Abstract

(1) Background: The incidence of hypertension in very low birthweight (VLBW) infants in a single neonatal intensive care unit (NICU) dropped markedly during a 2-year period when the IV fluid (IVF) in both the antenatal unit and the NICU temporarily changed to a di-2-ethylhexyl phthalate (DEHP)-free formulation. The objective of the current report is to document this observation and demonstrate the changes in incidence of hypertension were not associated with the variation in risk factors for hypertension; (2) Methods: The charts of all VLBW infants born in a single NICU during a 7-year span were reviewed. This time includes 32 months of baseline, 20 months of DEHP-free IVF, 20 months of IVF DEHP re-exposure, and two 4-month washout intervals. The group of interest was limited to VLBW infants with bronchopulmonary dysplasia (BPD). Chi-square analysis was used to compare incidence of hypertension among periods. Vermont Oxford NICU Registry data were examined for variation in maternal and neonatal risk factors for hypertension; Results: Incidence of hypertension in VLBW infants with BPD decreased from 7.7% (baseline) to 1.4% when IVF was DEHP-free, rising back to 10.1% when DEHP-containing IVF returned to use. Risk factors for neonatal hypertension were stable across the 3 study periods in the NICU’s group of VLBW infants; (3) Conclusions: Serendipitous removal of IVF containing DEHP resulted in near elimination of hypertension in one NICU—an effect entirely reversed after the same brand of DEHP-containing IVF returned to clinical use. These results suggest that DEHP exposure from IVF plays a major role in neonatal hypertension.

Highlights

  • Phthalates are a group of synthetic industrial chemical compounds used in the manufacturing of toys, cosmetics, pharmaceuticals, fragrances, baby-care products, food packaging, and medical supplies [1,2,3,4]

  • These results suggest that di-2-ethylhexyl phthalate (DEHP) exposure from IV fluid (IVF) plays a major role in neonatal hypertension

  • We found a linear relationship between cumulative IV DEHP exposure and systolic blood pressure (SBP) measured at 40 weeks postmenstrual age (PMA)

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Summary

Introduction

Phthalates are a group of synthetic industrial chemical compounds used in the manufacturing of toys, cosmetics, pharmaceuticals, fragrances, baby-care products, food packaging, and medical supplies [1,2,3,4]. Di-2-ethylhexyl phthalate (DEHP) remains the only phthalate approved for use in medical supplies by the FDA. Phthalate toxicity research first focused on cancer risk, followed by reproductive and developmental risks [7]. Given differences between animal and human metabolism, the risk to humans remained controversial through 2003 [7,8]. Attention turned to phthalate risks to small infants, as many studies identified alarming amounts of DEHP leaching from medical plastics into infants [9,10,11,12,13,14,15,16,17], yet the demonstration of actual toxicity in these infants remained scant [18]. Flynn et al raised awareness of the possible cardiovascular risks from phthalates in their 2017 guidelines [22]

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