Premature birth affects about 10% of worldwide births and is the leading cause of lost human capital in the global burden of disease. Preterm infants are born during the third trimester, which is a time of critical development of brain structure and function. A major World Health Organization 2023 report titled "Born Too Soon: Decade of Action on Preterm Birth" explicitly states that preterm birth complications serve as the leading cause of mortality for children under five and stand as a primary driver of lost human potential and capital globally.
In recent decades, survival rates have improved and in neonatal care practices, increased emphasis is being directed into ensuring neurocritical care, i.e. supporting the normal neurocognitive development in the abnormal ex utero environment of the neonatal intensive care unit (NICU). Sensory-based environmental enrichment interventions deliver specific external stimuli such as music or massage. Skin-to-skin care uses the parent's body to prompt the baby’s biological mechanisms and sensory experience. Amongst these interventions, Family Nurture Intervention (FNI) is unique in that it focuses on the innate mother-infant emotional connection that is broken by the NICU physical separation. The primary aim of FNI is to facilitate emotional connection and co-regulation between the mother-infant dyad.
The innate parent-infant emotional connection is biologically the fundamental context of the infant’s life. This is why FNI, rather than targeting specific sensory stimulation, emphasizes emotional engagement to support natural connection and co-regulation. In practice, FNI includes activities such as firm, sustained touch; vocal soothing; sustained eye contact; exchanging scent cloths; and skin-to-skin care paired with deep emotional expression, facilitated by nurture specialists several times a week. Earlier studies have shown that FNI improves mother-infant coregulation, infant autonomic regulation, physiological stability, neurobehavioral outcomes, and, most importantly, both local brain function and brain networks.
In our original paper (Yrjölä, P. et al., 2022), we found that supporting natural parent-infant contact during the NICU stay via FNI had a marked effect on the functional brain networks computed from electroencephalographic (EEG) recordings in preterm infants, leading to more mature brain networks. In fact, the networks of infants receiving FNI did not differ from those of healthy term-born infants. Furthermore, these network changes were linked to improved neurocognitive outcomes at 18 months of age. The results provided compelling evidence that facilitating mother-infant emotional connection in NICU improves brain network development.
The present study aimed to assess whether the original (RCT1) brain network effects of FNI would replicate in a second multisite randomized controlled trial (RCT2). We conducted RCT2 ten years after the original RCT1 both in the same NICU in New York, and in a second comparable NICU in San Antonio, Texas. The technical criteria for successful replication were defined as replicating the network directional difference (decrease/increase in network strength between groups), specific to each EEG rhythm (delta, theta, alpha), as identified in the original study.
We found that the brain network effects of FNI replicated fully in the RCT2 New York NICU. As in the RCT1 study, infants receiving FNI showed no detectable difference in their functional networks compared with healthy term-born counterparts at term-equivalent age, while infants receiving standard care (SC) showed significantly altered networks. Furthermore, longitudinal New York RCT2 group analysis showed differential brain network development from birth to term-equivalent age. Specifically, the networks did not differ between FNI and SC infants at birth but then diverged and followed different developmental trajectories. In other words, the six weeks of FNI improved the trajectory of infant brain development and resulted in more mature brain networks at term-equivalent age.
Notably, preterm infants in the San Antonio cohort were, on average, one week younger at the time of EEG recording, were primarily female, and had fewer but longer visits, likely due to the significantly larger catchment area. Together, these factors very likely affect FNI results on brain networks, which were somewhat inconsistent in this second NICU. In particular, subsequent analyses hinted that FNI may have a stronger effect on males, though this remains to be confirmed in future studies.
Altogether, the present results strongly support the idea that interventions such as FNI that target mother-infant emotional connection may modulate early developmental trajectories of cortical networks and mitigate the effects of prematurity. This is relevant across the globe as preterm birth remains the leading global cause of disabilities. In this context, FNI provides an accessible, cost-effective intervention that can be implemented in high- and low-resource settings, with potentially substantial global impact.
Cover figure created in BioRender. Yrjölä, P. (2026)