Risk factors for severe respiratory syncytial virus infection during the first year of life: development and validation of a clinical prediction model
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Bibliographic record
Abstract
BACKGROUND: Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal targeting of interventions against them. Our aims were to identify predictors for RSV hospital admission from registry-based data and to develop and validate a clinical prediction model to guide RSV immunoprophylaxis for infants younger than 1 year. METHODS: In this model development and validation study, we studied all infants born in Finland between June 1, 1997, and May 31, 2020, and in Sweden between June 1, 2006, and May 31, 2020, along with the data for their parents and siblings. Infants were excluded if they died or were admitted to hospital for RSV within the first 7 days of life. The outcome was hospital admission due to RSV bronchiolitis during the first year of life. The Finnish study population was divided into a development dataset (born between June 1, 1997, and May 31, 2017) and a temporal hold-out validation dataset (born between June 1, 2017, and May 31, 2020). The development dataset was used for predictor discovery and selection in which we screened 1511 candidate predictors from the infants', parents', and siblings' data, and developed a logistic regression model with the 16 most important predictors. This model was then validated using the Finnish hold-out validation dataset and the Swedish dataset. FINDINGS: In total, there were 1 124 561 infants in the Finnish development dataset, 130 352 infants in the Finnish hold-out validation dataset, and 1 459 472 infants in the Swedish dataset. In addition to known predictors such as severe congenital heart defects (adjusted odds ratio 2·89, 95% CI 2·28-3·65), we confirmed some less established predictors for RSV hospital admission, most notably oesophageal malformations (3·11, 1·86-5·19) and lower complexity congenital heart defects (1·43, 1·25-1·63). The prediction model's C-statistic was 0·766 (95% CI 0·742-0·789) in Finnish data and 0·737 (0·710-0·762) in Swedish validation data. The infants in the highest decile of predicted RSV hospital admission probability had 4·5 times higher observed risk compared with others. Calibration varied according to epidemic intensity. The model's performance was similar to a machine learning (XGboost) model using all 1511 candidate predictors (C-statistic in Finland 0·771, 95% CI 0·754-0·788). The prediction model showed clinical utility in decision curve analysis and in hypothetical number needed to treat calculations for immunisation, and its C-statistic was similar across different strata of parental income. INTERPRETATION: The identified predictors and the prediction model can be used in guiding RSV immunoprophylaxis in infants, or as a basis for further immunoprophylaxis targeting tools. FUNDING: Sigrid Jusélius Foundation, European Research Council, Pediatric Research Foundation, and Academy of Finland.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it