Paul Swamidhas Sudhakar Russell,Swetha Madhuri Chikkala,Richa Earnest,Shonima Aynipully Viswanathan,Sushila Russell,Priya Mary Mammen,Child and Adolescent Psychiatry Unit,Department of Psychiatry,Christian Medical College,Vellore 632 002,India

Abstract

Key words:Clinical-utility;Diagnostic-accuracy;Edinburgh Postnatal Depression Scale;Meta-analysis;India;Validation

INTRODUCTION

India is a low-middle income country with a birth rate of 20/1000 population,and the summary prevalence of Post-natal Depression (PND) was 22% in the country in 2017[1-3].There is compelling evidence that PND is associated with morbidity and mortality in the mother-infant dyad[4,5].Therefore,scaling-up identification and early,effective management of the identified mother-infant dyad is very much needed in India.

The Edinburgh Postnatal Depression Scale (EPDS) is an accurate screening measure[6,7]and improves the follow-up care of PND and maternal mental health[8].In India,it is the most commonly used screening measure for PND.A recent metaanalysis demonstrates that 29 of the 38 prevalence studies on PND have used EPDS in India[3].This measure has been translated and validated in the eight regional languages of India:Assamese,Bengali,Gujarati,Kannada,Konkani,Marathi,Punjabi and Tamil,and has been validated in both clinical and community settings in India against a variety of reference standards.The total EPDS threshold score for diagnosing PND has ranged from 6/7 to 12.5/13.Reflecting the possible effect of the varying prevalence of PND,the setting of the study,the threshold-score of EPDS,and the reference standard used or other methodological differences,the sensitivity and specificity have varied from 71%-100% and 77%-98%,respectively (further details are given in Table 1).Furthermore,good diagnostic accuracy does not always translate into good clinical utility among measures.The clinical utility of EPDS has not previously been studied in India.Therefore,because of the wide variation in diagnostic accuracy parameters,there is a need to generate summary diagnostic accuracy parameters from pooled studies for use across India,and its clinical utility needs to be demonstrated.

Using this meta-analysis,we aim to fill in the lacunae in the existing literature,namely the absence of a summary global diagnostic accuracy and clinical utility parameter for use in India for non-English EPDS.Hence we:(1) Establish the summary global diagnostic accuracy of the non-English EPDS versions in India;and(2) Evaluate the clinical utility of the measure for post-natal Depression.

Table1 Summary of the included and excluded studies with their individual Quality Assessment of Diagnostic-Accuracy Studies-2 details

MATERIALS AND METHODS

Literature search

Two researchers (SMC and ER) independently electronically searched for relevant published studies in the PubMed,EMBASE (international database),MEDKNOW and IndMED (regional database) databases as well as hand-searched to augment the search with cross-references,published conference abstracts,Government of India publications,and grey literature from January 2000 to February 2018.We combined the search terms as follows:"diagnosis"[MeSH Terms] OR "diagnosis"[All Fields] OR"diagnostic"[All Fields]) AND accuracy[All Fields] AND ("psychiatric status rating scales"[MeSH Terms] OR ("psychiatric"[All Fields] AND "status"[All Fields] AND"rating"[All Fields] AND "scales"[All Fields]) OR "psychiatric status rating scales"[All Fields] OR ("Edinburgh"[All Fields] AND "postnatal"[All Fields] AND"depression"[All Fields] AND "scale"[All Fields]) OR "Edinburgh postnatal depression scale"[All Fields]) AND ("India"[MeSH Terms] OR "india"[All Fields].

Study selection and data extraction

Two other researchers (SR and SAV) extracted the required details independently,resolved any differences in extraction by consultation with another researcher (PSSR),and entered the information as electronic data.They extracted the participants,index measure,comparative reference measure and outcome of diagnostic accuracy details of each study.For a study to be included in the final analysis,it should have been conducted in India or among Indian populations,and must have compared the diagnostic accuracy of EPDS against either the Diagnostic and Statistical Manual(DSM) or International Classification of Diseases (ICD) for PND as the reference standard.Finally,each study had to report sufficient data to construct 2 × 2 tables for calculating the true positive,false positive,false negative and true negative values of EPDS against the reference standard.

Quality appraisal and risk of bias

Two researchers (SAV and PMM) also appraised the quality of the studies with Quality Assessment of Diagnostic-Accuracy Studies,version 2 (QUADAS-2)[9].We calculated the Deek's plot for publication bias[10].

Statistical analysis

We used the Area Under the Characteristic Curve of the Hierarchical Summary Receiver Operating Curve (HSAUROC),with random effects model,to establish the global diagnostic accuracy of EPDS[11].This was the first outcome of this metaanalysis.Using the 2 × 2 table,we calculated the positive and negative likelihood ratios (+LR and -LR,respectively).From these likelihood ratios,we evaluated the post-test probabilities of EPDS using the Fagan's nomogram (Bayesian approach);these post-test probabilities indicating the clinical utility was the second outcome of our study[12].We calculated the 95% confidence interval (95%CI) whenever indicated.All analyses were done at the study level and not at the participant level.The analyses were done with STATA (version 15) using the MIDAS and METANDI modules.

RESULTS

Study characteristics

The search strategies provided 2108 titles and the diagnostic accuracy of EPDS was documented in nine studies in seven of the official languages of India[13-21].One study in Kannada was excluded,as it included participants during their third trimester of pregnancy and not the post-natal period[16].Another study in Bengali was excluded due to the poor quality of the study[20].Figure 1 captures the PRISMA details,and Table 1 summarises the participants,index measure,comparative reference measure and outcome of diagnostic accuracy details and QUADAS -2 appraisal of each of the studies that were included or excluded in the final analysis (n= 1227).The QUADAS-2 appraisal demonstrated that in the risk of bias criteria,one study was rated as “at low risk of bias” across all domains.A rating of an unclear risk of bias was the most common rating across the appraisal domains.The Deek's plot for publication bias is presented in Figure 2.In terms of applicability criteria,all seven studies were rated as applicable on all domains (Figure 3 for QUADAS-2 details).All studies had a crosssectional design.

Diagnostic accuracy and clinical utility

Figure1 Overview of PRlSMA selection process of studies.

The global diagnostic accuracy of EPDS as ascertained by HSAUROC was 0.97(95%CI:0.95-0.98) (Figure 4).The pre-test probability for the nomogram was 22%.For a +LR of 9,the positive post-test probability was 72% (95%CI:68%,76%) and for a -LR of 0.08,the negative post-test probability was 2% (95%CI:1%,3%) (Figure 5).

DISCUSSION

Firstly,the global diagnostic accuracy of EPDS was excellent for the five different non-English versions in India.This HSAUROC value of 0.97 when converted to a more comprehensible clinical effect size of Cohen'sdor correlation coefficientrwas 2.66 or 0.79,respectively[22].This was a large effect size in the context of the diagnostic accuracy of EPDS when used as a screening measure for PND.Secondly,for the pretest probability of 22%,the positive increment in diagnostic utility was 51% and the negative decrement was 20% for the post-test probability of EPDS.Given that the prevalence of PND in India is 22%[3],our incremental changes in post-test probability values have added considerable certainty to the diagnosis of PND when EPDS is used[12].Thus,if a postnatal mother tests positive for EPDS,the chance she has PND increases from 22% to 72%;the clinician might therefore decide to actively engage in treatment.Conversely,if the patient tests negative,the chance of having PND decreases from 22% to 2%,and the clinician might decide not to actively treat the PND but engage instead in watchful waiting.Our finding about the diagnostic accuracy of EPDS versions is comparable with the values reviewed for the English versions in native English-speaking countries[6,7].In comparison to some of the other selected non-English EPDS versions among African languages,the Chichewa version in Malawi,the Shona version in Zimbabwe,and the Nigerian version have relatively lower diagnostic accuracies than the summary value that is reported in this metaanalysis[23,24].The translated version of EPDS in Afrikaans,Zulu,Tswana,Sotha,and Xhosa has demonstrated higher diagnostic accuracy for EPDS in South Africa[25].Among European languages,the Danish version of EPDS has an Area Under the Curve of 0.96 and is comparable to our summary data[26],the Spanish version had an overall accuracy of 87.4%[27],and the French versions of EPDS has a sensitivity and specificity of 80% and 92%,and thus had lower diagnostic accuracy[28].The other Asian language where EPDS has been validated includes Arabic[29],Chinese[30],and Japanese[31];they have been found to have lower or similar diagnostic accuracies as in our meta-analysis.

Figure2 The Deek's plot for publication bias.

The strengths of this study from a methodological perspective are that we followed the guidelines recommended by the Cochrane Diagnostic Test Accuracy Protocol.To present the summary of the global diagnostic accuracy of the EPDS,we used a summary line (HSROC) then summary point,as studies with various EPDS threshold values and two reference standards were analysed together.Furthermore,we anticipated the sensitivity as well as specificity of EPDS to differ widely between studies from the literature,and used the random effects model over the fixed effects model for analysis[6,7].There was no publication or small study bias in our metaanalysis.Finally,from the policy implication standpoint,in about 69069 births expected per day in India[32],the need to identify the 22% of mothers with PND and deliver the integrated management of mother-baby dyad is a huge task.However,this can be achieved if PND is identified and EPDS is used as a valuable measure[33].The National Mental Health Program should routinely incorporate the use of EPDS as the screening measure for PND in India through its District Mental Health approach.

In light of these findings,we conclude that the EPDS,with its many language versions and its brevity,is eminently suited for the screening of PND in India,where mental health resources are low but burden is high.

Figure3 The average Quality Assessment of Diagnostic-Accuracy Studies,version 2 appraisal for all included studies.

Figure4 The Hierarchical Summary Receiver Operating Characteristic Curve of Edinburgh Postnatal Depression Scale with its confidence and prediction contours.

Figure5 The post-test probability of Edinburgh Postnatal Depression Scale calculated with Fagan's nomogram.

ARTICLE HIGHLIGHTS

Research background

Various language versions of Edinburgh Postnatal Depression (EPDS) have been validated in India.The summary global diagnostic accuracy and clinical utility of these versions was established.

Research motivation

The diagnosis of postnatal depression (PND) is often missed or misdiagnosed.This affects both the mother and the baby,with significant morbidity.The widely used EPDS in India has to be proven for the early identification of PND.

Research objectives

The aim of this meta-analysis was to document the summary diagnostic accuracy and clinical utility of the various language versions of EPDS in India.

Research methods

Seven studies were included in the analysis following the PRISMA guidelines.We used Area Under the Characteristic Curve of the Hierarchical Summary Receiver Operating Curve,with random effect model,to summarize the diagnostic accuracy of EPDS;Fagan's nomogram was used for calculating clinical utility.

Research results

The global diagnostic accuracy of EPDS,as ascertained by Area Under the Characteristic Curve of the Hierarchical Summary Receiver Operating Curve,was 0.97 (95%CI:0.95-0.98).For a PND prevalence of 22%,the positive post-test probability was 72% (95%CI:68%,76%) and the negative post-test probability was 2% (95%CI:1%,3%).

气候突变表示气候从一种稳定态跳跃式地转变到另一种稳定态的现象，它是普遍存在于气候变化中的一个重要现象。图3为天峻地区1961-2017年春季干旱指数M-K突变检验，从分析的结果来看，相对湿润度指数(M指数)和标准化降水指数(SPI指数)的M-K突变检验是一致的，在上下两条±1.96(α=0.05)的置信线内，两个指数的UF与UB两条曲线均在1966年和2016出现交叉点，UF曲线在1966年的交叉点后向负方向变化，并低于-1.96，说明交叉点后减小趋势显著，因此认为1966年为突变年，而2016年的交叉点是不是突变点，有待需要更长序列的数据验证。

Research conclusions

We established the summary global diagnostic accuracy and clinical utility of the various versions of EPDS.The EPDS is effective in the early identification of PND.

Research perspectives

The EPDS in its various versions in India could be used for the scaling-up of PND treatment.The specific diagnostic parameters need to be further studied.

ACKNOWLEDGEMENTS

We acknowledge Professor Antonisamy B,Department of Biostatistics,Christian Medical College,Vellore for endorsing the data,analysis and conclusions of this study.