Summary:To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0–31.3). Prenatal CD4*lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+level was <20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46–7.44;p= 0.004). Among mothers who developed premature rupture of membranes, those with a low CD4+level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78–10.5;p= 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48–2.70;p= 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61–2.74;p= 0.50), indicating that these factors modified the effect of CD4+level on transmission. Among all mothers without regard to CD4+level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07–4.69;p= 0.03). These findings suggest that it may be possible to decrease the risk of vertical transmission of HIV-1 among women with low CD4+levels by discontinuation of smoking during pregnancy and other interventions that reduce the risk of premature rupture of membranes.