Reduction of the Risk of Vertically Transmitted HIV by Cesarean Section

Abstract & commentary

Synopsis: Elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.

Source: The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1: A meta-analysis of 15 prospective cohort studies. N Engl J Med 1999;340:977-987.

Data from 15 prospective cohort studies in-volving HIV-infected mothers were subjected to meta-analysis. A uniform definition of "elective" cesarean section was used (i.e., one that was performed before the onset of labor or rupture of the membranes). The data were adjusted for receipt of retroviral therapy, maternal stage of disease, and birth weight. The likelihood of vertical transmission of HIV-1 was reduced approximately 50% with elective cesarean section as compared to other modes of delivery (vaginal, nonelective cesarean section). The likelihood was reduced by approximately 87% with elective cesarean section and receipt of retroviral therapy during the prenatal, intrapartum, and neonatal periods as compared to other modes of delivery and the absence of therapy. Among mother-child pairs receiving appropriate antiretroviral therapy, the rates of vertical transmission were 2.0% among 196 mothers who underwent elective cesarean section and 7.3% among the 1255 mothers with other modes of delivery.

Comment by Warren Andiman, MD, FAAP

It has been known for at least several decades that some viral pathogens pass most frequently from mother to infant, not in utero, but at the time of delivery. These microorganisms share particular characteristics: they are found in blood in very high titer or they are shed in large numbers in the female genital tract. Hence, as the baby passes through the birth canal, virus particles enter the infant’s body by way of the mucous membranes of the mouth, nose, or conjunctiva or through small tears in the skin. In addition, blood may be "transfused" from mother to baby during labor contractions. Obstetricians and pediatricians have learned that vertical transmission of herpes simplex virus can be interrupted, in most cases, if women actively shedding virus deliver by cesarean section within four hours of rupture of the membranes. Mother-to-child transmission of hepatitis B can be controlled if babies born to surface antigen-positive mothers receive hepatitis B hyperimmune globulin at birth, followed by serial vaccinations with bioengineered recombinant hepatitis B surface antigen. HIV shares a number of biologic characteristics with both herpes simplex and hepatitis B. Thus, it is not surprising that cesarean section has been entertained as one among several methods that might be used to avert mother-to-child transmission of the virus.

The report by the International Perinatal HIV Group, a consortium of five European and 10 North American prospective cohort study groups, pooled individual patient data on 8533 mother-child pairs and showed that elective cesarean section significantly reduced the risk of vertical transmission of HIV, independent of the already proven benefits of treatment of mother and infant with zidovudine. The two major advantages of this study over previous attempts to show a salutary effect of cesarean section were the large sample size and the application of uniform definitions that clarified the differences between elective and nonelective cesarean section.

The findings of this study are likely to affect obstetrical practice in the United States, at least for the time being. By combining antiretroviral therapy of mother and child with elective cesarean section, the risk of vertical transmission of HIV can be reduced approximately nine- to tenfold, to 2%, a long sought-after goal. Nevertheless, the durability of the study’s results may be limited. The study failed to take into account a number of critical co-variates, either because they were not collected uniformly by all participants or because the study ended before current pharmacologic interventions could be adequately evaluated. For example, data on viral load were not included in the analysis, and it is not inconceivable that viral load may greatly influence the risk of vertical transmission. Furthermore, most mother-child pairs included in the analysis by the International Perinatal HIV group received monotherapy or dual antiretroviral therapy. It will be critical to learn if receipt of highly active poly-antiretroviral therapy by childbearing women, a practice that has become commonplace only in the past two years, reduces vertical transmission more dramatically than previous regimens. Such a finding may eliminate or significantly abrogate the need for cesarean section.

In the meantime, women’s health care providers must use the data now available to weigh the risks of surgical morbidity against the benefits of cesarean section. Unfortunately, the benefits of cesarean section may not apply to countries in the undeveloped world, the site of the great majority of incident cases of perinatal HIV infection. In such settings, gestational age cannot be assessed accurately; hence, an increased frequency of preterm births could be expected following elective cesarean section. Also, the hazards associated with surgical procedures of any kind may outweigh the benefits. Alternative solutions, both medical and surgical, to the high prevalence of pediatric AIDS in less-developed countries remain elusive. (Dr. Andiman is Professor of Pediatrics and Director of the Pediatric HIV/AIDS Program at the Yale-New Haven Children’s Hospital and the Yale University School of Medicine.)