PLACENTAL ADENOVIRAL GENOME: POLYMERASE CHAIN REACTION DETECTION AND PLACENTAL HISTOLOGY IN PRETERM AND TERM INFANTS

Abstract

INTRODUCTION: Intrauterine infection is an important cause of spontaneous preterm birth. However, evidence-based etiology for the causative role of viral infection is still lacking. Intervillous trophoblasts express adenovirus receptor. Infection of trophoblast cells in vitro by adenovirus early in pregnancy has shown increased apoptosis. Adenovirus early in pregnancy may cause placental dysfunction. Mature syncytiotrophoblasts do not express adenovirus receptor. OBJECTIVE: The aim of this study was to test the hypothesis that detection of adenovirus in placental tissue is associated with preterm birth and correlates with placental histopathological findings that are suggestive of infection. METHODS: Placentas were prospectively collected from consecutive deliveries. Detection of the adenovirus genome was tested by polymerase chain reaction assay. Placental histology and immunohistochemistry studies with monoclonal antibody CD45 were evaluated for signs of placental inflammation in the samples that tested positive for adenovirus. RESULTS: Between January 2005 and December 2006, 193 placenta samples (71 from preterm deliveries and 122 from term deliveries) were collected in Alexandra's Maternity Hospital in Athens, Greece. The adenoviral genome was isolated in 54 (28%) of 193 placentas. The frequency of adenovirus detection in preterm placentas compared with those from term placentas was significantly increased (29 of 71[41%] vs 25 of 122 [20%]; P = .002; odds ratio [OR]: 2.6 [95% confidence interval (CI): 1.4–5.1]). Stratification by gestational age (GA) revealed a stronger association between preterm delivery and adenovirus detection as GA decreased below 33 weeks (GA ≤ 29 weeks, OR: 2.8 [95% CI: 1.1–7.0]; and GA 30–33 weeks, OR: 2.7 [95% CI: 1.1–6.5]). In the subgroup of deliveries at 34 to 36 weeks' GA, the association was no longer significant (OR: 2.6 [95% CI: 0.9–7.0]). Adenoviral genome detection followed the seasonal variation of adenovirus respiratory infections (beginning of March to end of June). Chorioamnionitis was present more frequently in the adenovirus-positive preterm placentas compared with term placentas (P = .006). The presence of villitis (P = .03) and chorioamnionitis (P = .02) was significantly increased in the adenovirus-positive preterm placentas compared with preterm adenovirus-negative placentas. CONCLUSIONS: Our results indicate that there is an association between placental adenoviral genome detection and spontaneous early premature birth. Adenovirus may cause preterm birth through placental inflammation (chorioamnionitis and villitis).