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 reduced perinatal transmission of HIV when compared with other modes of delivery.[,] In 1999, the International Perinatal HIV Group published 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. This analysis included 8533 mother-child pairs with the birth occurring prior to 1997, with data adjusted for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight; most did not receive antiretroviral therapy or they received zidovudine alone. The investigators found that elective cesarean section decreased the risk of HIV 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 1). For the 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 2). In a separate study performed during the years 1993 and 1998, the European Mode of Delivery Collaboration group randomized HIV-infected pregnant women at week 34 to 36 gestation to undergo elective cesarean section at week 38 or vaginal delivery at term. In an analysis of infants followed to 18 months, 7 (3.4%) of 203 infants whose mother had undergone cesarean section acquired HIV compared with 15 (10.2%) of 167 those born vaginally (Figure 3). The overall benefit of cesarean-section delivery occurred with elective cesarean section, but not with emergent cesarean section (Figure 4). Among those mothers who received zidovudine (Retrovir) during pregnancy, cesarean section did not appear to provide any benefit (Figure 5). 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.
Indications for Cesarean Section Based on Maternal HIV RNA Level Near Term
Available data suggest that most HIV transmission occurs very late in pregnancy or during the delivery, with HIV transmission that occurs during labor and delivery result primarily from transplacental maternal-fetal microtransfusion of blood during uterine contractions and fetal exposure to maternal cervicovaginal secretions and blood during delivery.[,] The key events related to maternal-child HIV transmission that occur during delivery serve as the rationale for utilizing all prevention measures related to labor and delivery. The HHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health and Interventions to Reduce Perinatal Transmission in the United States (commonly referred to as the perinatal guidelines) address the indications and timing of cesarean section in HIV-infected mothers. These guidelines recommend performing a scheduled cesarean section delivery at week 38 gestation in HIV-infected women who have an HIV RNA level greater than 1,000 copies/ml (or unknown) near the time of delivery; this recommendation holds regardless of the woman's antepartum antiviral history. In the modern era with use of combination antiretroviral therapy during pregnancy, mother-to-child HIV transmission rates are very low (approximately 1%), which makes it very difficult to determine whether scheduled cesarean benefit might provide benefit above and beyond the dramatic reduction caused by combination maternal antiretroviral therapy.[,,,] Thus, for HIV-infected women receiving combination antiretroviral therapy and have an HIV RNA level of 1,000 copies/ml or less, cesarean section is not routinely recommended. If the HIV-infected mother has an HIV RNA level of 1,000 copies/ml or less and a cesarean section is needed for a standard obstetrical indiction, the cesarean should be scheduled for week 39 gestation. 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.
Use of Intravenous Zidovudine in Women Undergoing Cesarean Section
Accordingly, the perinatal guidelines recommend that all women undergoing elective cesarean section (because of an HIV RNA level greater than 1,000 copies/ml) should receive intravenous zidovudine prior to the cesarean section procedure. The infusion of the intravenous zidovudine should start 3 hours prior to cesarean delivery, with an initial 1-hour loading dose (2 mg/kg), followed by a continuous 2 hour infusion (1 mg/kg/hour) prior to delivery. The rationale for administering zidovudine for 3 hours is based on a pharmacokinetic study that found a ratio of cord blood to maternal zidovudine levels nearly doubled (1.0 versus 0.55) if intravenous zidovudine was given to the mother for 3 to 6 hours before delivery versus less than 3 hours. If the cesarean section is not elective, it may not be possible to start the infusion 3 hours prior to the procedure; in this setting, some experts would recommend infusing the loading dose over 1 hour and then proceeding with delivery.
Timing of Planned Cesarean Section
For women scheduled to undergo cesarean section, the American College of Obstetrics and Gynecology (ACOG) and the HHS perinatal guidelines recommend that it takes 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 by ACOG for persons not infected with HIV, because of the substantially higher risk of entering labor or rupturing membranes that occurs 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. Overall, when considering the pros and cons of scheduling the cesarean section at week 38, the benefit of reducing HIV transmission to the infant outweighs the risk of immature fetal lung development.
Scheduled Cesarean Section and Woman Presents in Labor or With Ruptured Membranes
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. Available data from women not on antiretroviral therapy suggest that HIV transmission risk increases by about 2% with every hour post membrane rupture. Thus, the decision regarding cesaran should take into account the duration of labor or rupture of membranes. 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. 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. 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.[,,] 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, several studies have suggested that HIV-infected women who undergo cesarean section have higher complication rates than women who deliver vaginally.[,] Post-delivery complications most frequently consist of hemorrhage, postpartum fever, cesarean wound infection, endometritis, urinary tract infection, and sepsis.[,,,,] Among HIV-infected women who deliver via cesarean, those with CD4 counts less than 200 cells/mm3 have a higher rate of complications. Post-cesarean infections have consistently been the most common complication. Based on these findings, the perinatal guidelines recommend giving antimicrobial prophylaxis to all HIV-infected infected women undergoing cesarean section.
The National Perinatal HIV Hotline
In some circumstances, optimal management of HIV-infected pregnant women and their infants in an attempt to prevent HIV transmission may benefit from expert consultation. The National Perinatal HIV Hotline (888-448-8765) is a federally funded service providing free clinical consultation for medical providers caring for HIV-infected pregnant women and their infants. The perinatal hotline can also assist with referral to local or regional pediatric HIV specialists.