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Completed

NCT Number: NCT03061890

Developmental Impact of NICU Exposures (DINE)

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.

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Key information

Conditions

Prematurity Female Urogenital Diseases and Pregnancy Complications Obstetric Labor Complications Obstetric Labor, Premature Pregnancy Complications Premature Birth Urogenital Diseases

Age range

Up to 12 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Florida, Jacksonville, Florida, United States

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About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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
  • Newly recruited preterm and term infants who participated in the PRISM study at University of Rochester
  • 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

Treatment and study plan

Primary outcomes

  1. 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

  2. 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

  3. 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 between the ages of 8 to 12

    PhenX (consensus measures for Phenotypes and eXposures) Toolkit measures of spirometry and bronchodilator responsiveness to determine association between exposure and asthma

  4. Associations between NICU environmental exposures and lung health and asthma measured by the PROMIS Pediatric Asthma Impact item bank.

    Time frame: Twice between the ages of 8 to 12

    PROMIS Pediatric Asthma Impact item bank to determine the association between exposures and asthma

  5. 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

  6. 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

  7. 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

  8. Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Motor Battery

    Time frame: Twice between the ages of 8 to 12

    NIH Toolbox Motor Battery to determine the associations between exposures and neurocognitive behavioral development

  9. 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

  10. Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Cognitive Item bank

    Time frame: Three times between the ages of 5 to 12

    PROMIS Cognitive Item bank to determine the associations between exposures and neurocognitive behavioral development

  11. Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Pediatric Mobility Item bank

    Time frame: Three times between the ages of 5 to 12

    PROMIS Pediatric Mobility 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 Upper Extremity Item bank

    Time frame: Three times between the ages of 5 to 12

    PROMIS Pediatric Upper Extremity Item to determine the associations between exposures and neurocognitive behavioral development

  13. 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 12 years

    Measurement of height, weight, head circumference, mid-upper arm circumference and bioimpedence scale to determine associations between exposures and heathy growth and obesity

  14. Associations between NICU environmental exposures and growth and obesity as measured by parent report height and weight

    Time frame: Annually, up to 12 years

    Parent reported height and weight to determine associations between exposures and healthy growth and obesity

  15. Associations between NICU environmental exposures and pubertal development measured by PhenX Assessment of Pubertal Development

    Time frame: Annually, up to 12 years

    PhenX Assessment of Pubertal Development to determine associations between exposures and pubertal development

Sponsors and collaborators

Lead sponsor

Albert Einstein College of Medicine

Other

Collaborators

  • National Institutes of Health (NIH)

Registry information

Official study title

Developmental Impact of Neonatal Intensive Care Unit (NICU) Exposures: Environmental Influences on Child Health Outcomes (ECHO)

Acronym: DINE

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Feb 23, 2017
Registry last updated
Oct 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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