Research Initiative Treatment Action (RITA!); Vol 5, No. 1 January 1999
L. Joel Martinez

[As this issue of RITA! is being readied for press, The New England Journal of Medicine (NEJM)leased an article before its date of publication "because of its possible implications for the public health." The article concerns developments in the field of mother to child transmission (vertical transmission), a topic covered at some length in this issue. Since the NEJM article provides clearer and more precise clinical data that has important clinical implications, it, too, will be covered in this issue. Editor.]

In an article entitled "The Mode of Delivery and the Risk of Vertical Transmission of Human Immunodeficiency Virus Type 1—A Meta-Analysis of 15 Prospective Cohort Studies" (NEJM Online), the authors report on evidence showing that elective cesarean sections reduce the risk of transmission of HIV-1 from mother to child, independent of the effects of treatment with zidovudine (Retrovir). Despite prior contradictory reports, this study concludes that the likelihood of vertical transmission is decreased by 50% with elective cesarean section as compared to other modes of delivery. Further, when zidovudine was administered antepartum, intrapartum and postpartum as recommended by AIDS Clinical Trials Group (ACTG) Protocol 076 and an elective cesarean section was done, the risk of vertical transmission was reduced by 87%. That is to say, when zidovudine was given as outlined in PACTG 076 and the mother had an elective cesarean section the risk of transmission was reduced to an all time low of 2%.

These conclusions were reached through a meta-analysis of 15 eligible studies. Five of these were European studies and 10 were North American studies. After exclusions, 8,533 mother-child pairs were eligible for the analysis.

Scientists have speculated that vertical transmission may occur at birth through one of several mechanisms. Transmission may occur through the transfusion of the mother's blood to the fetus during labor contractions or after the rupture of membranes or when the fetus comes into direct contact with the infected secretions or blood from the maternal genital tract. An international collaborative effort was begun to analyze the data on individual patients in different studies to test the proposition that the method of delivery and risk of vertical transmission were directly associated.

Studies included in the meta-analysis included those where at least 100 mother-child pairs participated, where the mode of delivery and the children's infection status were known and where women were advised against breast-feeding, since breast-feeding can be an independent risk for vertical transmission.

Delivery was categorized into four different types. Elective cesarean section occurred when the procedure was performed before the rupture of membranes and the onset of labor. Non-elective cesarean section was a procedure performed after the rupture of membranes or the onset of labor or both. Instrumental vaginal delivery was a procedure in which forceps, vacuum suction, or both were used. Finally, non-instrumental vaginal delivery was a procedure in which neither forceps nor vacuum suction was used.

Elective cesarean section resulted in lower transmission rates than any other type of delivery. This reduction persisted even when the data were stratified according to the receipt or nonreceipt of antiretroviral therapy. When elective cesarean sections and non-elective cesarean sections were compared to all other modes of delivery, the pooled cesarean sections still had a lower incidence of transmission than all other modes of delivery although the reduction was not as great as when elective cesarean sections were separated out.

The authors point out the existence of an association between the time of rupture of membranes and delivery and the transmission of HIV. The longer the time interval between rupture and delivery, the greater the risk of transmission. It is for this reason that elective cesarean sections—those performed before the onset of labor and the rupture of membranes—produced the best results. The researchers reason that by performing a cesarean section before the onset of labor and the rupture of membranes microtransfusions of blood during labor and direct contact of the fetus with maternal genital tract secretions or blood during actual birth are avoided. Thus, the study suggests that the timing of the cesarean section may be critical. Mothers who have emergency cesarean sections or who have cesarean sections after the onset of labor and rupture of membranes do not have as low a transmission rate as those whose cesarean sections begin before labor and rupture of membranes.

The authors point out that the contribution of zidovudine prophylaxis and elective cesarean section appears to be independent of each other. Thus, there is a lower risk of transmission among women who have elective cesarean sections and receive zidovudine prophylaxis than among those who only chose to do one or the other.

As with any surgery there are possible complications with cesarean sections and the authors note that the risk of vertical transmission must be weighed against the dangers of a surgical delivery.

The role of combination therapy is still unknown. The authors pose the question of whether combination therapy will change the dynamics of vertical transmission and whether the association between mode of delivery and risk of vertical transmission will persist as women increasingly receive combination therapy (See News Briefs "Pregnancy and Combination Therapy" on p. 19 of this issue). The answers to these questions are still not known and will only be answered with experience.

Meta-analysis: an analysis of multiple studies where data are pooled and a common result is determined, despite the different goals or designs of the studies analyzed.

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Copyright © 1999 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org

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