Developmental Impact of NICU Exposures (DINE)

Prematurity Clinical Trial

— DINE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03061890
• Other study ID #: 2016-7369
• Secondary ID: UG3OD023320UH3OD
• Status: Completed
• Start date: April 1, 2017
• Est. completion date: August 31, 2023

Study information

• Verified date: October 2023
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Gender: All
• Age group: N/A to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Prematurity

Locations

Country	Name	City	State
United States	National Institute for Children's Health Quality	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	University at Buffalo State University of New York	Buffalo	New York
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	University of Florida	Jacksonville	Florida
United States	Children's Health Care, Inc.	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	University of Rochester	Rochester	New York
United States	University of Washington	Seattle	Washington
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (33)

Aris IM, Perng W, Dabelea D, Padula AM, Alshawabkeh A, Velez-Vega CM, Aschner JL, Camargo CA Jr, Sussman TJ, Dunlop AL, Elliott AJ, Ferrara A, Zhu Y, Joseph CLM, Singh AM, Hartert T, Cacho F, Karagas MR, North-Reid T, Lester BM, Kelly NR, Ganiban JM, Chu — View Citation

Aschner JL, Bancalari EH, McEvoy CT. Can We Prevent Bronchopulmonary Dysplasia? J Pediatr. 2017 Oct;189:26-30. doi: 10.1016/j.jpeds.2017.08.005. No abstract available. — View Citation

Bekelman TA, Knapp EA, Dong Y, Dabelea D, Bastain TM, Breton CV, Carroll KN, Camargo CA, Davis AM, Dunlop AL, Elliott AJ, Ferrara A, Fry RC, Ganiban JM, Gilbert-Diamond D, Gilliland FD, Hedderson MM, Hipwell AE, Hockett CW, Huddleston KC, Karagas MR, Kell — View Citation

Camerota M, McGowan EC, Aschner J, Stroustrup A, Karagas MR, Conradt E, Crowell SE, Brennan PA, Carter BS, Check J, Dansereau LM, DellaGrotta SA, Everson TM, Helderman JB, Hofheimer JA, Kuiper JR, Loncar CM, Marsit CJ, Neal CR, O'Shea TM, Pastyrnak SL, Sh — View Citation

Chandran A, Burjak M, Petimar J, Hamra G, Melough MM, Dunlop AL, Snyder BM, Litonjua AA, Hartert T, Gern J, Alshawabkeh AN, Aschner J, Camargo CA Jr, Dabelea D, Duarte CS, Ferrara A, Ganiban JM, Gilliland F, Gold DR, Hedderson M, Herbstman JB, Hockett C, — View Citation

Conradt E, Flannery T, Aschner JL, Annett RD, Croen LA, Duarte CS, Friedman AM, Guille C, Hedderson MM, Hofheimer JA, Jones MR, Ladd-Acosta C, McGrath M, Moreland A, Neiderhiser JM, Nguyen RHN, Posner J, Ross JL, Savitz DA, Ondersma SJ, Lester BM. Prenata — View Citation

Faro EZ, Sauder KA, Anderson AL, Dunlop AL, Kerver JM, McGrath M, Roary M, Roman CW, Weidinger C, Huddleston KC. Characteristics of Environmental influences on Child Health Outcomes (ECHO) Cohorts Recruited During Pregnancy. MCN Am J Matern Child Nurs. 20 — View Citation

Hedderson MM, Bekelman TA, Li M, Knapp EA, Palmore M, Dong Y, Elliott AJ, Friedman C, Galarce M, Gilbert-Diamond D, Glueck D, Hockett CW, Lucchini M, McDonald J, Sauder K, Zhu Y, Karagas MR, Dabelea D, Ferrara A; Environmental Influences on Child Health O — View Citation

Hofheimer JA, McGrath M, Musci R, Wu G, Polk S, Blackwell CK, Stroustrup A, Annett RD, Aschner J, Carter BS, Check J, Conradt E, Croen LA, Dunlop AL, Elliott AJ, Law A, Leve LD, Neiderhiser JM, O'Shea TM, Salisbury AL, Sathyanarayana S, Singh R, Smith LM, — View Citation

Knapp EA, Dong Y, Dunlop AL, Aschner JL, Stanford JB, Hartert T, Teitelbaum SL, Hudak ML, Carroll K, O'Connor TG, McEvoy CT, O'Shea TM, Carnell S, Karagas MR, Herbstman JB, Dabelea D, Ganiban JM, Ferrara A, Hedderson M, Bekelman TA, Rundle AG, Alshawabkeh — View Citation

Knapp EA, Kress AM, Parker CB, Page GP, McArthur K, Gachigi KK, Alshawabkeh AN, Aschner JL, Bastain TM, Breton CV, Bendixsen CG, Brennan PA, Bush NR, Buss C, Camargo CA Jr, Catellier D, Cordero JF, Croen L, Dabelea D, Deoni S, D'Sa V, Duarte CS, Dunlop AL — View Citation

Lucchini M, Bekelman TA, Li M, Knapp EA, Dong Y, Ballard S, Deoni S, Dunlop AL, Elliott AJ, Ferrara A, Friedman C, Galarce M, Gilbert-Diamond D, Glueck D, Hedderson M, Hockett CW, Karagas MR, LeBourgeois MK, Margolis A, McDonald J, Ngai P, Pellerite M, Sa — View Citation

Lyall K, Ning X, Aschner JL, Avalos LA, Bennett DH, Bilder DA, Bush NR, Carroll KN, Chu SH, Croen LA, Dabelea D, Daniels JL, Duarte C, Elliott AJ, Fallin MD, Ferrara A, Hertz-Picciotto I, Hipwell AE, Jensen ET, Johnson SL, Joseph RM, Karagas M, Kelly RS, — View Citation

Martenies SE, Zhang M, Corrigan AE, Kvit A, Shields T, Wheaton W, Around Him D, Aschner J, Talavera-Barber MM, Barrett ES, Bastain TM, Bendixsen C, Breton CV, Bush NR, Cacho F, Camargo CA Jr, Carroll KN, Carter BS, Cassidy-Bushrow AE, Cowell W, Croen LA, — View Citation

McGowan EC, McGrath M, Law A, O'Shea TM, Aschner JL, Blackwell CK, Fry RC, Ganiban JM, Higgins R, Margolis A, Sathyanarayana S, Taylor G, Alshawabkeh AN, Cordero JF, Spillane NT, Hudak ML, Camargo CA Jr, Dabelea D, Dunlop AL, Elliott AJ, Ferrara AM, Talav — View Citation

Miller RL, Schuh H, Chandran A, Aris IM, Bendixsen C, Blossom J, Breton C, Camargo CA Jr, Canino G, Carroll KN, Commodore S, Cordero JF, Dabelea DM, Ferrara A, Fry RC, Ganiban JM, Gern JE, Gilliland FD, Gold DR, Habre R, Hare ME, Harte RN, Hartert T, Hase — View Citation

Moog NK, Cummings PD, Jackson KL, Aschner JL, Barrett ES, Bastain TM, Blackwell CK, Bosquet Enlow M, Breton CV, Bush NR, Deoni SCL, Duarte CS, Ferrara A, Grant TL, Hipwell AE, Jones K, Leve LD, Lovinsky-Desir S, Miller RK, Monk C, Oken E, Posner J, Schmid — View Citation

Nanishi M, Chandran A, Li X, Stanford JB, Alshawabkeh AN, Aschner JL, Dabelea D, Dunlop AL, Elliott AJ, Gern JE, Hartert T, Herbstman J, Hershey GKK, Hipwell AE, Karagas MR, Karr CJ, Leve LD, Litonjua AA, McEvoy CT, Miller RL, Oken E, O'Shea TM, Paneth N, — View Citation

O'Shea TM, McGrath M, Aschner JL, Lester B, Santos HP Jr, Marsit C, Stroustrup A, Emmanuel C, Hudak M, McGowan E, Patel S, Fry RC; program collaborators for Environmental influences on Child Health Outcomes. Environmental influences on child health outcom — View Citation

Pourkaviani S, Zhang X, Spear EA, D'Agostino M, Satty RE, Liu SH, Stroustrup A. Clinical validation of the Neonatal Infant Stressor Scale with preterm infant salivary cortisol. Pediatr Res. 2020 Jun;87(7):1237-1243. doi: 10.1038/s41390-019-0713-0. Epub 20 — View Citation

Roubinov D, Musci RJ, Hipwell AE, Wu G, Santos H, Felder JN, Faleschini S, Conradt E, McEvoy CT, Lester BM, Buss C, Elliott AJ, Cordero JF, Stroustrup A, Bush NR. Trajectories of depressive symptoms among mothers of preterm and full-term infants in a nati — View Citation

Schantz SL, Eskenazi B, Buckley JP, Braun JM, Sprowles JN, Bennett DH, Cordero J, Frazier JA, Lewis J, Hertz-Picciotto I, Lyall K, Nozadi SS, Sagiv S, Stroustrup A, Volk HE, Watkins DJ; program collaborators for Environmental influences on Child Health Ou — View Citation

Stratakis N, Garcia E, Chandran A, Hsu T, Alshawabkeh A, Aris IM, Aschner JL, Breton C, Burbank A, Camargo CA Jr, Carroll KN, Chen Z, Claud EC, Dabelea D, Dunlop AL, Elliott AJ, Ferrara A, Ganiban JM, Gern JE, Gold DR, Gower WA, Hertz-Picciotto I, Karagas — View Citation

Stroustrup A, Bragg JB, Andra SS, Curtin PC, Spear EA, Sison DB, Just AC, Arora M, Gennings C. Neonatal intensive care unit phthalate exposure and preterm infant neurobehavioral performance. PLoS One. 2018 Mar 5;13(3):e0193835. doi: 10.1371/journal.pone.0 — View Citation

Stroustrup A, Bragg JB, Busgang SA, Andra SS, Curtin P, Spear EA, Just AC, Arora M, Gennings C. Sources of clinically significant neonatal intensive care unit phthalate exposure. J Expo Sci Environ Epidemiol. 2020 Jan;30(1):137-148. doi: 10.1038/s41370-01 — View Citation

Stroustrup A, Bragg JB, Spear EA, Aguiar A, Zimmerman E, Isler JR, Busgang SA, Curtin PC, Gennings C, Andra SS, Arora M. Cohort profile: the Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort, a prospective preterm b — View Citation

Stroustrup A, Teitelbaum SL, Aschner JL. The Value of Preterm Infant Environmental Health Cohorts: The Canary in the Coal Mine. JAMA Pediatr. 2017 Dec 1;171(12):1139-1140. doi: 10.1001/jamapediatrics.2017.3230. No abstract available. — View Citation

Stroustrup A, Zhang X, Spear E, Bandyopadhyay S, Narasimhan S, Meher AK, Choi J, Qi G, Poindexter BB, Teitelbaum SL, Andra SS, Gennings C, Aschner JL. Phthalate exposure in the neonatal intensive care unit is associated with development of bronchopulmonar — View Citation

Tylavsky FA, Ferrara A, Catellier DJ, Oken E, Li X, Law A, Dabelea D, Rundle A, Gilbert-Diamond D, Hivert MF, Breton CV, Cassidy-Bushrow AE, Mueller NT, Hunt KJ, Arteaga SS, Lombo T, Mahabir S, Ruden D, Sauder K, Hedderson MM, Zhu Y, Polk S, Mihalopoulos — View Citation

Wood CT, Churchill ML, McGrath M, Aschner J, Brunwasser SM, Geiger S, Gogcu S, Hartert TV, Hipwell AE, Lee-Sarwar K, Lyall K, Moog NK, O'Connor TG, O'Shea TM, Smith PB, Wright RJ, Zhang X, Zimmerman E, Huddleston KC, Brown CL; program collaborators for En — View Citation

Wright RO, Teitelbaum S, Thompson C, Balshaw D; CHEAR Network. The child health exposure analysis resource as a vehicle to measure environment in the environmental influences on child health outcomes program. Curr Opin Pediatr. 2018 Apr;30(2):285-291. doi: 10.1097/MOP.0000000000000601. — View Citation

Zhang X, Smith N, Spear E, Stroustrup A. Neighborhood characteristics associated with COVID-19 burden-the modifying effect of age. J Expo Sci Environ Epidemiol. 2021 May;31(3):525-537. doi: 10.1038/s41370-021-00329-1. Epub 2021 May 4. — View Citation

Zhang X, Spear E, Gennings C, Curtin PC, Just AC, Bragg JB, Stroustrup A. The association of prenatal exposure to intensive traffic with early preterm infant neurobehavioral development as reflected by the NICU Network Neurobehavioral Scale (NNNS). Enviro — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between NICU environmental exposures and lung health and asthma measured by Brief Respiratory Questionnaire	Brief Respiratory Questionnaire to determine association between exposure and lung health	One time between the ages of 3 to 4
Primary	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	PROMIS® (Patient-Reported Outcomes Measurement Information System) Parent Proxy Asthma Impact item bank to determine association between exposure and asthma	One time between the ages of 5 to 6
Primary	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	PhenX (consensus measures for Phenotypes and eXposures) Toolkit measures of spirometry and bronchodilator responsiveness to determine association between exposure and asthma	Twice between the ages of 8 to 12
Primary	Associations between NICU environmental exposures and lung health and asthma measured by the PROMIS Pediatric Asthma Impact item bank.	PROMIS Pediatric Asthma Impact item bank to determine the association between exposures and asthma	Twice between the ages of 8 to 12
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Early Childhood Cognition Battery	NIH Toolbox Early Childhood Cognition Battery to determine the associations between exposures and neurocognitive behavioral development	Twice within 24 months between the ages of 3 to 5
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Cognition Battery	NIH Toolbox Cognition Battery to determine the associations between exposures and neurocognitive behavioral development	Twice within 24 months between the ages of 7 to 9
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Early Childhood Motor Battery	NIH Toolbox Early Childhood Motor Battery to determine the associations between exposures and neurocognitive behavioral development	Twice within 24 months between the ages of 4 to 6
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by NIH Toolbox Motor Battery	NIH Toolbox Motor Battery to determine the associations between exposures and neurocognitive behavioral development	Twice between the ages of 8 to 12
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by Child Behavior Checklist (CBCL)	Child Behavior Checklist (CBCL) to determine the associations between exposures and neurocognitive behavioral development	One time between the ages of 3 to 4
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Cognitive Item bank	PROMIS Cognitive Item bank to determine the associations between exposures and neurocognitive behavioral development	Three times between the ages of 5 to 12
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Pediatric Mobility Item bank	PROMIS Pediatric Mobility Item bank to determine the associations between exposures and neurocognitive behavioral development	Three times between the ages of 5 to 12
Primary	Associations between NICU environmental exposures and neurocognitive behavioral development measured by PROMIS Pediatric Upper Extremity Item bank	PROMIS Pediatric Upper Extremity Item to determine the associations between exposures and neurocognitive behavioral development	Three times between the ages of 5 to 12
Primary	Associations between NICU environmental exposures and growth and obesity as measured by height, weight, head circumference, mid-upper arm circumference and bioimpedence	Measurement of height, weight, head circumference, mid-upper arm circumference and bioimpedence scale to determine associations between exposures and heathy growth and obesity	Annually, up to 12 years
Primary	Associations between NICU environmental exposures and growth and obesity as measured by parent report height and weight	Parent reported height and weight to determine associations between exposures and healthy growth and obesity	Annually, up to 12 years
Primary	Associations between NICU environmental exposures and pubertal development measured by PhenX Assessment of Pubertal Development	PhenX Assessment of Pubertal Development to determine associations between exposures and pubertal development	Annually, up to 12 years

External Links

•   ECHO DINE Community Collaboratory
•   NIH Environmental influences on Child Health Outcomes (ECHO) Program