Mapping early brain-body interactions: associations of fetal heart rate variation with newborn brainstem, hypothalamic, and dorsal anterior cingulate cortex functional connectivity.

The autonomic nervous system (ANS) regulates the body's physiology, including cardiovascular function. As the ANS develops during the second to third trimester, fetal heart rate variability (HRV) increases while fetal heart rate (HR) decreases. In this way, fetal HR and HRV provide an index of fetal autonomic nervous system development and future neurobehavioral regulation. Fetal HR and HRV have been associated with child language ability and psychomotor development behavior in toddlerhood. However, their associations with post-birth autonomic brain systems, such as the brainstem, hypothalamus, and dorsal anterior cingulate cortex (dACC), have yet to be investigated even though brain pathways involved in autonomic regulation are well established in older individuals. We assessed whether fetal HR and HRV were associated with the brainstem, hypothalamic and dACC functional connectivity in newborns. Data were obtained from 60 pregnant individuals (ages 14-42) at 24-27 and 34-37 weeks gestation using a fetal actocardiograph to generate fetal HR and HRV. During natural sleep, their infants (38 males and 22 females) underwent a fMRI scan between 40-46 weeks of postmenstrual age. Our findings relate fetal heart indices to brainstem, hypothalamic, and dACC connectivity and reveal connections with widespread brain regions that may support behavioral and emotional regulation. We demonstrated the basic physiologic association between fetal HR indices and lower and higher order brain regions involved in regulatory processes. This work provides the foundation for future behavioral or physiological regulation research in fetuses and infants. Significance statement Fetal heart rate indices are quantifiable, developmental markers of the fetal autonomic nervous system. Variations in their trajectories can signal compromised neurodevelopmental outcomes. We assessed associations between fetal heart rate indices and early infant brain development to identify unique or common associations corresponding to autonomic nervous system maturation patterns. We found associations between fetal heart rate indices and infant brainstem, hypothalamic, and dACC connectivity-areas that support autonomic and behavioral regulatory functions. The study demonstrates that these associations between ANS and brain regions involved in autonomic regulation exist early in life. These findings are a first step to understanding how these brain connections form the basis of future regulatory development.