Epidemiology of orofacial clefts in Africa: Methodological challenges in ascertainment.

Epidemiology of Orofacial clefts in Africa: Methodological challenges in ascertainment

Dr A. Butali ¹, Professor P.A Mossey ^2&

¹PhD candidate and ²Professor of Craniofacial abnormalities, Department of Dental Public health and Health Psychology, Dundee Dental Hospital and School, Park Place, Dundee., Scotland U.K, DD1 4HR., (WHO collaboration centres for craniofacial abnormalities)

^&Corresponding author

Dundee Dental Hospital and School, Park Place, Dundee, Scotland. U.K, DD1 4HR, Tel: 0044(0)1382425761, Fax: 0044 (0)138220632

Orofacial clefts (OFC), comprising cleft lip with or without palate (CLP) and cleft palate (CP) are amongst the most common birth defects of the head and neck. Although, the overall prevalence varies between 1/600-1/700, this rate varies based on geographic and ethnic distribution [1].

Africa, the second largest continent in the world, has a population of 967 million people as of mid-2008 with about 400 million (42 percent) below age 15. With an annual growth rate of about 2.4 percent (2.8 in middle Africa and 0.8 in Southern Africa), the continent is projected to reach 1.9 billion people by 2050 [2].

Reports of birth prevalence of orofacial clefts from different African populations vary widely, from as low as 0.3/1,000 reported in Nigeria [3] to 1.65/1,000 reported in Kenya [4]. Determining the exact prevalence of orofacial clefts in Africa is important for public health reasons as the prevalence rates will help identify cluster areas and possible etiological factors, which will in turn help governments plan strategies for preventive measures and treatment.

The aim of this study is to retrospectively evaluate the evidence available on the birth prevalence of orofacial cleft in Africa and implications for future research. The specific objective is to carry out a systematic review of the birth prevalence of cleft lip with or without cleft palate (CLP) and cleft palate (CP) in Africa, based on available published data

Data Sources

A systematic literature search was conducted using electronic databases Ovid MEDLINE (1966 to 2007), CINAHL {1982-March 2007}, Cochrane Database. Using the Cochrane search strategy, studies were found by using the following keywords: “cleft palate,” “prevalence,” “incidence,” “cleft lip,” and “Africa.” In addition, a combination of the following terms was also used: “incidence and cleft lip,” “incidence and cleft palate,” “cleft lip and Africa,” “cleft palate and Africa,” and “incidence of cleft lip and palate and Africa”

To identify eligible papers, we searched through the references of papers that mention orofacial clefts in Africa and read published articles on the topic (full text and abstracts), in English, Afrikkans, and Somali languages (translation was carried out using the language translation tool on the internet). 

The study selection

All identified published prospective and retrospective studies of birth prevalence of orofacial clefts in Africa were considered for inclusion in the review. The studies included reports on prevalence of orofacial clefts; prevalence of congenital birth defects including orofacial clefts; those that presented adequate information on the methodology of study; and studies on orofacial cleft cases that presented for treatment with a defined sample population.

We excluded the following: studies limited to clinical features and clefts pattern without a mention of the prevalence rate, reports on the aetiology, social impact or un-operated and adult clefts without a mention of prevalence rates of orofacial clefts; and studies that did not include data from which the prevalence rates can be calculated.

Data extraction

The following were extracted from the studies: dates and location of studies, source of data, birth number / total number of patient seen and number of cleft patients, birth outcomes (live births, still births, and patients for treatment), sex ratio and types of cases, cases with associated malformations.

In many of the studies, the birth prevalence rate, sex ratio and cleft types, and clefts with associated anomalies were published in readily accessible format. In some studies outcomes were published in the form of percentages. In these cases, we calculated the prevalence rates.

The sex ratio, cleft types and those associated with anomalies were presented using the number of cleft cases. All the studies stated criteria for diagnosis of orofacial clefts, clefts types, and associated anomalies.

The data obtained did not meet the requirements for a meta-analysis and thus we carried out a systematic literature review.

The search combination in the databases produced 131 hits in Ovid Medline (1966 to March 2007) (http://ovidsp.tx.ovid.com/spa/ovidweb.cgi); 33 hits in Pub Med (http://www.ncbi.nlm.nih.gov/pubmed), 3 hits in Scopus (http://www.scopus.com/scopus/home.url); Web-Google search gave 388 hits and no hits in CINAHL {1982-March 2007}.

Web – Google is a non-scientific search tool. It looks for a combination of two or more of the entered terms and even when these are not in context, they appear as hits. This explains the large number of hits using the above combination. Most of the hits were not relevant to the search criteria.

Further search through the computer databases (Ovid Medline, Pub Med, and Scopus), produced a combination of 33 hits which refer to orofacial clefts in Africa.

A thorough evaluation of these papers using the inclusion and exclusion criteria led to the exclusion of 27 papers leaving 7 papers that met the inclusion criteria.

The hand search produced 5 additional papers and a total of 11 papers (all published in peer-reviewed journals) were thus available for review.

Outcomes were OFC in infants, specifically cleft lip with or without cleft palate (CLP) and cleft palate only (CP). Isolated clefts without any congenital defects and orofacial clefts with associated anomalies were included in three of the studies (Kromberg and Jenkins, 1982; Krouf et al., 1986; and Sulieman et al., 2005) (Table 1).

For most of the studies, the birth prevalence rate was expressed by dividing the number of cleft cases born (numerator) by the population at risk (denominator) multiplied by 1,000 during a specified time period. The population at risk in most of the studies were live born infants in the hospitals and cases that presented for treatment within the study period. Two of the studies included still-births (Kromberg and Jenkins, 1982; Khrouf et al., 1986) in the population at risk and included still- born infants with clefts among the reported cases (Table 1).

Overall there were 58 CL/P, 55 CL and 37 CP reported from all the studies (isolated clefts and clefts associated with anomalies). From seven studies combined, 21 males and 20 females had CL, 10 males and 22 females had CP and 23 males and 27 females had CL/P. There were three cases with CL/P, two with CP and two with CL from the three studies that reported clefts with associated anomalies (Table 1)

Prevalence

The reviewed studies on the birth prevalence of orofacial clefts in Africa suggest that the prevalence is low compared to Europe, America, and Asia. However, compared to population-based studies, these studies are small and hospital-based (Table 1), carry a high tendency for under ascertainment of cases, and are more liable to bias. Ascertainment may be difficult in countries where a high proportion of births may occur in areas remote from structured healthcare systems, meaning that records may be incomplete. This factor may have contributed to lower estimates from some countries. Although hospital-based estimates give an indication of rate, they are subject to biases making them not directly comparable with those where complete ascertainment is achieved.

In some studies, less than 30% of births take place in a hospital [5] and in most cases a large proportion of births occur at home [6]. In severe cases of congenital abnormalities such as hydrocephalus where obstetrical problems may arise, there is likely to be bias towards these cases and numbers may appear higher than is the true incidence. To address these problems, a prospective study is required, based on a captive population where every birth (within and outside the hospital) is recorded by observers who are specifically examining for these conditions [7].

It has been suggested that a high infant mortality rate, including unreported infanticide in children with lip or palatal clefts could account for the low incidence and birth prevalence rates [3, 8]. The extremely low incidence of consanguineous marriages among Nigerians has been reported as a possible reason for low prevalence rate of cleft lip and palate in Nigeria [3]. (In Nigeria, it is virtually impossible to marry a cousin no matter how far removed and as a consequence, the possibility of summation of any genetic trait is extremely remote.)

Some studies reported high rates for cleft lip and palate in Africa [4, 6, 9-11] compared to other studies that reported low rates [3, 12] (Table 2). Although some of the studies with reported high rates included live birth and / or still births in the base population, the observed population was small with only one source of ascertainment limiting the source of information (Table 2). The studies were hospital-based which not a true representation of the general population. The study from Tunisia had a mixture of North African and sub-Saharan African populations which may account for a high rate reported from the study [11].

The longer the period over which observation is made, the more confidence can be placed in the significance of change [1]. It is ideal to have a longitudinal study extending over 12 months to 5 years, however, difficult or impossible follow up are likely limitations in developing countries [4].

Studies from South Africa reported similar prevalence rates (0.3/1,000, 0.33/1,000) for the same geographical area [12-13]. In one study [12], data were obtained retrospectively from hospital records between 1976 and 1977. These data were from three different sources and details of still births, neonatal deaths, congenital defects, and multiple births were recorded. The other study [13] was prospective between 1983 and 1984; data were collected on all live cases and those that presented for treatment from hospitals and private practices in West Cape. Although the reported prevalence rates appear similar, the first study had better method of ascertainment and the reported prevalence was more reliable.

The report of more CL in males and more CP in females from the African studies are consistent with the literature [14]. The overall report of CL/P being higher in males in the African studies is also consistent with the literature [14]. The wide range in the confidence intervals in most of the studies (Table 1) suggests that the precision is low, which may be as a result of poor ascertainment of cases.

Selection bias

The identification of subjects only in hospitals (Table 2) by all of the studies carried out on the epidemiology of orofacial clefts in Africa is a potential source of selection bias. Selection bias occurs when the subjects included are not likely to be representative of the source population as seen in the reviewed studies (Table 1). Another source of bias is the insufficient amount or quality of data reported by the authors. For example, studies by Simpkiss and Lowe, (1961) and Khan, (1965) did not provide data for cleft palate in the population. These are evidence of poor ascertainment. The selection bias and lack of homogeneity in the reviewed African studies meant a meta-analysis would be meaningless.

International comparisons

In the United States, the reported low prevalence rates for black Americans [15] are comparable to reported rates among Nigerians [3] and black South Africans [12]. Another study reported rates for whites in the United States [16] which are comparable to reported rates for white South Africans [13]. It is interesting to compare rates of other ethnic groups to those of Africans while recognising the limitations.

The difference in prevalence among whites and blacks in different geographical location points to the fact that there are different genetic components. Aetiology is thought to involve genetic predisposition to orofacial clefts coupled with environmental factors. The low prevalence figure of 0.41/1,000 reported in a hospital-based study in India [17] is similar to rates reported in hospital-based studies in Africa. Both places are developing and there is probably under ascertainment of orofacial cleft cases. Caution must however be taken when comparing rates of other continents to Africa because of the different types of ascertainment, sample sizes and method of analysis used in those studies.

Hospital based studies are known to be prone to bias and under ascertainment of cases is likely from the reported studies. For an improved ascertainment of cleft lip and palate cases in sub-Saharan Africa, there is a need to set up a birth defects surveillance system. This was a recommendation of the WHO [1] in 2003, and having identified the current unsatisfactory situation, we recommend beginning with a hospital-based birth defects surveillance system and then progressing to a regional population-based system. Future initiatives should then aim to include the entire population in geographically defined regions, country by country, ultimately aiming towards a national births and birth defects registry.

In the short term, cleft lip and palate might serve as a sentinel birth defect for the sake of epidemiology and a good birth defect to study, simultaneously establishing the infrastructure for inter-centre collaboration and the capacity for participating in research into prevention of clefts and improving quality of care

Additional research to determine birth prevalence and in due course incidence of orofacial clefts in Africa is needed. Reliable data on incidence is an essential pre-requisite for studies into aetiology and prevention.

None declared. This article was presented at the CLEFTSiS education meeting on the 17th of August 2006 at Perth Royal Infirmary in Perth Scotland U.K.

Professor P A Mossey initiated the project and designed the study; Dr A Butali carried out the systematic review and both authors contributed to the manuscript preparation.

Table 1: Study design, reported prevalence rates and sample sizes

Table 2: Epidemiology of orofacial clefts: Study characteristics

Figure 1: Flow diagram of literature search

We acknowledge the assistance of Professor D R Stirrups who was one of the independent assessors of eligible studies.

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