Background Early 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. We conducted a randomized controlled trial (RCT) with preterm neonates to determine whether increased exposure to maternal speech during NICU hospitalization is causally linked to structural white matter maturation. Methods We enrolled 46 preterm neonates (24 to 31 weeks gestational age). Participants were randomly assigned to receive increased (T: n=21) or routine (C: n=25) exposure to mother speech. The T group heard 10-minute audio recordings of their mothers reading a child storybook two times per hour between 10pm to 6am, increasing speech exposure by 2.67 hours/day. At near-term equivalent age, we obtained two high angular resolution diffusion MRI scans (scan 1 bvalue=700, scan 2 bvalue=1500) and quantitative T1 relaxometry scans. We assessed mean diffusivity (MD), the preregistered 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). Findings T 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 arcuate fasciculus (scan 1: mean difference = 0.11, 95% CI: 0.03-0.19; scan 2: mean difference = 0.13, 95% CI: 0.04-0.21) but not the right arcuate (scan 1: mean difference = 0.06, 95% CI: -0.23-0.15; scan 2: mean difference = 0.05, 95% CI: -0.05-0.13). The T group also demonstrated significantly higher FA (scan 1: mean difference = -0.02, 95% CI: -0.04-0.00; scan 2: mean difference = -0.03, 95% CI: -0.06-0.00) and R1 (mean difference = -0.02, 95% CI: -0.04-0.01) in the left, but not the right, arcuate fasciculus. Interpretation Preterm neonates who experienced increased exposure to maternal speech during hospitalization demonstrated more mature microstructure of the left arcuate fasciculus. Findings provide evidence for a causal link between speech experiences and brain development. Increasing speech exposure in the NICU may benefit preterm children.

The authors have declared no competing interest.

NCT02847689

https://clinicaltrials.gov/study/NCT02847689

This research work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K.E. Travis, PI: 5R00-HD84749; H.M. Feldman, PI: 2R01-HD069150).

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The study protocol was was approved by the Stanford School of Medicine Institutional Review Board and registered at Clincaltrials.gov with protocol description (NCT02847689).

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