Placental Pathology Findings and the Risk of Intraventricular and Cerebellar Hemorrhage in Preterm Neonates

Alessandro Parodi; Laura Costanza De Angelis; Martina Re; Sarah Raffa; Mariya Malova; Andrea Rossi; Mariasavina Severino; Domenico Tortora; Giovanni Morana; Maria Grazia Calevo; Maria Pia Brisigotti; Francesca Buffelli; Ezio Fulcheri; Luca Antonio Ramenghi

doi:10.3389/fneur.2020.00761

Placental Pathology Findings and the Risk of Intraventricular and Cerebellar Hemorrhage in Preterm Neonates

Front Neurol. 2020 Aug 14:11:761. doi: 10.3389/fneur.2020.00761. eCollection 2020.

Authors

Alessandro Parodi¹, Laura Costanza De Angelis¹, Martina Re¹, Sarah Raffa^{1

2}, Mariya Malova¹, Andrea Rossi^{3

4}, Mariasavina Severino³, Domenico Tortora³, Giovanni Morana³, Maria Grazia Calevo⁵, Maria Pia Brisigotti⁶, Francesca Buffelli⁶, Ezio Fulcheri^{6

7}, Luca Antonio Ramenghi^{1

2}

Affiliations

¹ Neonatal Intensive Care Unit, Department Mother and Child, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
² Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
³ Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
⁴ Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
⁵ Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
⁶ Gynaecologic and Fetal-Perinatal Pathology Centre, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
⁷ Division of Pathology, Department of Surgical Sciences (DISC), University of Genoa, Genoa, Italy.

Abstract

Placental pathology as a predisposing factor to intraventricular hemorrhage remains a matter of debate, and its contribution to cerebellar hemorrhage development is still largely unexplored. Our study aimed to assess placental and perinatal risk factors for intraventricular and cerebellar hemorrhages in preterm infants. This retrospective cohort study included very low-birth weight infants born at the Gaslini Children's Hospital between January 2012 and October 2016 who underwent brain magnetic resonance with susceptibility-weighted imaging at term-equivalent age and whose placenta was analyzed according to the Amsterdam Placental Workshop Group Consensus Statement. Of the 286 neonates included, 68 (23.8%) had intraventricular hemorrhage (all grades) and 48 (16.8%) had a cerebellar hemorrhage (all grades). After correction for gestational age, chorioamnionitis involving the maternal side of the placenta was found to be an independent risk factor for developing intraventricular hemorrhage, whereas there was no association between maternal and fetal inflammatory response and cerebellar hemorrhage. Among perinatal factors, we found that intraventricular hemorrhage was significantly associated with cerebellar hemorrhage (odds ratio [OR], 8.14), mechanical ventilation within the first 72 h (OR, 2.67), and patent ductus arteriosus requiring treatment (OR, 2.6), whereas cesarean section emerged as a protective factor (OR, 0.26). Inotropic support within 72 h after birth (OR, 5.24) and intraventricular hemorrhage (OR, 6.38) were independent risk factors for cerebellar hemorrhage, whereas higher gestational age was a protective factor (OR, 0.76). Assessing placental pathology may help in understanding mechanisms leading to intraventricular hemorrhage, although its possible role in predicting cerebellar bleeding needs further evaluation.

Keywords: cerebellar hemorrhage; chorioamnionitis; intraventricular hemorrhage; magnetic resonance imaging; maternal malperfusion; placenta; preterm infant.