Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/Hyperactivity Disorder: A Population-Based Cohort Study

Hamad, Amani F.; Alessi‐Severini, Silvia; Mahmud, Salaheddin M.; Brownell, Marni; Kuo, I fan

doi:10.1093/aje/kwz178

Cited by 23 publications

(19 citation statements)

References 39 publications

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“…13,25,29,32,61,64,76,78,93,103,109,111,115,116,121,123,148,154,176,181,182,191,195,197,198,201 Moreover, the risk of adverse long-term health outcomes is often higher for antibiotics with a broad-spectrum including cephalosporins and macrolides. 18,21,34,36,57,58,61,69,78,91,92,111,121,123,137,157,163,172,182,195,197 These findings underline the importance of antibiotic stewardship, specifically to avoid antibiotics for infections that are likely viral and to use the most narrow-spectrum antibiotic possible. 226 A recent large population-based prospective study sh...…”

Section: Discussionmentioning

confidence: 95%

“…Four studies investigated the association between antibiotic exposure and the development of attention deficit hyperactivity disorders (ADHD) in 756,348 children (25,143 cases with one study not reporting number of cases). 22,58,130,172 They evaluated children by ICD codes. All four studies evaluated antibiotic exposure before two years of age.…”

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

“…All four studies evaluated antibiotic exposure before two years of age. 22,58,130,172 Two studies reported a significant increased risk of developing ADHD in children who were exposed to antibiotics. 130,172 One study could not find a difference in the risk of developing ADHD after exposure to penicillins or broad-spectrum antibiotics, 22 while another study found an increased risk after exposure to penicillin in girls compared to other antibiotic classes.…”

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

“…172 Three (75%) studies were included in the meta-analysis and the overall OR was 1.30 (95%CI 0.97-1.75), p=0.08) (figure 2 and supplementary data figure 19). 22,58,172 Of the 528,497 children exposed to antibiotics 18,073 (3%) developed ADHD compared to 7,070 (3%) of the 227,405 children not exposed to antibiotics.…”

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

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Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Duong

Pittet

Curtis

et al. 2022

Journal of Infection

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Section: Discussionmentioning

confidence: 95%

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

Section: Attention Deficit Hyperactivity Disordermentioning

confidence: 99%

See 2 more Smart Citations

Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Duong

Pittet

Curtis

et al. 2022

Journal of Infection

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“…Previous research has shown conflicting results regarding exposure to antibiotics in early life and ADHD. For example, recent population-based Canadian and Danish studies 92,93 did not observe a significant association between antibiotic exposure in the first years of life and ADHD, particularly in sibling-controlled analysis that adjusted for familial confounding factors. However, a large Finnish study 94 suggested an association between exposure to antibiotics in early life and ADHD that may not be fully explained by familial confounding.…”

Section: Antibiotic Regimenmentioning

confidence: 99%

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records

Šumilo

Nirantharakumar

Willis

et al. 2022

Health Technol Assess

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Background Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby’s umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown. Objectives We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section. Design This was a controlled interrupted time series study. Setting The study took place in primary and secondary care. Participants Children born in the UK during 2006–18 delivered by caesarean section were compared with a control cohort delivered vaginally. Interventions In-utero exposure to antibiotics immediately prior to birth. Main outcome measures Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed. Data sources The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN–CPRD data set. Results In the THIN–CPRD and HES data sets, records of 515,945 and 3,945,351 mother–baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively. Limitations It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years. Conclusions There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006–18 had an impact on the incidence of asthma and eczema in early childhood in the UK. Future work There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children. Study registration This study is registered as researchregistry3736. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.

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Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

et al. 2023

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ImportanceExisting observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors.ObjectiveTo evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children.Design, Setting, and ParticipantsThis nationwide, cohort study included data from South Korea’s National Health Insurance Service mother-child–linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019.ExposuresPrenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]).Main Outcomes and MeasuresComposite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)–matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models.ResultsThe study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808 067 PS-matched pairs (763 755 received H2RAs, 36 529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses.Conclusions and RelevanceThe findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.

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Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/Hyperactivity Disorder: A Population-Based Cohort Study

Cited by 23 publications

References 39 publications

Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

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