Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe. The European Collaborative Study

C. Thorne, M.-L. Newell, A. Bailey, C.S. Peckham, C. Giaquinto, E. Ruga, A. De Rossi, D. Truscia, I. Grosch-Worner, A. Schafer, J. Mok, F. Johnstone, F. Omenaca, J. Jiminez, C.De Alba, M.C. Garcia-Rodriguez, I. Bates, I. De Jose, F. Hawkins, R. Martinez Zapico, F. Asensi-Botet, M.C. Otero, D. Perez-Tamarit, A. Gonzalez Molina, H. Canosa, H. Scherpbier, K. Boer, A.B. Bohlin, S. Lindgren, E. Belfrage, J. Levy, A. Alimenti, P. Barlow, A. Ferrazin, A. Dre Maria, C. Gotta, V. Maritati, A. Mur, M.T. Rovira, A. Paya, O. Coll, C. Fortuny, J. Boguna, M. Casellas Caro, Y. Canet, G. Pardi, A.E. Semprini, M. Ravizza, C. Castagna, S. Fiore, B. Guerra, S. Bianchi, L. Bovicelli, E. Prati, S. Zanelli, M. Duse, A. Soresina, G. Scaravelli, M. Stegagno, M. De Santis, M.-L. Muggiasca, P. Marchisio, A. Iasci, A. Spinillo, A. Bucceri, E. Grossi, L. Rancilio, R. Smith, A.-M. Lewi

Is zidovudine therapy in pregnant HIV-infected women associated with gestational age and birthweight?

Objective: Prophylactic zidovudine during pregnancy and labour reduces maternal viral load and, with neonatal therapy, has been shown to reduce vertical transmission. However, zidovudine may have additional effects. Advanced HIV disease is associated with premature delivery, which in turn results in increased vertical transmission. Data from the European Collaborative Study (ECS) were analysed to investigate whether zidovudine could be associated with decreased prematurity risk and/or with a reduced frequency of low birthweight. Methods: HIV-infected pregnant women enrolled in the ECS were followed prospectively according to a standard protocol. Gestational age was assessed by ultrasound, prematurity was defined as delivery before 37 weeks and the cut-off for low birthweight was 2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on the risk of premature or low birthweight delivery. Results: In 2299 mothers, zidovudine taken to reduce the risk of vertical transmission decreased the odds of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53-1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39-0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR values. A multivariate analysis suggested that prophylactic zidovudine and prematurity were independently associated with risk of transmission. Conclusion: Our findings suggest an additional health benefit of zidovudine. Even ii most vertical transmission occurs around the time of delivery, therapy earlier in pregnancy could have an indirect effect on transmission rates through delaying delivery. This hypothesis needs to be confirmed or refuted by more appropriate studies

Duration of ruptured membranes and vertical transmission of HIV-1: A meta-analysis from 15 prospective cohort studies

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV. Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis. Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded. Results: The primary analysis included 4721 deliveries with duration of ruptured membranes ≤ 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01). Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. © 2001 Lippincott Williams & Wilkins