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We present early life mortality rates in a largely rural population with high antenatal HIV prevalence, and investigate temporal and spatial associations with a prevention of mother-to-child transmission (PMTCT) programme, an HIV treatment programme, and maternal HIV.A retrospective cohort analysis.All births from January 2000 to January 2007 to women in the Africa Centre demographic surveillance were included. Under-two child mortality rates (U2MR) computed as deaths per 1000 live-births per year; factors associated with mortality risk assessed with Weibull regression. Availability of PMTCT (single-dose nevirapine; sdNVP) and antiretroviral therapy (ART) in a programme included in multivariable analysis.Eight hundred and forty-eight (6.2%) of 13 583 children under 2 years died. Deaths in under twos declined by 49% between 2001 and 2006, from 86.3 to 44.1 deaths per thousand live-births. Mortality was independently associated with birth season (adjusted hazard ratio 1.16, 95% confidence interval 1.02–1.33), maternal education (1.21, 1.02–1.43), maternal HIV (4.34, 3.11–6.04) and ART availability (0.46, 0.33–0.65). Children born at home (unlikely to have received sdNVP) had a 35% higher risk of dying than children born in a facility where sdNVP was available (1.35, 1.04–1.74). For 2005 births the availability of PMTCT and ART in public health programmes would have explained 8 and 31% of the decline in U2MR since 2000.These findings confirm the importance of maternal survival, and highlight the importance of the PMTCT and especially maternal HIV treatment with direct benefits of improved survival of their young children.