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Randall D. Jenkins
Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA

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Journal article
Published: 21 April 2021 in Toxics
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Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-positive IVT. The DEHP leached from most respiratory devices was relatively modest, except that detected from bubble CPAP. In 14 very low birthweight infants, the mean DEHP exposure was 182,369 mcg/kg over 81.2 days of the initial hospitalization. Ninety-eight percent of the exposure was from respiratory devices, with bubble CPAP accounting for 95% of the total DEHP exposure in these infants. Conclusions: The DEHP exposure in our neonatal unit can be reduced markedly by avoiding or modifying bubble CPAP equipment and avoiding IV tubing containing DEHP.

ACS Style

Randall Jenkins; Devlynne Ondusko; Luke Montrose; Ryan Forbush; David Rozansky. Phthalate Exposures in the Neonatal Intensive Care Unit. Toxics 2021, 9, 90 .

AMA Style

Randall Jenkins, Devlynne Ondusko, Luke Montrose, Ryan Forbush, David Rozansky. Phthalate Exposures in the Neonatal Intensive Care Unit. Toxics. 2021; 9 (5):90.

Chicago/Turabian Style

Randall Jenkins; Devlynne Ondusko; Luke Montrose; Ryan Forbush; David Rozansky. 2021. "Phthalate Exposures in the Neonatal Intensive Care Unit." Toxics 9, no. 5: 90.

Journal article
Published: 02 April 2021 in Toxics
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(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.

ACS Style

Randall Jenkins; Katia Farnbach; Sandra Iragorri. Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia. Toxics 2021, 9, 75 .

AMA Style

Randall Jenkins, Katia Farnbach, Sandra Iragorri. Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia. Toxics. 2021; 9 (4):75.

Chicago/Turabian Style

Randall Jenkins; Katia Farnbach; Sandra Iragorri. 2021. "Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia." Toxics 9, no. 4: 75.

Original research
Published: 01 September 2019 in Research and Reports in Neonatology
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Purpose: Preterm infants are at increased risk of systemic hypertension compared to term infants. Bronchopulmonary dysplasia (BPD) has been shown to be associated with hypertension in preterm infants albeit with no causation reported. BPD is characterized by abnormal pulmonary function tests (PFTs), specifically elevated passive respiratory resistance (Rrs), decreased passive respiratory compliance (Crs), and decreased functional residual capacity (FRC). There have been no studies comparing PFTs in very low birth weight (VLBW) infants with and without hypertension. We hypothesized that stable VLBW infants with hypertension will have altered PFTs. Patients and methods: Retrospective cohort study of infants <1500 g at birth (VLBW) who had PFTs performed near 34–36 weeks of corrected gestational age (CGA). We excluded infants with congenital anomalies, known hypertensive disorders or those at risk of medication-induced hypertension. Data obtained included PFT parameters (Rrs, Crs, FRC) and mean systolic blood pressure (SBP). Results: Fifty-nine VLBW infants were identified for analysis, 14 with and 45 without hypertension. Hypertensive and normotensive patients were similar in terms of mean gestational age (26.6 vs 27.4 weeks), mean CGA at PFTs (36.1 vs 34.6 weeks) and proportion of BPD (36% vs 36%). The Rrs was significantly higher in hypertensive versus normotensive patients [median Rrs of 0.080 (0.069, 0.090) versus 0.066 (0.054, 0.083) cmH2O/mL/s; p=0.04]. There was no difference in systolic blood pressure in the infants with and without BPD. Conclusion: In this cohort of contemporary VLBW infants, those with hypertension had increased Rrs. This finding warrants a prospective study with a larger sample size and long-term follow-up.

ACS Style

Ladawna L. Gievers; Randall D. Jenkins; Amy Laird; Marissa C. Macedo; Diane Schilling; Cindy T McEvoy. Pulmonary function and systolic blood pressure in very low birth weight infants at 34–36 weeks of corrected age. Research and Reports in Neonatology 2019, ume 9, 21 -30.

AMA Style

Ladawna L. Gievers, Randall D. Jenkins, Amy Laird, Marissa C. Macedo, Diane Schilling, Cindy T McEvoy. Pulmonary function and systolic blood pressure in very low birth weight infants at 34–36 weeks of corrected age. Research and Reports in Neonatology. 2019; ume 9 ():21-30.

Chicago/Turabian Style

Ladawna L. Gievers; Randall D. Jenkins; Amy Laird; Marissa C. Macedo; Diane Schilling; Cindy T McEvoy. 2019. "Pulmonary function and systolic blood pressure in very low birth weight infants at 34–36 weeks of corrected age." Research and Reports in Neonatology ume 9, no. : 21-30.

Journal article
Published: 06 August 2019 in Journal of Perinatology
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ACS Style

K. Farnbach; S. Iragorri; A. Al-Uzri; D. Rozansky; R. Forbush; R. Jenkins. The changing spectrum of hypertension in premature infants. Journal of Perinatology 2019, 39, 1528 -1534.

AMA Style

K. Farnbach, S. Iragorri, A. Al-Uzri, D. Rozansky, R. Forbush, R. Jenkins. The changing spectrum of hypertension in premature infants. Journal of Perinatology. 2019; 39 (11):1528-1534.

Chicago/Turabian Style

K. Farnbach; S. Iragorri; A. Al-Uzri; D. Rozansky; R. Forbush; R. Jenkins. 2019. "The changing spectrum of hypertension in premature infants." Journal of Perinatology 39, no. 11: 1528-1534.

Original article
Published: 26 April 2019 in Pediatric Nephrology
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Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05). Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2.

ACS Style

Randall Jenkins; Shane Tackitt; Ladawna Gievers; Sandra Iragorri; Kylie Sage; Tonya Cornwall; Declan O’Riordan; Jennifer Merchant; David Rozansky. Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study. Pediatric Nephrology 2019, 34, 1413 -1424.

AMA Style

Randall Jenkins, Shane Tackitt, Ladawna Gievers, Sandra Iragorri, Kylie Sage, Tonya Cornwall, Declan O’Riordan, Jennifer Merchant, David Rozansky. Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study. Pediatric Nephrology. 2019; 34 (8):1413-1424.

Chicago/Turabian Style

Randall Jenkins; Shane Tackitt; Ladawna Gievers; Sandra Iragorri; Kylie Sage; Tonya Cornwall; Declan O’Riordan; Jennifer Merchant; David Rozansky. 2019. "Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study." Pediatric Nephrology 34, no. 8: 1413-1424.