Conclusion

PTPN11 mutation accounts for 64.7% of cases with clinical features of Noonan syndrome in India. Majority of the mutations are in exon 3 and exon 13 of PTPN11, making them the hotspots in Indian population.

     

Prevalence of nonalcoholic fatty liver disease in normal-weight and overweight preadolescent children in Haryana,India

Objective

To document the prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic parameters among normalweight and overweight schoolchildren.

Design

Cross-sectional study.

Setting

Thirteen private schools in urban Faridabad, Haryana.

Participants

961 school children aged 5-10 years.

Methods

Ultrasound testing was done, and 215 with fatty liver on ultrasound underwent further clinical, biochemical and virological testing.

Outcome measures

Prevalence of fatty liver on ultrasound, and NAFLD and its association with biochemical abnormalities and demographic risk factors.

Results

On ultrasound, 215 (22.4%) children had fatty liver; 18.9% in normal-weight and 45.6% in overweight category. Presence and severity of fatty liver disease increased with body mass index (BMI) and age. Among the children with NAFLD, elevated SGOT and SGPT was observed in 21.5% and 10.4% children, respectively. Liver enzyme derangement was significantly higher in overweight children (27% vs 19.4% in normal-weight) and severity of fatty liver (28% vs 20% in mild fatty liver cases). Eleven (8.1%) children with NAFLD had metabolic syndrome. Higher BMI (OR 35.9), severe fatty liver disease (OR 1.7) and female sex (OR 1.9) had strong association with metabolic syndrome.

Conclusions

22.4% of normal-weight and overweight children aged 5-10 years had fatty liver. A high proportion (18.9%) of normal-weight children with fatty liver on ultrasound indicates the silent burden in the population.

     

Vitamin D supplementation for treatment and prevention of pneumonia in under-five children: <Emphasis Type="Italic">A randomized double-blind placebo controlled trial</Emphasis>

Objective

To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in underfive 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.

     

Glycogen storage disease type VI with a novel mutation in <Emphasis Type="Italic">PYGL</Emphasis> gene

Background

Glycogen storage disease type VI (GSD-VI) presents with failure to thrive and also fibrosis in some cases, without cirrhosis.

Case characteristics

2½-year-old girl presented with short stature, transaminase elevation and significant fibrosis, suggesting GSD-III.

Observation

A pathogenic mutation in PYGL gene suggested GSD-VI.

Message

GSD-VI should be a differential diagnosis whenever GSD-III is suspected.

     

Neonatal diabetes: A case series

Background

Neonatal diabetes mellitusis a rare disorder with an incidence of 1 in 2,60,000 live births.

Methods

Retrospective analysis of clinical and genetic profile of children admitted with neonatal diabetes mellitus in a tertiary-care hospital in Chennai, India over 11 years.

Results

Ten children were diagnosed with neonatal diabetes of whom 9 had permanent neonatal diabetes mellitus. The age range at onset was from 3 days- 5 months. Of the 9 children, KCNJ11 gene mutation was positive in one, and ABCC 8 and INS gene mutation in two children each. Children with KCNJ11 and ABCC 8 gene mutations were switched over to oral sulfonyl urea therapy.

Conclusion

Few genotypes causing NDM can be managed effectively with oral sulfonyl ureas.

     

Novel <Emphasis Type="Italic">OCRL1</Emphasis> gene mutations in six Chinese families with Lowe syndrome

Background

Lowe syndrome, an X-linked, inheritable disease with clinical symptoms of congenital cataracts, incomplete Fanconi syndrome, and mental retardation, has an approximate incidence of 1 in 500 000. Nearly 200 OCRL mutations related to Lowe syndrome have been found worldwide, with only ten mutations among the Chinese population. Since more mutations may exist in Chinese patients, we sequenced and analyzed the OCRL genes of six children with Lowe syndrome in a medical center in China.

Methods

Peripheral blood was collected from six children with Lowe syndrome and their relatives, and ten healthy adults. Genomic DNA was extracted from the blood and applied to amplify the twenty-four exons and flanking introns of the OCRL gene. The mutations were identified by sequencing.

Results

Five mutations (c.1528C>T, c.2187insG, c.1366C>T, c.1499G>A, and c.2581G>A) of the OCRL gene were found in five families; c.2187insG and c.1366C>T were novel mutations. None of the five mutations were detected in 20 normal chromosomes. No mutation was found in the sixth family.

Conclusion

Two novel mutations of the OCRL gene, c.2187insG and c.1366C>T, were found in Chinese patients with Lowe syndrome, which will provide new clues for the etiology of Lowe syndrome and could be beneficial to genetic diagnosis of the condition.

     

Fibroblast growth factor 23 (FGF23) gene polymorphism in children with Kawasaki syndrome (KS) and susceptibility to cardiac abnormalities

Background

Fibroblast Growth Factor (FGF) 23 influences endothelial integrity and few reports have studied the association between FGF23 and Kawasaki syndrome (KS), a childhood vasculitis displaying a high risk of subsequent cardiac abnormalities (CaA).

Aim

To investigate the genetic variation in the FGF23 gene in a cohort of KS children and its association with serum FGF23 levels and eventual development of CaA, including both coronary artery dilatations and aneurysms.

Patients and methods

84 Italian KS children were recruited; 24/84 (28.6%) developed CaA. Each patient underwent evaluation of serum FGF23 levels and FGF23 genotype: the frequency of the c.212-37insC (rs3832879) polymorphism in intron 1 was examined and compared with sex, age at disease onset, fever duration, laboratory data, and occurrence of CaA. Univariate statistical analysis of categorical parameters was performed by the Pearson’s Chi-square test or Fisher’s exact test as appropriate. Parametric variables were assessed by Student’s t-test for unpaired data. Independent predictors of disease were studied by a logistic regression model.

Results

28/84 patients carried the FGF23 polymorphism (33.3%) and had higher serum FGF23 levels (p <?0.01). FGF23 polymorphism was significantly associated with CaA compared to wild type FGF23 children (respectively, p =?0.03 and p =?0.05). The comparison with demographical, clinical or laboratory data was not significant.

Conclusions

The prevalent segregation of the c.212-37insC polymorphism in children with CaA advocates a possible functional FGF23 role in the predisposition to higher serum levels of FGF23 and potential occurrence of any coronary artery abnormalities in KS.

     

Family-centered care to complement care of sick newborns: <Emphasis Type="Italic">A randomized controlled trial</Emphasis>

Objective

To assess the impact of family-centered care in delivery of care to sick newborns, on nosocomial infection rate.

Design

Randomized controlled trial

Setting

Tertiary referral nursery (October 2010 to March 2012).

Participants

295 neonates randomized at the time of hospitalization in neonatal intensive care unit.

Intervention

Parent-attendant of intervention group were trained using an indigenously developed and pretested, culturally sensitive, simple audio-video tool that covered domains of personal hygiene, hand washing, danger signs recognition and feeding of sick neonate. Control group received routine care by nurses and doctors.

Outcome measure

Primary: culture positive nosocomial infection rate. Secondary: culture negative nosocomial infection rate, duration of hospitalization, mortality and breastfeeding rate.

Results

Two-thirds of family caregivers were fathers/ mothers and about 20% were grandparents. About 60% of family care givers were either illiterate (25%) or primary/middle pass (34%). Incidence of nosocomial episodes of sepsis was not different between groups (incidence rate difference 0.74, 95 % CI -4.21, 5.6, P = 0.76). Pre-discharge exclusive breastfeeding rates were significantly higher in intervention group [80.4% vs 66.7% (P=0.007)].

Conclusions

There was no significant difference in nosocomial infection rate between the two groups. Translating and adapting principles of family-centered care was feasible, and improved the pre-discharge exclusive breastfeeding rates.

     

Effects of <Emphasis Type="Italic">CYP3A5</Emphasis> polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies

Background

CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs.

Methods

A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken.

Results

The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5* 3/*3 variants (referred to as "non-expressers") and those carrying CYP3A5*1 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P=0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P<0.001).

Conclusion

Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.

     

Clinical and molecular characterization of children with neonatal diabetes mellitus at a tertiary care center in northern India

Objective

To study the genetic mutations and clinical profile in children with neonatal diabetes mellitus

Methods

Genetic evaluation, clinical management and follow-up of infants with neonatal diabetes

Results

Eleven infants were studied of which eight had permanent neonatal diabetes. Median age at presentation was 8 weeks and mean (SD) birth weight was 2.4 (0.5) kg. Pathogenic genetic mutations were identified in 7 (63.6%) children; 3 infants with mutations in KCNJ11 gene and 1 in ABCC8 were switched to oral sulfonylureas; 2 infants had mutations in INS and 1 in ZFP57.

Conclusion

Neonatal diabetes mellitus is a heterogeneous disorder. Identification of genetic cause guides clinical management.

     

Central venous catheter salvage in children with <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> central line-associated bloodstream infection

Background

Prompt central venous catheter (CVC) removal is currently recommended in children with Staphylococcus aureus central line-associated bloodstream infection (CLABSI). Our objective was to examine the outcome of attempted line salvage in children with S. aureus CLABSI and assess predictors of success.

Methods

A single-institution, retrospective cohort study was performed of all children with S. aureus CLABSI between 2012 and 2015. Patients with and without immediate CVC removal (≤?2 days after first positive culture) were compared. The primary outcome was failed CVC salvage (removal after 3+ days).

Results

Seventy-seven children met criteria for S. aureus CLABSI. Immediate CVC removal was performed in 27.3% of patients. Among the 72.7% patients in whom CVC salvage was attempted, 78.6% were successful and 21.4% required delayed CVC removal. Malignancy, short gut syndrome, neutropenia, methicillin-resistant S. aureus, and line type were not associated with salvage failure. No associated morbidity or mortality occurred in patients with a failed salvage attempt. New or recurrent bacteremia occurred in five patients, but three were successfully salvaged a second time.

Conclusions

CVC salvage was feasible in the majority of children with S. aureus CLABSI and was not associated with significant complications or attributable mortality as reported in adults.