103. EARLY ANTIBIOTIC EXPOSURE AND RISK OF PSYCHIATRIC INCREASED SENSITIVITY OF CENTRAL SEROTONERGIC NEURONS TO CORTICOSTEROIDS FOLLOWING MATERNAL IMMUNE ACTIVATION: SIGNIFICANCE FOR MOOD DISORDERS AND NEUROCOGNITIVE OUTCOMES: RESULTS OF A SYSTEMATIC REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Abstract Background There is a compelling body of data attesting to the role of the microbiota-gut-brain axis in mental health. The early life period poses a critical window wherein disturbances in the intestinal microbiota may adversely impact neurodevelopment. Antibiotics have a clear impact on the intestinal microbiome, yet their long-term safety regarding early exposure and later life psychiatric or neurocognitive outcomes has not been broadly evaluated. Aims & Objectives This systematic review and meta-analysis aimed to address a critical gap in literature by evaluating the association between in-utero and early childhood (ages 0-2) antibiotic exposure and the likelihood of psychiatric and neurocognitive problems in later life. Method We conducted a systematic review and meta-analysis of studies evaluating in-utero or early childhood (ages 0-2) antibiotic exposure compared to unexposed controls and later psychiatric or neurocognitive outcomes. We searched MEDLINE, PsychINFO and EMBASE on 20/11/23. Quality assessments included the GRADE certainty assessment and Newcastle-Ottawa Scale. Results Thirty studies were included (n=7,047,853 participants). There were weak associations between in-utero antibiotic exposure and later development of ASD (OR= 1.09, 95%CI: 1.02-1.16) and ADHD (OR=1.19, 95%CI: 1.11 to 1.27). Early-childhood exposure was associated with later development of ADHD (OR=1.33, 95%CI: 1.20 to 1.48), ASD (OR=1.19, 95%CI: 1.01 to 1.40), and MDD (OR=1.29, 95%CI: 1.04 to 1.60). However, in sibling-controlled studies, there were no associations between either exposure period and later ASD or ADHD. No studies in MDD used sibling-controls. All meta-analyses were rated very low certainty using the GRADE certainty assessment, largely owing to methodological and statistical heterogeneity, except for childhood antibiotic exposure and later ASD (sibling-controlled data), which was low certainty. Discussion & Conclusions Weak evidence was found supporting the association between in-utero and early-life antibiotic exposure, and later neurodevelopmental outcomes. However, these associations were attenuated in studies that used sibling controls, which is a more robust study design. Thus, genetic and familial confounding may explain the associations seen, and non-sibling-controlled data should be interpreted with caution. We recommend that future studies utilise sibling-controls.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.030 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.038 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".