The maternal-fetal neurodevelopmental groundings of preterm birth risk
Cesare Miglioli,
Matteo Canini,
Edoardo Vignotto,
Nicolò Pecco,
Mirko Pozzoni,
Maria-Pia Victoria-Feser,
Stéphane Guerrier,
Massimo Candiani,
Andrea Falini,
Cristina Baldoli,
Paolo I. Cavoretto,
Pasquale A. Della Rosa
Affiliations
Cesare Miglioli
Research Center for Statistics, University of Geneva, Boulevard Du Pont-d’Arve 40, 1205 Geneva, Switzerland
Matteo Canini
Department of Neuroradiology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
Edoardo Vignotto
Research Center for Statistics, University of Geneva, Boulevard Du Pont-d’Arve 40, 1205 Geneva, Switzerland
Nicolò Pecco
Department of Neuroradiology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
Mirko Pozzoni
Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60 Milan, 20132, Italy
Maria-Pia Victoria-Feser
Research Center for Statistics, University of Geneva, Boulevard Du Pont-d’Arve 40, 1205 Geneva, Switzerland
Stéphane Guerrier
Research Center for Statistics, University of Geneva, Boulevard Du Pont-d’Arve 40, 1205 Geneva, Switzerland; Faculty of Science, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland
Massimo Candiani
Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60 Milan, 20132, Italy
Andrea Falini
Department of Neuroradiology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
Cristina Baldoli
Department of Neuroradiology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
Paolo I. Cavoretto
Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60 Milan, 20132, Italy; Corresponding author.
Pasquale A. Della Rosa
Department of Neuroradiology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, 20132, Italy
Background: Altered neurodevelopment is a major clinical sequela of Preterm Birth (PTB) being currently unexplored in-utero. Aims: To study the link between fetal brain functional (FbF) connectivity and preterm birth, using resting-state functional magnetic resonance imaging (rs-fMRI). Study design: Prospective single-centre cohort study. Subjects: A sample of 31 singleton pregnancies at 28–34 weeks assigned to a low PTB risk (LR) (n = 19) or high PTB risk (HR) (n = 12) group based on a) the Maternal Frailty Inventory (MaFra) for PTB risk; b) a case-specific PTB risk gradient. Methods: Fetal brain rs-fMRI was performed on 1.5T MRI scanner. First, directed causal relations representing fetal brain functional connectivity measurements were estimated using the Greedy Equivalence Search (GES) algorithm. HR vs. LR group differences were then tested with a novel ad-hoc developed Monte Carlo permutation test. Second, a MaFra-only random forest (RF) was compared against a MaFra-Neuro RF, trained by including also the most important fetal brain functional connections. Third, correlation and regression analyses were performed between MaFra-Neuro class probabilities and i) the GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Results: First, fewer fetal brain functional connections were evident in the HR group. Second, the MaFra-Neuro RF improved PTB risk prediction. Third, MaFra-Neuro class probabilities showed a significant association with: i) GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Conclusion: Fetal brain functional connectivity is a novel promising predictor of PTB, linked to maternal risk profiles, ahead of birth, and clinical markers of neurodevelopmental risk, at birth, thus potentially “connecting” different PTB phenotypes.
