Observations of fetal brain activity via non‐invasive magnetoencephalography following administration of magnesium sulfate for neuroprotection in preterm labor

Cerebral palsy describes a complex, permanent, nonprogressive disorder of movement and posture that affects children born preterm at a disproportionate rate. Multiple randomized controlled trials summarized in meta-analyses demonstrate that administration of magnesium sulfate to women at risk of delivering preterm reduces the chance that their offspring will develop cerebral palsy with a number needed to treat of one in 46–56. Despite widespread clinical use, the precise means by which magnesium sulfate confers neuroprotection remains unknown. Potential mechanisms of action include antioxidant and/or anti-inflammatory effects, promoting hemodynamic stability, by preventing neuronal excitatory injury and by suppressing alterations in both the neuronal and nuclear membranes. If magnesium sulfate works in part by protecting neurons from damage from excessive excitatory neurotransmitters such as glutamate, differences in fetal brain activity pre and postmagnesium sulfate administration may be observed. While electroencephalography (EEG) can assess brain activity postnatally and has been used to predict developmental delay and cerebral palsy in infants born preterm, this technology cannot be applied in utero because of the inability of fetal electrocortical signals to be detected on the surface of the maternal abdomen with surface electrodes because of low signal strength. In contrast, magnetoencephalography (MEG) is a technique which is a homologue of EEG can non-invasively record fetal electrocortical signals over the maternal abdomen without being distorted. Therefore, MEG provides a noninvasive method to assess fetal brain activity. The objective of this study was to characterize the differences in fetal brain activity pre and post-magnesium sulfate administration in women diagnosed with preterm labor. This study was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences. Eight women diagnosed with spontaneous preterm labor based on regular uterine contractions and a cervical dilation of at least 2 cm and 80% or less cervical dilation/effacement but with observed cervical change over time were enrolled. Fetal MEG was recorded using a non-invasive 151-channel Superconducting Quantum Interference Device (SQUID) called SARA housed in a magnetically shielded room to reduce the effects of environmental noise. A baseline 30-min fetal MEG was recorded for each patient. After the baseline recording, each patient received an intravenous four gram bolus of magnesium sulfate. Approximately 60min after the infusion, a second 30-min MEG was obtained. Interfering maternal and fetal heart-signal components were removed by applying an orthogonalprojection algorithm. The data from each sensor was partitioned into disjointed time windows of 2 s, and the power spectrum in each window was computed. The power spectral estimate was defined as the average of the spectra over all the time windows. Estimated spectrum was averaged over all the sensors. Any interference from the power-line was removed by using a notch filter. The resulting spectrum from each recording was divided into difference bands: delta (0.5–4Hz), theta (4–8Hz), alpha (8–13Hz) and beta (13–25Hz). In each band, relative power (RP) was defined as the ratio of the average power in that band to the average power in the range from 0.5 to 50Hz. The power in each of the frequency bands was compared for pre and post magnesium sulfate administration. Statistical analysis was determined via one-way ANOVA. Fetal MEG activity was successfully recorded in seven of the eight subjects with a gestational age ranging from 27 to