Early Life Antibiotic Research Articles

Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts.

Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain. To explore the association between early-life infections, antibiotics and IBD development. We used population-based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997-2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non-penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort-specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random-effects model. Antibiotic analyses were adjusted for infection frequency. There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person-years of follow-up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96-1.07) and 1.00 (95% CI = 0.99-1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01-1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96-1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02-1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non-penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38-2.75]). Early-life antibiotic use was, a significant risk factor for childhood and early adult-onset IBD, independent of infection frequency.

Maternal diet in pregnancy and the risk of inflammatory bowel disease in the offspring: a prospective cohort study

BackgroundDiet has been hypothesized as a risk factor for development of inflammatory bowel disease (IBD). ObjectiveTo explore associations between maternal diet diversity and quality in pregnancy and the offspring’s risk of IBD. MethodsWe used data from a nationwide cohort study on 85,129 Norwegian children followed from birth (1999–2009) with information on maternal diet in pregnancy from validated food frequency questionnaires. Hazard ratios (aHRs) for IBD, Crohn’s disease (CD), and ulcerative colitis (UC) by maternal diet diversity, quality and intake amounts of individual food groups were adjusted for maternal body mass index, parental IBD, and socio-demographic factors. Sensitivity analyses adjusted for the child's early-life diet quality and antibiotic treatment. Dietary exposures were classified into tertiles, comparing low (reference) to medium, and high levels. ResultsDuring a mean follow-up time of 16.1 years (1,367,837 person-years of follow-up), 268 children developed IBD (CD, n=119; UC, n=76; IBD-unclassified, n=73). High compared with low diet diversity in pregnancy was associated with a lower risk of UC in the offspring (aHR 0.46, 95% confidence interval 0.25-0.87), with consistent findings after further adjustment for the child's early-life diet quality and antibiotic treatment. High compared with low diet diversity in pregnancy yielded aHRs of 0.81 for CD (0.51-1.28) and 0.75 for any IBD (0.55-1.02) in the offspring. A high compared with low diet quality in pregnancy or intakes of specific food groups were not associated with the offspring’s risk of IBD or its subtypes. ConclusionsOur findings suggest that a higher maternal diet diversity in pregnancy may be associated with a lower risk of UC in the offspring.

Oral supplementation with Bifidobacterium infantis and 2′-fucosyllactose revives gut microbiota perturbation and intestinal and immune developmental delay following early-life antibiotic challenge in BALB/c mice

Probiotics and synbiotics can mitigate the negative health consequences of early-life antibiotic exposure. This study aimed to determine whether supplementation with Bifidobacterium longum ssp. infantis 79 (B79) or synbiotics composed of B79 and 2'-fucosyllactose (2'-FL) could mitigate the negative impact of ceftriaxone exposure in early-life. We found that antibiotic-treated mice exhibited lower body weight, crypt depth, short-chain fatty acid content, and α-diversity indices at weaning, while they increased the relative abundance of opportunistic pathogens (such as Enterococcus and Staphylococcus) and decreased the relative abundance of intestinal commensal bacteria. Supplementation with B79 and 2'-FL revived these antibiotic-induced negative effects and reduced the mRNA expression of IL-6, IL-12p40, and TNF-α in the spleen at weaning. Moreover, B79 and 2'-FL supplementation persistently improved crypt depth, propionic acid synthesis, and IgG and sIgA production and revived the gut microbiota structure and composition in adulthood. In conclusion, our study suggests that early-life supplementation with B79 alone or in combination with 2'-FL can mitigate ceftriaxone-induced negative effects on the gut microbiota and intestinal and immune development of mice, and these improvements can partially last into adulthood.

Neonatal and early infancy antibiotic exposure is associated with childhood atopic dermatitis, wheeze and asthma

Antibiotics are frequently administered in the neonatal period and early infancy. Little is known about the long-term health consequences of early life antibiotic exposure. The objective is to investigate the association between neonatal and early life (0–6 months) antibiotic treatment and the development of atopic dermatitis, asthma and the use of inhaled corticosteroid medication later in childhood. We analyzed data obtained from hospital records and national registers in a cohort of 11,255 children. The association between early antibiotic exposure and the outcomes were analyzed using logistic regression. Confounding factors were included in the model. Neonatal antibiotic therapy for confirmed infection was associated with childhood atopic dermatitis (adjusted odds ratio 1.49; 95% confidence interval 1.15–1.94). Antibiotic therapy by six months of age was more common in children developing atopic dermatitis (adjusted odds ratio 1.38; 95% confidence interval 1.15–1.64), asthma (adjusted odds ratio 1.56; 95% confidence interval 1.32- 1.85) and inhaled corticosteroid medication use (adjusted odds ratio 1.88; 95% confidence interval 1.66–2.13). Conclusions: Neonatal antibiotic therapy for confirmed or clinically diagnosed infection is associated with increased risk of atopic dermatitis later in childhood. Antibiotic treatment before six months of age is associated with atopic dermatitis, asthma and inhaled corticosteroid use.What is known:• The use of antibiotics early in life has been associated with an increased risk of developing atopic dermatitis or asthma.• Confounding by indication or reverse causation may underlie the observed associations.What is new:• Our results demonstrate that neonatal antibiotic therapy for confirmed or clinically diagnosed infection was associated with increased risk of atopic dermatitis and antibiotic treatment before six months of age was associated with atopic dermatitis, asthma and inhaled corticosteroid use in analyses adjusted for confounding factors.

Early life antibiotics have lasting effects on the lung epithelium.

Early life antibiotics have lasting effects on the lung epithelium.

A gut reaction? The role of the microbiome in aggression

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.

Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.

Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study

BackgroundThe gut microbiota is believed to influence neurodevelopment through the gut–brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD.MethodsThis was a retrospective cohort study using 2003–2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk.ResultsThe final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01–1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90–0.94).ConclusionsThe results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

The role of antibiotic exposure and the effects of breastmilk and human milk feeding on the developing infant gut microbiome.

The World Health Organization (WHO) recommends exclusive breastfeeding for the first 6 months of life followed by complementary foods and sustained breastfeeding for at least 2 years, underscoring its pivotal role in reducing infant mortality and preventing various illnesses. This perspective delves into the intricate relationship between breastfeeding practices, early life antibiotic exposure, and infant gut microbiome development, highlighting their profound influence on child health outcomes. Antibiotics are extensively prescribed during pregnancy and childhood, disrupting the microbiome, and are related to increased risks of allergies, obesity, and neurodevelopmental disorders. Breastfeeding is a significant determinant of a healthier gut microbiome, characterized by higher levels of beneficial bacteria such as Bifidobacterium and lower levels of potential pathogens. Despite widespread recognition of the benefits of breastfeeding, gaps persist in healthcare practices and support mechanisms, exacerbating challenges faced by breastfeeding families. This highlights the pressing need for comprehensive research encompassing breastfeeding behaviors, human milk intake, and their impact on infant health outcomes. Additionally, promoting awareness among healthcare providers and families regarding the detrimental effects of unnecessary formula supplementation could facilitate informed decision-making and bolster exclusive breastfeeding rates. Moreover, donor human milk (DHM) is a promising alternative to formula, potentially mitigating disruptions to the infant gut microbiome after antibiotic exposure. Overall, prioritizing breastfeeding support interventions and bridging research gaps are essential steps towards improving child health outcomes on a global scale.

A pilot case-control study on the fecal microbiota of pediatric functional abdominal pain-not otherwise specified and the role of early life stress.

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients (n = 40) were compared to healthy controls (n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations.

Intrapartum antibiotic use is associated with higher child body mass index (BMI) z-score at 4 years of age

Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum.

Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD. This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD. We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD. Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR]= 1.81; 95% CI: 1.28-2.57; P< .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (βindirect= 0.072; P< .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways. These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD.

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Fetal and Early-Life Antibiotics and Risk of Pediatric Inflammatory Bowel Disease: A Population-Based Nationwide Register Study

ObjectiveTo assess whether antibiotic exposure prenatally and before two years of age are associated with subsequent pediatric inflammatory bowel disease (PIBD), as earlier studies diverge substantially in risk estimations or do not include prenatal exposure. MethodsWe performed a register-based cohort study including all children in Norway born 2004-2012 until study end December 31, 2020. Exposures were defined as dispensed antibiotics to mothers during pregnancy and to children before two years of age. Main outcome was ICD-10 code registrations consistent with PIBD. ResultsAmong 536 819 children 797 PIBD cases were identified.The adjusted odds ratio (aOR) for developing PIBD if exposed to antibiotics before two years of age compared to no exposure was 1.33 (95% CI 1.15–1.53), adjusted for sex and prenatal antibiotic exposure. An adjustment for maternal smoking during pregnancy increased the aOR to 1.42 (1.22–1.66), but with minimal changes after further adjustments for potential confounders related to pregnancy, birth, or socioeconomic status. A dose-response association was observed in those receiving more than two antibiotic courses (aOR 1.47, 1.25–1.73), and with higher effect estimates for broad-spectrum antibiotics (aOR 2.57, 1.82–3.63). Antibiotic exposure during pregnancy was numerically but not significantly associated with offspring PIBD (aOR 1.15, 0.99–1.34). ConclusionsChildren exposed to antibiotics before two years of age were more likely to develop pediatric IBD than controls. Exposure prenatally to maternal antibiotics was numerically but not statistically significant associated to subsequent PIBD.

Interaction of life-time and early-life exposure to antibiotics and indoor environmental factors on childhood plant allergy

BackgroundDoctor-diagnosed plant allergy (DPA) in children has emerged as a significant global public health concern. However, the role of antibiotics and indoor environmental factors (IEFs) in childhood DPA remains unknown. ObjectiveTo investigate the correlations between childhood DPA and exposure to antibiotics and IEFs during different time periods. MethodsA retrospective cohort study of 8,689 preschoolers was performed in Changsha, China. We collected data on each child's health outcomes, antibiotics use and home environment by a questionnaire, as well as temperature and air pollutants in Changsha, and calculated personal exposure to temperature and pollutants. Multiple logistic regression models were used to assess the independent and joint effects of antibiotics and IEFs on childhood DPA. ResultsLife-time and early-life antibiotics use was associated with childhood DPA with ORs (95% CI) = 1.58 (1.15–2.17) and 1.33 (1.04–1.69), with a higher risk for early-life exposure than later-life exposure. Renovation-specific indoor air pollution (IAP) during pre-birth (1 year before pregnancy and pregnancy) and smoke-specific IAP during early life (pregnancy and first year) had significantly impacts on childhood DPA. Furthermore, dampness-specific allergens throughout lifetime elevated the risk of DPA, with ORs ranging from 1.34 (1.00–1.81) to 1.93 (1.44–2.59). Moreover, life-time and early-life antibiotic use significantly increased the DPA risk attributed to some specific IEFs, such as ETS especially grandparental smoking, exposure during first year and previous year, with a significant interaction. ConclusionsLife-time and early-life exposure to antibiotics and IEFs independently and jointly played key roles in the development of DPA, supporting the “fetal origin of childhood PA” hypothesis.

Early life antibiotic exposure and inflammatory bowel disease

Inflammatory bowel disease (IBD) is known to affect millions of people worldwide and is primarily caused due to abnormal due to abnormal immune responses to intestinal microbes. IBD is primarily categorized under two main types – ulcerative colitis and Crohn’s disease. Although the cause of IBD is still an unsolved puzzle, its development can be attributed to the presence of various risk factors including antibiotic use. The intestinal immune system is the point of genesis of IBD and anything that creates an imbalance can trigger IBD. Alterations in the gut microbiota can lead to reduced microbial populations and lead a chronic inflammation state. Antibiotics may influence microbial maturity and can hamper the formation of a strong immune system. This makes an individual vulnerable to the threat of infections and subsequent development of a chronic inflammation state. Studies have implicated that the use of antibiotics during pregnancy, antepartum, and among neonates is associated with the development of IBD. Adequate development of the microbial niche takes place within the first 2 years of life and extensive administration of antibiotics during this period can pose a significant risk for the development of IBD. Animal studies have also documented the role of in utero antibiotic exposure during the antepartum period and the subsequent risk of developing IBD in the offspring. This review summarizes the role of antibiotic exposure during pregnancy and infancy in the development of IBD.

THE DEVELOPMENTAL WINDOWS WHEN EXPOSURE TO ANTIBIOTICS INCREASES THE RISK OF EARLY ONSET COLORECTAL CANCER

Abstract Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer deaths in the US. About 50,000 people die from colorectal cancer each year. Early onset Colorectal cancer (EOCRC) is a colon and rectum cancer occurring in people under 50. There has been a decline in cases in people over 50 due to healthier lifestyle choices. However, in the last few decades there has been a steady increase in EOCRC cases, and we do not know why. The increase in EOCRC has paralleled the increased use of antibiotics. Antibiotics are especially important for fighting infections, but overuse has become an epidemic. Our study tested the hypothesis that exposure to antibiotics in early life causes dysbiosis and inflammation in the colon that can lead to an increased risk for EOCRC. To test the hypothesis a mice model was used. Female mice who have given birth are giving antibiotic treatment for 7 days, so the children are exposed to the antibiotics through their mother’s milk at an early age. The children are weaned from their mothers and at 5 weeks old they are given Azoyxmethane (AOM) treatment once a week for 6 weeks. Fecal pellets were collected before and after the AOM treatment of the kids and antibiotic treatment of the mother. The results show if given multiple dosages of amoxicillin there will be tumor burden in the proximal colon which can increase the risk for EOCRC.

Atopic Dermatitis and Eczema Association Between Early Life Antibiotic Exposure and Development of Early Childhood Atopic Dermatitis.

Atopic Dermatitis and Eczema Association Between Early Life Antibiotic Exposure and Development of Early Childhood Atopic Dermatitis.

Association between early-life antibiotics use and the risk of attention-deficit/hyperactivity disorder: A real-world evidence study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Recently, children using antibiotics showed an increased incidence of neurodevelopmental disorders. AimsThe purpose of this study was to investigate the association between antibiotics use and the risk of ADHD in children. Study designPopulation-based retrospective cohort study. SubjectsThe Taiwan National Health Insurance Research Database was used to collect data of children. Prevalence of antibiotics use was analyzed in the children (age, <2 years) included in this study. There were 1,601,689 children included in this study between 2004 and 2012. Outcome measuresThe risk of developing ADHD was estimated using the Cox proportional hazards model. Results71.25 % of children used at least one antibiotic, and the mean follow-up period was 7.07 years. After controlling for other related influencing factors, children who used antibiotics had a 1.12 times higher risk of ADHD than those who did not. The risk of ADHD increased through the use of penicillin and cephalosporin regardless of the duration of antibiotics use. ConclusionsAntibiotics use in children—especially penicillin and cephalosporin—was associated with a higher risk of ADHD.

In utero or early-in-life exposure to antibiotics and the riskof childhood atopic dermatitis, a population-based cohort study.

Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early-life exposure of a child to antibiotics increases the risk of early-onset AD. We hypothesize that antibiotic exposure in utero or early in life (e.g. first 90 days) increases the likelihood that children developAD. Utilizing a large, prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HRs) with 95% confidence intervals (CIs). The risk of AD in childhood was increased after in utero or early-life antibiotic exposure. For any in utero antibiotic exposure the HR (CI) was 1.38 (1.36-1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure [1.43 (1.41-1.44)] and for childhood exposure [1.81 (1.79-1.82)]. HRs were higher in children born to mothers without AD than in those with AD pointing to effect modification by maternal AD status. Children born to mothers exposed to antibiotics while in utero had, depending on the mother's history of AD, approximately a 20-40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early in life had a 40-80% increased risk of developing AD. Our study supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying the skin microbiome.