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Developmental Impact of NICU Exposures (DINE) (DINE)

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ClinicalTrials.gov Identifier: NCT03061890
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Judy Aschner, Albert Einstein College of Medicine, Inc.

Brief Summary:
The DINE study will test the hypothesis that potentially avoidable NICU-based exposures contribute to the neuro-cognitive and somatic impairments prevalent among NICU graduates. This hypothesis is drawn from the documented impact of phthalate exposure on early development in term-born children, and the acknowledged presence of these toxic chemicals in the NICU. Third trimester in utero exposure to phthalates have been linked to poorer childhood performance in cognition, motor function, attention, hyperactivity and social behavior. Phthalate exposure is also associated with altered onset of puberty and asthma. The multi-site cohort and approach will clarify the role of NICU-based phthalate exposure on high-prevalence clinical outcomes.

Condition or disease
Prematurity

Detailed Description:

Background: Each year in the United States, over 300,000 preterm infants are admitted to neonatal intensive care units (NICUs) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. Many life-saving and supportive respiratory, nutritional, hematologic and pharmaceutical therapies in the NICU expose preterm infants to potentially harmful chemicals during a life stage analogous to the third trimester of gestation. The NIH-funded DINE study capitalizes on the infrastructure, biorepositories, and extensive clinical databases of four existing preterm cohorts to explore the hypothesis that early life exposure to phthalates adversely impacts neurodevelopment, lung function, growth, adiposity, and pubertal development in childhood.

The scientific premise of the DINE study is that early life exposure to phthalates, a class of chemical plasticizers ubiquitous in the NICU, has long-lasting harmful effects on child health and development, and that these harmful effects are magnified in children born preterm. This premise is based on strong evidence of multisystem adverse health effects in term-born children who are exposed to phthalates in utero during the third trimester of pregnancy or in early infancy. In preterm infants, however, rigorously obtained data on the health effects of phthalates are scant. Dermal, inhalational and intravenous exposures to phthalates are widespread in some NICUs, where preterm infants are cared for during the sensitive "third trimester" developmental window. Moreover, premature infants experience a high prevalence of the adverse health effects that are associated with early life exposures to phthalates in term-born children, including altered neurodevelopment, poor pulmonary function, and maladapted growth. A rigorous, well-designed, sufficiently powered study of NICU-based phthalate exposures and long-term health outcomes of preterm infants has the potential to change care practices, promote regulatory policy changes and lead to mitigation of phthalate exposures in the NICU.

Significance: The proposed research is expected to identify modifiable sources of developmental risk for NICU patients that can inform and improve hospital care and long-term outcome. Moreover, our findings could lead to relatively inexpensive NICU interventions, such as use of non-phthalate containing medical materials, dosing guidelines for elemental metals and guidance for parents and staff on infant stress-reduction, and policy changes (e.g. regulation of the phthalates used in medical devices or changes to the trace metal content of parenteral nutrition) with significant positive potential impacts on life-long morbidities common among NICU graduates. Information gleaned from studying our highly-exposed, highly-vulnerable population may elucidate health impacts of early life exposures that translate to risk reduction in the general population.


Study Type : Observational [Patient Registry]
Estimated Enrollment : 854 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 7 Years
Official Title: Developmental Impact of Neonatal Intensive Care Unit (NICU) Exposures: Environmental Influences on Child Health Outcomes (ECHO)
Actual Study Start Date : April 1, 2017
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2023

Group/Cohort
Prematurity and Respiratory Outcomes Program (PROP)
extant, NIH-supported preterm birth cohort NCT01435187
Trial of Late Surfactant (TOLSURF)
extant, NIH-supported preterm birth cohort NCT01022580
NICU Hospital Exposures and Long-Term Health (NICU-HEALTH)
extant, NIH-supported preterm birth cohort NCT01963065
Preterm Erythropoietin Neuroprotection Trial (PENUT)
extant, NIH-supported preterm birth cohort NCT01378273



Primary Outcome Measures :
  1. Association between NICU environmental exposures and lung health and asthma measured by Standardized Auscultation for Wheeze [ Time Frame: One time between the ages of 3 to 4 ]
    Standardized Auscultation for Wheeze by physical exam to determine association between exposure and lung health

  2. Association between NICU environmental exposures and lung health and asthma measured by Brief Respiratory Questionnaire [ Time Frame: One time between the ages of 3 to 4 ]
    Brief Respiratory Questionnaire to determine association between exposure and lung health

  3. Associations between NICU environmental exposures and lung health and asthma measured by the PROMIS® (Patient-Reported Outcomes Measurement Information System) Parent Proxy Asthma Impact item bank [ Time Frame: One time between the ages of 5 to 6 ]
    PROMIS® (Patient-Reported Outcomes Measurement Information System) Parent Proxy Asthma Impact item bank to determine association between exposure and asthma

  4. Associations between NICU environmental exposures and lung health and asthma measured by PhenX (consensus measures for Phenotypes and eXposures) Toolkit measures of spirometry and bronchodilator responsiveness [ Time Frame: Twice within 24 months between the ages of 8 to 10 ]
    PhenX (consensus measures for Phenotypes and eXposures) Toolkit measures of spirometry and bronchodilator responsiveness to determine association between exposure and asthma

  5. Associations between NICU environmental exposures and lung health and asthma measured by the PROMIS Pediatric Asthma Impact item bank. [ Time Frame: Twice within 24 months between the ages of 8 to 10 ]
    PROMIS Pediatric Asthma Impact item bank to determine the association between exposures and asthma

  6. Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Early Childhood Cognition Battery [ Time Frame: Twice within 24 months between the ages of 3 to 5 ]
    NIH Toolbox Early Childhood Cognition Battery to determine the associations between exposures and neurocognitive behavioral development

  7. Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Cognition Battery [ Time Frame: Twice within 24 months between the ages of 7 to 9 ]
    NIH Toolbox Cognition Battery to determine the associations between exposures and neurocognitive behavioral development

  8. Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Early Childhood Motor Battery [ Time Frame: Twice within 24 months between the ages of 4 to 6 ]
    NIH Toolbox Early Childhood Motor Battery to determine the associations between exposures and neurocognitive behavioral development

  9. Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Motor Battery [ Time Frame: Twice within 24 months between the ages of 8 to 10 ]
    NIH Toolbox Motor Battery to determine the associations between exposures and neurocognitive behavioral development

  10. Associations between NICU environmental exposures and neurocognitive behavioral development measured by Child Behavior Checklist (CBCL) [ Time Frame: One time between the ages of 3 to 4 ]
    Child Behavior Checklist (CBCL) to determine the associations between exposures and neurocognitive behavioral development

  11. Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Cognitive Item bank [ Time Frame: Three times within a 5 year time period between the ages of 5 to 10 ]
    PROMIS Cognitive Item bank to determine the associations between exposures and neurocognitive behavioral development

  12. Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Pediatric Mobility Item bank [ Time Frame: Three times within a 5 year time period between the ages of 5 to 10 ]
    PROMIS Pediatric Mobility Item bank to determine the associations between exposures and neurocognitive behavioral development

  13. Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Pediatric Upper Extremity Item bank [ Time Frame: Three times within a 5 year time period between the ages of 5 to 10 ]
    PROMIS Pediatric Upper Extremity Item to determine the associations between exposures and neurocognitive behavioral development

  14. Associations between NICU environmental exposures and growth and obesity as measured by height, weight, head circumference, mid-upper arm circumference and bioimpedence [ Time Frame: Annually, up to 10 years ]
    Measurement of height, weight, head circumference, mid-upper arm circumference and bioimpedence scale to determine associations between exposures and heathy growth and obesity

  15. Associations between NICU environmental exposures and growth and obesity as measured by parent report height and weight [ Time Frame: Annually, up to 10 years ]
    Parent reported height and weight to determine associations between exposures and healthy growth and obesity

  16. Associations between NICU environmental exposures and pubertal development measured by PhenX Assessment of Pubertal Development [ Time Frame: Annually, up to 10 years ]
    PhenX Assessment of Pubertal Development to determine associations between exposures and pubertal development


Biospecimen Retention:   Samples With DNA
Urine, hair, teeth, saliva for DNA (optional) samples retained, with potential for extraction of DNA from saliva with separate consent


Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Former preterm infants who were participants hospitalized in the NICU of one of the 8 clinical sites participating in the UH3 phase of the ECHO and DINE studies and whose parents had consented to participate in one of the 4 extent cohorts of the following NIH-supported studies: Prematurity and Respiratory Outcomes Program (PROP), the Trial of Late Surfactant (TOLSURF), the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) study and the Preterm Erythropoietin Neuroprotection Trial (PENUT) study and agreed to longitudinal follow up of infants as part of DINE
Criteria

Inclusion Criteria:

  • Children who were study participants in one of the four extant preterm cohorts (PROP, TOLSURF, NICU-HEALTH, and PENUT) that comprise the combined DINE cohort and who were followed to study endpoint at one of the clinical sites in DINE.
  • Newly recruited preterm infants admitted to the NICU at the Icahn School of Medicine at Mount Sinai
  • Parents agreed to be re-contacted or local Institutional Review Board (IRB) grants permission to recontact families to obtain consent to participate in DINE.

Exclusion Criteria:

  • Family requested that they not be contacted after their child completed the parent study
  • Family is unlikely to be available for long-term follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061890


Contacts
Contact: Judy L Aschner, MD 718-839-7009 judy.aschner@einstein.yu.edu
Contact: Annemarie Stroustrup, MD 212-241-6186 annemarie.stroustrup@mssm.edu

Locations
United States, Arkansas
Arkansas Children's Research Institute Terminated
Little Rock, Arkansas, United States, 72202
United States, California
University of California, San Francisco Terminated
San Francisco, California, United States, 94158
United States, Florida
University of Florida Active, not recruiting
Jacksonville, Florida, United States, 32209
Florida Hospital Terminated
Orlando, Florida, United States, 32804
United States, Indiana
Indiana University Terminated
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
National Institute for Children's Health Quality Active, not recruiting
Boston, Massachusetts, United States, 02108
United States, Minnesota
Children's Health Care, Inc. Active, not recruiting
Minneapolis, Minnesota, United States, 55404
United States, New York
Albert Einstein College of Medicine Active, not recruiting
Bronx, New York, United States, 10461
University at Buffalo State University of New York Active, not recruiting
Buffalo, New York, United States, 14222
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: AnneMarie Stroustrup, MD         
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Gloria S Pryhuber, MD         
United States, North Carolina
Wake Forest University Health Sciences Active, not recruiting
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Cincinnati Children's Hospital Active, not recruiting
Cincinnati, Ohio, United States, 45229
United States, South Carolina
Medical University of South Carolina Terminated
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center Active, not recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Health Science Center at Houston Terminated
Houston, Texas, United States, 77030
United States, Washington
University of Washington Terminated
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Albert Einstein College of Medicine, Inc.
National Institutes of Health (NIH)
Investigators
Principal Investigator: Judy L Aschner, MD Albert Einstein College of Medicine, Inc.

Additional Information:
Responsible Party: Judy Aschner, Professor of Pediatrics, Albert Einstein College of Medicine, Inc.
ClinicalTrials.gov Identifier: NCT03061890     History of Changes
Other Study ID Numbers: 2016-7369
1UG3OD023320 ( U.S. NIH Grant/Contract )
4UH3OD023320 ( U.S. NIH Grant/Contract )
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All efforts, within reason, are made to keep protected health information (PHI) private, including data gathered for research studies. Using or sharing ("disclosure") such data must follow federal privacy rules. All PHI about children in the study will be entered into REDCap, a secure, web-based data collection platform. Study patients will be identified only by a study identification (ID) number. Access to the REDCap study database is restricted to study personnel, password protected and behind a Medical Center firewall. The study child's name and medical record number will appear only on the Screening Log which contains no other PHI. Only the study team will have access to the Screening Log.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Judy Aschner, Albert Einstein College of Medicine, Inc.:
children's environmental health
prematurity
preterm birth
phthalates
NICU
stress
lung health
neurodevelopment
growth

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications