Phthalates and other plasticisers are extensively used in medical devices (MD) from which they can leach out and lead to potential multiple problems for the patients. This exposure is a major issue because it is associated with reproductive and neurodevelopment disorders. The Neonatal Intensive Care Units (NICU) population is at high risk due to the daily intensive medical interventions, the reduced ability of newborns to remove these contaminants and their higher sen-sitivity to endocrine disruptors.We conducted a multicentric biomonitoring study to assess and compare the urinary levels of DEHP (di-(2-ethylhexyl) phthalate), DEHTP (di-(2-ethylhexyl)terephthalate) and TEHTM (tri-(2-ethylhexyl)trimellitate) metabolites as bio-markers of this exposure during and after the newborns' stay in NICU.Daily urinary samples were collected in NICU and at discharge from the hospital for each patient. MD sources and ex-posure factors were also investigated.508 urinary samples from 97 patients enrolled in centres 1 and 2 (C1/C2) were collected. The exposure of newborns to DEHP was greater than that of DEHTP and TEHTM, with a median concentration of DEHP metabolites (C1:195.63 ng/mL;C2:450.87 ng/mL) respectively 5 to 10 times higher and 57 to 228 times higher than the median concentrations of DEHTP and TEHTM metabolites.The urinary concentrations of DEHP and TEHTM metabolites were significantly lower at discharge than in NICU, with a 18-and 35-fold decrease for DEHP and a 4 and 8-fold decrease for TEHTM, respectively for C1 and C2, but were sim-ilar for DEHTP metabolites. MD used for respiratory assistance, infusion therapy,enteral nutrition and transfusion were the main sources of expo-sure. Smaller gestational age and body weight significantly increased the newborns' exposure.The elevated levels of DEHP metabolites in NICU patients are still alarming. Additional efforts are necessary to pro-mote its substitution in MD by possibly safer alternatives such as TEHTM and DEHTP, particularly when used for the care of newborns.
Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers’ exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients’ urinary levels of each plasticizers’ metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites’ toxicity.
DiEthylHexylPhthalate (DEHP) can leach out of plasticized PVC medical devices (MD) and may enter into contact with patients. This phthalate is known for its reprotoxic and endocrine disrupting effects. Its use in medical devices (MD) has been restricted and alternative plasticizers have been developed. Nevertheless, no published clinical studies exist concerning patient exposure to these alternative plasticizers during medical care. This is particularly worrisome when high-risk populations, such as newborns, are exposed to these new plasticizers in intensive care units. Our study aimed to develop a novel sensitive and selective method to simultaneously identify and quantify DEHP and 17 other plasticizer metabolites (free or glucuronide conjugates), which are specific biomarkers of DEHTP, TOTM, DINP, DINCH and DEHA exposure in human urine. This robust method uses turbulent-flow online extraction technology coupled to high performance liquid chromatography - tandem mass spectrometry. Special care was taken to address two major problems in plasticizer analysis: contamination and chromatographic separation of interfering analogue structures. The validation was assessed in synthetic urine and the linearity of response was demonstrated for all compounds (R-2 > 0.99), with limits of quantification from 0.01 to 0.1 ng/ml. Accuracies ranged from 86% to 117% and inter- and infra-day precisions were < 20%. The clinical applicability and suitability of our new method was assessed in patients in a neonatal intensive care unit to measure urinary concentrations of DEHP and alternative plasticizer metabolites. These metabolites were found in the majority of urine samples, with a median detection frequency of 95.2% (ranging from 12.5% to 100%). The high sensitivity, selectivity and ruggedness make the method suitable for large-scale biomonitoring studies of high-risk and general populations.
Background: Human adenovirus (HAdV) infections, while common in infancy and childhood, occur rarely in the neonatal period but may be fatal.Objectives: To describe a transmission of HAdV from a patient with fatal pneumonia to heath-care workers that could be considered as a model of respiratory virus transmission in a care unit.Study design: Case report with virologic studies.Results: A 10-day-old neonate developed pneumonia with acute respiratory distress, external pulmonary bleeding and coagulopathy and died 36 h after admission of multivisceral failure. An adenovirus was isolated from pulmonary biopsy and detected by PCR in blood and respiratory secretions. Ten days later, three members of medical staff in charge of this infant, who used neither masks nor glasses for close patient contact, developed keratoconjunctivitis. Molecular analysis of the infant's and one of the pediatrician's isolates identified a species D HAdv and showed 100% identity, thereby demonstrating viral transmission.Conclusion: In view of the serious outcome, HAdV infections should be considered in the differential diagnosis of pneumonia in neonates. This case illustrates the epidemic potential of viruses with respiratory transmission and underlines the importance of complying with standard precautions to prevent viral spread in routine practice. (C) 2009 Elsevier B.V. All rights reserved.
Évaluer le pronostic obstétrical et néonatal d'une stratégie de naissance systématique des ruptures prématurées de membranes non compliquées au cours de la trente-cinquième semaine d'aménorrhée (SA). Nous avons mené une étude rétrospective sur 50 patientes déclenchées au cours de la trente-cinquième semaine d'aménorrhée dans un contexte de rupture prématurée des membranes sur singleton survenue depuis plus de 12 heures. Aucune n'était suspecte de chorioamniotite et toutes avaient reçu au moins une injection de corticoïdes. Nous avons évalué la voie d'accouchement, le poids de naissance, le score d'Apgar, et la survenue d'une infection maternofœtale, d'une détresse respiratoire ou d'une atteinte neurologique. Cinq patientes ont été césarisées de manière prophylactique et 4 l'ont été en cours de travail. Quarante-et-une patientes ont accouché par voie vaginale sous ocytocine éventuellement précédé de gels vaginaux de prostaglandines. Le poids moyen des enfants est de 2 187272 grammes avec 12 cas d'Apgar < 7 à 5 minutes. Nous rapportons 10 cas d'infection materno-fœtale, 22 cas de détresse respiratoire dont 10 justifiant une intubation pour une durée moyenne de 4 jours et 7 atteintes neurologiques. La durée d'hospitalisation est de 25,15,9 jours. Le délai de latence entre la rupture et l'accouchement n'était pas corrélé à la survenue d'une infection materno-fœtale (p = 0,85), ni à celle d'une atteinte neurologique (p = 0,63) ou d'une détresse respiratoire (p = 0,07). Aucun décès maternel ni néonatal n'a été observé. La morbidité néonatale de cette attitude n'est pas négligeable et le caractère iatrogène à l'égard du risque de détresse respiratoire est probable. L'absence de corrélation entre les complications et le délai depuis la rupture empêche de considérer l'âge gestationnel comme un critère suffisant pour imposer la naissance. En l'absence de complication avérée, une naissance prophylactique de principe ne semble pas judicieuse à cet âge gestationnel.