Maternal and early postnatal antibiotic exposure may increase the risk of autism spectrum disorder with regression.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Association between maternal antibiotic exposure and emotional and behavioural problems in children at four years of age: A biomonitoring-based prospective study

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritus and recurrent skin lesions, affecting a significant percentage of children globally. The prevalence of AD is rising, particularly in Asian populations, potentially due to rapid urbanization and environmental changes. This systematic review explores the impact of intrauterine antibiotic exposure on the risk of developing AD in Asian children, considering the multifactorial nature of the disease influenced by genetic and environmental factors. Objectives: The primary objective of this review is to synthesize existing research on the correlation between maternal antibiotic exposure during pregnancy and the incidence of AD in offspring within Asian populations. The review aims to identify potential modifiable risk factors and elucidate the underlying mechanisms contributing to AD development. Methods: The review adhered to the 2020 PRISMA guidelines, conducting a comprehensive literature search using PubMed and Cochrane Library. The search strategy focused on studies published in English between 2000 and 2025, involving keywords related to antibiotics, maternal exposure, and atopic dermatitis. Inclusion criteria encompassed studies with healthy mothers and accessible full texts, while exclusion criteria involved studies lacking essential details. Results: The review included 6 prospective cohort studies from China, Japan, South Korea, and Taiwan, with a total sample sizes of 1.073.245 mother-children pairs ranging from 412 to 900,584 participants. The studies employed various methods to assess antibiotic exposure, including maternal urine samples, parent-reported data, and medical records. Results varied, with some studies indicating a significant correlation between antibiotic exposure and increased AD risk, while others found no association. The inconsistency in findings highlights the complexity of AD and the influence of genetic and environmental factors. Discussion: The findings suggest a multifaceted relationship between maternal antibiotic exposure and AD risk, potentially mediated by alterations in gut microbiota and immune system development. The variability in results underscores the need for standardized methodologies and further research to clarify the mechanisms involved. The review emphasizes the importance of considering genetic predisposition and environmental influences in understanding AD etiology. Conclusion: This systematic review indicates a possible link between prenatal antibiotic exposure and AD in Asian children, though evidence remains inconclusive. Further research is necessary to elucidate the underlying mechanisms and identify modifiable risk factors. Understanding the impact of antibiotics on AD progression could inform clinical practices and public health strategies, potentially leading to targeted interventions to reduce AD prevalence in high-risk populations.

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

Pre- and postnatal antibiotic exposure and risk of developing attention deficit hyperactivity disorder–A systematic review and meta-analysis combining evidence from human and animal studies

SummaryBackgroundThe association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear.ObjectivesThe study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort.MethodsThe Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full‐term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years.ResultsIn the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes.ConclusionMaternal antibiotic exposure during mid/late pregnancy may result in child obesity.

Investigating Antibiotic Exposure and Risk of Severe Acute Graft Versus Host Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

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.

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.

Background: This study aimed to systematically evaluate the available evidence on prenatal and early infancy antibiotic exposure and the association with overweight and obesity in later childhood.Methods: We conducted a comprehensive search of Embase, MEDLINE, and Web of Science for observational studies assessing prenatal and early antibiotic exposure on the risk of overweight and obesity. We independently assessed the risk of bias using the ROBINS instrument and the overall quality of evidence using the GRADE approach.Results: Our search identified thirteen observational studies including 554,983 participants; most studies were at moderate risk of bias. We found a statistically significant impact of early antibiotic exposure and the risk of being overweight later in childhood (OR 1.18; 95% CI 1.05 to 1.34) (very low quality evidence). We also found that early childhood antibiotic exposure was associated with the risk for childhood obesity (OR 1.14; 95% CI 1.04 to 1.24) (very low quality evidence).Conclusions: Very low quality evidence suggests that exposure to antibiotics early in life may be associated with an increased risk of being overweight and obese in later childhood. However, very low quality evidence raises serious questions about the plausibility of prenatal and early infancy antibiotic exposure being causally related to weight in children.PROSPERO registration:CRD42016050011 (14/12/2016)

Background: This study aimed to systematically evaluate the available evidence on prenatal and early infancy antibiotic exposure and the association with overweight and obesity in later childhood. Methods: We conducted a comprehensive search of Embase, MEDLINE, and Web of Science for observational studies assessing prenatal and early antibiotic exposure on the risk of overweight and obesity. We independently assessed the risk of bias using the ROBINS instrument and the overall quality of evidence using the GRADE approach. Results: Our search identified thirteen observational studies including 554,983 participants; most studies were at moderate risk of bias. We found a statistically significant impact of early antibiotic exposure and the risk of being overweight later in childhood (OR 1.18; 95% CI 1.05 to 1.34) (very low quality evidence). We also found that early childhood antibiotic exposure was associated with the risk for childhood obesity (OR 1.14; 95% CI 1.04 to 1.24) (very low quality evidence). Conclusions: Very low quality evidence suggests that exposure to antibiotics early in life may be associated with an increased risk of being overweight and obese in later childhood. However, very low quality evidence raises serious questions about the plausibility of prenatal and early infancy antibiotic exposure being causally related to weight in children. PROSPERO registration: CRD42016050011 (14/12/2016).

This study was conducted to assess this association between early life antibiotic exposure and the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in later life. The results showed that early life antibiotic exposure was associated with an increased risk of ASD (OR = 1.13, 95% confidence interval (CI): 1.07-1.21) or ADHD (OR = 1.18, 95% CI: 1.1-1.27). However, this association for ASD (OR = 1.04, 95% CI: 0.97-1.11) or ADHD (OR = 0.98, 95% CI: 0.94-1.02) disappeared when data from sibling-matched studies were pooled. The statistically significant association between early life antibiotic exposure and ASD or ADHD in later life can be partially explained by unmeasured genetic and familial confounding factors.

Increasing studies suggest that antibiotic exposure during pregnancy may increase the risk of childhood allergic diseases; however, controversy still exists. Thus, we conducted this meta-analysis to evaluate the association between antibiotic use during pregnancy and childhood asthma/wheeze, eczema/atopic dermatitis, and food allergy. CENTRAL, EMBASE, and PubMed were searched for studies up to July 20, 2020. Cohort studies and case-control studies that estimated the association of antibiotic exposure in pregnancy with the risk of childhood asthma/wheeze, eczema/atopic dermatitis, and food allergy were included. A random-effects model or fixed-effects model was used to calculate the pooled estimates. The quality of the included studies was assessed by the Newcastle-Ottawa Scale (NOS). Stata12.0 software was used to analyze the association through a meta-analysis. A total of 26 studies were included in the meta-analysis. The results showed that maternal antibiotic exposure in pregnancy and the summary OR for the risk of childhood asthma/wheeze was 1.29 (95% CI=1.16-1.43), the summary OR for eczema/atopic dermatitis was 1.62 (95% CI=1.16-2.27), and the pooled OR for food allergy was 1.36 (95% CI=0.94-1.96). Our results indicated that maternal antibiotic use during pregnancy might increase the risk of asthma/wheeze and eczema/atopic dermatitis but not food allergy in children. Further studies with larger sample size and robust multivariable adjustment are needed to confirm our findings. Nevertheless, the appropriate use of antibiotics during pregnancy is incredibly important, and healthcare professionals should be selective when prescribing antibiotics for pregnant women.

The early life microbiome contributes to immune development. Antibiotics during pregnancy alter the microbiome and may influence disease risks in the offspring. We investigated the relationship between maternal antibiotic exposure before and during pregnancy, and risk of childhood hospitalization with infection. We used population-based Danish national databases for pregnancies between 1995 and 2009. Infants were followed from birth until their first infection-related hospitalization, death, 14th birthday, emigration or end-2009. Exposure was maternal antibiotics prescribed before and during pregnancy. Outcome was infection-related hospitalization. 141 359 (18%) mothers had at least one antibiotic prescription during pregnancy, 230 886 (29.4% of those with complete data) in the 18 months before pregnancy. Of 776 657 live-born singletons, 443 546 infection-related hospitalizations occurred in 222 524 (28.6%) children. Pregnancy antibiotic exposure was associated with increased risk of childhood infection-related hospitalization [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.17-1.19]. In mothers prescribed antibiotics only during pregnancy whose child did not receive pre-hospitalization antibiotics, this association was present only in those born vaginally. Higher risks of infection-related hospitalization occurred when pregnancy antibiotic prescriptions were closer to birth and in mothers receiving more pregnancy antibiotics. Children born to mothers exposed to antibiotics before (but not during) pregnancy also had increased risk of infection-related hospitalization (HR 1.10, 95% CI 1.07-1.12). Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.