Prenatal maternal stress, non-invasive fetal biomarkers and infant neurocognitive development: a prospective cohort study.

CAMILA ZELGERT; RITIKA SHARMA; SCHMIDT, G.; BIBIANA FABRE; FRASCH, MARTIN G.; ANTONELLI, MARTA C.; M SOL MOLINET; ALEXANDER MUELLER; BERG G; HERMONA SOREQ; SHANI VAKNINE; PETER ZIMMERMANN; BERHARD HALLER; HAUTIENG WU; LOBMAIER, SILVIA M.

Congreso; Society for Neuroscience Annual Meeting; 2019

Maternal stress during pregnancy and during early parenting may program physiological responses and lifetime trajectories of the infant, interact with genetic liabilities and early-life challenges and determine ultimate health status. Seeking a prenatal measure with a preventive clinical significance, we hypothesized that the coordinated roles of the autonomic nervous system (ANS) and the hypothalamic?pituitary?adrenal axis (HPA) in the integrated stress response may be monitored by measuring several maternal and fetal molecular and biophysical biomarkers. We performed a prospective study in stressed mothers with controls matched 1:1 for parity, maternal age and gestational age at study entry. Pregnant women were administered the Cohen Perceived Stress Scale questionnaire (PSS-10), which categorized them as Stressed Group (SG) for PSS-10 score ≥19. The extent of coupling between maternal and fetal heart rate (mHR, fHR) derived from maternal abdominal ECG was quantified. Assessment by the bivariate phase-rectified signal averaging algorithm (BPRSA) yielded fetal stress index (FSI) values. On the day of parturition, maternal blood and hair strands from the posterior vertex region on the head were collected for cortisol measurements. Cord blood samples and saliva/buccal samples from the newborns were also collected. Maternal and newborn serum was used to measure acetylthiocholine hydrolytic activity of acetyl- and butyrylcholinesterases (AChE, BChE). Infants? cognitive development was assessed by Bayley Scale III of Infant Development (BSID) at 24 months of age when a new saliva sample was taken to be processed for epigenetic biomarkers. Preliminary results show that prenatal maternal stress identified in the third trimester by PSS-10 has an impact on the coordination of fetal and maternal heart rate (captured by FSI) and on fetal oxygenation at birth. Machine learning approaches (with internal validation) indicated that the fetal AChE/BChE ratio is predicted best by joint fetal-maternal stress biomarker FSI, but not by maternal stress levels alone. In conclusion, the maternal and fetal stress status may be shaped by both maternal cortisol and the maternal and fetal AChE/BChE balance, validating our hypothesis that PS-induced programming is reflected in mHR and fHR biomarkers of ANS activity.