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Maternal-fetal microtransfusions and HIV-1 mother-to-child transmission in Malawi.

Kwiek JJ, Mwapasa V, Milner DA, Alker AP, Miller WC, Tadesse E, Molyneux ME, Rogerson SJ, Meshnick SR - PLoS Med. (2005)

Bottom Line: Among vaginal deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml PLAP; 95% confidence interval, 0.95-5.32) but not in utero MTCT.These results suggest that during vaginal deliveries, placental microtransfusions are a risk factor for IP HIV-1 MTCT.Future studies are needed to identify factors that increase the risk for microtransfusions in order to prevent IP HIV-1 MTCT.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA. kwiek@unc.edu

ABSTRACT

Background: Between 25% and 35% of infants born to HIV-infected mothers become HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could be through a breakdown in the placental barrier (i.e., maternal-fetal microtransfusions).

Methods and findings: Placental alkaline phosphatase (PLAP) is a 130-kD maternal enzyme that cannot cross the intact placental barrier. We measured PLAP activity in umbilical vein serum as an indicator of maternal-fetal microtransfusion, and related this to the risk of HIV-1 MTCT. A case-cohort study was conducted of 149 women randomly selected from a cohort of HIV-1-infected pregnant Malawians; these women served as a reference group for 36 cases of in utero MTCT and 43 cases of intrapartum (IP) MTCT. Cord PLAP activity was measured with an immunocatalytic assay. Infant HIV status was determined by real-time PCR. The association between cord PLAP activity and HIV-1 MTCT was measured with logistic regression using generalized estimating equations. Among vaginal deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml PLAP; 95% confidence interval, 0.95-5.32) but not in utero MTCT. In a multivariable model adjusted for HIV-1 RNA load, chorioamnionitis, and self-reported fever, the risk of IP MTCT almost tripled for every log10 increase in cord PLAP activity (risk ratio, 2.87; 95% confidence interval, 1.05-7.83).

Conclusion: These results suggest that during vaginal deliveries, placental microtransfusions are a risk factor for IP HIV-1 MTCT. Future studies are needed to identify factors that increase the risk for microtransfusions in order to prevent IP HIV-1 MTCT.

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Related in: MedlinePlus

Case-Cohort Profile
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pmed-0030010-g001: Case-Cohort Profile

Mentions: We constructed a case cohort study from the parent MHP prospective cohort. With this study design, a rare disease assumption is unnecessary and the odds ratio provides a direct estimate of the risk ratio (RR) [21]. Between December 2000 and February 2003, 2,557 pregnant women were recruited in the MHP study, of whom 744 (29.1%) were HIV infected. After identifying all cases of in utero (IU) and IP MTCT in the parent cohort, we randomly selected 160 women, regardless of their HIV-1 transmission status, from the 744 HIV-1-positive women to serve as a reference cohort. Of these mother–offspring pairs, three were excluded because of multiple gestations, six were excluded because they delivered at home (therefore cord serum was unavailable), and two were excluded because the mother died during delivery; the remaining 149 HIV-infected women formed the reference cohort of the case-cohort study (Figure 1). All cases of IU MTCT were selected from women enrolled in the MHP study through February 2003, and all cases of IP MTCT were selected from women enrolled in the MHP study through June 2003. IP transmission cases selected from February to June 2003 did not differ from the other IP transmission cases in terms of age, peripheral HIV-1 RNA load, PLAP activity, hemoglobin concentration, placental malaria infection, or mode of delivery (data not shown). HIV-1 MTCT cases were considered IU transmissions if the infant was positive for HIV-1 DNA within 48 h of birth, and were considered IP transmissions (i.e., HIV-1 infection occurring at or around the time of delivery) if the infant was both negative for HIV-1 DNA within 48 h of birth and positive for HIV-1 DNA 6 wk after delivery [22].


Maternal-fetal microtransfusions and HIV-1 mother-to-child transmission in Malawi.

Kwiek JJ, Mwapasa V, Milner DA, Alker AP, Miller WC, Tadesse E, Molyneux ME, Rogerson SJ, Meshnick SR - PLoS Med. (2005)

Case-Cohort Profile
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1285069&req=5

pmed-0030010-g001: Case-Cohort Profile
Mentions: We constructed a case cohort study from the parent MHP prospective cohort. With this study design, a rare disease assumption is unnecessary and the odds ratio provides a direct estimate of the risk ratio (RR) [21]. Between December 2000 and February 2003, 2,557 pregnant women were recruited in the MHP study, of whom 744 (29.1%) were HIV infected. After identifying all cases of in utero (IU) and IP MTCT in the parent cohort, we randomly selected 160 women, regardless of their HIV-1 transmission status, from the 744 HIV-1-positive women to serve as a reference cohort. Of these mother–offspring pairs, three were excluded because of multiple gestations, six were excluded because they delivered at home (therefore cord serum was unavailable), and two were excluded because the mother died during delivery; the remaining 149 HIV-infected women formed the reference cohort of the case-cohort study (Figure 1). All cases of IU MTCT were selected from women enrolled in the MHP study through February 2003, and all cases of IP MTCT were selected from women enrolled in the MHP study through June 2003. IP transmission cases selected from February to June 2003 did not differ from the other IP transmission cases in terms of age, peripheral HIV-1 RNA load, PLAP activity, hemoglobin concentration, placental malaria infection, or mode of delivery (data not shown). HIV-1 MTCT cases were considered IU transmissions if the infant was positive for HIV-1 DNA within 48 h of birth, and were considered IP transmissions (i.e., HIV-1 infection occurring at or around the time of delivery) if the infant was both negative for HIV-1 DNA within 48 h of birth and positive for HIV-1 DNA 6 wk after delivery [22].

Bottom Line: Among vaginal deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml PLAP; 95% confidence interval, 0.95-5.32) but not in utero MTCT.These results suggest that during vaginal deliveries, placental microtransfusions are a risk factor for IP HIV-1 MTCT.Future studies are needed to identify factors that increase the risk for microtransfusions in order to prevent IP HIV-1 MTCT.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA. kwiek@unc.edu

ABSTRACT

Background: Between 25% and 35% of infants born to HIV-infected mothers become HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could be through a breakdown in the placental barrier (i.e., maternal-fetal microtransfusions).

Methods and findings: Placental alkaline phosphatase (PLAP) is a 130-kD maternal enzyme that cannot cross the intact placental barrier. We measured PLAP activity in umbilical vein serum as an indicator of maternal-fetal microtransfusion, and related this to the risk of HIV-1 MTCT. A case-cohort study was conducted of 149 women randomly selected from a cohort of HIV-1-infected pregnant Malawians; these women served as a reference group for 36 cases of in utero MTCT and 43 cases of intrapartum (IP) MTCT. Cord PLAP activity was measured with an immunocatalytic assay. Infant HIV status was determined by real-time PCR. The association between cord PLAP activity and HIV-1 MTCT was measured with logistic regression using generalized estimating equations. Among vaginal deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml PLAP; 95% confidence interval, 0.95-5.32) but not in utero MTCT. In a multivariable model adjusted for HIV-1 RNA load, chorioamnionitis, and self-reported fever, the risk of IP MTCT almost tripled for every log10 increase in cord PLAP activity (risk ratio, 2.87; 95% confidence interval, 1.05-7.83).

Conclusion: These results suggest that during vaginal deliveries, placental microtransfusions are a risk factor for IP HIV-1 MTCT. Future studies are needed to identify factors that increase the risk for microtransfusions in order to prevent IP HIV-1 MTCT.

Show MeSH
Related in: MedlinePlus