{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:22:10Z","timestamp":1772713330039,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>(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\u2019s group of VLBW infants; (3) Conclusions: Serendipitous removal of IVF containing DEHP resulted in near elimination of hypertension in one NICU\u2014an 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.<\/jats:p>","DOI":"10.3390\/toxics9040075","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T04:13:51Z","timestamp":1617336831000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-3680","authenticated-orcid":false,"given":"Randall","family":"Jenkins","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Farnbach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Iragorri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","first-page":"34","article-title":"Phthalates and children\u2019s health","volume":"38","author":"Sathyanarayana","year":"2008","journal-title":"Curr. Prob. Pediatr. Adolesc. Health Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1365-2605.2005.00567.x","article-title":"Human exposure to phthalates via consumer prouducts","volume":"29","author":"Schettler","year":"2006","journal-title":"Int. J. Androl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0013-9351(03)00083-5","article-title":"Internal exposure of the general population to DEHP and the other phthalates\u2014Determination of the secondary and primary phthalate monoester metabolites in urine","volume":"93","author":"Koch","year":"2003","journal-title":"Environ. Res."},{"key":"ref_4","unstructured":"National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction (2021, March 31). NTP-CERHR Expert Panel Report on Di(2-ethylhexyl) Phthalate, Available online: http:\/\/ntp.niehs.nih.gov\/ntp\/ohat\/phthalates\/dehp\/dehp-monograph.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lorz, P.M., Towae, F.K., Enke, W., Jackh, R., and Bhargava, N. (2007). Phthalic acid and derivatives. Ullmann\u2019s Encyclopedia of Industrial Chemistry, Wiley-VCH. [7th ed.].","DOI":"10.1002\/14356007.a20_181.pub2"},{"key":"ref_6","unstructured":"National Research Council, Division on Earth and Life Studies, Board on Environmental Studies and Toxicology, and Committee on the Health Risks of Phthalates (2008). Phthalates and Cumulative Risk Assessment\u2014The Tasks Ahead, The National Academies Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1542\/peds.111.6.1467","article-title":"Pediatric exposure and potential toxicity of Phthalate plasticizers","volume":"111","author":"Shea","year":"2003","journal-title":"Pediatrics"},{"key":"ref_8","first-page":"e14","article-title":"Review and consensus statement. A scientific evaluation of health effects of two plasticizers used in medical devices and toys: A report from the American Council on Science and Health","volume":"22","author":"Koop","year":"1999","journal-title":"Med. Gen. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1177\/0148607102026005305","article-title":"Kinetics of diethylhexyl-phthalate extraction from polyvinylchloride-infusion lines","volume":"26","author":"Loff","year":"2002","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_10","first-page":"341","article-title":"Extraction of di-ethylhexyl-phthalate from perfusion lines of various material, length and brand by lipid emulsions","volume":"39","author":"Loff","year":"2004","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1159\/000181161","article-title":"Di-(2-ethylhexyl)phthalate leakage and color changes in endotracheal tubes after application in high-risk newborns","volume":"95","author":"Latini","year":"2009","journal-title":"Neonatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ijpharm.2011.02.024","article-title":"Physical-chemical assessment of di-(2-ethylhexyl)-phthalate leakage from poly(vinyl chloride) endotracheal tubes after application in high risk newborns","volume":"409","author":"Chiellini","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1289\/ehp.7932","article-title":"Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants","volume":"113","author":"Green","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1289\/ehp.8926","article-title":"Exposure to phthalates in neonatal intensive care unit infants: Urinary concentrations of monoesters and oxidative metabolites","volume":"114","author":"Weuve","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e429","DOI":"10.1542\/peds.113.5.e429","article-title":"Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit","volume":"113","author":"Calafat","year":"2004","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/jp.2014.157","article-title":"Phthalates and critically ill neonates: Device-related exposures and non-endocrine toxic risks","volume":"34","author":"Mallow","year":"2014","journal-title":"J. Perinatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41370-018-0069-2","article-title":"Sources of clinically significant neonatal intensive care unit phthalate exposure","volume":"30","author":"Stroustrup","year":"2020","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1001\/jamapediatrics.2017.3230","article-title":"The value of preterm infant environmental health cohorts: The canary in the coal mine","volume":"171","author":"Stroustrup","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.3390\/ijerph110605989","article-title":"Higher urinary heavy metal, phthalate, and arsenic but not parabens concentrations in people with high blood pressure, U.S. NHANES, 2011\u20132012","volume":"11","author":"Shiue","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.jpeds.2013.03.072","article-title":"Urinary phthalates are associated with higher blood pressure in childhood","volume":"163","author":"Trasande","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1161\/HYPERTENSIONAHA.115.05603","article-title":"Association of exposure to di-2-ethylhexylphthalate (DEHP) replacements with increased blood pressure in children and adolescents","volume":"66","author":"Trasande","year":"2015","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Flynn, J.T., Kaelber, D.C., Baker-Smith, C.M., Blowey, D., Carroll, A.E., Daniels, S.R., de Ferranti, S.D., Dionne, J.M., Falkner, B., and Flinn, S.K. (2017). Subcommittee On Screening and Management Of High Blood Pressure In Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics, 140.","DOI":"10.1542\/peds.2017-1904"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00467-019-04244-4","article-title":"Phthalate-associated hypertension in premature infants: A prospective mechanistic cohort study","volume":"34","author":"Jenkins","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s11906-013-0375-y","article-title":"Determinants of neonatal blood pressure","volume":"15","author":"Kent","year":"2013","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jpeds.2012.12.074","article-title":"Systemic hypertension requiring treatment in the neonatal intensive care unit","volume":"163","author":"Sahu","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1542\/peds.71.5.763","article-title":"Hypertension screening in the follow-up of premature infants","volume":"71","author":"Sheftel","year":"1983","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/ajh\/5.2.51","article-title":"Neonatal hypertension. Incidence and risk factors","volume":"5","author":"Singh","year":"1992","journal-title":"Am. J. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1007\/s00467-007-0603-2","article-title":"Antenatal and postnatal risk factors for neonatal hypertension and infant follow-up","volume":"22","author":"Seliem","year":"2007","journal-title":"Pediatr. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Farnbach, K., Iragorri, S., Al-Uzri, A., Rozansky, D., Forbush, R., and Jenkins, R. (2019). The changing spectrum of hypertension in premature infants. J. Perinatol.","DOI":"10.1038\/s41372-019-0457-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s00467-017-3722-4","article-title":"Characteristics of hypertension in premature infants with and without chronic lung disease: A long-term multi-center study","volume":"32","author":"Jenkins","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4103\/jcn.JCN_57_18","article-title":"Transient hyperaldosteronism and neonatal hypertension: Case series and literature review","volume":"7","author":"Yusuf","year":"2018","journal-title":"J. Clin. Neonatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/0002-9149(79)90182-6","article-title":"Increased systemic vascular resistance in neonates with pulmonary hypertension","volume":"44","author":"Milstein","year":"1979","journal-title":"Am. J. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1203\/pdr.0b013e318030d0ef","article-title":"Abnormal circulatory stress responses of preterm graduates","volume":"61","author":"Cohen","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/BF01958959","article-title":"Dexamethasone and hypertension in preterm infants","volume":"151","author":"Greenough","year":"1992","journal-title":"Eur. J. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00467-010-1755-z","article-title":"Hypertension in infancy: Diagnosis, management and outcome","volume":"27","author":"Dionne","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/MOP.0b013e32834f8329","article-title":"Hypertension in the neonatal period","volume":"24","author":"Flynn","year":"2012","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cbi.2009.09.014","article-title":"Structure-dependent inhibition of human and rat 11B-hydroxysteroid dehydrogenase 2 activities by phthalates","volume":"183","author":"Zhao","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0889-8529(18)30102-6","article-title":"Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess","volume":"23","author":"Walker","year":"1994","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_39","first-page":"29","article-title":"Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland","volume":"6","author":"Papadopoulos","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/15592294.2018.1448680","article-title":"Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation","volume":"13","author":"Montrose","year":"2018","journal-title":"Epigenetics"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/9\/4\/75\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:35Z","timestamp":1760362415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/9\/4\/75"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,2]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["toxics9040075"],"URL":"https:\/\/doi.org\/10.3390\/toxics9040075","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,2]]}}}