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PEDIATRICS Vol. 113 No. 5 May 2004, pp. e429-e434

ELECTRONIC ARTICLE

Exposure to Di-(2-Ethylhexyl) Phthalate Among Premature Neonates in a Neonatal Intensive Care Unit

Antonia M. Calafat, PhD^*, Larry L. Needham, PhD^*, Manori J. Silva, PhD^* and George Lambert, MD

^* Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia
Department of Pediatrics, Center for Childhood Neurotoxicology and Exposure Assessment, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, New Jersey

Objective. Premature neonates who spend time in a neonatal intensive care unit may be at increased risk of adverse health effects from exposure to di-(2-ethylhexyl) phthalate (DEHP) because of their increased risk of high exposure, their small body size, and their physical condition. DEHP, a reproductive toxicant in animals, is a major component in polyvinyl chloride (PVC) plastics, which are frequently used in medical tubing and blood storage bags. DEHP is not covalently bound to PVC, and it may be easily released from the PVC medical devices. The objective of this study was to determine whether premature infants who undergo medical procedures, such as blood transfusions, intravenous therapy, enteral and parenteral nutrition support, and dialysis, are at increased risk of exposure to DEHP than the general population. Because of their smaller size, children and especially premature and small infants may receive a larger dose of DEHP on a milligram per kilogram basis than adults when the same-size medical device is used for all ages.

Methods. Premature neonates who seemed to have the potential to be on intravenous infusion for >2 weeks and were expected to survive were eligible for enrollment in the study. We assessed exposure to DEHP in 6 premature newborns by measuring in 41 urine samples the levels of 3 DEHP metabolites: mono-(2-ethylhexyl) phthalate (mEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP).

Results. mEHHP and mEOHP were detected in all 41 urine samples, and mEHP was detected in 33. Because only 33 of the samples had detectable amounts for all 3 metabolites, statistical analyses were limited to those 33. The levels of all 3 DEHP metabolites varied widely, and the urinary mean and median concentrations of mEOHP and mEHHP were 1 order of magnitude higher than those for mEHP. Furthermore, the geometric mean urinary concentrations of mEOHP (1617 ng/mL), mEHHP (2003 ng/mL), and mEHP (100 ng/mL) in these 6 premature infants who underwent intensive therapeutic interventions were found to be severalfold higher than in the US general population (for mEHP, geometric mean in those 6 years and older was 3.43 ng/mL).

Conclusions. This study provides the first quantitative evidence confirming that newborns who undergo intensive therapeutic medical interventions are exposed to higher concentrations of DEHP than the general population. Although the overall benefits of medical procedures using PVC devices outweigh the risks associated with exposure to DEHP, more research is needed to determine whether infants and children who undergo intensive therapeutic interventions using DEHP-containing devices are at higher risk for altered health outcomes than infants and children who undergo similar treatments but are not potentially exposed to DEHP.

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Key Words: DEHP • phthalate • plasticizer • urine • biomarker

Abbreviations: PVC, polyvinyl chloride • DEHP, di-(2-ethylhexyl) phthalate • mEHP, mono-(2-ethylhexyl) phthalate • mEHHP, mono-(2-ethyl-5-hydroxyhexyl) phthalate • mEOHP, mono-(2-ethyl-5-oxohexyl) phthalate • IV, intravenous • CERHR, Center for the Evaluation of the Risks to Human Reproduction • RfD, reference dose

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Received for publication Nov 10, 2003; Accepted Dec 22, 2003.

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