Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from Prevalence of antenatal in South Asia: a and meta-analysis Rahini Mahendran,1 Shuby Puthussery,‍ ‍ 2 Mahendran Amalan3

5 ►► Additional material is Abstract carried over into adulthood. While untreated ante- published online only. To view Objective To estimate the prevalence of antenatal natal depression itself is a significant contributor to please visit the journal online depression in South Asia and to examine variations the development of depression during the postnatal (http://dx.​ ​doi.org/​ ​10.1136/​ ​ 6 jech-2018-​ ​211819). by country and study characteristics to inform policy, period, women who suffer antenatal depression practice and future research. are at an increased risk of developing other psycho- 1 Smile Train Project, Faculty Methods We conducted a comprehensive search of logical problems such as bipolar, anxiety and panic of Dental Sciences, University 13 databases including international databases and disorders.7 Despite its significant adverse impact of Peradeniya, Peradeniya, Sri Lanka databases covering scientific literature from South Asian on the health and well-being of women, babies, 2Maternal and Child Health countries in addition to Google Scholar and grey sources families and the society at large, the issue remains Research Centre, University of from 1 January 2007 to 31 May 2018. Studies reporting unrecognised in many countries and regions of the Bedfordshire, Luton, UK 3 prevalence estimates of antenatal depression using world partly due to the lack of reliable prevalence Department of Statistics and 2 8 Computer Science, Faculty a validated diagnostic/screening tool were identified, estimates. of Science, University of screened, selected and appraised. Primary outcome was Prevalence of perinatal mental disorders in Peradeniya, Peradeniya, Sri proportion (%) of pregnant women identified as having low-income and lower-middle-income countries Lanka antenatal depression. tends to be higher compared with their prevalence Results Thirty-three studies involving 13 087 pregnant in high-income countries,9 and wide variations Correspondence to women were included in the meta-analysis. Twelve have been reported between countries in some Dr Shuby Puthussery, 10 Maternal and Child Health studies were rated as high quality and 21 studies were of regions. South Asia is the most densely populated Research Centre, University moderate quality. Overall pooled prevalence of antenatal region in the world with a high rate. The of Bedfordshire, Luton, depression was 24.3 % (95% Confidence Interval (CI) region accounts for the second highest maternal Bedfordshire, UK; ​shuby.​ 19.03 to 30.47). Studies showed a high degree of mortality rate globally.11 Countries in South Asia— copyright. puthussery@beds.​ ​ac.uk​ heterogeneity (I2=97.66%) and evidence of publication Afghanistan, Bangladesh, Bhutan, India, Maldives, RM and SP contributed equally. bias (p=0.668). Prevalence rates for India (17.74%, Nepal, Pakistan and Sri Lanka—are predominantly 95% CI 11.19 to 26.96) and Sri Lanka (12.95%, 95% CI economically underprivileged. Despite a number of Received 26 October 2018 8.29 to 19.68) were lower compared with the overall initiatives to improve maternal health,12 maternal Revised 10 February 2019 prevalence, whereas prevalence rates for Pakistan mental health remains largely overlooked in the Accepted 28 March 2019 13 Published Online First (32.2%, 95% CI 23.11 to 42.87) and Nepal (50%, region. 22 April 2019 95% CI 35.64 to 64.36) were higher. Existing prevalence studies on antenatal depres- Conclusions While robust prevalence studies are sion in South Asian countries have reported great sparse in most South Asian countries, available data variation in prevalence, with rates ranging from suggest one in four pregnant women is likely to 16.2% in India14 to 9.5% in the neighbouring Sri experience antenatal depression in the region. Findings Lanka.15 In Pakistan, the reported prevalence rates http://jech.bmj.com/ highlight the need for recognition of the issue in health varied from 18%16 to 25% between rural and policy and practice and for resource allocation for urban areas.17 While individual studies provide capacity building at regional and national levels for some insights about the likely magnitude of the prevention, diagnosis and treatment. problem in the countries of the region, the issue remains largely unrecognised in the region as a whole, and individual studies do not provide suffi- cient evidence on their own to warrant appropriate on September 29, 2021 by guest. Protected Introduction action. A previous review that has attempted a Depression in pregnancy, known as antenatal descriptive synthesis of the evidence on prevalence, depression, is characterised by symptoms of depres- associated factors and cultural aspects of perinatal sion—a persistent depressed mood, loss of interest, depression in some of the Asian countries reported low energy and appetite, feelings of guilt or low that the prevalence of antenatal depression ranged self-worth, and disturbed sleep or concentration.1 from 8.7% in Hong Kong to 45.5% in Iran.10 This Antenatal depression carries significant adverse review included studies from two countries in South implications for the health and well-being of women, Asia, India and Pakistan, and has reported descrip- © Author(s) (or their 2–7 employer(s)) 2019. No babies and their families. Women with antenatal tive prevalence estimates on antenatal depression. commercial re-use. See rights depression are more likely to develop a number The review, however, found only two studies from and permissions. Published of complications during pregnancy including an South Asia (India and Pakistan) and was limited in by BMJ. increased risk of nausea, vomiting, miscarriage, scope and methodological approaches in terms of 2–4 To cite: Mahendran R, preterm birth and poor fetal growth. Babies of search strategy, quality appraisal and synthesis. Puthussery S, Amalan M. J mothers who were depressed in pregnancy are at Our systematic review and meta-analysis aimed Epidemiol Community Health higher risk of low birth weight and poor cognitive to derive a pooled estimate of the prevalence of 2019;73:768–777. development in infancy and childhood that may get antenatal depression in South Asia and to examine

768 Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from variations by individual country and study characteristics to inform policy, practice and future research. Box 1 Criteria for assessment of study quality

Sampling (maximum score=3) Methods 1. Was the target population defined clearly by shared Search strategy and selection criteria characteristics such as age, sex, language, ethnicity, income The review followed the Preferred Reporting Items for System- and residency? 18 atic Reviews and Meta-Analyses (PRISMA) guidelines. We 2. Was probability sampling including sampling frame used to conducted a comprehensive search of the following 13 databases: identify potential respondents? PubMed, Science Direct, Scopus, Web of Science, PsycINFO, 3. Were the characteristics of respondents match the target CINAHL, Global Health, Bangladesh Journals Online, Indian population and was the response rate higher than 80%? Citation Index, Index Medicus for South-East Asia Region, Measurement (maximum score=3) LILACS, Nepal Journals Online and PakMediNet for articles 1. Was the data collection method standardised, including published between 1 January 2007 and 31 May 2018. Additional identical methods of assessment with all the respondents, sources searched included Google Scholar, authors’ institutional interviewer training and supervision? libraries, conference proceedings, and the reference list of identi- 2. Were the study instruments reliable? fied articles and reports. Key journals from the region such as the 3. Were the study instruments valid? Asia Pacific Journal of Public Health, World Health Organization Analysis (maximum score=2) South-East Asia Journal of Public Health and Journal of South 1. Were special features such as design effect of the sampling Asian Development were hand searched for potentially relevant design accounted for in the analysis? articles. 2. Was the study included CIs for statistical estimates or the South Asian countries were classified according to the World information needed to calculate them? Bank classification and included Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka.19 A combination of text words and MeSH terms were used to setting and duration; methodological characteristics—sample conduct the searches as follows: (prevalen* OR occurren* OR size and response rate, sampling method and data collection inciden* OR frequen* OR rate*) AND (antenatal* OR prenatal method; and outcome measures particularly prevalence esti- OR perinatal OR antepartum OR maternal OR pregnan*) AND mates of antenatal depression. Two reviewers (RM, SP) under- (depress* OR mood disorder*) AND (South Asia* OR Afghan* took the data extraction, with RM taking the lead in extracting OR Bangladesh* OR Bhutan* OR India* OR Maldiv* OR data from the articles and SP cross-checking for accuracy. Nepal* OR Pakistan* OR Sri Lanka*). copyright. Studies were included if they have reported quantitative prev- Statistical analysis alence estimates of antenatal depression using a validated diag- Meta-analysis was conducted to estimate the pooled preva- nostic/screening tool in any of the South Asian countries between lence and forest plot was generated using prevalence data for 1 January 2007 and 31 May 2018. Studies conducted in specific South Asia as a whole and for individual countries with 95% groups such as pregnant women living with HIV or any chronic CI. Heterogeneity was assessed across studies using I2 statis- diseases were excluded. The screening was conducted in two tics; I2 greater than 50% indicated substantial heterogeneity.22 stages. The first stage involved screening the titles and abstracts We used a random-effects model to combine prevalence data for relevance followed by the retrieval of the full texts of all of individual studies, assuming that variance exists between ‘included’ and ‘may be included’ articles. In stage 2, a compre- individual studies.23 Subgroup analysis was conducted to assess hensive assessment of the full-text articles was undertaken. the sources of heterogeneity, using univariate comparisons and http://jech.bmj.com/ meta-regression. First, we tested individual associations between Quality appraisal and data extraction the pooled estimate and the following covariates: individual The selected studies were critically appraised for methodological countries, study settings, screening instruments, study quality, 2 quality using a modified version of ‘Guidelines for evaluating sampling strategies and risk of bias. Significant covariates (R not prevalence studies’20 which consists of eight items (box 1). The equal to zero) were entered into a multivariate meta-regression quality assessment was done on three main domains: sampling, model. Publication bias was assessed using funnel plot in which measurement and analysis. These three domains were further log-transformed prevalence rates were plotted against Standard on September 29, 2021 by guest. Protected divided into subcategories, and for each category, one point was Error and Egger test. The ‘meta’ package (versions 3.2-0, 4.7-1) given if the answer was ‘yes’ and zero points for the answer ‘no’. and ‘metafor’ package (versions 1.5-0, 2.0-0) in R statistical Two authors (RM, SP) rated the methodological quality of each software and R Studio as Integrated Development Environment 24 of the reviewed studies, calculating a total score for each study were used for the meta-analysis. ranging from 0 to 8. Studies that achieved a score of 0–2 were Ethics approval was obtained from the Institute for Health regarded as of ‘low quality’, a score of 3–5 were regarded as of Research Ethics Committee at the University of Bedfordshire. ‘moderate quality’ and a score of 6–8 were regarded as ‘high A review protocol was developed and published (PROSPERO quality’. Alongside quality appraisal, each study was assessed 2017 CRD42017078795). for the risk of bias using a modified risk of bias tool for preva- lence studies21 and was rated as high or low risk of bias for each Public and patient involvement component in the tool. No patients or public were involved in formulating the research To extract data, a sample data extraction form from the Centre question, defining the outcome, analysis and interpretation, for Reviews and Dissemination, University of York (https://www.​ or writing up of results. No data were directly collected from york.​ac.​uk/media/​ ​crd/​Systematic_​Reviews.​pdf) was adapted and patients during the course of the study. Where possible, results of employed. The following data were extracted: study character- the study will be disseminated to the public and patient commu- istics—authors, year of publication, aims and objectives, design, nity by the authors.

Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 769 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from copyright. Figure 1 Flow diagram of the study selection process.

Results six studies27 32 49 51 54 55 recruited pregnant women from the Characteristics of included studies community and one study52 recruited women from both commu- The initial search process produced 2644 titles and 2196 records nity and health facility. Edinburgh Postnatal Depression Scale were retrieved after removing duplicates (figure 1). After the (EPDS) was the most frequently used screening tool reported exclusion of 2140 articles due to discordance with the inclu- in 17 studies.26 27 29 30 32 34 35 37 40 42 43 47–49 51 53 54 Other tools sion criteria, 56 articles were identified for full-text screening of included Beck Depression Inventory (BDI),41 Hospital Anxiety which full texts of six articles were inaccessible. One additional Depression Scale (HADS),28 38 44 45 56 the Aga Khan University full-text article was retrieved following reference list searches. Anxiety Depression Scale (AKUADS),46 55 Kessler Psychological http://jech.bmj.com/ Fifty-one full-text articles underwent stage 2 screening and Distress Scale (K-10),25 39 the Montogomery and Asberg Depres- 33 were selected25–57 after further exclusions of 18 due to the sion Rating Scale (MADRS),36 Hamilton Depression Scale following reasons: antenatal depression prevalence not reported (HAM-D),50 57 Centre for Epidemiological Studies—Depression (n=8); comparison studies (n=3); duplicate publication from a (CES-D) Scale,52 Patient Health Questionnaire (PHQ-9)33 and single study (n=3); inadequate information to measure preva- Depression Anxiety Stress Scale (DASS-42).31 There were vari- lence of antenatal depression (n=2); standardised diagnostic or ations in the threshold scores for identifying antenatal depres- screening instrument not used (n=1); situation analysis using sion both among the tools used and among the studies that used on September 29, 2021 by guest. Protected secondary data (n=1). the same tool. The cut-off score ranged from 9 to 13 for EPDS Majority of the studies were conducted in Pakistan (14), (table 1). followed by India (12). Fewer studies were conducted in Fourteen studies included pregnant women in all three trimes- Bangladesh (3), Sri Lanka (2), Maldives (1) and Nepal (1). ters, while 10 studies sampled pregnant women in their third There were no studies from Afghanistan and Bhutan. Majority trimester only. A few studies recruited pregnant women in either (25) of the studies were cross-sectional studies whereas seven first (n=1) or second (n=3) or first and second (n=1), or second 25 26 34 48 50 53 54 studies used a prospective cohort design to deter- and third (n=4) trimesters. Based on the quality appraisal scores mine the prevalence. (online supplementary table S1), nearly one-third of the included The participants included 13 087 pregnant women reported studies were rated as high quality, and the remaining 21 studies in 33 studies. The overall sample size in individual studies were moderate quality (table 1). ranged from 45 to 1400. Among the 13 studies that reported sampling methods, three used simple random sampling,32 41 49 one used stratified random sampling,51 and the remaining used Primary outcomes either cluster or convenient sampling techniques. Participants Among the 13 087 pregnant women included, 3172 were were recruited from a health facility such as a hospital or ante- identified as depressed with prevalence rates ranging from natal clinic in 26 studies.25 26 28–31 33–48 50 53 56 57 Among the rest, 6.1% in India47 to 75.1% in Pakistan.42 The pooled prevalence

770 Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from

Table 1 Summary of study characteristics Study instrument Number of and cut-off Pregnancy Total women with Study Country Study setting Study design score trimester participants depression Study quality Shakya et al, 200857 Nepal Health facility Cross-sectional HAM-D score All three 44 22 Moderate >7 Hamid et al, 200856 Pakistan Health facility Cross-sectional HADS All three 100 18 Moderate score not reported Karmaliani et al, 200955 Pakistan Community Prospective cohort AKUADS score Second 1369 246 High ≥13 Gausia et al, 200954 Bangladesh Community Prospective cohort EPDS Third 361 119 High score ≥10 Imran and Haider, 201053 Pakistan Health facility Prospective cohort EPDS Third 213 91 Moderate score >12 Zahidie et al, 201152 Pakistan Both – CES-D Second 375 229 Moderate score ≥16 Shah et al, 201151 Pakistan Community Cross-sectional EPDS All three 128 60 Moderate score ≥13 Sadaf et al, 201150 Pakistan Health facility Prospective cohort HAM-D All three 150 15 Moderate score not reported Nasreen et al, 201149 Bangladesh Community Cross-sectional EPDS Third 720 132 High score ≥10 Husain et al, 201148 Pakistan Health facility Cohort EPDS Third 1357 350 Moderate score ≥12 Dubey et al, 201147 India Health facility Cross-sectional EPDS Third 213 13 Moderate score ≥10 46 Mir et al, 2012 Pakistan Health facility Cross-sectional AKUADS Second and 328 111 High copyright. score >13 third Mina et al, 201245 India Health facility Cross-sectional HADS Third 59 10 Moderate score ≥11 Ali et al, 201244 Pakistan Health facility Cross-sectional HADS All three 167 28 Moderate score ≥8 Pai Keshava et al, 201343 India Health facility Cross-sectional EPDS All 3 253 93 Moderate score ≥13 Humayum et al, 201342 Pakistan Health facility Cross-sectional EPDS Third 506 380 Moderate score ≥10 41

Ajinkya et al, 2013 India Health facility Cross-sectional BDI All three 185 17 High http://jech.bmj.com/ score ≥17 Agampodi and Agampodi, Sri Lanka Health facility Cross-sectional EPDS Second and 376 61 High 201340 score >9 third Lukose et al, 201439 India Health facility Cross-sectional K-10 First 365 121 Moderate score ≥6 Waqas et al, 201538 Pakistan Health facility Cross-sectional HADS All three 500 159 Moderate score ≥11 on September 29, 2021 by guest. Protected Srinivasan et al, 201537 India Health facility Cross-sectional EPDS All three 100 65 Moderate score ≥13 Natasha et al, 201536 Bangladesh Health facility Cross-sectional MADRS score First and 748 137 Moderate ≥13 second Jaju et al, 201535 India Health facility Cross-sectional EPDS Third 368 36 High score ≥12 Saeed et al, 201634 Pakistan Health facility Prospective cohort EPDS Second 82 35 High score ≥9 Rao et al, 201633 India Health facility Cross-sectional PHQ-9 Second and 150 32 High retrospective score ≥5 third George et al, 201632 India Community Cross-sectional EPDS All three 202 33 High score >10 Din et al, 201631 Pakistan Health facility Cross-sectional DASS-42 score Third 230 67 Moderate ≥9

Continued

Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 771 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from

Table 1 Continued Study instrument Number of and cut-off Pregnancy Total women with Study Country Study setting Study design score trimester participants depression Study quality Bavle et al, 201630 India Health facility Cross-sectional EPDS All three 318 33 Moderate score ≥10 Shidhaye et al, 201729 India Health facility Cross-sectional EPDS All three 302 51 Moderate score >12 Rabia et al, 201728 Pakistan Health facility Cross-sectional HADS All three 520 120 Moderate score >8 Herath et al, 201727 Sri Lanka Community Cross-sectional EPDS Second and 1017 106 High score >9 third Raheem et al, 201826 Maldives Health facility Cohort EPDS Third 458 110 High score ≥13 Babu et al, 201825 India Health facility Cohort K-10 All three 823 72 Moderate score ≥20 AKUADS, Aga Khan University Anxiety Depression Scale; BDI, Beck Depression Inventory; CES-D, Centre for Epidemiological Studies—Depression Scale; DASS-42, Depression Anxiety Stress Scale; EPDS, Edinburgh Postnatal Depression Scale; HADS, Hospital Anxiety Depression Scale; HAM-D, Hamilton Depression Scale; K-10, Kessler Psychological Distress Scale; MADRS, Montogomery and Asberg Depression Rating Scale; PHQ-9, Patient Health Questionnaire. of antenatal depression was 24.3% (95% CI 19.03 to 30.47; 95% CI 23.11 to 42.87) and Nepal (50%, 95% CI 35.64 to figure 2). Higgins I2=97.66% showed the presence of substan- 64.36) were higher (table 2; figure 3). tial heterogeneity between individual studies. There was no significant difference in pooled prevalence The pooled prevalence for individual countries, except between studies conducted in health facilities (23.75%) and Maldives (24.02%, 95% CI 20.32 to 28.14) and Bangladesh community settings (21.8%) (table 2). The pooled preva- (22.52%, 95% CI 14.86 to 32.6), showed substantial variations lence was higher, but not significantly, for studies using EPDS compared with the overall pooled prevalence. Compared with (25.74%) as the screening instrument compared with studies the overall pooled prevalence, the estimates for India (17.74%, that have used HADS (21.82%), AKUADS (24.98%), HAM-D copyright. 95% CI 11.19 to 26.96) and Sri Lanka (12.95%, 95% CI 8.29 (24.93%) and other instruments (22.86%) such as K-10, CES-D- to 19.68) were lower whereas the estimates for Pakistan (32.2%, 20, PHQ-9, BDI, MADRS and DASS-42 (table 2). http://jech.bmj.com/ on September 29, 2021 by guest. Protected

Figure 2 Pooled prevalence of antenatal depression in South Asia.

772 Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from

bias lowered the prevalence estimates to 14.79% (95% CI 7.79 Table 2 Subgroup analysis of the prevalence of antenatal depression to 26.29) and 19.16% (95% CI 13.85 to 25.91), respectively in South Asia (table 2). Pooled A high degree of heterogeneity (I2=97.66%) was seen in Study Number of Number of prevalence included studies. Initial univariate regression analysis (online characteristic women studies (%) 95% CI supplementary table S2) guided the selection of covariates for All 13 087 33 24.3 19.03 to 30.47 inclusion in the meta-regression model. The final meta-regres- Country sion model quantified the impact of country, study quality, risk Bangladesh 1829 3 22.52 14.86 to 32.6 of bias in sampling, and the reliability and validity of the study India 3338 12 17.74 11.19 to 26.96 instruments on prevalence of antenatal depression. The attrib- 2 Maldives 458 1 24.02 20.32 to 28.14 utable variance to these covariates was 10.8% (R =10.8%, Nepal 44 1 50 35.64 to 64.36 p<0.125) (online supplementary table S2). The analysis showed country and risk of bias in sampling method as statistically signif- Pakistan 6025 14 32.2 23.11 to 42.87 icant sources of heterogeneity on prevalence estimates while Sri Lanka 1393 2 12.95 8.29 to 19.68 study quality and risk of bias in reliability and validity of study Setting instruments were not statistically significant. Both the funnel Health facility 8915 26 23.75 17.91 to 30.69 plot (figure 4) and Egger test (p=0.668) showed evidence of Community 3797 6 21.8 13.54 to 33.16 publication bias. Both 375 1 61.07 56.03 to 65.87 Screening instrument Discussion EPDS 6974 17 25.74 17.44 to 36.27 To our knowledge, this is the first systematic review and HADS 1346 5 21.82 16.5 to 28.28 meta-analysis that has quantitatively synthesised the prevalence AKUADS 1697 2 24.98 12.67 to 43.33 of antenatal depression in South Asia and for individual coun- HAM-D 194 2 24.93 3.71 to 74.09 tries in the region from estimates derived using a comprehen- Other 2876 7 22.86 12.59 to 37.86 sive search. We found an overall pooled prevalence of 24.3% instruments (95% CI 19.03 to 30.47), with the rates ranging from 6.1% Study quality to 75.1% in individual studies. The overall prevalence found in our meta-analysis was higher compared with existing global Moderate 7471 21 27.42 19.62 to 36.89 estimates as well as estimates from low-income and middle-in- copyright. High 5616 12 19.47 14.52 to 25.59 come countries for perinatal mental disorders in general.1 8 58 Sampling strategy For example, globally approximately 10% of pregnant women Simple 1107 3 14.66 9.89 to 21.2 were estimated to suffer from depression,1 with prevalence rates random of 15.6% in low-income and lower-middle-income countries.8 A sampling recent meta-analysis has reported a 19.2% prevalence of ante- Stratified 128 1 46.88 38.41 to 55.53 natal depression in low-income and middle-income countries.58 random The higher prevalence found in our meta-analysis may reflect sampling a high prevalence of risk factors within the pregnant popula- Cluster 1393 2 12.95 8.29 to 19.68 tion of the region as a whole. The South Asia region includes sampling both low-income and middle-income countries, and the rampant Convenient 2014 7 34.91 24.81 to 46.57 poverty in the region coupled with factors such as food inse- http://jech.bmj.com/ sampling curity, inadequate housing, low socioeconomic status, high cost Not reported 8445 20 23.28 16.5 to 31.77 of living, financial stress, breakdown of traditional family struc- Risk of bias in sampling tures and increased out-of-pocket expenditure on healthcare Low 2121 6 14.79 7.79 to 26.29 could all be risk factors in this respect.59 We found variations High 10 966 27 26.87 20.89 to 33.83 in pooled prevalence rates when study quality was taken into Risk of bias in reliability and validity of instruments consideration. Two-thirds of the included primary studies were on September 29, 2021 by guest. Protected Low 5015 11 19.16 13.85 to 25.91 of moderate methodological quality with a high risk of selec- tion and measurement bias. We also found substantial hetero- High 8072 22 27.18 19.76 to 36.12 geneity among the included studies that could be attributed to AKUADS, Aga Khan University Anxiety Depression Scale; EPDS, Edinburgh Postnatal the variations in methodological approaches including sample Depression Scale; HADS, Hospital Anxiety Depression Scale; HAM-D, Hamilton Depression size, sampling approach, study setting and the characteristics of Scale. pregnant women such as age, socioeconomic status and level of education, pregnancy trimester and previous history of psychi- The pooled prevalence from high-quality studies was lower atric illnesses, although the information was not reported in (19.47% (95% CI 14.52 to 25.59), 12 studies, n=5616) some studies.60 compared with moderate-quality studies (27.42% (95% CI With respect to individual countries, India and Sri Lanka had 19.62 to 36.89), 21 studies, n=7471). None of the included lower rates compared with the overall prevalence for the region studies used nationally representative samples. Of the 13 studies whereas the rates for Pakistan and Nepal were higher. The vari- that have reported sampling strategies, pooled prevalence was ation in rates with respect to individual countries appeared to lower for studies that used simple random sampling (14.66%) correspond with their progress in terms of overall maternal and cluster sampling (12.95%) compared with studies that used health indicators.61 We found very little difference in the pooled convenient sampling (34.91%) and stratified random sampling prevalence rates between studies conducted in health facilities (46.88%) techniques. Exclusion of studies with higher risk of and community settings. The pooled prevalence was higher, but

Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 773 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from copyright. http://jech.bmj.com/

Figure 3 Prevalence of antenatal depression by country in South Asia.

not significantly, for studies that used EPDS as the screening precision for identifying true cases of depression among women on September 29, 2021 by guest. Protected instrument compared with studies that have used other instru- compared with the original English version.64 ments and with the overall pooled prevalence rate. However, Although robust prevalence studies are sparse, our review the estimated pooled prevalence from studies conducted in Sri indicated relatively high prevalence rates of antenatal depres- Lanka with EPDS as study instrument with low cut-off scores of sion which would imply that antenatal depression is of common 9 was significantly lower compared with the overall pooled prev- occurrence among pregnant women in South Asia. The rigorous alence. There were wide variations in prevalence rates in indi- methodological approach followed in our study focused on a vidual studies from India that used the EPDS tool ranging from well-defined research question with a comprehensive search 9.78% to 65% with an overall pooled prevalence of 17.74%. strategy involving a wide range of international and regional The variations could be attributed to different cut-off scores databases and other grey literature sources, clear inclusion and used across studies. While it is evident that various screening exclusion criteria, and structured data extraction and quality tools for antenatal depression produce broader rates overall,62 it assessment using standardised techniques make our findings has been argued the tool’s sensitivity improves when used with robust and reliable. The methodological precision was enhanced lower cut-off scores.63 Although EPDS is one of the most widely by the use of PRISMA guidelines.18 used screening tools for assessing symptoms of depression, most The review has certain limitations, however. More than of the local language versions of the EPDS from non–English- three-fourth of the included studies were confined to two speaking low-income and middle-income countries had lower countries, India and Pakistan. A few studies were conducted in

774 Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from copyright.

Figure 4 Funnel plot of publication bias. other countries with the exception of Afghanistan and Bhutan by some studies. The findings from this review have important where we could not identify any eligible studies for inclu- implications for a range of stakeholders such as planners, poli- sion. This points to an important evidence gap, but the lack cy-makers, academics and researchers in medical and public http://jech.bmj.com/ of evidence from some counties may limit the generalisability health both at regional and individual country levels towards of the findings to the region as a whole. Many of the included developing appropriate preventive, diagnostic and treatment studies were of moderate methodological quality with high interventions for antenatal depression and calls for increased risk of bias, although we were able to carry out subgroup investment to improve maternal mental health in South Asian 23 analysis to assess how the risk of bias influenced the results. countries. There was also significant heterogeneity across the studies, and Our review shows that there is a dearth of robust nation- this should be taken into consideration while interpreting the on September 29, 2021 by guest. Protected ally representative data in many of the countries of the pooled estimates to draw overall conclusions.22 61 Although no region to inform concerted action to tackle the issue, espe- language restriction was applied in our search, all the eligible cially in Afghanistan, Bangladesh, Bhutan, Maldives, Nepal studies were published in English which might imply inadver- and Sri Lanka where studies are extremely sparse. Future tent exclusion of relevant papers published in other languages. This is likely to be minimum as English is the official language research should employ scientifically rigorous methodolog- in the region. ical approaches to boost our ability both to derive accurate country level prevalence estimates and to make comparisons Conclusion across countries in the region as well as with other regions Our meta-analysis concludes that antenatal depression can be and countries internationally. There is also a need for more argued to be a significantly prevalent issue in South Asia based in-depth understanding of the associated cultural, social and on available data, likely to be experienced by one in four preg- environmental factors of antenatal depression. Qualitative nant women. However, determining an overall, synthesised studies can be of great value in this respect. Evidence about accurate prevalence rate of antenatal depression in this region any existing interventions to deal with the issue in the country based on existing evidence presents a challenge due to the lack appears to be very limited. Progress on both of these fronts of evidence from some countries and the wide-ranging and, in will boost the development of local, national and regional many cases, problematic methodological approaches adopted policies and practice guidelines.

Mahendran R, et al. J Epidemiol Community Health 2019;73:768–777. doi:10.1136/jech-2018-211819 775 Review J Epidemiol Community Health: first published as 10.1136/jech-2018-211819 on 22 April 2019. Downloaded from

11 El-Saharty S, Ohno N, Sarker I, et al. Knowledge Brief—South Asia: maternal and What is already known on this subject reproductive health at glance, 2014. Available: http://documents​ .worldbank.​ org/​ ​ curated/en/​ ​970501468219011275/pdf/​ ​935520BR​ ​I0Box30p​ ​ro0Healt​ ​h0Sept02014.​ ​ pdf [Accessed 19 Sep 2017]. ► ► Individual studies have reported great variations in 12 Akseer N, Kamali M, Arifeen SE, et al. Progress in maternal and child health: how has prevalence of antenatal depression both within and across South Asia fared?. BMJ 2017;2017:357–1608. countries in South Asia. 13 Baron EC, Hanlon C, Mall S, et al. Maternal mental health in primary care in five low- ►► Previous descriptive reviews have provided limited and middle-income countries: a situational analysis. BMC Health Serv Res 2016;16. prevalence estimates of antenatal depression in South Asia. 14 Chandran M, Tharyan P, Muliyil J, et al. Post-partum depression in a cohort of women from a rural area of Tamil Nadu, India. Br J Psychiatry 2002;181:499–504. 15 Kulathilaka S, Hanwella R, de Silva VA. Depressive disorder and grief following spontaneous abortion. BMC Psychiatry 2016;16. 16 Asad N, Karmaliani R, Sullaiman N, et al. Prevalence of suicidal thoughts What this study adds and attempts among pregnant Pakistani women. Acta Obstet Gynecol Scand 2010;89:1545–51. 17 Husain N, Munshi T, Jafri F, et al. Antenatal depression is not associated with low-birth ► Our study is the first meta-analysis that synthesised the ► weight: a study from urban Pakistan. Front Psychiatry 2014;5. prevalence rates of antenatal depression in South Asia and 18 Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews examined variations by country and study characteristics. and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. ►► The findings highlight the need for robust nationally 19 World Bank. One South Asia—South Asia regional integration, 2017. Available: http:// representative prevalence studies, especially in Afghanistan, www.worldbank.​ ​org/en/​ ​programs/south-​ ​asia-regional-​ ​integration [Accessed 14 Sep 2017]. Bangladesh, Bhutan, Maldives, Nepal and Sri Lanka, where 20 Boyle MH. Guidelines for evaluating prevalence studies. Evid Based Ment Health studies are extremely sparse. 1998;1:37–9. ►► The study concludes that antenatal depression can be argued 21 Hoy D, Brooks P, Woolf A, et al. Assessing risk of bias in prevalence studies: to be a significantly prevalent issue in South Asia based modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol on available data, likely to be experienced by one in four 2012;65:934–9. 22 Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med pregnant women. 2002;21:1539–58. 23 Bennett HA, Einarson A, Taddio A, et al. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol 2004;103:698–709. Acknowledgements The first author (RM) was supported by a fellowship from the 24 Schwarzer G. meta: An R package for meta-analysis. R News 2007;7:40–5. Commonwealth Commission UK and the University of Bedfordshire. 25 Babu GR, Murthy GVS, Singh N, et al. Sociodemographic and medical risk factors associated with antepartum depression. Front Public Health 2018;6. Contributors RM and SP designed the study and SP oversaw its implementation. 26 Raheem RA, Chin HJ, Binns CW. Factors associated with maternal depression in the RM did the searches, study selection, and RM and SP did the data extraction and Maldives: a prospective cohort study. Asia Pac J Public Health 2018:1–8. quality appraisal. MA developed and conducted the meta-analyses and developed 27 Herath INS, Balasuriya A, Sivayogan S. Physical and psychological morbidities among copyright. the tables. RM and SP wrote the manuscript. All authors reviewed and approved the selected antenatal females in Kegalle district of Sri Lanka: a cross sectional study. J final draft of the manuscript before submission. Obstet Gynaecol 2017;37:849–54. Funding The authors have not declared a specific grant for this research from any 28 Rabia S, Nusrat U, Qazi S, et al. Frequency and risk profiles associated with antenatal funding agency in the public, commercial or not-for-profit sectors. anxiety and depression in middle socioeconomic women. Annals Abbasi Shaheed Hospital and Karachi Medical and Dental College 2017;22:88–96. Competing interests None declared. 29 Shidhaye P, Shidhaye R, Phalke V. Association of gender disadvantage factors and Patient consent for publication Not required. gender preference with antenatal depression in women: a cross-sectional study from rural Maharashtra. Soc Psychiatry Psychiatr Epidemiol 2017;52:737–48. 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