Postnatal Antibiotic Exposure Research Articles

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

Post-natal antibiotic exposure in mother rat (F0) induces anxiety like behavior in adult rat offspring (F1) by activating HPA axis and down-regulating the Nr3c1 gene.

Early postnatal administration of antibiotics has been linked to lasting effects on brain development and behavior. Research conducted on animals that are free from germs has demonstrated that the impact of microbiome colonization on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine pathways is substantial, which play a crucial role in stress management. Nevertheless, it is still uncertain if the exposure to antibiotics in rat dams (F0-generation) before weaning is associated with neurobehavioral changes in rat offspring (F1-generation) during adulthood. In order to investigate the effects, we perturbed the intestinal microbiota of rat dams (F0 generation) by administering cefixime (CEF), an antibiotic commonly used for obstetric purposes, at clinically relevant doses (1 mg/kg, 2.5 mg/kg or 5 mg/kg). Anxiety-like behaviors in adult offspring was evaluated through the utilization of elevated plus maze (EPM) and open field paradigm (OFP) following a six-week interval from birth (PND42). Subsequent to behavioral assessments, the rats were euthanized, and their brains and blood was collected for biochemical analysis. Plasma corticosterone concentration was used to assess HPA activity, whereas the quantitative real-time polymerase chain reaction (PCR) was employed to determine the transcription levels of the glucocorticoid receptor (GR) Nr3c1. The offspring of F1 that were administered antibiotics before being weaned spent less time in the EPM open arm. The alterations were accompanied by increased levels of corticosterone in the bloodstream. The gene expression study revealed a decrease in the levels of mRNA transcription of Nr3c1. This research emphasizes the possible long-term effects of antibiotic exposure before weaning on the development of anxiety in offspring upon adulthood.

Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis

BackgroundThe association between early-life exposure to antibiotics and overweight/obesity is unclear. We conducted a systematic review and meta-analysis to address this issue. MethodsWe searched PubMed, Web of Science, Scopus, and grey literature from inception to August 10, 2022, for cohort studies investigating the association between early-life exposure to antibiotics and weight outcomes. Two independent reviewers screened studies for eligibility, extracted data, assessed risk of bias, and examined the certainty of the evidence. Random-effects meta-analyses was used for pooling the data. The review was registered in PROSPERO, CRD42021265417. ResultsWe included 42 studies and data from 28 of them were pooled in the quantitative synthesis. Overall antenatal (OR 1.10, 95% CI 1.04–1.16; 518,095 children, very low certainty) and second trimester (OR 1.11, 95% CI 1.08–1.14, 248,469 children, low certainty) exposure to antibiotics were associated with increased risk of overweight/obesity in childhood/adolescence. Overall early postnatal antibiotic exposure was also associated with increased likelihood of overweight/obesity in childhood/adolescence (OR 1.09, 95% CI 1.05–1.12, 1,488,316 children, very low certainty). The magnitude of the association increased from exposure to one (OR 1.07, 95% CI 1.00–1.15, 512,954 children) to four or more courses of antibiotics (OR 1.31, 95% CI 1.17–1.46, 543,627 children). ConclusionAntenatal and early postnatal exposure to antibiotics is associated increased likelihood of overweight/obesity, although the findings are limited by the very low certainty of evidence. We highlight the need for homogeneous prospective studies addressing potential confounding factors to further explore the link between exposure to antibiotics and the risk of excess body weight.

Prenatal and early-life antibiotic exposure and the risk of atopic dermatitis in children: A nationwide population-based cohort study.

Atopic dermatitis (AD) contributes to substantial social and financial costs in public health care systems. Antibiotic exposure during pregnancy has been proposed as a risk factor, but findings remain inconsistent. The aim of this study was to investigate the association between prenatal antibiotic use and childhood AD. We performed a population-based cohort study using data collected from the Taiwan Maternal and Child Health Database from 2009 to 2016. Associations were determined using Cox proportional hazards model and were adjusted for several potential covariates, including maternal atopic disorders and gestational infections. Children with and without maternal predispositions of atopic diseases and postnatal antibiotic/acetaminophen exposures within 1 year were stratified to identify the subgroups at risk. A total of 1,288,343 mother-child pairs were identified and 39.5% received antibiotics prenatally. Maternal antibiotic use during pregnancy was slightly positively associated with childhood AD (aHR 1.04, 95% CI 1.03-1.05), especially in the first and second trimesters. An apparent dose-response pattern was observed with an 8% increased risk when the exposure was ≥5 courses prenatally (aHR 1.08, 95% CI 1.06-1.11). Subgroup analysis showed the positive association remained significant regardless of postnatal infant antibiotic use, but the risk attenuated to null in infants who were not exposed to acetaminophen (aHR 1.01, 95% CI 0.96-1.05). The associations were higher in children whose mothers were without AD compared to those whose mothers were with AD. In addition, postnatal antibiotic or acetaminophen exposure of infants was associated with an increased risk of developing AD after 1 year of age. Maternal antibiotic use during pregnancy was associated with an increased risk of childhood AD in a dose-related manner. Further research may be warranted to investigate this variable using a prospectively designed study, and also to examine whether or not this association is specifically related to pregnancy.

Association between antibiotic exposure and adverse outcomes of children and pregnant women: evidence from an umbrella review.

Antibiotics are widely prescribed among children and pregnant women, but their safety profile is controversial. This study aimed to summarize and appraise current evidence for the potential impact of antibiotic exposure on pregnancy outcomes and children's health. PubMed, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception to June 2022. Meta-analyses of any study design comparing the impact of antibiotic exposure with nonexposure among children, pregnant women and prepregnant women on adverse health outcomes of children and pregnancy were retrieved. The quality of evidence was assessed by a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR2) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Data were reanalyzed, and the credibility of the evidence was determined. Out of 2956 studies identified, 19 articles with 39 associations were included. Totally 19 of the associations (48.72%) were statistically significant with a P value ≤ 0.05, while only six were supported by highly suggestive evidence. Children with postnatal antibiotic exposure had a higher risk of developing asthma odds ratio (OR): 1.95, 95% confidence interval (CI): 1.76-2.17, wheezing (OR: 1.81, 95% CI 1.65-1.97) and allergic rhinoconjunctivitis (OR: 1.66, 95% CI 1.51-1.83), with prediction intervals excluding the nulls. Quality assessed by both AMSTAR2 and GRADE of included meta-analyses were very low in general. Antibiotic exposure in early life was associated with children's long-term health, especially in cases of allergic diseases. Prenatal exposure might also influence children's health in some aspects but requires more high-quality evidence. Potential adverse effects of antibiotics on pregnancy outcomes were not observed in our study. Studies with higher quality and better quantification of antibiotic exposure are needed in the future.

Evidence for Causal Associations Between Prenatal and Postnatal Antibiotic Exposure and Asthma in Children

Evidence for Causal Associations Between Prenatal and Postnatal Antibiotic Exposure and Asthma in Children

S124 Antibiotic Exposure Before 2 Years of Age is Associated With Increased Risk of Pediatric IBD in a Norwegian Nation-Wide Study

Background: The incidence of pediatric IBD (PIBD) rises. This development is likely related to environmental factors that cause disturbances in the gut microbiota. The infant’s microbiome is shaped among other factors by exposure to the maternal microbiome and reaches adult diversity around 3 years age. Antibiotics impact the developing microbiome. Earlier studies have shown an association between PIBD and postnatal antibiotic exposure but lack information on prenatal antibiotic exposure and potential confounders. Thus, the primary aim of this study was to determine whether prenatal antibiotic exposure and antibiotics the first 2 years of life are independently associated with subsequent PIBD, before a mature and stabilized gut microbiome is established. Methods: We conducted a nationwide register-based cohort study using data from the Norwegian Patient Registry to identify children with pediatric IBD <18 years born from 2004 to 2012. Dispensed antibiotics were retrieved from the Norwegian Prescription Database, and the Medical Birth Registry of Norway and Statistics Norway contributed with potential confounding factors. The unique personal ID number given to all new-born in Norway was used to connect the registers. All children were followed until December 31, 2020. We analyzed whether use of pre- and postnatal antibiotics until 2 years of age were associated with subsequent IBD by logistic regression adjusted for potential confounders. Results: The study-population included 536,821 children; 758 were classified as PIBD cases distributed as: 403 (53%) Crohn`s Disease, 243 (32%) Ulcerative Colitis and 112 (15%). IBD Unclassified. The IBD cases included 423 boys and 335 girls with a male predominance among the CD cases (2.2: 1). In the main analysis, sex-adjusted odds ratio (aOR) for developing IBD when exposed to antibiotics before 2 years of age compared to no exposure was 1.40 (95% CI: 1.21-1.61). After adjustment for prenatal antibiotic exposure the aOR was 1.39 (95% 1.20-1.59). Further adjustments for potential confounders as mode of delivery, preeclampsia, birthweight and gestational age, season of birth and maternal age, education, smoking, and parity did not change the OR estimates more than +/- 0.01. We found the strongest association for ≥2 courses of antibiotic exposures (aOR 2.14 (95% 1.34-3.43) and for broad-spectrum AB (aOR 2.36 95%CI: 1.45-3.83) compared to no exposure. This association was driven by the CD cases (aOR 1.59 with 95%CI: 1.31-1.94 P<0.01) while no significant association to antibiotic exposure was observed for the UC cases (aOR 1.12 95%CI: 0.87-1.44 P=0.89). Antibiotic exposure during the last trimester was associated with offspring PIBD (aOR 1.23 95%CI: 1.01-1.51), but this association was borderline significant after adjustment for postnatal antibiotic exposure (P = 0.07). Conclusion(s): In a nation-wide, register-based study from Norway, children exposed to antibiotics before 2 years of age were 1.4 -fold more likely to develop IBD before the age 18 years than controls. This association was found for CD only and was robust to adjustments for prenatal antibiotic exposures and other potential confounders.

Association between early life antibiotic exposure and development of early childhood atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease commonly onset during infancy. We examine the association between pre-and postnatal antibiotic exposure and the development of AD. A retrospective, observational study analyzed 4106 infants at the University of Florida from June 2011 to April 2017. Antibiotic exposure during the first year of life was associated with a lower risk of AD. The association was strongest for exposure during the first month of life. There were no significant differences in the rates of AD in infants with or without exposure to antibiotics in months 2 through 12, when examined by month. Antibiotic exposure during week 2 of life was associated with lower risk of AD, with weeks 1, 3, and 4 demonstrating a similar trend. Retrospective data collection from a single center, use of electronic medical record, patient compliance with prescribed medication, and variable follow-up. Early life exposures, such as antibiotics, may lead to long-term changes in immunity. Murine models of atopic dermatitis demonstrate a "critical window" for the development of immune tolerance to cutaneous microbes. Our findings suggest that there may also be a "critical window" for immune tolerance in human infants, influenced by antibiotic exposure.

Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: A population-based birth cohort study.

BackgroundEarly life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre‐ and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.MethodsWe included 1387 mother–child dyads from the prospective, population‐based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web‐based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician‐diagnosed asthma; parents (n = 1025) reported physician‐diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.ResultsPrenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants.ConclusionPre‐ and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

Antibiotic exposure and childhood attention-deficit/hyperactivity disorder: systematic review and meta-analysis.

Disturbances of gastrointestinal microbiome may result in the development of attention-deficit/hyperactivity disorder (ADHD). Antibiotic therapy is commonly known to influence the gastrointestinal microbiome. However, results from studies on the association between antibiotic exposure and ADHD have been inconsistent. Several databases (PubMed, PsychInfo, EMBASE) were searched on January 1, 2021, to identify relevant studies. A random effects model was used to calculate the pooled risk estimate. Statistical heterogeneity was tested using the chi-square test and the I2 statistic. There were four risk estimates on antibiotic intake during pregnancy and eight risk estimates on antibiotic intake after birth. The pooled odds ratio for ADHD comparing antibiotic exposure with non-exposure during pregnancy was 1.14 (95% confidence interval [CI], 1.10-1.18). The pooled odds ratio with postnatal antibiotic exposure was 1.12 (95% CI, 0.99-1.26). Substantial heterogeneity existed among these analyses. The timing of antibiotic exposure, type of antibiotic, and number of antibiotic intakes might influence the association between antibiotic exposure and ADHD. Our findings suggest that maternal antibiotic intake during pregnancy may be associated with an increased risk of ADHD in the offspring. However, there was insufficient evidence for the association between antibiotic intake after birth and ADHD risk. Further studies should be performed before a definitive conclusion can be established.

Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England.

Higher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear. To assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5-8years of life, and the impact in the target population. Data were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0-24months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. There was an association between prenatal exposure at 7-27days before the child's birth and asthma (adjusted OR=1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR=0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p>.25). The interaction between prenatal and postnatal exposures was also inconclusive (p=.287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal). We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.

BackgroundDelivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants.ObjectiveThe aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years.MethodsPediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37–42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures.ResultsThe mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0–1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1–3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34).ConclusionOur results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.

The Association between Autism Spectrum Disorder and Pre- and Postnatal Antibiotic Exposure in Childhood-A Systematic Review with Meta-Analysis.

Autism spectrum disorder (ASD) is a developmental disorder that begins in early childhood and has been associated with several environmental and genetic factors. We aimed to conduct two-side meta-analyses to determine the association between ASD and pre- and postnatal antibiotic exposure in childhood. We searched PubMed, Embase, Web of Science, and Cochrane Library for articles published up to February 2019. We evaluated observational studies that assessed the association between ASD and antibiotic exposure. Of 1459 articles, nine studies were used in the meta-analysis. We found that early antibiotic exposure, including pre- and postnatal, significantly increased the ASD risk in children. Furthermore, early antibiotic exposure, including pre- and postnatal, was significantly increased in children with ASD. Specifically, prenatal antibiotic exposure was significantly increased in children with ASD; however, postnatal antibiotic exposure was not. Our results indicate an association between ASD and early antibiotic exposure; specifically, that prenatal antibiotic exposure is an important risk factor of ASD in children.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), β-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

Early Life Exposure to Antibiotics and Autism Spectrum Disorders: A Systematic Review

We systematically reviewed evidence from observational studies on the associations between autism spectrum disorders (ASD) and early-life antibiotic exposure. Eleven articles were included in the review. Prenatal antibiotic exposure was associated with a slightly increased risk of ASD in two cohort studies on overlapping populations and in one case–control study; in three other case–control studies, no significant association was found. One cohort study found a slightly reduced risk of ASD after postnatal antibiotic exposure, while two other cohort studies on overlapping populations and three case–control studies reported an increased risk. Meta-analysis of the eligible studies showed no significant associations. Current data are conflicting and do not conclusively support the hypothesis that early-life antibiotic exposure is associated with subsequent ASD development.

The Perturbation of Infant Gut Microbiota Caused by Cesarean Delivery Is Partially Restored by Exclusive Breastfeeding.

Early establishment of the infant gut microbiome has been attributed to various environmental factors that may influence long-term health. The aim of this study was to determine the single and combined impacts of the delivery mode, feeding pattern and postnatal antibiotic exposure on the initial establishment of infant gut microbiome at 6 weeks postpartum. A cross-sectional study was conducted at a single center in China. Fecal samples were collected from 120 infants at 6 weeks postpartum. The V3-V4 regions of 16S rRNA gene were analyzed by Illumina sequencing, and clinical information was obtained from medical records and questionnaire survey. Compared with vaginally delivered infants, the gut microbial community structure of cesarean delivered infants were significantly different (P = 0.044), in parallel with the decreased relative abundance of Bifidobacterium (P = 0.028), which contrasts with the normal gut microbial establishment. Using the vaginally delivered and exclusively breastfed (VB) infants as a reference, the comparative analysis of cesarean delivered and exclusively breastfed (CB) infants with cesarean delivered and mixed-fed (CM) infants showed that both within- and between-group UniFrac distance were significantly smaller in CB infants (P < 0.001, P < 0.001). LEfSe analysis showed that the relative abundances of Enterococcus, Veillonella, and Faecalibacterium were significantly different between CB and CM infants, whereas the relative abundances of those genera in VB infants were close to those of CB infants, and distinct from those of CM infants. Additionally, no significant difference of microbial composition, alpha diversity, or community structure was observed between postnatal antibiotics exposed infants and unexposed infants. In summary, delivery mode had a significant impact on the infant gut microbial community structure and composition, and the gut microbiota was disturbed in infants delivered by cesarean section. However, our study showed that this disturbance of gut microbiota in cesarean delivered infants was partially restored by exclusive breastfeeding in comparison with mixed feeding. No distinct impact of postnatal antibiotic exposure on infant gut microbiome was found at 6 weeks of age.

Association between antibiotic treatment during pregnancy and infancy and the development of allergic diseases.

Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre- and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6years (aOR 1.65, 95% CI 0.95-2.86). Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.

Eliminating Risk of Intubation in Very Preterm Infants with Noninvasive Cardiorespiratory Support in the Delivery Room and Neonatal Intensive Care Unit.

Introduction Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. Objective Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). Materials and Methods We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. Results Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). Conclusion Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants.

623. Dynamic Nature of the Gut Resistome Among Infants in Singapore

BackgroundThe gut microbiome harbors antibiotic resistance genes (ARGs), known as the resistome, that has the potential to spread and contribute to the global crisis of antibacterial resistance. Little is known about the genomic traits of the infant resistome, especially in areas with high endemic antibacterial resistance.MethodsWe analyzed ARGs among a subset of infants from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort. The subset included 75 mostly term, healthy Singaporean infants born from November 2009 to May 2011. Stool samples collected at Week 3 (W3), months 3 (M3), 6 (M6) and 12 (M12) were analyzed using shotgun metagenomics. Sequencing reads were assembled into contigs using MEGAHIT. ARGs were identified using ResFinder 2.1. Demographic, perinatal factors, pre- and postnatal antibiotic exposure were collected.ResultsOne hundred and eighty-eight stool samples from 75 infants were studied. Of the 169 ARGs detected, the four commonest ARGs were blaZ, fosA, tet(M) and mef(A), conferring resistance to β-lactams, fosfomycin, tetracyclines, and macrolides respectively. The number of ARGs per infant increased over time (median: W3 = 18.0, M12 = 22.0, P < 0.05). At W3, 118 ARGs were detected among 28 infants. The most prevalent ARGs were fos(A) and blaZ (both 96.4%) at W3. Among the 22 infants who had samples at W3 and M12, only six of 118 ARGs detected at W3 were also present at M12. These were mef(A), msr(D), tet(W), erm(B), tet(M) and fosA, conferring macrolide and tetracycline resistance. Their prevalence among at M12 was 100%, 93.3%, 90.9%, 84.6%, 68.8% and 52.4%, respectively. ARGs were not associated with gender, race, delivery mode, peripartum or postnatal antibiotics in infancy. Of note, longitudinal analysis showed that only the cfxA gene, which confers β-lactam resistance, was more prevalent in infants whose mothers received antibiotics in pregnancy than those whose mothers did not (adjusted P < 0.05).ConclusionIn regions with high endemic antimicrobial resistance such as Singapore, the infant gut harbors a diversity of ARGs as early as 3 weeks of age. Few ARGs persisted through infancy, implying the dynamic nature of the infant resistome. The lack of association of ARGs with most clinical variables evaluated here suggests that other unrecognized factors may contribute to the plasticity of ARGs in the infant gut resistome.Disclosures R. Banerjee, Accelerate Diagnostics, Biomerieux, BioFire: Grant Investigator, Research grant and Research support.

Prenatal and postnatal antibiotic exposure influences the gut microbiota of preterm infants in neonatal intensive care units

BackgroundTo explore the influences of prenatal antibiotic exposure, the intensity of prenatal and postnatal antibiotic exposure on gut microbiota of preterm infants and whether gut microbiota and drug resistant strains in the neonatal intensive care unit (NICU) over a defined period are related.MethodsAmong 28 preterm infants, there were two groups, the PAT (prenatal antibiotic therapy) group (12 cases), and the PAF (prenatal antibiotic free) group (12 cases). Fecal samples from both groups were collected on days 7 and 14. According to the time of prenatal and postnatal antibiotic exposure, cases were divided into two groups, H (high) group (11 cases) and L (low) group (11 cases), and fecal samples on day 14 were collected. Genomic DNA was extracted from the fecal samples and was subjected to high throughput 16S rRNA amplicon sequencing. Bioinformatics methods were used to analyze the sequencing results.ResultsPrenatal and postnatal antibiotic exposure exercised influence on the early establishment of intestinal microflora of preterm infants. Bacteroidetes decreased significantly in the PAT group (p < 0.05). The number of Bifidobacterium significantly decreased in the PAT group and H group (p < 0.05). The early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure was similar to resistant bacteria in NICU during the same period.ConclusionPrenatal and postnatal antibiotic exposure may affect the composition of early gut microbiota in preterm infants. Antibiotic-resistant bacteria in NICU may play a role in reshaping the early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure.