Listening to Mom 2: Neural, Clinical and Language Outcomes

The purpose of this study is to examine whether playing recordings of a mother's voice to her infant while in the hospital nursery is an effective treatment for promoting healthy brain and language development in infants born preterm.

Children born preterm are at-risk for developmental language delays. Language problems in preterm children are thought to be related to neurobiological factors, including injuries to white matter structures of the brain and environmental factors, including decreased exposure to maternal speech in the hospital nursery. There is evidence to suggest that maternal speech input may be important for promoting healthy brain and language development. Participants will be randomly assigned to one of two study groups. Each infant has a 50% chance of being assigned to the group that will listen to a recording of his/her mother's voice and a 50% chance of being assigned to the group that will not be played a voice recording. Mother's of participating infants will have her voice recorded as she reads a common children's storybook. Recordings will be played to infants each day until s/he is discharged from the hospital. To assess the long term impacts of this treatment, research participants and their families will be asked to return for follow-up visiting to perform an MRI brain scan and complete questionnaires and test that assess language development. Follow-up visit occur when infants are between 12 to 18 months of age.

An infant participant randomized to the language treatment arm will be played recordings of his/her mother's voice 2-3 hours daily in the intermediate care nursery until discharge.

An infant participant randomized to the control treatment arm will receive standard of care. Standard of care does not include being played recordings of his/her mother's voice while admitted to the intermediate care nursery. However, an infant randomized to the control treatment will have the same auditory equipment placed in his/her isolette or crib as an infant randomized to the Language Treatment Arm.

Standard and Raw Scores of Receptive and Expressive Language on MacArthur-Bates Communicative Development Inventory (CDI): Words and Sentences

Parent questionnaire of receptive and expressive language skills. Will be used to assess the long-term impact of intervention on language outcomes. Standard scores are based on percentiles for age and sex and range from <1 to 99th percentile. Raw scores range from 0 to 680. Both higher standard scores and raw scores indicate better performance.

Diffusion MRI metric that measures the average rate of water diffusion. It is used to assess white matter development and structure.

Assessed at near-term equivalent age MRI scan (approx. 36-37 weeks postmenstrual age) or at time of hospital discharge, whichever comes first

Diffusion MRI metric that measures the directionality of water diffusion in the brain. It is used to assess white matter development and structure.

Assessed at near-term equivalent age MRI scan (approx. 36-37 weeks postmenstrual age) or at time of hospital discharge, whichever comes first

Diffusion MRI metric that measures the average rate of water diffusion. It is used to assess white matter development and structure

Diffusion MRI metric that measures the directionality of water diffusion in the brain. It is used to assess white matter development and structure.

Parent questionnaire of receptive and expressive language skills. Will be used to assess the long-term impact of intervention on language outcomes. Standard scores are based on percentiles for age and sex and range from <1 to 99th percentile. Raw scores range from 0 to 396. Both higher standard scores and raw scores indicate better performance.

measured daily and beginning at start of treatment and until end of treatment, approximately 37-40 weeks PMA

measured daily and beginning at start of treatment and until end of treatment, approximately 37-40 weeks PMA

measured daily and beginning at start of treatment and until end of treatment, approximately 37-40 weeks PMA

Inclusion Criteria: Infants born preterm at Stanford Children's Hospital between 24 0/7 - 31 6/7 weeks gestational age Exclusion Criteria: Congenital anomalies Recognizable malformation syndromes Active seizure disorders History of Central Nervous System infections Hydrocephalus Major sensori-neural hearing loss Likelihood to be transferred from NICU to alternate care facility or home environment prior to 36 weeks PMA and/or brain MRI scan Intraventricular Hemorrhage Grades III-IV Cystic periventricular leukomalacia (PVL) Surgical treatment for necrotizing enterocolitis Small for gestational age (SGA) <3 percentile and/or Intra-uterine growth restriction (IUGR) no head sparing Twin-to-twin transfusions

Brignoni-Perez E, Morales MC, Marchman VA, Scala M, Feldman HM, Yeom K, Travis KE. Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm. Trials. 2021 Jul 13;22(1):444. doi: 10.1186/s13063-021-05385-4.