Listening to Mom in the Neonatal Intensive Care Unit: A randomized trial of increased maternal speech exposure on white matter connectivity in infants born preterm

BackgroundEarly speech experiences have been proposed to contribute to the development of brain structures involved in processing spoken language. However, previous research has been limited to correlational studies. Here, we conducted an RCT with preterm neonates to determine whether increased exposure to maternal speech during NICU hospitalization is causally linked to structural white matter maturation. MethodsWe enrolled 46 preterm neonates (24-31 weeks gestational age). Participants were randomly assigned to receive increased (T: n=21) or routine (C: n=25) exposure to mothers speech. The T-group heard 10-minute audio recordings of their mothers reading a childrens story two times/hour between 10pm-6am, increasing speech exposure by 2.67 hours/day. At near-term-equivalent age, we obtained two high-angular resolution diffusion MRI (scan 1 bvalue=700, scan 2 bvalue=1500) and quantitative T1 relaxometry scans. We assessed mean diffusivity (MD), pre-registered primary outcome (NCT02847689), of the left and right arcuate fasciculus, tracts implicated in language processing. Secondary outcomes included fractional anisotropy (FA) and R1 (1/T1). FindingsT- and C-groups were equivalent on medical and demographic variables. Compared to the C- group, the T-group demonstrated significantly lower MD in the left (scan 1: mean difference{Delta} =0.11, 95% CI:0.03 - 0.19; scan 2:{Delta} =0.13, 95% CI:0.04 - 0.21) but not right arcuate (scan 1:{Delta} =0.06, 95% CI: -0.23 - 0.15; scan 2:{Delta} =0.05, 95% CI:-0.05 - 0.13). The T-group also demonstrated significantly higher FA (scan 1:{Delta} = -0.02, 95% CI:-0.04 - -0.00; scan 2:{Delta} = -0.03, 95% CI:-0.06 - -0.00) and R1 ({Delta} =-0.02, 95% CI:-0.04 - -0.01) in the left but not right arcuate. InterpretationPreterm neonates who experienced increased exposure to maternal speech during hospitalization demonstrated more mature microstructure of the left arcuate. Findings provide evidence for a causal link between speech experiences and brain development. Increasing speech exposure in the NICU may benefit preterm children. Research in Context PanelO_ST_ABSEvidence before this studyC_ST_ABSObservational studies document the importance of early speech experience for language learning and brain development in term and preterm children. Children born preterm are at-risk for adverse language outcomes that have been attributed to alterations in brain development from limited exposure to speech in the neonatal intensive care unit (NICU). However, evidence that early speech experiences causally effect the development of brain structures relevant for language is lacking. Added value of this studyThe Listening to Mom in NICU study is the first randomized controlled trial specifically designed to test the causal effects of maternal speech exposure on white matter brain development in neonates born preterm. This study demonstrates that speech experiences during neonatal development directly contribute to the maturation of the left arcuate fasciculus, a white matter tract implicated in language. Implications of all the available evidenceStudy findings advance understandings for how early speech experiences contribute to neonatal brain development. This study also demonstrates that increasing exposure to speech via audio recordings among infants born preterm could serve as an inexpensive and scalable intervention to support recovery from alterations in brain development related to the NICU experience.