Autonomic nervous system maturation in preterm neonates: Correlation with gestational and postmenstrual age (ProMote)

BACKGROUND: Autonomic nervous system (ANS) maturation is crucial for neonatal adaptation, but in preterm infants, this process is often delayed, leading to increased vulnerability. Heart rate variability (HRV) provides a non-invasive measure of ANS function, yet existing evidence is contradictory regarding how birth gestational age influences HRV development at comparable postmenstrual ages. OBJECTIVE: This study aims to investigate HRV metrics at 35-36 weeks postmenstrual age in preterm neonates with a wide range of birth gestational ages. We hypothesize that lower birth gestational age correlates with reduced HRV, indicating delayed ANS maturation and diminished parasympathetic tone. METHODS: We conducted a longitudinal cohort study of preterm neonates divided into two groups: Group A (28-33 weeks GA) and Group B (34-36 weeks GA). Short-term HRV recordings (mean duration 17 minutes, SD 4.3) were obtained within 24 hours after birth, on the 3rd-4th postnatal day, and again at 35-36 weeks PMA for neonates born before 35 weeks. HRV features included time-domain, frequency-domain, and non-linear measures. RESULTS: Of 132 recruited preterm neonates, 88 were included in the final analysis. Preterm neonates with higher gestational age at birth (Group B) exhibited elevated time-domain measures (HTI, SDNN, RMSSD, pNN50) and higher frequency-domain indices (LF, LF/HF, TP) compared with those born earlier (Group A). Compared with Group B, Group A (28-33 weeks GA) had higher mean heart rates and exhibited stronger long-range correlations in heart rate dynamics. CONCLUSION: This study demonstrates that advancing gestational age is associated with greater parasympathetic modulation and more balanced sympathovagal control. Birth gestational age is a strong determinant of autonomic nervous system development at 35-36 weeks postmenstrual age. These findings highlight the importance of stratifying by gestational age in HRV studies and may inform neurodevelopmental monitoring and NICU care strategies.