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Case 3: Discussion

Background

The last two decades has seen significant improvements in the therapeutic options for HIV-infected individuals, resulting in increased longevity and improved quality of life. Concomitant with these improvements in therapy, there has been an increase in the number of perinatally HIV-infected girls anticipating the birth of their own children[1]. The case history presented here illustrates some of the challenges in managing an HIV-infected pregnant adolescent. Although reducing the risk of vertical transmission is a primary concern, it is important to keep in perspective the patient's commitment to taking the medications, her likely adherence while taking antiretroviral medications, and the potential long-term implications of non-adherence. If effective highly active antiretroviral therapy (HAART) is taken during pregnancy, the risk of maternal-to-child HIV transmission is very low (Figure 1)[2]. Unfortunately, in some situations, such as with this 15-year-old girl, pregnant HIV-infected mothers may go through pregnancy without taking antiretroviral therapy. In such scenarios, efforts to prevent HIV transmission at the time of delivery are of paramount importance. Indeed, it is estimated that among newborns with perinatally-acquired HIV, approximately 60% become infected during labor and delivery[3]. The mother-to-child transmission of HIV that occurs during labor and delivery is believed to result from transplacental maternal-fetal microtransfusion of blood during uterine contractions and fetal exposure to maternal cervicovaginal secretions and blood during delivery[4]. Investigators have identified a number of factors prior to and during delivery that may affect the risk of HIV transmission (Figure 2). The remaining discussion will focus on the impact, indications, timing, and complications of cesarean section delivery in HIV-infected mothers, as well as use of antiretroviral therapy administered during delivery.

Impact of Cesarean Section on Perinatal HIV Transmission

Prior to the widespread use of viral load testing and the use of combination antiretroviral therapy during pregnancy, several studies clearly established that cesarean section, if performed before the onset of labor and rupture of membranes, significantly reduces perinatal transmission of HIV when compared with other modes of delivery[5,6]. In 1999, the International Perinatal HIV Group published the findings of a meta-analysis of 15 prospective cohort studies that addressed the impact of elective cesarean section versus vaginal delivery on the risk of mother-to-child HIV transmission[6]. These studies involved a cumulative total of 8533 mother-child pairs, and the data were adjusted for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight. The investigators found that elective cesarean section decreased the risk of transmission by approximately 50%, with a transmission rate of 8.4% for women who underwent elective cesarean section versus 16.7% for those with any other mode of delivery (Figure 3)[6]. For those mother-child pairs who received antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, transmission occurred in 4 (2%) of the 196 women who underwent elective cesarean-section delivery compared with 92 (7.3%) among the 1255 with other modes of delivery (Figure 4).

In a separate article published in 1999, the European Mode of Delivery Collaboration group reported findings from their trial involving 436 HIV-infected pregnant women randomized to undergo elective cesarean section at week 38 or vaginal delivery at term[7]. The study was performed between 1993 and 1998. In an analysis of 346 infants followed to 18 months, 7 (3.5%) of 196 infants whose mother had undergone cesarean section acquired HIV compared with 17 (10.2%) of 150 those delivered vaginally (Figure 5). The overall benefit of cesarean-section delivery occurred with elective cesarean section, but not with emergent cesarean section (Figure 6)[7]. Among those mothers who received zidovudine (Retrovir) during pregnancy, cesarean section did not appear to provide any benefit (Figure 7). In addition, studies have not demonstrated additional reduction in the risk of vertical transmission following cesarean section if the near term maternal HIV RNA level is less than 1000 copies/ml[5].

Indications for Cesarean Section

In May 2000, the American College of Obstetricians and Gynecologists (ACOG) revised its recommendations regarding the management of HIV-infected pregnant women. These revised guidelines, as well as the current 2005 Public Health Task Force guidelines, recommend that women with viral loads above 1,000 copies/ml near term should undergo scheduled cesarean section at 38 completed weeks of gestation, prior to the onset of labor or the rupture of membranes[4,5]. In addition, intravenous zidovudine should be started 3 hours prior to delivery and continued throughout delivery[4]. For women with a near term HIV RNA level less than 1,000 copies/ml, cesarean section probably does not significantly reduce the risk of HIV transmission and thus most experts would not recommend scheduled cesarean section in that situation[5]. If a near term viral load has not been performed, decisions regarding cesarean section should be made based on the most recent HIV RNA level. Women taking antiretroviral therapy should remain on therapy through delivery and continue therapy after delivery if indicated for maternal purposes.

Timing of Planned Cesarean Section

For women scheduled to undergo cesarean section, the ACOG and the US Public Health Task Force guidelines recommend that it take place at 38 completed weeks of gestation (determined by best clinical estimate), prior to the onset of labor or the rupture of membranes. The ACOG recommends performing a scheduled cesarean section delivery at 38 completed weeks of gestation, as opposed to the 39 weeks recommended for persons not infected with HIV, because of the substantially higher risk of entering labor or rupturing membranes after 38 weeks of completed gestation. On the other hand, performing a cesarean delivery at 38 versus 39 completed weeks of gestation confers a small increased risk of infant respiratory distress possibly requiring mechanical ventilation. Although it would be ideal to know the status of the fetal lung maturity prior to cesarean section, the ACOG recommends avoiding amniocentesis, primarily to avoid fetal exposure to maternal blood[4].

Scheduled Cesarean Section and Woman Presents in Labor

When a woman is scheduled to undergo cesarean section, but presents early in labor (or shortly after rupture of membranes), the benefit of cesarean section is unknown and decisions regarding the approach to delivery should be individualized. If the woman has minimal cervical dilatation and is likely to have extended labor, one option is to immediately give the loading dose of intravenous zidovudine and then proceed to cesarean section[5]. Alternatively, one could immediately give the loading dose of intravenous zidovudine and then start oxytocin (Pitocin) to expedite delivery, with vaginal delivery performed as long as rapid labor ensues[5]. For any vaginal delivery, the duration of ruptured membranes should be as short as possible, given the increased risk of HIV transmission with longer duration of membrane rupture. Rupture of membranes for longer than 4 hours doubles the risk of HIV transmission[5,6,8]. For any vaginal delivery, the clinician should, if possible, avoid using scalp electrodes or other invasive monitoring devices, forceps, or the vacuum extractor.

Complications of Cesarean Section

Although limited data exist regarding maternal morbidity following cesarean section in HIV-infected women[9], several studies have suggested that HIV-infected women who undergo cesarean section have higher complication rates than women who deliver vaginally[10,11]. Post-delivery complications most frequently consist of hemorrhage, postpartum fever, cesarean wound infection, endometritis, urinary tract infection, and sepsis[4,7,10,12]. Among HIV-infected women who deliver via cesarean, those with CD4 counts less than 200 cells/mm3 have a greater rate of complications[10]. Because of the increase in infectious complications, the PHS guidelines recommend that following cord clamping with a cesarean delivery, the mother should receive prophylactic antibiotics, which reduces the risk of postpartum maternal infection[5].

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    Figure 1 - Prenatal Antiretroviral Therapy and Impact on Perinatal HIV Transmission Figure 1
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    Figure 2 - Factors Associated with Increased Risk of Perinatal HIV Transmission Figure 2
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    Figure 3 - Risk of HIV Transmission According to Mode of Delivery: Meta-Analysis of 15 Prospective Cohort Studies Figure 3
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    Figure 4 - Risk of HIV Transmission According and Mode of Delivery: Analysis Based on Antiretroviral Use in the Prenatal, Intrapartum, and Neonatal Periods Figure 4
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    Figure 5 - Risk of HIV Transmission Among Women Randomized to Elective Cesarean or Vaginal Delivery Figure 5
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    Figure 6 - Risk of HIV Transmission Among Women who Underwent Delivery Either by Elective or Emergent Cesarean Figure 6
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    Figure 7 - Vertical HIV Transmission Rates Based on Actual Cesarean or Vaginal Delivery and Based on Receipt of Zidovudine or No Zidovudine During Pregnancy Figure 7