Antibiotic Use In Infants Research Articles

The association between antibiotic use in infancy and childhood overweight or obesity: a systematic review and meta-analysis.

Antibiotic use is associated with alteration of the gut microbiome and metabolic activity. As childhood obesity is a predisposing factor for adult obesity, addressing childhood risk factors to weight gain in early life is important. This review aims to investigate the association between infant antibiotic exposure (aged<24months) and childhood obesity or overweight. Articles were retrieved from CINAHL, Cochrane CENTRAL, Embase and MEDLINE. Eligible articles investigated antibiotic use in exposed versus unexposed infants and measured childhood weight change. Data were synthesized narratively and meta-analysed where possible. After title/abstract and full-text screening, 17 articles representing 15 unique studies were included for narrative synthesis. We found a small association between antibiotic exposure in infancy (<24months) and childhood overweight or obesity. The strongest associations were observed in boys versus girls and children exposed to multiple antibiotic courses or broad-spectrum drugs. Meta-analysis of 12 sets of results comparing the earliest age of exposure to any antibiotic with overweight or obesity at the latest age of outcome found a pooled odds ratio of 1.05 (95% confidence interval: 1.00-1.11). Antibiotic exposure in infants, aged<24months, was associated with a small increase in odds of childhood overweight or obesity in some subgroups of children.

Evaluation of Early Onset Sepsis, Complete Blood Count, and Antibiotic Use in Gastroschisis

Gastroschisis is a congenital defect in which the abdominal viscera herniate through the abdominal wall. In this population, antibiotics are often initiated immediately following delivery; however, this may be unnecessary as infections typically develop as a consequence of chronic issues in gastroschisis. The objective of this study was to evaluate the incidence of culture positive early onset sepsis, the reliability of the immature to mature neutrophil count (I:T) ratio as an infectious biomarker, and antibiotic use in infants with gastroschisis. This retrospective chart review analyzed clinical data from 103 infants with gastroschisis and 103 weight-matched controls that were evaluated for early onset infection. Compared with the control group, there was a significantly increased percentage of infants with an I:T ratio > 0.2 in the gastroschisis group (43% vs. 12%, p < 0.001) and an increased percentage of infants exposed to greater than 5 days of antibiotics regardless of their I:T ratio (75% vs. 6%, p < 0.001). There were no episodes of culture positive early onset sepsis in either group. Our results indicate that I:T ratio is not a reliable marker of infection in gastroschisis, and suggest that empiric septic evaluation and antibiotic use, immediately following delivery in gastroschisis infants, may be unnecessary.

Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis

Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development. We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home). We conducted a case-control study using hospital-based cases (n=127) and control subjects representative of the hospital catchment area (n=121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE. Case-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P=.02) and rs17815905 (LOC283710/KLF13) and NICU admission (P=.02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66). The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.

Antibiotic use in infancy and neurocognitive outcomes in children: the role of bacterial denitrification.

Slykerman et al. (1) recently investigated the role of antibiotic use in early life and later adverse neurocognitive outcomes in children. The authors utilized as their cohort 871 mothers and their children at birth from the Auckland Birthweight Collaborative Study. Data on antibiotic use during early life were collected from maternal interview, and behavioral assessments and intelligence test scores were obtained at the ages of 3.5, 7, and 11. The authors reported that those individuals treated with antibiotics experienced more behavioral difficulties and depressive symptomatology during the follow-up periods. This finding led the authors to conclude that there was an association between early antibiotic use and adverse neurocognitive outcomes in children, highlighting the potential need for a reevaluation of antibiotic overuse during infancy, especially if future studies are able to confirm these findings. This is a polarizing conclusion made by the authors and warrants a closer inspection of potential confounders to this discovered association. This article is protected by copyright. All rights reserved.

Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study

Data from previous studies have suggested a possible association between antibiotic use in infancy and risk of childhood obesity, with implications for health-care delivery and obesity prevention strategies. However, whether the observed association was due to antibiotic use or underlying infection, or both, is unclear. We aimed to disentangle the effect of antibiotic use in infancy from that of underlying infection on the risk of childhood obesity. In this longitudinal birth cohort study, we included infants in the Kaiser Permanente Northern California population born between Jan 1, 1997, and March 31, 2013. We used electronic medical records to ascertain data for antibiotic use, infection diagnosis, and anthropometric measurements (and thus BMI and obesity status) from birth up to age 18 years. We used standard mixed-effects logistic regression for repeated measurements to analyse multiple BMI measurements per child (median five measurements) and to obtain odds ratios (ORs) and 95% CIs for obesity risk. We also did a substudy in 547 same-sex twin pairs with discordant exposure status to substantiate our findings. 260 556 individuals were included in our analysis. After controlling for maternal age, race or ethnic origin, pre-pregnancy BMI, preterm delivery, low birthweight, maternal antibiotic use, and infection during pregnancy, infection without antibiotic use in infancy was associated with an increased risk of childhood obesity compared with controls without infection (OR 1·25, 95% CI 1·20-1·29). A clear dose-response relation was seen between infection episodes and risk of childhood obesity (ptrend <0·0001). By contrast, compared with infants with untreated infection, antibiotic use during infancy was not associated with risk of childhood obesity (1·01, 0·98-1·04). Neither broad-spectrum nor narrow-spectrum antibiotics were associated with risk of childhood obesity. These findings were supported by the results of the twin set analysis. Infection, but not antibiotic use, during infancy is associated with risk of childhood obesity. This finding will need to be replicated in future studies. Although our results do not rule out a potential effect of antibiotics on microbiome composition and the use of antibiotics should always be judicious, they suggest that treatment of common infections with antibiotics in infancy is unlikely to be a main contributor to childhood obesity. Kaiser Permanente Center for Effectiveness & Safety Research.

Gene-environment Interaction in Pediatric Eosinophilic Esophagitis

Introduction: The rapid increase in the incidence of eosinophilic esophagitis (EoE) may be due to interactions between a genetic predisposition and changing environmental factors. While EoE has been associated with several early life factors, gene-environment interactions have not been explored. Here, we test for interactions between SNPs or SNPs in high linkage disequilibrium with SNPs previously associated with EoE (TSLP, LOC283710/ KLF13, CAPN14, and CCL26) and early life factors (antibiotic use in infancy, cesarean delivery, breastfeeding, NICU admission, and absence of pets in the home). Methods: We conducted a case-control study using hospital-based cases identified from a registry of EoE patients (n=127) and population-based controls representative of the hospital catchment area (n=121). Early life environmental factors were assessed through a self-administered questionnaire provided to mothers. Cases and controls had been previously genotyped. We computed case-only interaction tests and where there was evidence of possible interaction, secondary analyses were used to describe the combined and independent effects of genotype and environmental factor on risk of EoE. Models were adjusted for maternal education and population stratification. Results: The case-only analyses identified interactions between CAPN14 and breastfeeding (p=0.02), TSLP and NICU admission (p=0.06), TSLP and not having a furry pet in infancy (p=0.05), and LOC283710/ KLF13 and NICU admission (p=0.02), but not with CCL26 and any of the early life factors examined. Case-control analyses of these associations showed the interactive effects for all associations were antagonistic; specifically the risk of having EoE for those with both the susceptibility genotype and early life factor was attenuated as compared to the risk of disease among those with only the genotype or early life factor (Figure). Examination of the effect of early life factors, among those with the CAPN14 susceptibility SNP, identified a strong protective association for breastfeeding (OR: 0.09, 95% CI: 0.01-0.63). Conclusion: In this first study of gene-environment interactions in EoE, there is preliminary evidence that certain early life factors may interact with susceptibility genotypes to modify risk of disease. In particular, interactions between CAPN14 and breastfeeding, LOC283710/ KLF13 and NICU admission, TSLP and NICU admission, and TSLP and pets merit further examination.Figure 1

Reducing unnecessary antibiotic use in the neonatal intensive care unit (SCOUT): a prospective interrupted time-series study

Antibiotics are used frequently in the neonatal intensive care unit. We aimed to inform antibiotic stewardship strategies in a level 3 neonatal intensive care unit by surveillance and assessment of all antibiotic use during a 14-month period, identifying scenarios where antibiotic use can be reduced, and implementing interventions while monitoring safety. The SCOUT study is an observational study in the level 3 neonatal intensive care unit at Parkland Hospital, Dallas, TX, USA. All antibiotic use in infants admitted to the neonatal intensive care unit between March 1, 2012, and Nov 30, 2012 (9 months), was monitored and analysed. After the baseline period (Oct 3, 2011, to Nov 30, 2012), continuation of empirical antibiotic therapy for ruled-out sepsis courses beyond 48 h, pneumonia, and "culture-negative" sepsis were selected as targets for antibiotic stewardship interventions. During the intervention period (Oct 1, 2013, to June 30, 2014), empirical antibiotic therapy was set to discontinue after 48 h in the electronic medical record and the duration of therapy for pneumonia and culture-negative sepsis was limited to 5 days. Antibiotic use, defined as days of therapy per 1000 patient-days, was compared between the baseline and intervention periods. The primary outcome was the change in total antibiotic days of therapy per 1000 patient-days between the baseline and intervention periods. Safety outcomes measured were instances in which infants received 5 or more days of therapy and subsequently had antibiotic therapy reinstituted within 14 days for any indication; a composite of late-onset sepsis, necrotising enterocolitis (modified Bell stage ≥2), or death in infants 32 weeks' gestation or younger; prevalence of multidrug-resistant organism colonisation; and length of hospital stay. 2502 infants were admitted to the neonatal intensive care unit during the two study periods (1607 in the baseline period and 895 in the intervention period). Antibiotic use declined from 343·2 days of therapy per 1000 patient-days during the baseline period to 252·2 days of therapy per 1000 patient-days in the intervention period (p<0·0001), representing an overall decrease of 27%. No difference in safety outcomes was observed between the intervention and baseline periods. Thorough assessment of antibiotic consumption in a neonatal intensive care unit can inform high-yield stewardship targets tailored to the individual centre. Effective interventions to reduce antibiotic use can then be designed and implemented in a collaborative manner. The Gerber Foundation.

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

BackgroundEnvironmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.MethodsWe conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated.ResultsAmong 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home.ConclusionEarly-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma.

Effect of Antibiotic Use and Mold Exposure in Infancy on Allergic Rhinitis in Susceptible Adolescents

To explore the risk of allergic rhinitis (AR) in adolescents with the independent and combined effect of antibiotic use and mold exposure in infancy.The study population consisted of 7389 students recruited from 8 middle schools in Seoul, Korea.The International Study of Asthma and Allergies in Childhood written questionnaire was obtained from 7389 adolescents. Interleukin 13 (IL-13) (rs20541) and toll-like receptor 4 (rs1927911) polymorphisms were performed on TaqMan genotyping in 1395 randomly selected adolescents.Of the total 7286 completed surveys, almost one-third used antibiotics, and 10.3% were exposed to mold in infancy. The data showed age, parental history of AR, antibiotic use in infancy, and pet ownership during pregnancy or infancy were linked with an increased risk of current AR. The presence of an older sibling was noted to have a protective effect. Increased odds ratio for current AR was seen with combined antibiotic use and mold exposure in infancy. Antibiotic use had an adjusted odds ratio of 1.25, whereas mold exposure had an adjusted odds ratio of 0.99 when considered independently. Patients also had increased risk of current AR with IL-13 (rs20541) GA or AA genotype and CT + TT genotype of toll-like receptor 4 (rs1927911).In genetically susceptible adolescents, with specific IL-13 polymorphisms, antibiotic use and mold exposure in infancy have additive effects on the risk of current AR.Certain genetic polymorphisms may increase the risk of different types of atopic disease. Studies such as this aim to identify future risk factors of development of atopy. AR is a common diagnosis in childhood. Unfortunately, as is often noted, AR appears to be a multifactorial condition and, as such, is difficult to isolate single or even combined risk factors. Although recall bias is a potential limitation of the study, the information collected appears important. Limitation of mold exposure and judicious use of antibiotics in children appear to be even more important than previously thought, to prevent the development of allergic rhinitis in some adolescents later in life.

Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans - towards treatment with probiotics.

Changes in the gut microbiota are associated with metabolic disorders, such as overweight and elevated blood glucose. Mouse studies have shown that gut microbiota can regulate metabolism with a mechanism related to gut barrier function. An impaired gut barrier permits the translocation of bacteria and their components which, when in contact with the sub-mucosal immune system, evoke metabolic inflammation and distract signalling in metabolically active tissues. Despite thorough research of the topic in animals, the hypothesis is yet to be proven in humans. Cross-sectional studies have shown that certain bacterial populations - such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Methanobrevibacter smithii and Christensenellaceae - are better represented in lean individuals compared to those who are overweight or metabolically unhealthy. Although these differences reflect those seen in mice, it is possible that they are caused by different dietary or other lifestyle habits. Diet has an indisputable influence on gut microbiota making it very difficult to draw conclusions on microbiota-host interactions from cross-sectional studies. Certain research areas do, however, indicate that gut microbiota could causally influence metabolism. Several studies show that antibiotic use in infancy increases body weight in later childhood. Also, probiotics are emerging as a potential therapy for metabolic syndrome. In fact, a handful of human studies and numerous animal studies show promise for probiotics in reducing blood glucose levels or improving insulin sensitivity. For weight management human evidence is scarcer. Nevertheless, it is becoming increasingly recognised that gut microbiota plays a part regulating metabolism, also in humans, which gives rise to novel opportunities for preventative and treatment strategies.

Impact of maternal bifidobacteria and the mode of delivery on Bifidobacterium microbiota in infants.

The aim of this study is to examine the influence of maternal intestinal and vaginal bifidobacteria on the colonisation of bifidobacteria in the gut of infants. Faecal samples from 120 healthy pregnant mothers within 1 month of delivery and from their infants at 1 month of age and 98 vaginal swabs from the mothers at the time of delivery were collected at a maternity hospital in Chiang Mai, Thailand. The faecal and vaginal samples were assayed by real-time PCR assays to detect Bifidobacterium species and to estimate the bifidobacterial copy numbers. After adjusting for the numbers of each Bifidobacterium species, delivery mode, and antibiotic use in infants by the age of 1 month, total counts of bifidobacteria in the mothers' faeces were associated with increased copy numbers of bifidobacteria in the faeces of breastfed infants. A caesarean section was also significantly associated with a decrease in the copy numbers of bifidobacteria in the faeces of infants. No significant correlation was found between the bifidobacterial copies of the vaginal swabs and those of the infants' faeces. The intestinal bifidobacterial status of exclusively breastfed infants was significantly positive affected by vaginal delivery and high bifidobacterial copy numbers in their mothers' gut.

Antibiotic use in infancy and the risk of asthma in Mexican American children

Objective: This study examined the associations of antibiotic use in infancy with lifetime doctor-diagnosed asthma and current wheeze among Mexican American children. Methods: In a population-based, cross-sectional investigation, parents of 2023 children 4–18 years of age completed a questionnaire/interview addressing respiratory conditions, antibiotic use, and covariates. Results: In adjusted analyses, among children without history of ear infections in infancy, children who used antibiotics ≥3 times and 1–2 times were more likely to report doctor-diagnosed asthma compared with their peers who did not use antibiotics in infancy [adjusted odds ratio (aOR) = 5.14, 95% confidence interval (CI): 2.88–9.17, and aOR = 2.15, 95% CI: 1.26–3.69, respectively, p trend < 0.0001]. The respective aORs for current wheeze were 3.67 (95% CI: 1.95–6.89) and 1.63 (95% CI: 0.91–2.95). Antibiotic use in infancy was not associated with asthma or current wheeze in children who had ear infections in infancy. In additional analyses, antibiotic use in infancy was associated with asthma in children without parental history of asthma or allergies (aOR = 2.73, 95% CI: 1.70–4.39) but not in those with parental history of asthma or allergies. Among Mexico-born participants born in rural areas, antibiotic use in infancy was associated with a seven-fold increase in risk of asthma (aOR = 7.21, 95% CI: 1.46–35.65), while the association was non-significant in Mexico-born children born in urban areas in Mexico. Conclusions: Antibiotic use in infancy may increase the risk of asthma and wheezing, but these associations were limited to subgroups of children.

Antibiotic administration for prevention or treatment of meconium aspiration syndrome in neonates: A systematic review

Objectives: To conduct a systematic review of the clinical trials evaluating the role of antibiotics for prevention or treatment of meconium aspiration syndrome (MAS). Methods: We searched several electronic databases including MEDLINE, EMBASE, CINAHL, SCOPUS (until September 2013), and CENTRAL (until August 2013). Additional citations were retrieved from the bibliographies of the selected articles. Studies were included if they were: Randomized or quasi-randomized trials, compared use of antibiotics with no antibiotics for treatment or prevention of MAS, and reported on clinical outcomes in the neonatal period. Results: Four randomized controlled trials (RCTs) were identified; three studies enrolled subjects for treatment of MAS and one study evaluated the prophylactic use of antibiotics in infants exposed to meconium stained amniotic fluid (MSAF). These trials enrolled 695 infants, with the duration of antibiotics between 3 and 7 days. All studies excluded subjects considered to be at higher risk for neonatal sepsis at onset. There were no differences noted for the outcomes of infection rates (relative risk [RR] [95% confidence interval: 0.85 [0.42, 1.73] for clinical sepsis, and 0.93 [0.36, 2.40] for culture-proven sepsis), need for mechanical ventilation (RR: 1.39 [0.68, 2.82]), air leaks syndrome (RR: 1.65 [0.68, 3.99]), hospital stay (mean difference − 0.34 days [−1.13, 0.45]), or mortality (RR: 1.25 [0.36, 4.39]) between the intervention and control groups. Conclusions: In neonates at low-risk for sepsis, insufficient evidence exists to support the routine use of antibiotics following exposure to MSAF or for the treatment of for suspected MAS. We discuss the implications and limitations of review findings for clinical practice.

The prevalence and risk factors of allergic rhinitis from a nationwide study of Korean elementary, middle, and high school students

ratio (aOR), 1.486; 95% confidence interval (CI), 1.189-1.856), family history of paternal AR (aOR, 3.208; 95% CI, 2.460-4.182), family history of maternal AR (aOR, 3.138; 95% CI, 2.446-4.025), antibiotic use in infancy (aOR, 1.547; 95% CI, 1.228-1.949), mold exposure during infancy (aOR, 1.416; 95% CI, 1.103-1.819), mold exposure during the last 12 months (aOR, 1.285; 95% CI, 1.012-1.630), and sensitization on skin prick tests (aOR, 2.596; 95% CI, 2.055-3.279). Risk factors for atopic current AR were the same as those of current AR, whereas breast-milk feeding (aOR, 0.720; 95% CI, 0.530-0.976) was a protective factor. Sensitized allergens as risk factors for cur- rent AR were Dermatophagoides pteronyssinus, Dermatophagoides farina, ragweed, mugwort, oak, alder, birch, Japanese hop, cat, and dog.

Effect of antibiotic use and mold exposure in infancy on allergic rhinitis in susceptible adolescents

BackgroundAntibiotic use in infancy induces alteration in intestinal microbiota and is associated with the development of allergic diseases. Mold exposure is also associated with allergic diseases. Genetic susceptibility may interact with specific environmental factors in allergic disease development. ObjectiveTo investigate independent and combined effects of antibiotic use and mold exposure in infancy on the risk of allergic rhinitis (AR) in adolescents. MethodsData on AR and environmental factors were collected using the International Study of Asthma and Allergies in Childhood questionnaire from 7,389 adolescents from Seoul, Korea. TaqMan genotyping was performed for interleukin 13 (IL-13) (rs20541) and Toll-like receptor 4 (rs1927911) polymorphisms in 1,395 adolescents. ResultsAge, parental history of AR, antibiotic use in infancy, and pet ownership during pregnancy or infancy were associated with an increased risk of current AR (diagnosis of AR and symptoms of AR within the preceding 12 months). Having older siblings was a protective effect. The adjusted odds ratio (aOR) for current AR for combined antibiotic use and mold exposure in infancy was 1.45 (95% confidence interval [CI], 1.01–2.09). For each factor separately, aORs were 1.25 (95% CI, 1.04–1.50) and 0.99 (95% CI, 0.75–1.31), respectively. Antibiotic and mold exposure in infancy, GA or AA genotypes of IL-13 (rs20541) (aOR 4.53; 95% CI, 1.66–12.38; P for interaction = .05), and CT+TT genotype of Toll-like receptor 4 (rs1927911) (aOR, 3.20; 95% CI, 1.24–8.26; P for interaction = .18) increased the risk of current AR. ConclusionAntibiotic use and mold exposure in infancy have additive effects on the risk of current AR in genetically susceptible adolescents. Gene-environment interactions between IL-13 (rs20541) and antibiotics or mold may play a role in AR.

44: Antibiotic Administration for Meconium Aspiration Syndrome in Neonates: A Systematic Review

Meconium aspiration syndrome (MAS) is a common cause of respiratory distress in neonatal period. Antibiotic treatment is one of medical therapy which widely used in newborns with MAS but the efficacy of routine antibiotic administration is doubtful. To conduct a systematic review of the clinical trials evaluating the role of antibiotics in MAS. We searched Medline, EMBASE, CENTRAL AND CINAHL, SCOPUS, International Pharmaceutical Abstracts, Proquest Dissertations and Theses and EBM Reviews (until August 2013). Studies were included if they satisfied the following criteria: randomized or quasi-randomized trials comparing the use of antibiotics to no antibiotics for treatment or prevention of MAS and reporting on any of the following outcomes: development of infection, need for ventilation or oxygen support, duration of hospital stay, air leaks syndrome, PPHN, need for ECMO or inhaled nitric oxide (iNO), and mortality. We calculated relative risks (RR) for the dichotomous outcomes and mean differences (MD) for the continuous outcomes, along with the 95% CIs. Four RCTs were identified; three studies enrolled subjects for treatment of MAS and one study evaluated prophylactic use of antibiotics in infants exposed to meconium stained amniotic fluid (MSAF). These trials enrolled 693 infants in total and the duration of antibiotics used was three to seven days. All studies excluded subjects considered to be at higher risk for neonatal sepsis at onset due to antenatal risk factors and/or positive septic screen. There were no difference in development of infection (RR 0.67 [95% CI 0.28 to 1.59] for clinical sepsis and 0.93 [95% CI 0.36 to 2.40] for culture-proven sepsis), mortality (RR 1.25 [95% CI 0.36 to 4.39]), need for ventilation (RR 1.16 [95% CI 0.50 to 2.66] for mechanical ventilation and 1.09 [95% CI 0.71 to 1.69] for CPAP), duration of oxygen (MD −0.64 [95% CI −1.49 to 0.21]), air leaks syndrome (RR 1.56 [95% CI 0.62 to 3.91]) and hospital stay (MD 0.16 days [95% CI −1.16 to 1.48]) between the two groups. In neonates who are otherwise at low-risk for neonatal sepsis, there is insufficient evidence to support the routine use of antibiotics for treatment of MAS or for prophylaxis in infants exposed to MSAF.

Antibiotic use in infancy increases risk of childhood asthma

Antibiotic use in infancy increases risk of childhood asthma

Chorioamnionitis: epidemiology of newborn management and outcome United States 2008.

Current American Academy of Pediatric recommendations call for the empirical use of antibiotics for all well-appearing term newborn infants born to women given a diagnosis of chorioamnionitis. The objective of this analysis was to determine among term infants (37-42 weeks gestation) the prevalence of exposure to clinical chorioamnionitis, intrapartum antibiotics, infant antibiotic use and neonatal intensive care unit (NICU) admission and the relationship of these risk factors to neonatal mortality. United States-linked infant birth and death certificate files for the year 2008 were used. Maternal demographic variables, labor and delivery risk factors and infant characteristics were analyzed for associations with a reported diagnosis of chorioamnionitis and neonatal death, NICU admission and antibiotic usage. There were 2,281,386 births available with information on the diagnosis of chorioamnionitis. The prevalence of chorioamnionitis in this population was 9.7 per 1000 live births (LB) and the neonatal mortality rate for exposed infants was 1.40/1000 LB vs 0.81/1000 LB for infants without chorioamnionitis, odds ratio (OR)=1.72, 95% confidence interval 1.20-2.45. The OR for neonatal death for infants with chorioamnionitis exposure who received antibiotics vs those who did not was 0.69 (95% confidence interval=0.21-2.26). Exposure to chorioamnionitis is associated with an increased risk of neonatal mortality. Guidelines for treatment of infants exposed to chorioamnionitis with antibiotics are followed in only a small proportion of such cases.

Consequences of antibiotics and infections in infancy: bugs, drugs, and wheezing

BackgroundThe prevalence of asthma has increased alarmingly in the past 2 to 3 decades. Increased antibiotic use in infancy has been suggested to limit exposure to gastrointestinal microbes and to predispose to asthma in later life. ObjectiveTo evaluate the association between antibiotic exposure during the first year of life and the development of asthma up to the age of 7 years. MethodsA retrospective population-based study of a cohort of children enrolled in a nationwide employer-provided health insurance plan from January 1, 1999, through December 31, 2006, in the United States (n = 62,576). We evaluated the association between antibiotic exposure during the first year of life and subsequent development of 3 asthma phenotypes: transient wheezing (began and resolved before 3 years of age), late-onset asthma (began after 3 years of age), and persistent asthma (began before 3 years of age and persisted through 4-7 years of age). ResultsAntibiotic use in the first year of life was associated with the development of transient wheezing (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.9-2.2; P < .001) and persistent asthma (OR, 1.6; 95% CI, 1.5-1.7; P < .001). A dose-response effect was observed. When 5 or more antibiotic courses were received, the odds of persistent asthma doubled (OR, 1.9; 95% CI, 1.5-2.6; P < .001). There is no association between antibiotic use and late-onset asthma. ConclusionAntibiotic use in the first year life is associated with an increased risk of early-onset childhood asthma that began before 3 years of age. The apparent effect has a clear dose response. Heightened caution about avoiding unnecessary use of antibiotics in infants is warranted.

Early Life Exposures as Risk Factors for Pediatric Eosinophilic Esophagitis

Few etiologic studies of eosinophilic esophagitis (EoE) have been conducted. Early life exposures have been shown to predispose to other allergic disease, but their role has not been assessed in EoE. The present study sought to explore early life exposures as possible risk factors for developing EoE in the pediatric population. This was a 2-phase case-control study conducted at the University of North Carolina. The first phase consisted of survey development for early life exposures via cognitive interview. In the second phase, a telephone-based questionnaire was administered to cases with EoE (n = 31) and 2 sets of controls, patients with gastroesophageal reflux disease, and siblings of nonsyndromic cleft lip/palate patients (n = 26 in each). Different controls were explored to identify controls reflective of the source population of the cases. Siblings of cleft lip/palate patients were identified as the more suitable control population. Odds ratios were calculated to evaluate the association between early life exposures and the development of pediatric EoE. Early life exposures were associated with increased odds of developing pediatric-onset EoE. Antibiotic use in infancy was associated with 6 times the odds of having EoE (95% confidence interval 1.7-20.8). Cesarean delivery, preterm birth, and formula-only or mixed (infant formula and breast milk) feeding also have trends toward increased odds for developing EoE. A number of early life exposures may be associated with the development of EoE. These are potentially modifiable risk factors that if confirmed would have implications for improved understanding of EoE pathogenesis and disease prevention.