Vaginal Delivery Is Associated with Neurochemical Evidence of Increased Neuroaxonal Remodelling in Infants from the KUNO-Kids Health Study: Cross-Sectional Analysis

Abstract

<b><i>Aim:</i></b> Little is known about neonatal brain plasticity or the impact of birth mode on neurointegrity. As a reflection of neuroaxonal damage, the neuronal structural protein neurofilament light chain (NfL) has emerged as a highly specific biomarker. Our purpose was to test the hypothesis that vaginal delivery is associated with increased NfL in neonates. <b><i>Methods:</i></b> NfL concentrations were measured using single-molecule array immunoassay in umbilical cord serum from healthy term neonates enrolled in the prospective KUNO-Kids Health Study. NfL values were investigated for independent influencing factors using linear and logistic models, followed by post hoc propensity score-matching. <b><i>Results:</i></b> Of 665 neonates, <i>n</i> = 470 (70.7%) were delivered vaginally and <i>n</i> = 195 (29.3%) by cesarean section. Median serum NfL was significantly higher after vaginal delivery 14.4 pg/mL (11.6–18.5) compared to primary 7.5 pg/mL (6.1–8.9) and secondary cesarean delivery 9.3 pg/mL (7.5–12.0). Multivariable logistic regression models showed delivery mode and gestational age to be independently associated with NfL. Propensity score-matching analysis confirmed that assisted vaginal delivery generated higher NfL compared to vaginal (non-assisted), while lowest levels were associated with cesarean section. <b><i>Interpretation:</i></b> Our data confirm the significant impact of birth mode on neonatal NfL levels. The persistence of these differences and their potential long-term impact have yet to be investigated.

Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model

“…Shah et al found that NfL cutoff levels associated with adverse neurodevelopmental outcomes increased from 28 pg/ml at 18 h after perinatal HI to 436 pg/ml at 98 h after HI (18). Time after birth alone may also have an effect; Depoorter et al showed that NfL plasma concentrations in healthy preterm and term infants increase after birth from 18.2 pg/ml in umbilical cord blood to 50.9 pg/ml on day 3 (5) which is in part related to delivery mode (6) and might in addition be related to transition from the intra-uterine environment to extra-uterine life. To explore a possible contribution in our model of time after birth without HI, we analysed serum samples from four control piglets not subjected to HIE, but to anaesthesia and mechanical ventilation only.…”

“…NfL levels increase with acute or chronic neuronal injury, including stroke and traumatic brain injury in adults ( 4 ). NfL can be measured in newborns and has been found to be higher after vaginal delivery than after caesarean section and further increased in newborns suffering from intraventricular haemorrhage ( 5 , 6 ). Clinical interpretation of NfL in HIE is challenged by competing aetiologies of neonatal encephalopathy and uncertain timing of hypoxic-ischemic events.…”