Nucleic Acid-Based Screening of Maternal Serum to Detect Viruses in Women with Labor or PROM

Ankit A. Shah, David Wang, Emmet Hirsch

The purpose of this study was to determine whether timing of the initiating event of spontaneous labor (either uterine contractions with intact fetal membranes or rupture of membranes prior to labor (PROM)) is associated with maternal viral infection. It was a prospective case control study of women with either spontaneous labor or PROM occurring < 37 weeks' gestation ("cases") or at term ("controls"). An initial unbiased screen for viruses was performed with next-generation sequencing (NGS) in serum pooled from eight cases delivered by C/S and represents a range of gestational ages, membrane rupture status, and presence or absence of chorioamnionitis. Custom PCR was used to query individual patient samples from the original cohort. The NGS screen generated 15 million reads. Seven unique viral sequences were detected in two cases, all identified as torque teno virus (TTV), an ubiquitous DNA anellovirus of no known pathogenicity. Using nested and semi-nested PCR, sera from 72 patients (47 cases and 25 matched controls, stratified by ROM status) were screened for the 3 subtypes of anelloviruses (TTV, TTMDV, or TTMV). These were found in 43/47 cases (91%) and 16/25 controls (64%) (p = 0.012, OR = 5.9 (95% CI = 1.4-29.9)). In logistic regression, pregnant women with at least one type of anellovirus were more likely to experience preterm labor than those with no anellovirus (p = 0.03, aOR = 4.6, CI = 1.2-18.7). Among women experiencing a spontaneous initiating event of labor, TTV virus was more likely to be present in the serum of preterm than term patients. TTV may have a role in determining the timing of parturition.