Article Text
Abstract
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.
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Sickle cell disease (SCD) related mortality is at its highest in the first years of life, and one out of four deaths occurs during the first complication.1–5 Thus, neonatal screening and early enrolment in comprehensive medical care programmes, prior to the onset of the first symptoms, are now recognised as the most reliable approach to decreasing SCD-related mortality and morbidity rates.6–9However, strategies developed in industrialised countries for newborn screening,10 11 either systematic or targeted to populations at risk, may not always be effective in developing countries of sub-Saharan Africa. Indeed, most often, the concept of genetic diseases and preventive medicine in the population is not rational and this seriously impairs enrolment and compliance with systematic follow-up programmes. To overcome these drawbacks, we have developed a strategy based upon active information and sensitisation of pregnant women and voluntary enrolment in the programme. This pilot programme was initiated more than 10 years ago in the two largest maternity services of Cotonou, the economic capital of the Republic of Benin (West Africa). The results presented below demonstrate that this specifically tailored strategy is relevant to our setting given the unique cultural, socioeconomic and basic health structure conditions of our country.
METHODS
Our pilot programme was initiated in May 1993. It was conducted at the Gynaecology and Obstetric Clinic of the National Teaching Hospital (3500 deliveries per year) and at the major public Maternity Service of Cotonou (3000 deliveries per year). Prior to this date, there was no structured health programme for SCD in Benin.
The strategy involved 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 of affected neonates in the comprehensive clinical care and follow-up programme. Information was given either in French or in a local language appropriate to the woman.
Women attending the National Teaching Hospital are routinely tested for their haemoglobin (Hb) status by classical methods11 and, after thorough provision of information, we offered Hb testing to the women attending the private maternity service at the low cost of US$3 (ie, one-tenth of the actual cost of alkaline acetate electrophoresis). Initial funding that made this possible was through CAMPUS and EU grants; present funding is through March of Dimes grants. Women considered at risk because they were carriers for HbS or HbC were all identified before 28 weeks of gestation. Testing of their partner was suggested.
As stated above, pregnant women at risk were thereafter the target of repeated sensitisation and information on SCD at every visit to the clinic throughout the rest of their pregnancy and neonatal testing of the offspring was performed within the first 8 weeks of life when the woman voluntarily asked for it. Neonate Hb testing was done by thin-layer agarose isoelectric focusing (Pharmacia LKB Biotechnology, Uppsala, Sweden) on dried blood collected on Guthrie paper after heel puncture.11 Suspected Hb SS, SC and CC phenotypes were confirmed using citrate agar electrophoresis (compound heterozygosity for either S or C and β0 is very unlikely in Benin and was generally excluded by studies of both parents). Mothers were provided with the results before the offspring reached the age of 3 months. Infants with SCD (mainly SS and SC genotypes) and with CC phenotype were enrolled into the comprehensive follow-up programme when their mothers volunteered.
Affected infants were evaluated at monthly intervals for the first 12 months of life and then every 3 months. Basic management was as described previously12 and mostly consisted of anti-pneumococcal and anti-malarial prophylaxis, supplementation with folic and ascorbic acids, and specific immunisations (hepatitis B and Hemophilus influenzae B vaccines as soon as possible, and anti-pneumococcal and anti-Salmonella typhi vaccines at 18 months) in addition to the six vaccines of the World Health Organization programme. During these medical visits, parental education was continued, emphasising the importance of keeping clinic appointments and regular follow-up. Since most of the parents had health insurance (provided at their own expense or by an employer), medical visits were free up to the age of 2 years and thereafter the cost was limited to a token payment (ie, one-tenth of the actual cost). For those without health insurance, generally those on the lowest incomes, the charge was the same token payment.
The study was approved by the ethical committee of the Faculty of Health Sciences.
RESULTS
Even though our programme is still ongoing, in order to evaluate its long-term effects on the affected children we will report results collected on women enrolled over a period of 3 years from May 1993 to April 1996.
Among the women attending the private maternity service, about one-third requested Hb testing after receiving proper information. Almost 35% of those were at risk of giving birth to an affected child: 32.6% because they were S or C heterozygotes, or were homozygous for C, and 2.1% because they themselves had SCD (SS or SC) (table 1). Only 12.5% of the partners of these women accepted testing.
Table 2 shows the overall outcome of our specifically designed strategy for newborn screening for SCD and enrolment in the comprehensive clinical care and follow-up programme. Among the women known to be at risk enrolled in the information and sensitisation programme in the two maternity services, 79.5% asked for the testing of their offspring. In addition, because the mean duration of stay at the maternity hospital in Cotonou is short, and because sampling could not be done during weekends in the initial stages of our programme, only 75% of the sampling was done while the mother and baby were still in hospital; 25% of the newborns tested were brought back to the clinic by their mother for sampling. An additional proof of the women’s motivation was that 81.6% of them spontaneously came back to request the result of the test. Over the 3 years, 140 neonates with SS, SC or CC phenotypes were identified. Among them, two SS infants died before the age of 2 months (one from acute diarrhoea and dehydration, the second one from fetal cytomegalovirus infection) and three mothers left Benin with their infant; thus, 135 infants remained eligible for enrolment in the clinical care and follow-up programme; 85.2% of the mothers of eligible infants volunteered to enrol them into the programme.
Since the initiation of the project, the programme has continued and to date, 85% of the children enrolled during the initial 3 years are still regularly visiting the clinic. It is not within the scope of this paper to report in detail the clinical results of the follow-up programme, but in brief we have now more than 840 patient-years of follow-up and our initial analysis indicates a mortality rate of 15.5 per 1000 in our series of SCD children. Amazingly, this rate is amazingly 10 times lower than the overall under-five mortality rate in the Republic of Benin; the overall rate is 160 per 1000 in the first 5 years of life.
DISCUSSION
There are very few published studies concerning newborn screening for SCD in sub-Saharan Africa.13 14 The published studies have addressed epidemiological issues and none have addressed the crucial issue of the efficiency of newborn screening programmes in leading to the early enrolment of affected children in comprehensive follow-up programmes. In sub-Saharan African countries, the state of the basic health structure, the absence of dedicated SCD clinics, and the lack of medical education are major obstacles to enrolment and regular follow-up of infants with SCD. Except for the recently introduced general immunisation programmes, preventive medicine is a concept unknown to the general population. In addition, the attitude of the majority of the population in Benin toward SCD is not rational. It is regarded as a shameful condition, meaning inevitable death, often attributed to witchcraft, thus leading desperate mothers to seek miraculous cures and the help of “Marabou”.
This is why we based our approach on repeated information and sensitisation of pregnant women and on the promotion of volunteer action at each step of the process. Our results show that two out of three informed pregnant women at risk were motivated to get their offspring screened. Four out of five eligible infants were enrolled in the clinical care programme and more than four out of five enrolled children were not lost to follow-up after a follow-up length exceeding 5 years. These figures demonstrate that parental understanding, voluntary participation, and informed consent are instrumental to the success of any project intended to reduce SCD burden in Africa.
A first report on the effect of our comprehensive clinical care programme on the disease course in severely affected SS children has been published.12 It provides evidence that such programmes, now sustained by our newborn screening programme, may significantly decrease SCD-related morbidity and mortality rates, as already shown in industrialised countries, and this despite the scanty healthcare facilities. The overall strategy did not require significant increase in healthcare expenditures and could therefore be implemented in communities with limited resources in which SCD incidence is high.
Acknowledgments
We are indebted to our dedicated team of midwifes Chantal Deguenon, Roselyn Adjou, and Stephanie Goussanou for their active participation to the sensitisation and repeated information on SCD given to pregnant women. We express our gratitude to Drs Jacques Elion and Rolande Ducrocq of the French National Neonatal SCD Screening programme and to Dr Rajagopal Krishnamoorthy at Inserm U763, Mother and Child Robert Debré University Hospital, Paris, France, for the training of a laboratory technician from Benin to allow the transfer of IEF technology to Cotonou, for their help in the preparation of this manuscript, and for their continuous support exemplifying a longstanding and equitable North–South partnership.
REFERENCES
Footnotes
Funding: The study was supported by grants from the CAMPUS Program of the French Ministry for Cooperation (grant nos 92 341 06 and 98 341 202), the European Union (grant no. TS3-CT93 0244) and the March of Dimes Birth Defects Foundation (grant nos 6-FY99-623 and 6-FY03-056).
Competing interests: None declared.