BOSTON — New findings have shown that high levels of phthalates in the blood are responsible for attention deficit disorders later in children who undergo frequent treatment in the ICU.

“The long-term legacy of pediatric critical illness comprises a severe and unexplained attention deficit,” said Sören Verstraete, MD, a PhD student at Katholieke Universiteit Leuven in Leuven, Belgium. “We found a clear match between previously hospitalized children’s long-term neurocognitive test results and their individual exposure to the phthalate DEHP during intensive care.”

Dr Verstraete presented the findings at ENDO 2016.

Di(2-ethylhexyl)phthalate, or DEHP, is the most commonly used plastic softener in medical devices made of polyvinyl chloride (PVC). Congress banned 3 types of phthalates including DEHP from children’s toys because of their potential toxic and hormone-disrupting effects in 2008, but the chemical is still used in medical devices such as plastic tubes and catheters.

Dr Verstraete and his colleagues hypothesized that circulating phthalates leaching from indwelling medical devices contribute to long-term attention deficit in children treated in the pediatric ICU.

To test their hypothesis, the researchers measured circulating plasma concentrations of DEHP metabolites in 100 healthy children, and 449 children who were treated in the pediatric ICU and underwent neurocognitive testing 4 years later. Most patients underwent heart surgery, while others were treated for seizures, accidental injuries, or severe infections.

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. Those independent associations were validated in a second patient cohort (n=221).

Dr Verstraete said plasma concentrations of DEHP metabolites were 4.41 μmol/L in critically ill children upon admission to the pediatric ICU but nearly undetectable in healthy children (0.029 μmol/L).

The potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with attention deficit and impaired motor coordination, even after researchers adjusted for baseline risk factors and duration of stay in the ICU, and for further complications and treatments. The association with attention deficit was confirmed in the validation cohort (all P≤0.01). This phthalate exposure effect explained half of the attention deficit in patients treated in the pediatric ICU.

“Exposure to phthalates leaching from indwelling medical devices used for intensive medical care in children is associated with their important attention deficit,” Dr Verstraete said.

He noted that at present, this leaching may be unavoidable because all the medical devices tested by the researchers included phthalates.

“We need the soft and pliable indwelling medical devices. But on the other hand, the No. 1 rule of modern medicine is ‘Do not harm,’” he said. “When you know that you potentially induce a long-term attention deficient in the children, one can ask if we need to develop alternative plasticizers.”

Reference

  1. Verstraete S. OR04-6. Circulating Phthalates during Critical Illness in Children and Their Long-Term Attention Deficit Legacy: An Association Study of a Development and a Validation Cohort. Presented at: ENDO 2016; April 1-4, 2016; Boston, MA.