Prevalence of khat chewing during pregnancy in Ethiopia: a systematic review and meta-analysis

Abstract


Background
Khat (Catha edulis) also known as qat, chat, African salad, Abyssinian tea, and African tea, is a owering green plant containing a natural amphetamine like stimulant called amphetamine (1)(2)(3). Khat chewing practice is rapidly increasing worldwide and currently an estimated of 20 million people chew khat (4,5).
In East Africa, 18-90% of male and 10-60% females chew khat on a daily basis (6)(7)(8)(9). In Ethiopia, chewing of khat is becoming habitual and increasing at an alarming rate with an estimated prevalence ranged from 30% to50% (10)(11)(12)(13). According to 2016 Ethiopia Demographic and Health Survey (EDHS), around 27% of men and 12% of women had history of khat chewing (14) with up to 65% during pregnancy (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Khat chewing has different socio-economic, psycho-social, physical and environmental impact (1,5,12,13,32). Inaddition to these adverse effect, the practice of chewing khat go beyond the life of the pregnant women and affect the neonate (15-18, 33, 34) by reduced daily food intake, anaemia, low birth weight and to the extent of maternal and infant death (15-18, 33, 34) (19,20,(35)(36)(37). Factors such as: peer pressure, accessibility, acceptability, and cultural beliefs of relief for headache, weight loss and assistance during birth were associated with khat chewing during pregnancy (15,(17)(18)(19)(20). However, Ethiopian government had an initiative to control the adverse effect of substance use for cigarette smoking, but there is no similar action for khat use. However individual studies is is important and showed the existence of khat use among pregnant mothers, the inconsistence of reported epidemiological nding need a comprehensive up to date information for all concerned bodies and the focus of most of the available studies were among the general population and college students. To the authors' knowledge, there is no systematic review and meta-analysis that address this gap. Thus, the main purpose of this systematic review and meta-analysis was to determine the pooled prevalence of khat chewing during pregnant and synthesize its associated factors in Ethiopia.

Search strategy
Databases such as: PubMed/Medline, CINAHL, AJOL and SCOPUS were searched using the search terms: (khat OR Catha edulis OR khat use OR khat consumptions OR khat chewing OR khat abuse OR khat dependence OR khat use disorder OR substance OR substance use OR psychoactive substance OR substance use disorder OR substance abuse) AND (prevalence OR incidence) OR magnitude) AND (factors OR risk factor OR risk OR determinant) AND (maternal OR mother OR primigravida OR wom*n OR pregnant OR prenatal) AND Ethiopia for PubMed/MEDLINE. A Google scholar search was also performed.
We formulated a comprehensive search strategy by the combination of Medical Subject Headings (MeSH) thesaurus, text words, and appropriate Boolean Operators tailored to each database. No time and language restrictions were imposed on the search strategy. Reference lists of all articles were searched. Moreover, Google Scholar was searched for gray literature. All searches were performed until August-14-2019. Similarly, CINAHL, AJOL and SCOPUS were searched. using similar search terms tailored to each database. We adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) (38).

Selection of studies
All studies retrieved through search strategy were imported to EndNote X7 (Thomson Reuters, New York, USA) then, duplicated studies were removed from EndNote Library. The title and abstracts of the remaining articles were assessed independently by two reviewers (BBB and YDG). Disagreements were resolved by taking the mean score of the two reviewers.

De nition of concepts
In this study, khat use during pregnancy is de ned as use of khat (any amount) at least once.

Eligibility Criteria
Setting: This review included studies carried out in Ethiopia.
Participants: This review included the results of khat use and its associated factors that assessed during pregnancy.
Outcome measure: This systematic review and meta-analysis have two main outcomes. The rst outcome was to determine the pooled prevalence of khat use during pregnancy. The second outcome of the study was to identify factors associated with khat use. Prevalence was calculated by dividing the number of khat chewer during pregnancy to the total number of pregnant women included in the study (total sample size) multiplied by 100. For the associated factors, the reported odds ratio, 95% con dence interval and p-value were used to tabulate and described the results thematically.
Study design: Observational studies (cross-sectional and cohort/longitudinal) were included. Studies that focused on case reports, conference and abstracts were excluded if the required data are not accessed.

Data extraction
Data were extracted from the eligible studies using a pre-conceived and piloted data abstraction form.
Data were simultaneously extracted by two independent reviewers (BBB and YDG). The extracted data include: name of the rst author last name, year of publication, study area/region, study design, sample size, number of cases/prevalence and associated factors.

Quality assessment
The Newcastle-Ottawa quality assessment tool, adapted for cross-sectional studies (39) was used for quality assessment. This tool had three main parts (selection, comparability and outcome). The rst part (selection) has ve stars and assesses the methodological quality of the study. The second part of the tool evaluates the comparability of the study. The third part of the tool assesses the quality of the original article's outcome with respect to the statistical analysis. Individual paper was graded with score ranged from zero to ten stars. The overall quality of each article was determined using the sum of each star of the three parts and de ned as high quality for score ≥ 6 out of 10, medium (ful lling 50% of quality assessment criteria) and poor for < 4.

Data synthesis and statistical analysis
The extracted data were entered into a Microsoft Excel Database and then imported into STATA version 14 (Stata Corp LLC, Texas, USA) software with packages of Meta-analysis for analysis. Meta-analysis was performed with STATA 14 using the "Metaprop" command with random-effects models to calculate the pooled effect size at 95% con dence intervals (40) with the Dersimonian and Laird method based transformed values and their variance (41). The Freeman-Tuckey variant of the arcsine square root transformation of proportions was tted to avoid variance instability when handling proportions close to one (42). Heterogeneity between studies was measured by the index of heterogeneity (I 2 statistics) test (43). I 2 statistics values of 25%, 50% and 75% was used as low, medium and high heterogeneity respectively. Sub-group analysis was performed by years of publication, study setting, study design, sample size and quality of included studies. Publication bias was examined by the visual inspection of funnel plot (44) and egger test (45) with p-value of < 0.05 was considered as statistically signi cant.
Sensitivity analyses was conducted to examine in uential studies (46). However, we planned for metaanalysis of associated factors, because of the inconsistent and insu cient of data; results were analyzed thematically and presented using texts and table.

Results
The initial database literature search resulted in 954 published articles. Additional, 13 studies were located through other source. Finally, the overall literature search resulted in 967 articles. Of these articles, 678 were excluded during the initial assessments as their title and abstract were found to be irrelevant. Of the remaining 289 studies, 186 articles were excluded through abstract reading because of different outcome and unclear results. Finally, 81 papers were excluded because of different eligibility. Then, the remained 22 studies were included in the systematic review and meta-analysis (Fig. 1).

Study characteristics
In this study, a total of 9,915 study participants were included from 22 studies. These studies were carried out between 1997 to 2019 years in four different regions: Addis Ababa (n = 6), Amhara (n = 3), Oromia (10), and Southern Nation and Nationalities of People (SNNP) (n = 3). Majority (73%) of the included studies are institution based cross-sectional study design. All studies presented data on self-report. The sample size of study participants ranged from 112 to 1065. The qualities of included studies were between 5 and 8. Of these, majority 60% had an overall good quality and the remaining studies had fair quality (Table: 1).

Prevalence of khat chewing
The pooled prevalence of khat chewing was found to be 20% (95% CI; 14%-27%) (Fig. 2). Tests of heterogeneity demonstrated evidence of heterogeneity (I 2 = 98.46%, p < 0.001). The analysis of sensitivity tests showed that none of the point estimates was outside of the overall 95% con dence interval con rming that: (i) there was no in uential study and (ii) based on these 22 studies the pooled estimated prevalence of khat chewing was important. We did not nd evidence of publication bias from the visual inspection of the funnel plot (Fig. 3) and Egger's test (P < 0.02)].

Psycho-social
Those pregnant women who had family history of mental illness were six times (OR = 6.33, p < 0.001) more likely engaged in khat chewing. Moreover, those pregnant women who had history of khat chewing were around two times (AOR, 1.65;95%CI, 1.10, 2.47) more likely experienced CMDs (17). Those pregnant women who had history of khat chewing were around two times (AOR, 1.65;95%CI, 1.10, 2.47) more likely experienced CMDs (47).

Discussion
The main purpose of this systematic review and meta-analysis was to assess the pooled prevalence of khat chewing and its associated factors during pregnancy in Ethiopia. The present study indicated that one in ve of pregnant women had history of khat use. This implies despite the international recommendation of pregnant women's abstinence to any substance (50), in Ethiopia, there is limitation in the implementations of internationally accepted measures for safe motherhood and infants. This may be attributed to the lack of knowledge toward the adverse effect of substance on the health mother and the fetus. In Ethiopia, there is a perception of khat use as medicine for headache, socialization, stress reduction and easy delivery that may be the reason for khat use (15)(16)(17)(18)(19)(20). Even though similar studies are scarce, the results of this nding is within the reported prevalence of khat chewing in Yeme (40.7-47%) (51,52). Previous meta-analysis showed that the association of khat chewing on birth weight (53), perinatal and young infant death, intrauterine growth retardation, low foetal birth weight (54), sleep disturbance and memory problems of pregnant women (20).
In the current systematic review and meta-analysis, however; the study level characteristics by subgroup analysis such: sample size, study design, study quality, publication year and study setting showed statistical signi cance; this implies the presence of other characteristics for the contribution of heterogeneity; the overall highest and lowest pooled prevalence of khat chewing was reported from study with small sample size [33% (95% CI: 15%-55%)].. This may be due to the research methodology, sociocultural norms and the availability of khat in the study area. For example, "Jimma" is the name of place in Ethiopia, Oromia region, as the same time, it is the common name for khat (place where its name is originated). This is consistent with other studies (15)(16)(17)(18)(19)(20) and supported by EDHS 2011 (10,11).
Regarding the associated factors limited number of studies identi ed socio-demographic, pregnancy related psychological and behavioural related factors of associated factors (19,20,35). From this limited studies, we observed the scarcity of studies about factors associated with khat chewing that suggests the needs of future researchers to address this gap because identi cation of health determinant factors are important public health issues to design appropriate interventions.
Strengths and limitations of the study To our knowledge, this is the rst systematic review and meta-analysis about khat chewing among pregnant women in Ethiopia. To manage heterogeneity, bias and make the ndings more meaningful, four different methods were performed. First; during analysis, we used appropriate model (a random effect model) to control the effects of the observed heterogeneity. Secondly; we conducted a leave one out sensitivity analysis to identify in uential study. Third; we conducted subgroup analysis by sample size, study design, study quality, publication year and study setting. Finally, funnel and egger test was performed to identify small study effect. However, some limitations such as: use of reference lists and Google Scholar may have the possibility of having some overlooked articles and lack of similar study limited the discussion.

Conclusion
In Ethiopia, one in ve pregnant women has experience of khat chewing. Factors such as: being Muslim, lower educational status, family history of mental illness, and pregnant women and partner previous history of khat chewing were associated with khat chewing. Thus, authors' suggest the need of pregnant women screening for khat chewing as an integrated part of ANC. Authors' also suggest the needs of strengthening awareness about the adverse effect of khat chewing.  Forest plot presenting prevalence of khat chewing