Impact of Reading on Endogenous Oxytocin System of Preterm Infants

The purpose of this study is to learn how early language exposure may be related to changes in DNA in parents and their premature infants. While a person's genetic code is determined at the time of conception, the way that some genes are expressed in the body can be changed even after an individual is born. These changes are called epigenetic changes. In this study, the investigators want to learn about the epigenetic changes that happen after a premature baby is born and whether a parent's interaction with their baby can influence these epigenetic changes. The investigators will look at epigenetic changes by collecting saliva samples from parents and their preterm babies, here defined as babies born at <33 weeks gestation. Specifically, the investigators will be looking at salivary levels of DNA methylation of the oxytocin receptor gene (OXTRm). The investigators will track changes in OXTRm levels over time in parents and their babies and see if these levels change in relation to how much time parents spend with their babies and how much time they spend reading to their babies. The investigators will ask mothers and, if desired, their partners to read to their babies for at least 15 minutes per week. The investigators will ask them to track time spent with the baby and reading time on a log, and will also measure word count with a commercially-available LENA device. The investigators will use logistic regression analysis to identify the independent association between OXTR DNA methylation and time spent with parent(s) and word count.

Study Overview

• Status: Recruiting
• Conditions: Development, Infant; Premature Infant Disease
• Intervention / Treatment: Behavioral: reading

Detailed Description

Student's t-test and Pearson's chi-square tests will be used to compare continuous and categorical variables, respectively. Logistic regression analysis will used to identify the independent association between OXTR DNA methylation and time spent with parent(s) and word count. Variables with p≤0.20 in the univariate analysis will be entered into a stepwise logistic multivariate regression model. Odds ratios with 95% confidence intervals will be calculated. p value of less than 0.05 will be considered statistically significant.

A protocol modification was submitted to and approved by the University of Virginia IRB due to slower than expected participant enrollment. The protocol was modified such that:

• Enrollment of <33 week instead of <32 week infants was permitted
• Enrollment was permitted through the first 2 weeks after birth instead of through the first 1 week after birth

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Kelsey Sullivan, MD; Phone Number: 434-305-9356; Email: ptf3df@hscmail.mcc.virginia.edu
      • Contact: Santina Zanelli, MD; Phone Number: 434-924-2335; Email: SZ5D@hscmail.mcc.virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants <33 week gestational age at birth
• Mother must be able to visit at least once per week
• Mother or primary caregiver must participate; father or secondary caregiver may participate as well
• Mother must commit to minimum of 15 minutes reading at least once per week

Exclusion Criteria:

• Infant with life-limiting conditions
• Mother is non-English speaking
• Illiteracy of mother

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Reading; Mother and, if desired, mother's partner will read to infant for at least 15 minutes per week, but will be encouraged to read to infant as much as possible. Saliva will be collected from infants and parents for OXTRm assay at pre-specified time points, and at these time point parents will also complete standardized questionnaires including PSS-NICU, PROMIS depression, and PROMIS anxiety to assess parental mood and stress. Reading time will be measured with a reading log provided to the parents, as well as with a commercially-available LENA device to measure word count.

Behavioral: reading; Mothers and, if desired, mother's partner will read to preterm infant as frequently and as much as they are able to. Reading is the intervention. The variable of interest is parents' and infants' change in salivary oxytocin receptor gene methylation (OXTRm) over time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary oxytocin receptor gene DNA methylation (OXTRm)	Salivary oxytocin receptor gene DNA methylation (OXTRm), change in time as related to amount of time parents spend reading to infant	Birth to discharge from neonatal intensive care unit (approximately 1-4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parental stress	Parental stress, as measured by PSS-NICU, and its correlation with amount of time parents spend reading to infants	Birth to discharge from neonatal intensive care unit (approximately 1-4 months)
Parental depression	Parental stress, as measured by the PROMIS depression short form, and its correlation with amount of time parents spend reading to infants	Birth to discharge from neonatal intensive care unit (approximately 1-4 months)
Parental anxiety	Parental stress, as measured by the PROMIS anxiety scale, and its correlation with amount of time parents spend reading to infants	Birth to discharge from neonatal intensive care unit (approximately 1-4 months)

Collaborators and Investigators

• Sponsor: University of Virginia

Publications and helpful links

General Publications

• Caskey M, Stephens B, Tucker R, Vohr B. Importance of parent talk on the development of preterm infant vocalizations. Pediatrics. 2011 Nov;128(5):910-6. doi: 10.1542/peds.2011-0609. Epub 2011 Oct 17.
• Perkeybile AM, Carter CS, Wroblewski KL, Puglia MH, Kenkel WM, Lillard TS, Karaoli T, Gregory SG, Mohammadi N, Epstein L, Bales KL, Connelly JJ. Early nurture epigenetically tunes the oxytocin receptor. Psychoneuroendocrinology. 2019 Jan;99:128-136. doi: 10.1016/j.psyneuen.2018.08.037. Epub 2018 Aug 31.
• Caskey M, Stephens B, Tucker R, Vohr B. Adult talk in the NICU with preterm infants and developmental outcomes. Pediatrics. 2014 Mar;133(3):e578-84. doi: 10.1542/peds.2013-0104. Epub 2014 Feb 10.
• Krol KM, Moulder RG, Lillard TS, Grossmann T, Connelly JJ. Epigenetic dynamics in infancy and the impact of maternal engagement. Sci Adv. 2019 Oct 16;5(10):eaay0680. doi: 10.1126/sciadv.aay0680. eCollection 2019 Oct.
• Neri E, De Pascalis L, Agostini F, Genova F, Biasini A, Stella M, Trombini E. Parental Book-Reading to Preterm Born Infants in NICU: The Effects on Language Development in the First Two Years. Int J Environ Res Public Health. 2021 Oct 29;18(21):11361. doi: 10.3390/ijerph182111361.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Infant, Premature, Diseases
• Other Study ID Numbers: HSR220058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No