Hospital-Based Phthalate Exposure in Very Low Birth Weight Neonates

Low Birth Weight Neonates Clinical Trial

Official title:

Hospital-Based Phthalate Exposure in Very Low Birth Weight Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01420029
• Other study ID #: GCO 11-0664
• Secondary ID: 0285-7451
• Status: Completed
• Phase: N/A
• First received: August 17, 2011
• Last updated: September 19, 2013
• Start date: August 2011
• Est. completion date: September 2013

Study information

• Verified date: September 2013
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

In this observational pilot project, the investigators plan to document duration and sources of exposure to plasticizers in infants born at birth weights less than 1500 grams. The investigators will examine the association between exposure to plasticizers and outcomes such as performance on a neurological screening tool, extrauterine growth, and thyroid function.

Description:

High levels of exposure to certain plasticizers, specifically, phthalates and Bisphenol-A (BPA) have been shown to affect intelligence and behavior in school-age children, as well as to disrupt growth and some endocrine functions. Items used in the care of infants in the Neonatal Intensive Care Unit (NICU) contain phthalates and BPA. Babies admitted for long periods of time to the NICU, could be exposed to high levels of these potentially harmful plastics. In this study, the investigators are interested in documenting duration and sources of exposure to plasticizers during the NICU admission of infants born weighing less than 1500 grams. The investigators will examine the association between NICU exposure to plasticizers and performance on a neurological screening test that predicts future behavior, growth after birth, and the presence of any thyroid dysfunction.

The investigators plan to enroll 50 neonates in our study. The investigators will catalog all exposure to plasticizers during the infant's NICU admission and assign each baby a risk level of exposure. The investigators will then test each infant's performance on a neurological screening tool, measure growth from birth and assess whether or not each infant has thyroid dysfunction and correlate each outcome with exposure risk level. The investigators will also collect urine samples from each baby to store for possible future analysis.

The investigators hypothesize that neonates with higher levels of exposure will demonstrate worse performance on the neurological screening tool, poor growth, and abnormal thyroid function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Neonates born less than 1500 grams that are admitted to the Mount Sinai Hospital NICU

Exclusion Criteria:

• Chromosomal abnormality or other genetic disorder

• Diagnosis of hypoxic-ischemic encephalopathy

• Inborn error of metabolism

• Congenital renal disease

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Birth Weight
• Body Weight
• Low Birth Weight Neonates

Locations

Country	Name	City	State
United States	Mount Sinai Hospital Neonatal Intensive Care Unit	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (25)

Brazelton T, Nugent J. Neonatal Behavioral Assessment Scale, 3rd edition. 1995. Cambridge: MacKeith Press.

Calafat AM, Needham LL, Silva MJ, Lambert G. Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. Pediatrics. 2004 May;113(5):e429-34. — View Citation

Calafat AM, Weuve J, Ye X, Jia LT, Hu H, Ringer S, Huttner K, Hauser R. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Perspect. 2009 Apr;117(4):639-44. doi: 10.1289/ehp.0800265. Epub 2008 Dec 10. — View Citation

Cho SC, Bhang SY, Hong YC, Shin MS, Kim BN, Kim JW, Yoo HJ, Cho IH, Kim HW. Relationship between environmental phthalate exposure and the intelligence of school-age children. Environ Health Perspect. 2010 Jul;118(7):1027-32. doi: 10.1289/ehp.0901376. Epub 2010 Mar 1. — View Citation

Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics. 2003 May;111(5 Pt 1):986-90. — View Citation

De Curtis M, Rigo J. Extrauterine growth restriction in very-low-birthweight infants. Acta Paediatr. 2004 Dec;93(12):1563-8. — View Citation

Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. Am J Epidemiol. 2007 Jun 15;165(12):1397-404. Epub 2007 Apr 3. — View Citation

Engel SM, Miodovnik A, Canfield RL, Zhu C, Silva MJ, Calafat AM, Wolff MS. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect. 2010 Apr;118(4):565-71. doi: 10.1289/ehp.0901470. Epub 2010 Jan 8. — View Citation

Engel SM, Zhu C, Berkowitz GS, Calafat AM, Silva MJ, Miodovnik A, Wolff MS. Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort. Neurotoxicology. 2009 Jul;30(4):522-8. doi: 10.1016/j.neuro.2009.04.001. Epub 2009 Apr 16. — View Citation

Fenster L, Eskenazi B, Anderson M, Bradman A, Hubbard A, Barr DB. In utero exposure to DDT and performance on the Brazelton neonatal behavioral assessment scale. Neurotoxicology. 2007 May;28(3):471-7. Epub 2007 Jan 10. — View Citation

Ferguson SA, Flynn KM, Delclos KB, Newbold RR. Maternal and offspring toxicity but few sexually dimorphic behavioral alterations result from nonylphenol exposure. Neurotoxicol Teratol. 2000 Jul-Aug;22(4):583-91. — View Citation

Hinton RH, Mitchell FE, Mann A, Chescoe D, Price SC, Nunn A, Grasso P, Bridges JW. Effects of phthalic acid esters on the liver and thyroid. Environ Health Perspect. 1986 Dec;70:195-210. — View Citation

Johnson S, Hollis C, Kochhar P, Hennessy E, Wolke D, Marlow N. Psychiatric disorders in extremely preterm children: longitudinal finding at age 11 years in the EPICure study. J Am Acad Child Adolesc Psychiatry. 2010 May;49(5):453-63.e1. — View Citation

Kim BN, Cho SC, Kim Y, Shin MS, Yoo HJ, Kim JW, Yang YH, Kim HW, Bhang SY, Hong YC. Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children. Biol Psychiatry. 2009 Nov 15;66(10):958-63. doi: 10.1016/j.biopsych.2009.07.034. Epub 2009 Sep 12. — View Citation

Loff S, Kabs F, Witt K, Sartoris J, Mandl B, Niessen KH, Waag KL. Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers. J Pediatr Surg. 2000 Dec;35(12):1775-81. — View Citation

Ohgi S, Arisawa K, Takahashi T, Kusumoto T, Goto Y, Akiyama T, Saito H. Neonatal behavioral assessment scale as a predictor of later developmental disabilities of low birth-weight and/or premature infants. Brain Dev. 2003 Aug;25(5):313-21. — View Citation

Pereira C, Mapuskar K, Vaman Rao C. A two-generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate on histology of adrenal cortex and thyroid of rats. Acta Histochem. 2007;109(1):29-36. Epub 2006 Nov 17. — View Citation

Price SC, Chescoe D, Grasso P, Wright M, Hinton RH. Alterations in the thyroids of rats treated for long periods with di-(2-ethylhexyl) phthalate or with hypolipidaemic agents. Toxicol Lett. 1988 Jan;40(1):37-46. — View Citation

Silva MJ, Reidy JA, Herbert AR, Preau JL Jr, Needham LL, Calafat AM. Detection of phthalate metabolites in human amniotic fluid. Bull Environ Contam Toxicol. 2004 Jun;72(6):1226-31. — View Citation

Subotic U, Hannmann T, Kiss M, Brade J, Breitkopf K, Loff S. Extraction of the plasticizers diethylhexylphthalate and polyadipate from polyvinylchloride nasogastric tubes through gastric juice and feeding solution. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):71-6. — View Citation

Sugiyama S, Shimada N, Miyoshi H, Yamauchi K. Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis. Toxicol Sci. 2005 Dec;88(2):367-74. Epub 2005 Sep 22. — View Citation

Tamaru S, Kikuchi A, Takagi K, Wakamatsu M, Ono K, Horikoshi T, Kihara H, Nakamura T. Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors. Early Hum Dev. 2011 Jan;87(1):55-9. doi: 10.1016/j.earlhumdev.2010.10.004. — View Citation

Tanaka T. Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice. Food Chem Toxicol. 2005 Apr;43(4):581-9. — View Citation

Weuve J, Sánchez BN, Calafat AM, Schettler T, Green RA, Hu H, Hauser R. Exposure to phthalates in neonatal intensive care unit infants: urinary concentrations of monoesters and oxidative metabolites. Environ Health Perspect. 2006 Sep;114(9):1424-31. — View Citation

Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, Wetmur J, Calafat AM. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. 2008 Aug;116(8):1092-7. doi: 10.1289/ehp.11007. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exposure to plasticizers	Extent of exposure to plasticizers	Length of stay in NICU which averages 8-10 weeks	No
Primary	Performance on neonatal neurological screening tool		4 weeks of age	No
Primary	Performance on neonatal neurological screening tool		34 weeks postconceptual age	No
Secondary	Extrauterine growth	Weight, head circumference and length will be recorded weekly during the neonate's stay in the NICU	Weekly during NICU stay with average stay of 8-10 weeks	No
Secondary	Thyroid dysfunction	Presence of thyroid dysfunction on thyroid function tests	4 weeks of age	No