(140) Placental Immune Markers for Early Postnatal Detection of Infants at High-Risk of Adverse Neurodevelopment

Marie-Eve Brien^1,2,*, Jonathan Charron^1,*, Catherine Bernard¹, Véronique Belval¹, Léanne Brabant ^1,3, Mathieu Dehaes^1,4, Marie-Noëlle Simard^1,3, Thuy Mai Luu^1,5, Dorothée Dal Soglio⁶, Sylvie Girard^2,7

¹Ste-Justine Hospital Research Center, Montreal, Quebec, Canada;

²Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA;

³School of rehabilitation, Université de Montréal, Montreal, Quebec, Canada;

⁴Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Montreal, Quebec, Canada;

⁵Department of Pediatrics, Université de Montréal, Montreal, Quebec, Canada;

⁶Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec, Canada;

⁷Department of Obstetrics and Gynecology, Department of Immunology, Mayo Clinic, Rochester, MN, USA;

*Contributed equally to this work.

Abstract Text:

Preterm birth (PTB) is a major global health concern linked to higher incidence of neonatal mortality and morbidity, with significant implications especially for neurodevelopmental outcomes. Early identification of infants which would require follow-up remains challenging. Our goal was to investigate the association between placental histomorphology, inflammatory markers, and neurodevelopment in preterm infants. We followed a cohort of 156 preterm infants (i.e. 29-36 weeks’ gestation). Maternal demographic and obstetric data were collected. Placenta and fetal membrane were evaluated by histopathology (hematoxylin & eosin – HE staining) and immunohistochemical analysis for immune cells (CD45, CD68 and CD163). Adverse neurodevelopment was defined as scoring below the normal range on any of the cognitive, motor, or language scale on the Bayley Scales of Infant and Toddler Development, 3rd edition. There were 68 infants who presented with an adverse neurodevelopment at 24 months of age. Within this subgroup, mothers had elevated pre-pregnancy BMI, and higher incidence of gestational hypertension/diabetes vs those without adverse outcome. Placental analysis revealed no correlation between adverse developmental outcome and general histopathological assessment aside from, increased inflammatory lesions (i.e. deciduitis/villitis) in the placenta of infants with adverse neurodevelopment. Furthermore, increased CD45+ cells were observed in the placenta of infants with language and cognitive delays (p<0.05). CD163+ macrophages were decreased in the placenta of infants with adverse neurodevelopment, primarily those with impaired expressive communication. In fetal membranes, CD68+ macrophages were increased especially in the decidua of infants with any neurodevelopment outcome (p<0.05), more particularly in those with language and motor delays (p<0.05). Our study highlights the potential to use the placenta as a tool for identifying preterm infants at high-risk for adverse neurodevelopment and those who may need closer clinical monitoring. Further investigation is needed to increase predictive accuracy beyond classical histopathology evaluation.