Rotavirus Vaccine in Offspring Exposed in Utero to Tumor Necrosis Factor Inhibitors Was Not Associated with an Increased Risk of Diarrhea Events During the First 6 Months of Life
Bibliographic record
Abstract
Objectives Guidelines previously recommended withholding the rotavirus vaccine among in utero TNFi-exposed infants until 6 months due to infection risk in immunosuppressed infants.[1] However, delaying vaccination may increase diarrhea-associated morbidity compared to routine immunization starting at 2 months. We compared the risk of diarrhea-associated healthcare events (“diarrhea events”) during the first 6 months among in utero TNFi-exposed and -unexposed infants based on vaccination status. Methods We created a cohort of offspring born to mothers with chronic inflammatory diseases (MarketScan; 2011-2021) and identified those exposed to ≥1 TNFi prescription in utero and those not. Infants born in the 13 US states with a state-funded universal rotavirus vaccine program were excluded due to the absence of private insurer claims. Time-varying vaccine status was identified by ≥1 billing code for RV1 or RV5 vaccines administered between 2 and 6 months. Follow-up began at 2 months and ended at 6 months. Diarrhea events were defined by relevant ICD-9/10 codes for hospitalizations or outpatient visits. We estimated the association of the vaccine with diarrhea risks among TNFi-exposed and -unexposed offspring using Cox proportional hazards models, as well as among infants exposed to TNFi in the third trimester and those exposed in the first and second trimesters. Models were adjusted for in utero drug exposure (non-biologic immunomodulators, corticosteroids), preterm birth, sex, geographic region, year and season of birth, and TNFi placental transfer. Results We identified 49,585 offspring; 3,167 were TNFi-exposed in utero; 83% received at least 1 dose of the rotavirus vaccine between 2-6 months (Figure 1A). Among TNFi-unexposed offspring, the vaccine was associated with a 32% increase in diarrhea events (hazard ratio, HR, 1.32; 95% confidence interval, CI, 1.13, 1.54) (Figure 1B). However, among TNFi-exposed offspring, no statistically significant association was found between the vaccine and diarrhea event risk (HR 1.07; 95% CI 0.72, 1.61), including in those TNFi-exposed during the third trimester (HR 1.13; 95% CI 0.68, 1.86), or only during the first and/or second trimesters (HR 0.89; 95% CI 0.45, 1.76). When looking at the vaccine’s effect among those exposed to high placental transfer TNFi in the third trimester, no statistically significant association was found (HR 0.97; 95% CI 0.57, 1.66). Figure 1. Baseline Characteristics and Survival Analysis. Panel A shows the baseline characteristics of infants exposed in utero to tumour necrosis factor inhibitors (TNFi) and unexposed offspring born to mothers with chronic inflammatory diseases during their first 6 months of age and stratified based on their rotavirus vaccination status during the first 2-6 months. Panel B shows the adjusted hazard ratios for the association of the rotavirus vaccine with the risk of diarrhea-related healthcare events during the first 6 months of life in TNFi-exposed and -unexposed offspring. The model was adjusted for TNFi trimester of exposure, in utero drug exposures (i.e. corticosteroids, non-biologic immunomodulators), sex, preterm birth, gestational diabetes, geographic region, year of birth (odd vs even), birth season (October-March vs April-September), TNFi placental transfer. Conclusion Our findings suggest no increased risk of diarrhea events related to rotavirus vaccination during the first 6 months of life among in utero TNFi-exposed offspring, even for late TNFi exposure during pregnancy. These results support the updated recommendation not to delay rotavirus vaccination in TNFi-exposed infants.[2] [1.] Bass AR. Arthritis Care Res 2023;75(3):449-64. [2.] Förger F. Ann Rheum Dis 2024;83(Suppl 1):2075. Best Abstract by a Post-Graduate Research Trainee Award
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".