Early oxygen levels contribute to brain injury in extremely preterm infants

Abstract

Background: Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO₂), arterial pO₂ levels, and supplemental oxygen (FiO₂) would associate with later neuroanatomic changes.

Methods: SpO₂, arterial blood gases, and FiO₂ from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58).

Results: The ELGANs with later WM abnormalities exhibited lower SpO₂ and pO₂ levels, and higher FiO₂ need during the first 3 days than those with normal WM. They also had higher pCO₂ values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO₂ and pO₂ levels and lower FiO₂ need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment.

Conclusions: Low oxygen levels and high FiO₂ need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets.

Impact: This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

Fig. 1. Study design.

DQ developmental quotient, ELGAN extremely low gestational age newborn, preterm babies born before 28 weeks of GA, GA gestational age, GMDS Griffiths Mental Developmental Scales, MEG-SII secondary cortical somatosensory processing in magnetoencephalography, HEMPEL Hempel neurological examination, NICU neonatal intensive care unit, TEA term equivalent age, WM white matter, white matter injury in MRI.

Fig. 2. Oxygen saturations (first 3 days).

ELGANs with WM changes exhibit lower and with MEG-SII abnormalities higher SpO₂ than those with normal findings. a SpO₂ (% of total measurements, mean +/− SEM, *p < 0.05) in ELGANs with normal (n = 43) or abnormal (n = 26) WM and b normal (n = 25) or abnormal (n = 14) MEG-SII.

Fig. 3. Partial pressures of oxygen (arterial pO₂).

Arterial pO₂ (averages and percentage of total measurements in subgroups; mean +/− SEM, *p < 0.05) during the first 3 days of life in ELGANs a with normal (n = 43) or abnormal (n = 26) white matter (WM) and b with normal (n = 25) or abnormal (n = 14) MEG-SII.

Fig. 4. Supplemental oxygen (FiO₂, first 3 days).

ELGANs with WM injury have higher and with abnormal MEG-SII lower need for FiO₂ than those with normal findings. a Time spent with FiO₂ > 21% (%, mean +/− SEM); b average FiO₂ (%, mean +/− SEM); and c percentage of time (%, mean +/− SEM) spent with different FiO₂ levels. *p < 0.05, **p < 0.01.

Fig. 5. Bradycardia and low oxygen saturations (apneas), and partial pressures of carbon dioxide.

a Bradycardia (HR <100 bpm) and low oxygen saturations (SpO₂). Cumulative times, i.e., percentage of time (mean +/− SEM) during the first 3 days of life, when having at the same time heart rate (HR) below 100 bpm and SpO₂ < 85% or SpO₂ < 90% in ELGANs with normal (n = 43) or abnormal (n = 26) white matter (WM) in MRI at TEA. b Partial pressures of carbon dioxide (pCO₂, arterial samples). Arterial pCO₂ (averages and percentage of total measurements in subgroups; mean +/− SEM, *p < 0.05) obtained during the first 3 days of life in ELGANs with normal (n = 43) or abnormal (n = 26) white matter (WM) in MRI at TEA.