BACKGROUND: Autonomic nervous system (ANS) activity is fundamental to infant health. ANS activity of preterm newborns seems to be reduced at term equivalent age, but follow-up of ANS activity has rarely been performed in that population during the weeks after birth. The aim of the study was to perform such a follow-up in preterm newborns of different gestational ages, up to their term equivalent ages. METHODS: Prolonged electrocardiographic recordings were prospectively performed in a group of 39 premature newborns, each week, up to term equivalent age before discharge. Control values were obtained from a group of 19 full-term newborns, recorded at the first week of their life. ANS indices were calculated from recordings during quiet sleep periods by spectral-domain analysis (Fourier transform): Ptot (total power), VLF (very low-frequencies), LF (low-frequencies), HF (high-frequencies), LF/HF ratio, LFnu (normalized low-frequencies) and HFnu (normalized high-frequencies) values. RESULTS: Ptot, VLF, LF and HF were significantly lower in the preterm group at birth compared to the control group, while LFnu, HFnu and LF/HF ratio were not significantly different. The results were similar when comparing the control group to any ANS values at a given post-natal corrected age of preterm newborns. Furthermore, preterm newborns did not demonstrate any significant increase in ANS values from birth to theoretical term. CONCLUSION: The finding of substantial reduced ANS activity and failure of maturation in preterm infants up to term equivalent age needs confirming by other research groups, and mechanisms and implications for infant health explored.