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. 2021 Mar;89(4):863-868.
doi: 10.1038/s41390-020-0952-0. Epub 2020 May 12.

Autonomic nervous system maturation in the premature extrauterine milieu

Sarah B Mulkey  1   2   3 , Rathinaswamy B Govindan  4   5 , Laura Hitchings  4 , Tareq Al-Shargabi  4 , Nicole Herrera  6 , Christopher B Swisher  4 , Augustine Eze Jr  7 , Stephanie Russo  4 , Sarah D Schlatterer  4 , Marni B Jacobs  5   6   8 , Robert McCarter  6   8 , Alex Kline  7   9 , G Larry Maxwell  7 , Robin Baker  7   9 , Adre J du Plessis  4   5   10
Affiliations

Autonomic nervous system maturation in the premature extrauterine milieu

Sarah B Mulkey et al. Pediatr Res. 2021 Mar.

Abstract

Background: In premature infants, we investigated whether the duration of extrauterine development influenced autonomic nervous system (ANS) maturation.

Methods: We performed a longitudinal cohort study of ANS maturation in preterm infants. Eligibility included birth gestational age (GA) < 37 weeks, NICU admission, and expected survival. The cohort was divided into three birth GA groups: Group 1 (≤29 weeks), Group 2 (30-33 weeks), and Group 3 (≥34 weeks). ECG data were recorded weekly and analyzed for sympathetic and parasympathetic tone using heart rate variability (HRV). Quantile regression modeled the slope of ANS maturation among the groups by postnatal age to term-equivalent age (TEA) (≥37 weeks).

Results: One hundred infants, median (Q1-Q3) birth GA of 31.9 (28.7-33.9) weeks, were enrolled: Group 1 (n = 35); Group 2 (n = 40); and Group 3 (n = 25). Earlier birth GA was associated with lower sympathetic and parasympathetic tone. However, the rate of autonomic maturation was similar, and at TEA there was no difference in HRV metrics across the three groups. The majority of infants (91%) did not experience significant neonatal morbidities.

Conclusion: Premature infants with low prematurity-related systemic morbidity have maturational trajectories of ANS development that are comparable across a wide range of ex-utero durations regardless of birth GA.

Impact: Heart rate variability can evaluate the maturation of the autonomic nervous system. Metrics of both the sympathetic and parasympathetic nervous system show maturation in the premature extrauterine milieu. The autonomic nervous system in preterm infants shows comparable maturation across a wide range of birth gestational ages. Preterm newborns with low medical morbidity have maturation of their autonomic nervous system while in the NICU. Modern NICU advances appear to support autonomic development in the preterm infant.

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Figures

Figure 1:
Figure 1:
ANS Spectral Metrics Over Time in Preterm Newborn Cohort Abbreviations: nLF = normalized low frequency; nHF = normalized high frequency; LF = low frequency; HF = high frequency Infant ANS metrics of nLF (A), nHF (B), LF (C), and HF (D), at each measurement session are shown as a colored dot. Red dots are for infants in group 1 with birth GA ≤29 weeks, blue dots are for infants in group 2 with birth GA of 30–33 weeks, and green dots are for infants in group 3 with birth GA ≥34 weeks. The solid colored lines represent the modeled ANS metric trajectory over time in postnatal age in days for each birth GA group.
Figure 2:
Figure 2:
ANS Time Domain Metrics Over Time in Preterm Newborn Cohort Abbreviations: alpha 1= alpha short; alpha 2 = alpha long; RMS 1 = root mean square 1; RMS 2 = root mean square 2 Infant ANS metrics of alpha 1 (A), alpha 2 (B), RMS 1 (C), and RNS 2 (D), at each measurement session are shown as a colored dot. Red dots are for infants in group 1 with birth GA ≤29 weeks, blue dots are for infants in group 2 with birth GA of 30–33 weeks, and green dots are for infants in group 3 with birth GA ≥34 weeks. The solid colored lines represent the modeled ANS metric trajectory over time in postnatal age in days for each birth GA group.
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