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Aims: To develop a strategy for neonatal screening of sickle cell disease (SCD) and effective enrolment of affected neonates in a comprehensive follow-up programme adapted to the socioeconomic conditions, health structures and cultural background of an African setting. Methods: The strategy implemented at the two largest maternity services of Cotonou, the economic capital of the Republic of Benin, involves a team of specifically trained midwives, first to identify pregnant women at risk, and second to provide active and repeated information and sensitisation to these women to encourage voluntary demand for newborn screening and enrolment in the follow-up programme. Results: Among the consecutive pregnant women studied (about 3000), 79.5% of the informed women at risk for fetal SCD asked for testing of their offspring, 85.2% of the newborns who tested positive were enrolled in the programme, and more than 80% were still being followed up after 5 years. The under-five mortality rate in this series was 15.5 per 10000, a figure that is 10 times lower than the general rate recorded in the Republic of Benin. Conclusions: The results demonstrate that this specifically tailored strategy is relevant to this setting, given the unique conditions of this African country. [ABSTRACT FROM AUTHOR]