313 - Impact of Cytomegalovirus (CMV) infection and exposure at the Maternal-Fetal Interface.

Poster Number: 313
Publication Number: 313.124

Kylee Miller, University of Alabama - Birmingham Hospitals, Birmingham, AL, United States; Ailing Lu, Children's of Alabama, Birmingham, AL, United States; Mao Li, University of Alabama School of Medicine, Birmingham, AL, United States; Veronica Sanchez, University of Alabama School of Medicine, Birmingham, AL, United States; David W. Kimberlin, University of Alabama at Birmingham, Birmingham, AL, United States; Swetha Pinninti, University of Alabama at Birmingham, Birmingham, AL, United States; Charitharth Vivek Lal, University of Alabama at Birmingham, AL, Birmingham, AL, United States; Amit Gaggar, University of Alabama School of Medicine, Birmingham, AL, United States; Suresh Boppana, University of Alabama School of Medicine, Birmingham, AL, United States; William Britt, University of Alabama School of Medicine, Birmingham, AL, United States; Virginia Duncan, University of Alabama at Birmingham, Birmingham, AL, United States; Nitin Arora, University of Alabama School of Medicine, Birmingham, AL, United States

Background: Congenital cytomegalovirus (CMV) infection is present in up to 0.5-2% of infants delivered each year, with a large number of neonates requiring long-term medical management. Although epidemiology and natural history of congenital CMV have been well-studied, the mechanisms of intrauterine transplacental transmission and severe disease is not well understood.

Objective: Our objective is to evaluate the impact of CMV infection and exposure at the maternal-fetal interface using higher sensitivity staining assays in addition to novel spatial and molecular transcriptome profiling techniques.

Design/Methods: From November 2010 to August 2020, 24 placental specimens with evidence of CMV infection were collected. Pathological findings of lymphoplasmacytic villitis, hemosiderosis, and presence of viral inclusions were used for confirmation. 24 additional samples were collected during this time period from CMV seropositive mothers without features of placental involvement to be used as control specimens. Higher sensitivity assays of immunohistochemistry, immunofluorescence, and in situ hybridization techniques were further utilized to identify the extent of CMV infection in FFPE (formalin fixed paraffin embedded) placental tissue samples.

Results: Of the 24 placental samples with CMV infection, the average gestational age was 35 weeks and 4.7 days compared to 38 weeks and 5.3 days in the CMV-exposed group. The mode of delivery was vaginal for 54% of the CMV-infected samples compared to 79% of the CMV-exposed samples. Of the neonates that were born to the CMV-infected cohort, 91.7% had congenital CMV, compared to 8.7% in the CMV-exposed cohort. We established higher sensitivity techniques of immunohistochemistry, immunofluorescence, and in situ hybridization using a subset of placental samples and identified CMV DNA and viral proteins associated with virus replication within the sample as shown in Figure 1.Conclusion(s): Congenital CMV transmission occurs more frequently in CMV seropositive mothers though the underlying mechanisms are poorly understood. This study would help us evaluate the impact of CMV infection at the maternal fetal interface between the maternal seropositive CMV-infected placental tissue and maternal seropositive CMV-exposed placental tissue. Preliminary data suggests that our higher sensitivity staining techniques are robust and can be applied to the larger cohort. Next steps involve performing novel spatial and molecular transcriptome profiling, techniques that have been well established on FFPE placental samples at our institution.
Baseline Maternal CharacteristicsTable 1. Baseline maternal characteristics for CMV-infected placental tissue samples and CMV-exposed placental tissue samples.
Neonatal Clinical, Laboratory, and Imaging DataTable 2. Neonatal clinical, laboratory, and imaging data for those with CMV-infected placental tissue and CMV-exposed placental tissue.