Background: Although hundreds of thousands of infants are infected each year by HIV-1 through mother-to-child transmission (MTCT), the route of HIV-1 MTCT is not well understood. Intrauterine and intrapartum HIV-1 infection could occur through birth canal exposure or transplacental HIV-1 passage. The latter could involve HIV-1 trafficking through an intact cellular barrier or through breaches in the placental barrier. Our group has previously shown that placental micro-transfusions are associated with intrapartum MTCT. In this study, we measure placental micro-transfusions by quantifying the amount of maternal DNA present in umbilical cord blood.

Methods:  Matched maternal and umbilical cord genomic DNA was available from 328 of the 565 HIV-1⁺ women who vaginally delivered live, singleton infants with a definitive HIV-1 result 6 weeks post partum. Matched pairs were screened by polymerase chain reaction (PCR) to identify discordant ACE and GSTM1 alleles. We considered 91 pairs informative, meaning that the maternal isolate contained an ACE or GSTM1 allele not present in the infant (69 non-transmitters, 13 in utero-infected, and 9 intrapartum infected). The amount of maternal DNA present in the umbilical cord of informative pairs was quantified with real-time PCR and normalized to the amount of total genomic DNA. Associations were tested with the Wilcoxon-rank sum test.

Results:  As expected, maternal DNA was significantly higher in cord blood of intrapartum-infected infants than of uninfected infants (p = 0.02). Elevated amounts of maternal/fetal DNA admixture were associated with low birth weight (<2500 g; p = 0.02), preterm delivery (<37 weeks; p = 0.005), and low CD4 T cell count (<200 copies/mL; p = 0.04). Admixture was non-significantly associated with intrauterine MTCT (p = 0.06) and not associated with the following characteristics (p >0.2):  delayed placental delivery, visible placental tears, sex of the newborn, vaginal/vulval tears, episiotomy, syphilis sero-reactivity, rupture of membranes >4 hours, labor >10 hours, chorioamnionitis, the presence of placental Plasmodium falciparum parasites, high HIV-1 RNA concentration, primigravidity, or low placental weight.

Conclusions:  These data confirm our previous observation of the association between intrapartum MTCT and placental micro-transfusion. The associations between placental micro-transfusion, intrauterine MTCT, low CD4 count, and poor birth outcome should be followed-up in a larger study.