温州地区汉族儿童脓毒症与Toll样受体基因多态性

目的 研究温州地区汉族脓毒症(sepsis)患儿TLR4(Asp299Gly、Thr399Ile)和TLR2 (Arg753Gln)基因多态性的分布特征及与脓毒症严重程度的相关性.方法 采用病例-对照研究和测序法对2006年1月至2008年6月期间收住温州医学院附属育英儿童医院的59例脓毒症患儿、38例 严重脓毒症患儿(包括脓毒性休克20例)和57例健康对照组儿童进行TLR4(Asp299Gly、Thr399Ile)和TLR2(Arg753Gln)基冈多态性检测,计算多态位点在三组中的分布频率,按Hardy-Weinberg遗传平衡定律检验,比较不同组别之间各等位基因频率和基因型频率差异是否有显著性.结果 59例脓毒症组患儿、38例严重脓毒症组患儿和57例健康对照组儿童中均未发现TLR4突变基因(Asp299Gly、Thr399Ile);在38例严重脓毒症组患儿中发现2例TLR2突变基因(Arg753Gln),且均为金黄色葡萄球菌感染休克死亡病例,而59例脓毒症组患儿和57例健康对照组儿童中均未发现TLR2突变基因(Arg753Gln).结论 TLR4基因(Asp299Giy、Thr399Ile)多态性与温州地区汉族儿童脓毒症易感性无明显相关性;TLR2基因(Arg753Gln)多态性是否与温州地区汉族儿童致命性阳性菌感染有关,尚需积累更多的儿童脓毒症病例进行研究.     

Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population

Premature birth causes significant health risks of the neonate and increases the cost for neonatal care. Urogenital infection, often caused by Gram-negative bacteria, is a known risk factor. Toll-like receptor-4 (TLR4) is the major endotoxin-signaling receptor and as such is crucial for the initiation of the innate immune response against Gram-negative bacteria. Recently, a variant in the human TLR4 gene was shown to be associated with impaired receptor function and an increased likelihood of Gram-negative sepsis. In the present study, we determined whether the same polymorphism in TLR4 gene is associated with an increased risk for premature birth. We analyzed genotypes for a Finnish study population consisting of a total of 351 term infants and 440 premature infants (gestational age <35 wk; 282 singletons, 158 multiples) and 94 mothers for the presence of the TLR4 polymorphisms Asp299Gly and Thr399Ile. These polymorphisms were in linkage disequilibrium. The 299Gly allele frequencies were 10.6% (93 of 880) in premature infants and 8.3% (58 of 72) in term infants. Excluding multiple pregnancies that often result in premature births, 23.8% (67 of 282) of premature infants and 24.2% (15 of 62) of the mothers of premature infants compared with 15.9% (55 of 345) of term infants and 15.0% (3 of 20) of the mothers delivering at term were carriers of the TLR4 variant. The frequencies of 299Gly allele and Asp/Gly or Gly/Gly genotype carrier status in premature singleton infants were higher than in term singleton infants (p = 0.024, p = 0.028, respectively) or in premature multiples (p = 0.036, p = 0.044, respectively). According to the present results an allelic variation in the TLR4 receptor was associated with increased risk of premature birth.     

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.     

A toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal disease

Aims: Toll-like receptor 4 (TLR4) is the major endotoxin signalling receptor of the innate immune system and is required for efficient recognition of bacterial infections. Here, we analysed a possible association between the TLR4 variant Asp299Gly and disease outcome in children with invasive meningococcal disease.
Methods: In total, 197 children with invasive meningococcal disease were analysed for the TLR4 Asp299Gly variant. Genotyping results were correlated with mortality, the frequency of ventilation support, application of inotropic substances, skin grafting, and limb loss.
Results: The overall Asp299Gly allele frequency was 9.4%. Detection of a heterozygous Asp299Gly TLR4 mutation was significantly associated with fatal outcome (non-survivor group: 31.6% vs. survivor group: 12.1%; p = 0.021) and was even more pronounced in patients with disease onset less than 24 months of age (non-survivor group: 42.8% vs. survivor group: 10.2%; p = 0.006). In this age group, ventilation support was also more frequent in patients with the Asp299Gly genotype (37.5% vs. 6.2%).
Conclusion: Our data suggest that the heterozygous TLR4 Asp299Gly genotype is associated with an increased mortality in children with invasive meningococcal disease.     

Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease

Studies in adult inflammatory bowel disease (IBD) patients have highlighted associations with genetic and serologic markers and suggest an association with disease location, behaviour and natural history. Data on patients with Crohn’s disease (CD, n = 80), ulcerative colitis (UC, n = 15) and indeterminate colitis (n = 4) were collected. All individuals were analysed for CARD15 R702W, G908R and L1007fs for toll-like receptor 4 (TLR4) Asp299Gly and for anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmatic antibodies (pANCA). After a mean of 10.7 years of follow up, the disease behaviour changed in 45% of CD patients, in contrast to disease location, where only 12.5% had a change (p < 0.001). The younger the age at diagnosis, the more patients presented with colonic disease (p = 0.021). Also, more TLR4 Asp299 Gly variants were found when the age at onset was younger (p = 0.018). A large number of concomitant diseases were observed. There was no difference in the prevalence of TLR4 variants nor ASCA or pANCA between the patients with or without concomitant diseases. Patients who progressed more often needed surgery as compared to patients who remained free of stenosing or fistulising disease (27/32 or 84% versus 3/35 or 8.6%, respectively, p < 0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA.     

Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis

Purpose

Internal anal sphincter (IAS) achalasia is a clinical condition with presentation similar to Hirschsprung’s disease, but with the presence of ganglion cells on rectal suction biopsy (RSB). The diagnosis is made by anorectal manometry (ARM), which demonstrates the absence of the rectosphincteric reflex on rectal balloon inflation. The recommended treatment of choice is posterior IAS myectomy. Recently, intrasphincteric botulinum toxin (Botox) injection has been effectively used for treatment of IAS achalasia. The aim of this meta-analysis was to compare the efficacy of posterior IAS myectomy with intrasphincteric Botox injection for treatment of IAS achalasia.

Methods

A systematic literature search for relevant articles was conducted using the following databases: MEDLINE ^® , EMBASE^®, ISI Web of Science^SM and the Cochrane Library. A meta-analysis was performed with the studies where IAS achalasia was diagnosed based on the results of ARM and RSB. Odds ratio (OR) with 95 % confidence intervals were calculated.

Result

Sixteen prospective and retrospective studies, published from 1973 to 2009, were identified. A total of 395 patients with IAS achalasia were included in this meta-analysis. Fifty-eight percent of patients underwent IAS myectomy and 42 % Botox injection. Regular bowel movements were significantly more frequent after IAS myectomy (OR 0.53, [95 % CI 0.29–0.99]; p = 0.04). There was no significant difference in continued use of laxatives or rectal enemas (OR 0.92, [95 % CI 0.34–2.53], p = 0.89) and in overall complication rates between both procedures (OR 0.68, [95 % CI 0.38–1.21]; p = 0.19). Looking at specific complications, the rate of transient faecal incontinence was significantly higher after Botox injection (OR 0.07, [95 % CI 0.01–0.54]; p < 0.01). Constipation and soiling were not significantly different between both procedures (OR 0.66, [95 % CI 0.30–1.48]; p = 0.31 and OR 0.24, [95 % CI 0.03–2.07]; p = 0.25). The rate of non-response was significantly higher after Botox injection (OR 0.52, [95 % CI 0.27–0.99]; p = 0.04). Subsequent surgical treatment was significantly more frequent after Botox injection (OR 0.18, [95 % CI 0.07–0.44]; p < 0.0001). Short- and long-term improvements were significantly more frequent after IAS myectomy (OR 0.56, [95 % CI 0.32–0.97]; p = 0.04 and OR 0.25, [95 % CI 0.15–0.41]; p < 0.0001).

Conclusion

This meta-analysis indicates that in patients with IAS achalasia, posterior IAS myectomy appears to be a more effective treatment option compared to intrasphincteric Botox injection. After Botox injection, the rate of transient faecal incontinence, non-response and subsequent surgical procedures were significantly higher compared to IAS myectomy.     

Helicobacter pylori infection in children: population‐based age‐specific prevalence and risk factors in a developing country

Aim: We estimated the prevalence, age of acquisition and risk factors for Helicobacter pylori (H. pylori) seroprevalence in children aged 1–15 years. Methods: Exposure was assessed using ELISA. Parents responded to a questionnaire regarding number of individuals sharing house, rooms, water source, latrines, housing and assessment of socioeconomic status (SES) by Hollingshead Index. Results: Serum of 1976 children was tested. Helicobacter pylori seropositivity in children aged 11–15 years was 53.5% (OR: 2.0, 95% CI: 1.58–2.5). It increased with moderate crowding index (CRI) of 2–4 to 45.9% (OR: 1.23, 95% CI: 0.92–1.63) and to 51.2% with CRI >4 (OR: 1.52, 95% CI: 1.12–2.06). In middle SES, seropositivity was 50.5% (331/655) (OR: 1.7, 95% CI: 1.29–2.35), whereas in lower SES, it was 47.1% (500/1062) (OR: 1.5, 95% CI: 1.1–2.0). Multivariate analysis showed that Helicobacter pylori seroprevalence was high in children aged 6–10 and 11–15 years (OR: 1.5, 95% CI: 1.2–1.9 and OR: 1.9, 95% CI: 1.56–2.47 respectively), in lower‐middle SES (OR: 1.6, 95% CI: 1.2–2.1 and OR: 1.5, 95% CI: 1.10–2.0 respectively) and in uneducated fathers (OR: 1.58, 95% CI: 1.27–1.95). Conclusion: Helicobacter pylori seropositivity increases with age, in low‐middle SES and is related to father’s educational status. Reducing H. pylori seroprevalence will require improvement in sanitary conditions and educational status of the population.     

Neonatal hyperbilirubinemia and Gly71Arg mutation of UGT1A1 gene: a Chinese case-control study followed by systematic review of existing evidence

Aim: To determine whether the UDP‐glucuronosyltransferase 1A1 gene (UGT1A1) Gly71Arg (211G>A) mutation is associated with neonatal hyperbilirubinemia. Methods: The study consisted of two parts. The case–control study included 112 hyperbilirubinemic infants and 105 control subjects from the Fifth People’s Hospital of Shenzhen. Polymerase chain reaction, restriction fragment length polymorphisms and agarose gel electrophoresis techniques were used to detect the UGT1A1 211G>A mutation. Meta‐analyses was performed to assess the association between neonatal hyperbilirubinemia and UGT1A1 211G>A. Results: Our case–control study revealed that the likelihood of developing neonatal hyperbilirubinemia was 2.65 times higher in the infants with the A allele in the UGT1A1 211G>A than in the infants with the G allele (95% CI, 1.60–4.39). Meta‐analyses (including data from our study) revealed that UGT1A1 211G>A is associated with an increased risk of neonatal hyperbilirubinemia [ odds ratio (OR), 2.37; 95% CI, 2.05–2.74]. In the subgroup analyses based on ethnicity, significantly elevated risks were found in Asian populations (OR, 2.45; 95% CI, 2.10–2.84), but no significant associations were present in Caucasian populations (OR, 1.54; 95% CI, 0.87–2.75). Conclusion: The UGT1A1 211G>A mutation is associated with neonatal hyperbilirubinemia in Asians, but not in Caucasians.     

Association of adrenergic receptor gene polymorphisms with adolescent obesity in Taiwan

Background: Polymorphisms of β2‐adrenergic receptor (ADRB2) and β3‐adrenergic receptor (ADRB3) have been reported to be associated with obesity in adults and adolescents, although study results have been controversial. The aim of the present study was to investigate the association of polymorphisms of ADRB2 (Arg16Gly, Gln27Glu) and ADRB3 (Trp64Arg) with adolescent obesity in Taiwan. Methods: A total of 559 adolescent volunteers with equal numbers female and male were enrolled. Participants were divided into two groups: obese (body mass index [BMI]≥ 95th percentile) and normal weight (BMI 15th–85th percentile). Genomic DNA was extracted from buccal mucosa cells and genotyped in TaqMan assays. Genotype results and clinical subject characteristics were analyzed. Results: Among the three ADRB polymorphisms, only Arg16Gly polymorphism was found to be significantly correlated with adolescent obesity, especially in girls. Girls with genotype Gly/Gly had a lower probability of obesity than those with genotypes Arg/Gly or Arg/Arg (P= 0.006; Arg/Gly: odds ratio [OR], 2.57, 95% confidence interval [95%CI]: 1.22–5.41; Arg/Arg: OR, 3.03, 95%CI: 1.50–6.12). Girls with genotype Gly/Gly had lower BMI than those with genotype Arg/Arg (P= 0.049). Obese adolescents with genotype Gly/Gly had a lower probability of hypertension than those with genotype Arg/Gly or Arg/Arg (P= 0.005). Conclusions: Arg16Gly polymorphism of ADRB2 was significantly associated with obesity in female adolescents, and those with the Gly/Gly genotype were associated with a lower possibility of obesity and lower BMI. This polymorphism was also associated with a lower probability of hypertension in obese adolescents. The other two polymorphisms of ADRB (Gln27Glu and Trp64Arg) were not associated with adolescent obesity in Taiwan.     

Sleep disorders in boys with Duchenne muscular dystrophy

Aim: Determine the frequency and predictors of sleep disorders in boys with Duchenne Muscular Dystrophy (DMD). Method: Cross-sectional study by postal questionnaire. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (validated on 1157 healthy children). A total sleep score and six sleep disturbance factors representing the most common sleep disorders were computed. Potential associations between pathological scores and personal, medical and environmental factors were assessed. Results: Sixteen of 63 boys (25.4%) had a pathological total sleep score compared with 3% in the general population. The most prevalent sleep disorders were disorders of initiating and maintaining sleep (DIMS) 29.7%, sleep-related breathing disorders 15.6% and sleep hyperhydrosis 14.3%. On multivariate analysis, pathological total sleep scores were associated with the need to be moved by a carer (OR = 9.4; 95%CI: 2.2–40.7; p = 0.003) and being the child of a single-parent family (OR = 7.2; 95%CI: 1.5–35.1; p = 0.015) and DIMS with the need to be moved by a carer (OR = 18.0; 95%CI: 2.9–110.6; p = 0.002), steroid treatment (OR = 7.7; 95%CI: 1.4–44.0; p = 0.021) and being the child of a single-parent family (OR = 7.0; 95%CI: 1.3–38.4; p = 0.025). Conclusion: Sleep disturbances are frequent in boys with DMD and are strongly associated with immobility. Sleep should be systematically assessed in DMD to implement appropriate interventions.     

Predictors of remission in children with newly diagnosed immune thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants

1 Background

Immune thrombocytopenia (ITP) during childhood spontaneously remits in up to 80% of children. Predictors of remission are not well understood.

2 Procedure

We analyzed data from Intercontinental Cooperative ITP Study Group (ICIS) Registry II, a large prospective cohort of children with ITP, to investigate factors that might predict remission.

3 Results

In ICIS Registry II, 705 patients had data collected through 12 months following diagnosis, with 383 patients having data available at 24 months as well. Younger age and pharmacologic treatment at diagnosis were significantly associated with disease resolution at 12 and 24 months (P < 0.0001 for both) as was bleeding at diagnosis (P < 0.0001 and P = 0.0213, respectively). Gender and platelet count at diagnosis were not significantly correlated with remission. In the multivariable analysis, remission at 12 months was associated with younger age, higher bleeding grade at diagnosis, and treatment with a combination of intravenous immunoglobulin (IVIG) and corticosteroids at diagnosis. Only younger age and treatment with IVIG and steroids in combination at diagnosis were associated with remission at 24 months. Patients <1 year of age had the highest odds of achieving remission at both 12 months (OR 4.7, 95% CI: 2.0–10.6) and 24 months (OR 7.0, 95% CI: 2.3–20.8).

4 Conclusions

Younger age, bleeding severity at diagnosis, and initial treatment with a combination of corticosteroids and IVIG are associated with remission at 12 months in the ICIS Registry II. Patients <1 year of age have the highest likelihood of remission. The relationship of bleeding and treatment at diagnosis requires further study to clarify whether these are independent predictors of remission.     

Breastfeeding practices and child growth outcomes in Haiti: an analysis of data from Demographic and Health Surveys

Haiti's national nutrition policy prioritises breastfeeding, but limited data are available to inform strategy. We examined national trends in early initiation of breastfeeding (ErIBF) and exclusive breastfeeding (EBF) over a 10‐year period using data from three Haitian Demographic and Health Surveys (1994–1995, 2000 and 2005–2006). We used multivariate regression methods to identify determinants of ErIBF and EBF in the 2005–2006 data set and to examine relationships to growth. There was no change in ErIBF across surveys [1994–1995: 36.6%, 95% confidence interval (CI) 29.9–43.9; 2000: 49.4%, 95% CI 44.1–54.8; 2005–2006: 43.8%, 95% CI 40.5–47.1]. EBF among 0–5‐month‐olds increased sharply (1994–18995: 1.1%, 95% CI 0.4–3.2; 2000: 22.4%, 95% CI 16.5–29.5; 2005–2006: 41.2%, 95% CI 35.4–47.2). The proportion of breastfeeding children 0–5 months who received soft, solid or semi‐solid foods decreased (1994–1995: 68.5%, 95% CI 57.3–77.9; 2000: 46.3%, 95% CI 39.3–53.4; 2005–2006: 30.9%, 95% CI 25.9–36.5). Child age at time of survey [odds ratio (OR) 1.73; P = 0.027], lower maternal education (OR = 2.14, P = 0.004) and residence in the Artibonite Department (OR 0.31; P = 0.001) were associated with ErIBF among children 0–23 months. Age group and department were significant predictors of EBF among children 0–5 months. ErIBF was associated with higher weight‐for‐age z‐scores [effect size (ES) 0.22; P = 0.033] and height‐for‐age z‐scores (ES 0.20; P = 0.044). There was no statistically significant relationship between EBF and growth. The 10‐year ErIBF and EBF trends in Haiti echo global and regional trends. ErIBF and EBF are related practices but with different determinants in the Haitian context. These differences have implications for intervention delivery.     

Feeding behaviors during home‐based treatment of moderate acute malnutrition using corn‐soy blends or lipid‐based nutrient supplements

Feeding behaviors have an important impact on children's nutritional status and are essential to consider when implementing nutrition programs. The objective of this study was to explore and compare feeding behaviors related to supplementary feeding with corn‐soy blends (CSB) and lipid‐based nutrient supplements (LNS) based on best practice feeding behaviors. The study was conducted as part of a randomized controlled trial assessing the effectiveness of new formulations of CSB and LNS and comprised 1,546 children from 6 to 23 months. The study included a mixed methods approach using questionnaires, focus group discussions and home visits and interviews with a subsample of 20 caretakers of trial participants. We found that LNS, compared to CSB, were more likely to be mixed into other foods (OR [95% CI] 1.7 [1.3–2.2], p = <.001), served with a meal (OR [95% CI] 1.6 [1.1–2.3], p = <.018)or between meals (OR [95% CI] 1.5 [1.1–1.9], p = <.005), and fed using an encouraging feeding style (mean difference in percentage points [95% CI] 23% [6%:40%], p = .01). CSB were more likely to be fed using a forced feeding style (mean difference in percentage points [95% CI] 18% [3%:33%], p = .02) and were often observed to be served unprepared. The main differences in feeding behaviors between the two diet groups were linked to how and when supplements were served. Educational instructions should therefore be adapted according to the supplement provided; when providing CSB, efforts should be made to promote an encouraging feeding style, and emphasis should be made to ensure preparations are made according to recommendations.     

Sleep quality in children and adolescents with attention-deficit and hyperactivity disorder

Sleep disturbances are associated with an increased risk of attention-deficit and hyperactivity disorder (ADHD), which can also lead to sleep problems. In this study we aimed to determine the variables that affect the relationship between ADHD and sleep quality. Moreover, we aimed to compare these variables in children and adolescents with ADHD and healthy controls. This cross-sectional study was conducted using a random sample of 122 ADHD patients and 100 healthy children in Turkey. A self-administered questionnaire was distributed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The risk of impairment in sleep quality was associated with the presence of ADHD (OR: 13.3; 95% CI: 6.1–29.1), the presence of somatic disease (OR: 4.9; 95% CI: 1.9–12.2), and a family history of the psychiatric disorder (OR: 4.2; 95% CI: 1.3–13.1). The PSQI total score was higher in children with parental separation compared to those without parental separation (p=0.006). As the economic level of the participants decreased, the PSQI total score increased significantly (p=0.006). It was determined that combined-type ADHD was associated with impairment in sleep quality more than the other subtypes (p<0.001 and p=0.031, respectively). Our findings show that children with ADHD have significantly more sleep problems than healthy controls and that sociodemographic variables and familial characteristics affect sleep quality in healthy children and children with ADHD.     

Comparison of different growth curves in the assessment of extrauterine growth restriction in very low birth weight preterm infants

BackgroundPreterm infants are at risk of extrauterine growth restriction (EUGR) and associated complications in the long term. Growth curves are important in assessing postnatal growth in these infants. The aim of this study was to determine the prevalence of EUGR in preterm infants and the factors associated with EUGR using two different growth curves.MethodsWe retrospectively evaluated 596 preterm infants with birth weight ≤1500 g. Small for gestational age (SGA) was defined as birth weight <10th percentile for gestational age. EUGR was defined as discharge weight z score <?2. All z scores were determined using both the Fenton 2013 and Intergrowth-21st (IG-21) growth curves.ResultsThe infants’ median gestational age was 28 weeks (27–29) and median birth weight was 1080 g (900–1243). The prevalence of SGA was 9.2% with IG-21 curves and 5% with Fenton curves (p < 0.001). The median discharge weight was 2060 g (1860–2363). The prevalence of EUGR was significantly higher with the Fenton curves than with the IG-21 curves (38% vs. 31.7%, p < 0.001). The mean discharge weight z score was ?1.82±1.29 with Fenton and ?1.44±1.49 with IG-21 curves. In multivariate analysis, significant risk factors for EUGR according to the Fenton curves were SGA (odds ratio [OR]: 19.15, 95% confidence interval [CI]: 4.4–82.59), respiratory distress syndrome (RDS) (OR 1.64, 95% CI 1.12–2.4), late neonatal sepsis (LNS) (OR: 2.27, 95% CI: 1.5–3.44), and >16 days to full enteral feeding (OR: 1.8, 95% CI: 1.22–2.68). Similarly, independent risk factors for EUGR according to the IG-21 curve were SGA (OR: 16.3, 95% CI: 7.23–36.9), RDS (OR: 1.81, 95% CI: 1.16–2.83), LNS (OR: 2.29, 95% CI: 1.43–3.68), and >16 days to full enteral feeding (OR: 2.11, 95% CI: 1.38–3.23).ConclusionThe growth curves used for diagnosis may lead to differences in EUGR rates in intensive care units and the factors identified as associated with EUGR. At-risk infants should be evaluated for EUGR and their weight and nutritional support should be monitored carefully. Comparisons of long-term outcomes are needed to assess the suitability of growth curves used for EUGR follow-up.     

Genetic polymorphisms and haplotypes of DNA repair genes in childhood acute lymphoblastic leukemia

BACKGROUND: Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL). PROCEDURES: We genotyped polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and 715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP method. The allele, genotype, and haplotype frequencies of these polymorphisms were compared between cases and controls using Chi-square or Fisher's exact test. PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and XPD polymorphisms. RESULTS: The frequency of XRCC1 194Trp allele in patients was significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children with ALL when compared to controls. The XRCC1 399Gln allele was associated with a significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls. CONCLUSION: The XRCC1 194Trp allele and haplotype B showed a protective effect against development of childhood ALL. In contrast, individuals with the XRCC1 399Gln allele and haplotype C were associated with increased risk for this disease.     

Incidence and Management of Life-Threatening Adverse Events During Cardiac Catheterization for Congenital Heart Disease

Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133–3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8–2.4 %], whereas mortality was 0.28 % (95 % CI 0.18–0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age <1 year [odd ratio (OR) 1.9, 95 % CI 1.4–2.7, p < 0.001], hemodynamic vulnerability (OR 1.6, 95 % CI 1.1–2.3, p < 0.01), and procedure risk (category 3: OR 2.3, 95 % CI 1.3–4.1; category 4: OR 4.2, 95 % CI 2.4–7.4) were predictors of life-threatening events. Using this model, standardized life-threatening event ratios were calculated, thus showing that one institution had a life-threatening event rate greater than expected. Congenital cardiac catheterization and intervention can be performed safely with a low rate of life-threatening events and mortality; preprocedural evaluation of risk may optimize preparation of emergency rescue and bailout procedures. Risk predictors (age < 1, hemodynamic vulnerability, and procedure risk category) can enhance preprocedural patient risk stratification and planning.     

Association of maternal characteristics and behaviours with 4‐year‐old children's dietary patterns

This study examined the association of family and maternal characteristics with preschool children's dietary patterns. Trained interviewers evaluated subsample 3422 mothers and children enrolled in the population‐based birth cohort Generation XXI (Porto, Portugal, 2005–2006). Maternal characteristics and behaviours (exercise, smoking habits, diet and child‐feeding practices) and family characteristics were evaluated. Maternal diet was classified by a dietary score, and children's dietary patterns were identified by latent class analysis. Odds ratios (OR) and confidence intervals (95% CI) were estimated by multinomial regression models. The analysis was based on a framework with four conceptual levels: maternal socio‐economic position (SEP) at 12 years, maternal socio‐economic and demographic characteristics at child's delivery, family characteristics and maternal behaviours at child's 4 years. Three dietary patterns were identified in children: high in energy‐dense foods (EDF); low in foods typically consumed at main meals and intermediate in snacks (Snacking); higher in healthy foods; and lower in unhealthy ones (Healthier, reference). Lower maternal SEP had an overall effect on children's diet (low vs. high SEP; EDF, OR = 1.76, 95% CI: 1.42–2.18; Snacking, OR = 1.73, 95% CI: 1.27–2.35), while maternal education was directly associated with it (≤9 vs. >12 schooling years, EDF, OR = 2.19, 95% CI: 1.70–2.81; Snacking, OR = 2.22, 95% CI: 1.82–3.55). Children whose mothers had worse dietary score were significantly more likely to follow unhealthier patterns (first vs. fourth quartile; EDF, OR = 9.94, 95% CI: 7.35–13.44, P‐trend < 0.001; Snacking, OR = 4.21, 95% CI: 2.94–6.05, P‐trend < 0.001). Maternal diet was the key factor associated with children's diet, above and beyond socio‐economic and demographic characteristics, accounting for one‐third of the determination coefficient of the fully adjusted model. At preschool age, interventions should give a particular focus on maternal diet and low SEP groups.     

Incomplete clinical manifestation as a risk factor for coronary artery abnormalities in Kawasaki disease: a meta-analysis

Incomplete Kawasaki disease (KD) comprises a large proportion of the total number of cases. Although it has the potential of delaying diagnosis, it is not conclusive whether an incomplete presentation is a risk factor for coronary artery abnormalities (CAAs). We performed a meta-analysis to establish the risk of CAA in 20 studies including 4,504 cases and 32,519 controls, and the risk of giant aneurysm in two studies including 5,390 cases and 37,648 controls. The pooled results indicated that incomplete KD was associated with an increased risk of CAA [odds ratio (OR)?=?1.447, 95 % confidence interval (CI)?=?1.158–1.808, p?=?0.001]. Subgroup analyses demonstrated higher associations in patients younger than 12 months (OR?=?2.023, 95 % CI?=?1.252–3.271, p?=?0.004), Asians and Indians (OR?=?1.57, 95 % CI?=?1.234–1.999, p?<?0.001 and OR?=?7.088, 95 % CI?=?1.640–30.631, p?=?0.009, respectively). Subgroup analysis according to the period of patient enrollment before and after 2004 showed increased association of incomplete KD with CAA only among studies with patients enrolled after 2004 (OR?=?1.969, 95 % CI?=?1.240–3.127, p?=?0.004). In conclusion, incomplete KD seems to be associated with an increased risk of CAA, and this is more prominent in patients younger than 12 months, Asians and Indians.     

Indoor environment,atopy and the risk of asthma in children in New Zealand

The objective of this study was to examine the relationship between the indoor environment, atopy and asthma in 7–9-year-old children. Cases and controls were randomly selected from children who participated in the International Study of Asthma and Allergies in Childhood (ISAAC) in Wellington, New Zealand. Cases were children with a previous diagnosis of asthma and current medication use (n = 233) and controls were children with no history of wheezing and no diagnosis of asthma (n = 241). Information was recorded about the indoor environment during the first year of life and currently. Dust was sampled from floors and beds and Der p 1 and Fel d 1 measured using enzyme-linked immunosorbent assays. Skin-prick tests were performed with eight common allergens. Sensitization to Dermatophagoides farinae (OR = 3.19; 95% CI 1.74–5.84), Dermatophagoides pteronyssinus (OR = 2.06; 95% CI 1.16–3.65) and cat (OR = 3.89; 95% CI 1.06–14.30) were independently associated with current asthma. The use of a sheepskin in the first year of life (OR = 1.91; 95% CI 1.11–3.33) was also independently associated with current asthma but current Der p 1 levels showed no association with current asthma. Exposures in early life may be more important than current exposures in determining asthma at age 7–9 years. Prospective studies are needed in New Zealand to determine the relative importance of early life exposures to Der p 1 and other risk factors for asthma.