Hum. Reprod. Advance Access originally published online on October 31, 2007
Human Reproduction 2008 23(1):29-36; doi:10.1093/humrep/dem360
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Adverse reproductive outcomes in urban women with adeno-associated virus-2 infections in early pregnancy
Center for Research on Reproduction and Women’s Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
1 Correspondence address. 2000 Courtyard Building, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +215-662-6913; Fax: +215-349-5625; E-mail: parry{at}mail.med.upenn.edu
BACKGROUND: We demonstrated recently that adeno-associated virus-2 (AAV-2) DNA was detected significantly more frequently in placental trophoblast cells from cases of severe pre-eclampsia than from normal term deliveries. Here, we sought to determine if maternal AAV-2 infection early in pregnancy preceded adverse outcomes resulting from placental dysfunction.
METHODS: We collected first trimester maternal serum samples and compared anti-AAV-2 IgM antibody levels (indicating primary infection or reactivation of latent AAV-2) between controls delivered at term (n = 106) and three groups of cases: spontaneous abortions (n = 34), spontaneous preterm deliveries (n = 24) and women with at least one outcome usually attributed to placental dysfunction, including pre-eclampsia, intrauterine growth restriction (IUGR) or stillbirth (n = 20). The seroprevalence of immunoglobulin G (IgG) antibodies against AAV-2 and IgM antibodies against viruses that promote AAV-2 replication [adenovirus and cytomegalovirus (CMV)] were also determined.
RESULTS: First trimester maternal IgM seropositivity was 5.6 times more prevalent among pre-eclampsia/IUGR/stillbirth cases (P = 0.0004) and 7.6 times more prevalent among preterm deliveries (P < 0.0001) than among controls. CMV and adenovirus IgM antibodies and chronic AAV-2 infections (IgG seropositivity) were not associated with adverse pregnancy outcomes.
CONCLUSIONS: Primary or reactivated AAV-2 infection (maternal IgM seropositivity) early in pregnancy was associated with adverse reproductive outcomes associated with placental dysfunction, including pre-eclampsia, stillbirth and spontaneous preterm delivery.
Key words: adeno-associated virus/antibodies/placenta/pre-eclampsia/preterm birth
Drs F.A.-V. and L.G. contributed equally to this study. Submitted on April 23, 2007; resubmitted on July 16, 2007; accepted on July 25, 2007.
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