ArticleIntensive care medicine2016
Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort.
Article in Intensive care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00214916 (KULeuven Intensive Insulin Study in Pediatric Intensive Care Patients), which is not on this map. Cited by 27 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
KULeuven Intensive Insulin Study in Pediatric Intensive Care Patients
Who cites it
27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Neurocognitive functioning and health-related quality of life of children after pediatric intensive care admission: a systematic review.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2022Pooled it
- Phthalates exposure and attention-deficit/hyperactivity disorder in children: a systematic review of epidemiological literature.Environmental science and pollution research international · 2020Pooled it
- Phthalate exposure and neurodevelopment: A systematic review and meta-analysis of human epidemiological evidence.Environment international · 2020Pooled it
- Impact of critical illness and withholding of early parenteral nutrition in the pediatric intensive care unit on long-term physical performance of children: a 4-year follow-up of the PEPaNIC randomized controlled trial.Critical care (London, England) · 2022Trial
- Respiratory Support as a Source of Plasticizer Exposure in Premature Neonates.Journal of applied toxicology : JAT · 2026Article
- Neurodevelopmental care across pediatric critical care settings: toward brain-focused critical care.European journal of pediatrics · 2026Review
- A Machine Learning-Based Clustering Analysis to Explore Bisphenol A and Phthalate Exposure from Medical Devices in Infants with Congenital Heart Defects.Environmental health perspectives · 2025Article
- Article
- Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness.Clinical epigenetics · 2024Article
- Article
- Medical devices as a source of phthalate exposure: a review of current knowledge and alternative solutions.Arhiv za higijenu rada i toksikologiju · 2022Review
- Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?Environment international · 2022Article
- Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease.PloS one · 2022Article
- Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study.Environmental research · 2021Article
- Phthalate Exposure Pattern in Breast Milk within a Six-Month Postpartum Time in Southern Taiwan.International journal of environmental research and public health · 2021Article
- Prenatal Exposure to Endocrine-Disrupting Chemicals and Subsequent Brain Structure Changes Revealed by Voxel-Based Morphometry and Generalized Q-Sampling MRI.International journal of environmental research and public health · 2021Article
- Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes.Birth defects research · 2020Review
- Early Supplemental Parenteral Nutrition in Critically Ill Children: An Update.Journal of clinical medicine · 2019Review
- Perioperative Exposure to Suspect Neurotoxicants From Medical Devices in Newborns With Congenital Heart Defects.The Annals of thoracic surgery · 2019Article
- Developmental Exposure to Di-(2-ethylhexyl) Phthalate Induces Cerebellar Granule Cell Apoptosis via the PI3K/AKT Signaling Pathway.Experimental neurobiology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeEnvironmental phthalate exposure has been associated with attention deficit disorders in children. We hypothesized that in children treated in the pediatric intensive care unit (PICU), circulating phthalates leaching from indwelling medical devices contribute to their long-term attention deficit.
methodsCirculating plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were quantified in 100 healthy children and 449 children who had been treated in PICU and were neurocognitively tested 4 years later. In a development patient cohort (N = 228), a multivariable bootstrap study identified stable thresholds of exposure to circulating DEHP metabolites above which there was an independent association with worse neurocognitive outcome. Subsequently, in a second patient cohort (N = 221), the observed independent associations were validated.
resultsPlasma concentrations of DEHP metabolites, which were virtually undetectable [0.029 (0.027-0.031) µmol/l] in healthy children, were 4.41 (3.76-5.06) µmol/l in critically ill children upon PICU admission (P < 0.001). Plasma DEHP metabolite concentrations decreased rapidly but remained 18 times higher until PICU discharge (P < 0.001). After adjusting for baseline risk factors and duration of PICU stay, and further for PICU complications and treatments, exceeding the potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with the attention deficit (all P ≤ 0.008) and impaired motor coordination (all P ≤ 0.02). The association with the attention deficit was confirmed in the validation cohort (all P ≤ 0.01). This phthalate exposure effect explained half of the attention deficit in post-PICU patients.
conclusionsIatrogenic exposure to DEHP metabolites during intensive care was independently and robustly associated with the important attention deficit observed in children 4 years after critical illness. Clinicaltrials.gov identifier: NCT00214916.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.