291 - Determination of the pharmacokinetic profile of common phthalate diesters in preterm neonates using blood transfusion as the source of intravenous exposure.

In the neonatal intensive care unit (NICU), infants face treatments that convey high-dose exposure to phthalates, a family of ubiquitous endocrine-disrupting organic chemicals found in plastics and personal care products, during a life stage equivalent to the third trimester of in utero development. Past research shows that preterm infants are at significant risk of adverse multisystem outcomes potentially impacted by early life phthalate exposure, including the interrelated domains of neurodevelopment, somatic growth, and pulmonary function. Blood product transfusion is a recognized significant source of di (2-ethylhexyl) phthalate (DEHP) exposure.

Objective:

To determine the pharmacokinetics of common phthalate diester metabolism in a preterm population.


Design/Methods: Clinically indicated blood transfusions were used as distinct phthalate exposures. A urine specimen was obtained from each participant weekly during the NICU hospitalization to ensure that a “pre-transfusion” baseline specimen was available prior to the index transfusion. Urine was collected every 3 hours from time the transfusion was ordered until 72 hours post-transfusion, allowing for urinary metabolite measurement through the entire expected period of phthalate metabolism. Urine specimens were analyzed for quantitative detection of biomarkers of exposure to an expanded panel of phthalate monoesters and novel replacements chemicals. Half-lives of individual phthalate metabolites were calculated.

Results: We present data from our first study participant (figure 1 - DEHP Metabolites). 17 urine specimens were collected from a female infant born at 30 weeks gestation after blood transfusion. MECPP, MEHHP, MEHP and MEOHP showed exposure and elimination patterns consistent with sentinel exposure. Half-lives were MEHP 5.83 hours, MECPP 6.83 hours, MEHHP 4.75 hours, MEOHP 5.33 hours. As expected, measured metabolites not related to DEHP did not demonstrate a sentinel exposure elimination pattern.

Conclusion(s): Clinically indicated blood transfusion led to increases in specific urinary phthalate metabolite concentrations in this 30-week gestation infant as shown in our pilot data. The half-life of phthalate metabolites tended to be shorter than in adults. Further study with additional participants is needed to fully understand phthalate pharmacokinetics in the preterm population.