Elsevier

The Lancet

Volume 353, Issue 9158, 27 March 1999, Pages 1035-1039
The Lancet

Articles
Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial

https://doi.org/10.1016/S0140-6736(98)08084-2Get rights and content

Summary

Background

Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.

Methods

Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.

Findings

We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1·8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10·5%) of 200 born to women assigned vaginal delivery (p<0·001). Seven (3·4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10·2%) of 167 born vaginally (p=0·009). There were few postpartum complications and no serious adverse events in either group.

Interpretation

Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother.

Introduction

Mother-to-child transmission of HIV-1 infection usually occurs around the time of delivery.1 Elective caesarean-section delivery, before rupture of membranes and labour, might therefore reduce the risk of vertical transmission by avoiding direct contact with maternal vaginal secretions and infected blood during the infant's passage through the birth canal, and reducing influx of maternal blood during uterine contractions.

In 1992, results from the European Collaborative Study suggested that infants of HIV-1 infected women delivered by elective caesarean section had a lower risk of HIV-1 infection than infants delivered vaginally, although the difference was not significant.2 Similar reductions in risk were reported from the Swiss perinatal study3 and the Italian Paediatric Register.4 A subsequent analysis of a larger dataset from the European Collaborative Study,5 with allowance for other risk factors such as prematurity and maternal clinical and immunological disease progression, showed that elective caesarean-section delivery significantly reduced the risk of vertical transmission by about 50%. On the other hand, no protective effect of elective caesarean section on vertical transmission of HIV-1 was shown in the French perinatal study,6 or in several US studies.7 However, few studies distinguished elective from emergency procedures, and analyses could not always take account of other factors known to be associated with increased transmission risk.

We therefore set up a randomised clinical trial to assess the relative risks and benefits of elective caesarean-section versus vaginal delivery in the overall population of randomised women and in subgroups of zidovudine use in pregnancy and viral load. Since caesarean-section delivery carries a potential risk of postoperative complications, particularly in HIV-1-infected women who may be immunocompromised,8 and when carried out as an emergency procedure,9 a secondary objective was to assess the extent of postdelivery complications in HIV-1-infected women. This trial was initiated in Italy in 1993, and extended to other European centres in 1995.

Section snippets

Patients

Women between 34 and 36 weeks of pregnancy with a confirmed diagnosis of HIV-1 infection were eligible for study. Those with an obstetric indication that necessitated caesarean-section delivery (such as central placenta praevia or fetal-pelvic disproportion) or with a contraindication to elective caesarean-section delivery for non-obstetric reasons (for example, women who had a contraindication to anaesthetics, or those who came from countries where caesarean delivery is not an option and who

Study design

Women assigned to the elective caesarean-section group were scheduled for surgery at 38 weeks of pregnancy. If signs of obstetric disorders were detected before this time, routine clinical procedures were followed and the respective clinicians decided whether to induce delivery before the 38th week of pregnancy and the appropriate mode of delivery. If a woman who had been assigned elective caesarean section went into labour before 38 weeks of gestation. Caesarean section was undertaken if

Statistical analysis

In the original Italian trial planned in 1993, the required sample size was estimated to be about 450 women. This estimate was based on the rate of vertical transmission of HIV-1 in Italy at that time (15%) and an estimated 50% reduction associated with caesarean-section delivery.12 Similarly, the international trial aimed to show a 50% decrease in vertical transmission associated with caesarean-section delivery, but with the publication of the results of the US/French trial of zidovudine in

Results

Between 1993 and March, 1998, 436 women were randomised (figure). 15 women withdrew from the trial before delivery, and for 13 women delivery information is not yet available. 408 women delivered 410 liveborn infants (this number includes two sets of twins). 28 children were lost to follow-up, and 12 infants are currently too young to have their infection status determined. Thus, 370 infants were included in this preliminary analysis. The two groups were similar in terms of the proportions of

Discussion

The results of this randomised trial confirm the results from European prospective studies14, 15, 17 that an elective caesarean-section delivery decreases the risk of vertical transmission of HIV infection by more than half compared with vaginal delivery. The data presented are based on information from more than 80% of all women randomised. Therefore, although caution is indicated when results are interim the findings can be considered closer to a definitive analysis, than a preliminary one.

References (20)

  • TF Nielsen et al.

    Postoperative caesarean section morbidity: a prospective study

    Am J Obstet Gynecol

    (1983)
  • MJ Mayaux et al.

    Acceptability and impact of zidovudine prevention on mother-to-child HIV 1 transmission in France

    J Pediatr

    (1997)
  • ML Newell

    Mechanisms and timing of mother-to-child transmission of HIV-1

    AIDS

    (1998)
  • Risk factors for mother-to-child transmission of HIV-1

    Lancet

    (1992)
  • C Kind et al.

    Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study

    Eur J Pediatr

    (1992)
  • C Gabiano et al.

    Mother-to-child transmission of human immunodeficiency virus: I, risk of infection and correlates of transmission

    Pediatrics

    (1992)
  • Caesarean section and risk of vertical transmission of HIV-1 infection

    Lancet

    (1994)
  • L Mandelbrot et al.

    Obstetric factors and mother-to-child transmission of human immunodeficiency virus type I: the French perinatal cohort

    Am J Obstet Gynecol

    (1996)
  • DT Dunn et al.

    Perinatal AIDS Collaborative Transmission Studies. Mode of delivery and vertical transmission of HIV-1: a review of prospective studies

    J Acquir Immune Defic Syndr Hum Retrovirol

    (1994)
  • AE Semprini et al.

    The incidence of complication after caesarean section in 156 HIV-positive women

    AIDS

    (1995)
There are more references available in the full text version of this article.

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