SAT-724 Endocrine Disruption by Phthalate Exposure in the Pediatric Intensive Care Unit
Bibliographic record
Abstract
Abstract Aim: Pediatric intensive care relies on plastic indwelling medical devices softened by phthalates. Phthalates leach into the circulation and concerns about toxicity were raised. Exceeding a certain threshold of di(2-ethylhexyl)phthalate (DEHP) exposure in the pediatric intensive care unit (PICU) has been associated with an attention deficit 4 years later (1). Moreover, DEHP and its metabolites have endocrine disrupting properties. Critically ill children reveal the non-thyroidal illness syndrome (2) and unexplained relatively low cortisol (3). Whether DEHP exposure in PICU has endocrine disruptive effects is unknown. We investigated whether DEHP exposure in the PICU, exceeding the previously identified “toxic” threshold for attention, is independently associated with thyroid- and HPA-axis alterations upon PICU discharge. Methods: In this preplanned secondary analysis of the PEPaNIC RCT (N=1440) (4), plasma DEHP metabolite concentrations (MEHP, 5OH-MEHP, 5cx-MEPP, 5oxo-MEHP) were quantified for all patients with a last PICU day sample (N=920). Minimal DEHP exposure was defined as the product of the total DEHP metabolite concentrations on the last PICU day and duration of PICU stay, with 0.551 µmol/L.days identified as “toxic” threshold (1). Serum TSH, total T4, total T3 and rT3 concentrations were quantified for patients with an available last day sample (N=913). For patients with a last day plasma sample and who did not receive corticosteroids (N=391), plasma ACTH, total cortisol, albumin and CBG concentrations were quantified and free cortisol calculated. Multivariable linear regression analyses, adjusted for baseline risk factors and for duration of PICU stay, assessed whether exceeding the previously determined threshold of toxic DEHP exposure was independently associated with the hormone levels on the last PICU day. Main results: Median total DEHP metabolite concentration was 0.101 (IQR 0.049 - 0.279) µmol/L on the last PICU day. Minimal DEHP exposure was 0.337 (IQR 0.161 - 0.880) µmol/l.days, and 328 patients (35.7%) exceeded the toxic threshold. Exceeding this threshold was independently associated with lower total T4 (P=0.002), total T3 (P=0.02) and total cortisol (P=0.001), and higher rT3 (P=0.01) concentrations on the last PICU day, but not with TSH, ACTH or free cortisol. Conclusion: Critically ill children had DHEP metabolites in plasma upon PICU discharge and more than a third were exposed to toxic levels. Toxic DEHP exposure was an independent contributor to the severity of the non-thyroidal illness phenotype and to lower cortisol upon PICU discharge. Future research should assess whether such endocrine-disruptive impact of DHEP exposure in the PICU plays a role in the long-term developmental legacy of critical illness in children. 1 Verstraete et al Intensive Care Med 2016 2 Jacobs et al Thyroid 2019 3 Jacobs et al Intensive Care Med 2019 4 Fivez et al N Engl J Med 2016
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How this classification was reachedexpand
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".