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. 2020 Oct 6;15(10):e0239929. doi: 10.1371/journal.pone.0239929

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies

Roy Arokiam Daniel 1,#, Partha Haldar 1,*,#, Manya Prasad 1,#, Shashi Kant 1,#, Anand Krishnan 1,#, Sanjeev Kumar Gupta 1,#, Rakesh Kumar 1,#
Editor: Simeon-Pierre Choukem2
PMCID: PMC7537899  PMID: 33022021

Abstract

Background

Despite the well-known short-term and long-term ill effects of elevated blood pressure in children and adolescents, pooled data on its burden among Indian adolescents have not yet been synthesized.

Objectives

We did a systematic review with meta-analysis to calculate the pooled prevalence of hypertension among adolescents (10–19 years) in India.

Methods

We searched PubMed, Embase, Cochrane library, Google Scholar and IndMed, and included cross-sectional studies reporting data on hypertension prevalence among 10 to19 years old and published in English language from their inception till 1st March 2020. Modified New castle Ottawa scale was used to assess risk of bias based on research design, recruitment strategy, response rate and reliability of outcome determination. A random effects model was used to estimate pooled prevalence, and heterogeneity was assessed using Cochrane’s Q statistic test of heterogeneity and I2 statistic. To explore the heterogeneity, we did a meta-regression, and sub-group analyses based on region, study setting and number of blood pressure readings.

Results

Out of 25 studies (pooled sample of 27,682 participants) six studies were of high, eighteen of moderate, and one was of low quality. The prevalence of hypertension across studies ranged from 2% to 20.5%, with a pooled estimate of 7.6% (95% CI: 6.1 to 9.1%), I2 = 96.6% (p-value <0.001). Sub-group analysis restricted only to the western India demonstrated a smaller heterogeneity (I2 = 18.3%). In univariate model of meta-regression, diagnostic criteria was significantly associated with pooled prevalence (-4.33, 95%CI: -7.532, -1.134)

Conclusion

The pooled prevalence of hypertension among adolescent in India is 7.6% with substantial heterogeneity between the studies. To tackle the high prevalence of hypertension among adolescents, early detection by screening under school health programme and opportunistic screening at Paediatric OPD should be implemented by Policy makers.

Introduction

Non communicable diseases (NCDs) accounted for 72% of global deaths in 2016 [1]. In developed nations cardiovascular Diseases (CVD) are one of the major causes of death [2]. Raised blood pressure is a leading risk factor for NCDs [3], which is responsible for 9.2% (95% CI: 8.3 to 10.2%) of DALYs for men and 7.8% (95%CI: 6.9 to 8.7%) of DALYs globally for women in 2015 [4]. Globally, it affects about 1 billion adults and is associated with more than 9 million deaths annually [5]. The prevalence of hypertension among adults is estimated to be 31.1% globally [6] and 27.6% in India [7]. With increasing prevalence, hypertension is becoming a rising health problem not only in adults, but also in children and adolescents [8, 9]. Meta-analysis on hypertension for children and adolescents in Africa showed a pooled prevalence of 5.5% [4, 10].

Cardiovascular disease events are seen most frequently after the fifth decade. Also likely, hypertension in young did not receive a public health attention, which might be due to the lack of awareness [11], considering it as a problem of adults only [12]. However, pathophysiological and epidemiological evidence suggests that essential hypertension and the precursors of cardiovascular diseases such as left ventricular hypertrophy, atherosclerosis and reduced cognitive function [13] originate in childhood but go undetected unless specifically looked for during this age-group [14]. There is strong evidence that raised BMI during adolescence is associated with raised risk of developing hypertension and/or CVD as an adult [15] and also there is a 12% increase in risk of developing CVD for each unit increase in BMI among adolescents [16].

Childhood Blood pressure (BP) is a strong indicator of adult blood pressure, hence, early intervention is important [17]. Thus, early detection of hypertension and its precipitating or aggravating factors is important so that future burden and complications of hypertension can be prevented. In India, the prevalence of hypertension among adolescents, who comprise one-fifth (21%) [18] of India’s population, ranges from as low as 2% [19] to 21.5% [20]. Previously, studies have reported pooled country-wide estimate on the prevalence of hypertension among adults [7] and tribal population in India [21], the same among adolescents is lacking. Hence, to overcome this gap, we aimed to perform a systematic review with a meta-analysis of cross-sectional studies to calculate the pooled prevalence of hypertension among adolescents.

Methods

Literature search strategy

A comprehensive literature search was carried out between November 2018 to March 2020. The studies published between their inception to 1st March 2020 were searched in Medline via PubMed, Embase, IndMed, Cochrane library and Google Scholar. The combinations of Medical Subject Headings (MeSH) and free text words (e.g., BP, raised BP, elevated BP, essential hypertension, primary hypertension, and high BP) were combined with search terms related to the outcomes (prevalence, epidemiology, risk). The details about the search strategy is provided in the supplement (S1 Table). We used the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement for reporting systematic reviews and meta-analyses as a guide for this study [22]. The protocol for the review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) database under the number CRD42019132159.

Selection criteria

The eligible studies were identified by performing an initial screening of identified titles and abstracts, followed by a full-text review. We included only observational studies adhering to the following criteria: 1) the study was cross-sectional, 2) conducted among adolescent population (10 to 19 years) on prevalence of hypertension, 3) it should be population/community-based (including school-based) studies, 4) sufficient data was available in the article to extract the numerator and denominator for the prevalence of hypertension between 10–19 years and 5) Studies must be in English language. Exclusion criteria were as follows: 1) if studies were conducted exclusively in the age group of less than 10 years or more than 19 years, 2) studies assessing adolescents with specific conditions like adolescents with hypertension or parents with hypertension, obesity, diabetes, chronic kidney disease because studies that included only children pre-disposed to develop secondary hypertension will yield a higher than expected prevalence of hypertension and thus, selection bias and 3) letters, abstracts, conference proceedings, reviews and studies not conducted on humans.

Study selection

Two independent reviewers (RAD and MP) screened all the titles of retrieved records from the databases, followed by screening of abstracts of relevant titles. Abstracts were selected if they satisfied the selection criteria. Any disagreements about selection were discussed with PH for resolution. All duplicates were removed after verifying the most recent and complete version. Full-text studies were retrieved for the selected abstracts. Reference lists of the retrieved studies were searched (additional sources). The retrieved full text studies were assessed further to ensure they satisfied the inclusion criteria.

Data extraction

We designed a data collection form in Microsoft Excel [23] to extract and enter the relevant data-fields from the selected full text studies. The data collection sheet included author information, year of publication, study-setting (rural or urban), sampling strategy, sample size, methodology adopted to record blood pressure and the reported prevalence of hypertension. New Castle Ottawa Scale (NOS) [24], modified for cross-sectional study was used to assess the quality of studies included in this review [25]. Studies with score ≥ 8 were considered high quality, score between 4–7 were considered as moderate quality, and score ≤ 3 were considered as low-quality studies.

Statistical analysis

The outcome measure was the prevalence of hypertension. The standard error (SE) of the prevalence was calculated from the reported prevalence, and the sample size for each of the study, using the formula “square root of p x (1-p)/n. We used 95% confidence interval (CI) to gauge the precision of the summary estimates. The meta-analysis was performed by package metan [26] in Stata [27] using random effects model, weighted by inverse of variance. Cochrane’s Q statistic test of heterogeneity and I2 statistic (percentage of residual variation attributed to heterogeneity) were performed to evaluate heterogeneity. We reported the pooled prevalence and its 95% confidence intervals (CIs) in the pooled analysis. Publication bias was assessed by visual inspection of funnel plot and small-study effect was assessed by Egger’s test. Subgroup analysis was done by zonal divisions of India (region) [28], number of readings and study setting. Sensitivity analysis was done based on the study quality, diagnostic criteria and number of BP readings. Test of interaction was also done to find out if any significant difference was present in the prevalence of hypertension between subgroups. Meta-regression analysis was carried out using metareg [29] package of Stata and to explore the cause of heterogeneity using the test by Knapp and Hartung to test the following variables: sample size, mean age, proportion of females, year of publication, diagnostic criteria and number of BP measurements. All the covariates with p-value <0.2 in bivariate model were added to the multivariable model and a p-value <0.05 was considered statistically significant. The goodness of fit of the model was assessed using R2 value and Monte Carlo permutation test was conducted to control for false-positive findings (type I error) when performing meta-regression with multiple covariates. All analyses were performed using the Stata Software (version 13.0).

Results

Study selection

Overall, 1707 studies were initially retrieved from the databases. After removing the duplicates, 842 studies were screened and of which, a total of 88 eligible abstracts were screened by inclusion criteria, followed by screening of full text studies. Finally, 25 studies satisfied the eligibility criteria and were included in the meta-analysis (Fig 1).

Fig 1. Flow of selection of studies for meta-analysis.

Fig 1

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Characteristics of studies included in the meta-analysis

We included a total of 27,682 individuals (females– 41%) in the meta-analysis (Table 1).

Table 1. The characteristics of the studies included in the systematic review and meta-analysis.
S.No Author & year of publication Study area Study setting Sample size Age group included (in years) No. of mean readings Sampling strategy Diagnostic criteria for hypertension Prevalence of hypertension (%)
1. Mohan et al. 2004 [30] Punjab Urban and rural, school-based 3326 11–17 2 NA* #NHBPEP 5.7
2. Anjana 2005 [31] Punjab Urban, school-based 529 6–14 3 NA NHBPEP 8.1
3. Saha 2007 [32] Kolkata Urban, community-based 1081 10–19 3 Simple random sampling NHBPEP 2.9
4. Savitha 2007 [33] Karnataka Urban, school-based 503 10–16 3 Stratified random sampling NHBPEP 6.2
5. Sharma 2009 [34] Himachal Pradesh Urban and rural, school-based 1085 11–17 3 NA NHBPEP 5.9
6. Goel 2010 [35] Delhi Urban, school-based 1022 14–19 2 Multistage cluster sampling NHBPEP 6.4
7. Khan 2010 [36] Gujarat Urban, school-based 1093 12–19 2 Simple random sampling NHBPEP 9.8
8. Buch 2011 [37] Gujarat Urban, school-based 535 6–18 3 Purposive sampling NHBPEP 8.8
9. Durrani and Waseem 2011 [38] Uttar Pradesh Urban, school-based 701 12–16 3 Stratified random sampling NHBPEP 9.4
10. Mujumdar 2012 [19] Karnataka Urban, school-based 772 6–15 NA NA NHBPEP 2.0
11. Kumar 2012 [39] Maharashtra Rural, community-based 1055 10–19 3 Simple random sampling NHBPEP 3.4
12. Yuvaraj 2014 [40] Karnataka NA, school-based 1732 9–16 3 NA NHBPEP 2.5
13. Lone 2014 [41] Maharashtra Urban, school-based 540 12–16 3 Simple random sampling NHBPEP 11.8
14. Anand 2014 [42] New Delhi Urban, school-based 315 12–17 2 Complete enumeration NHBPEP 7.0
15. Faujdar 2014 [43] Maharashtra Urban, school-based 999 11–17 One Complete enumeration NHBPEP 11.2
16. George 2014 [44] New Delhi Urban, school-based 485 9–18 NA Convenience sampling NHBPEP 8.2
17. Garg 2015 [45] Uttar Pradesh Urban, school-based 1000 10–14 3 NA NHBPEP 9.4
18. Mahajan and Negi 2015 [46] Himachal Pradesh Urban, school-based 3385 10–19 3 Simple random sampling NHBPEP 11.3
19. Kumar 2015 [47] Puducherry Urban and rural, school-based 1100 11–17 3 Stratified random sampling Not Available 4.1
20. Maiti and Bandyopadhyay 2016 [48] West Bengal Urban, school-based 129 10–19 Last 2 Simple random sampling NHBPEP 10.1
21. Reddy and Vamsheedar 2017 [49] Andhra Pradesh Urban, school-based 568 5–14 NA NA Self-determined cut-off 4.4
22. Kumar 2017 [50] Bihar Rural, school-based 2913 13–15 3 Stratified cluster sampling NHBPEP 4.6
23. Singh et al. 2017 [51] Madhya Pradesh Urban, school-based 404 10–18 3 Simple random sampling NHBPEP 15.3
24. Rai 2018 [52] Karnataka Rural, school-based 400 8–17 3 Stratified random sampling NHBPEP 4.3
25. Gupta et al. 2018 [53] Himachal Pradesh Urban, school-based 2100 10–16 2 Population proportionate to size Modified ATP@ classification 20.5
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#NHBPEP- National High Blood Pressure Education Program.

@ATP- Adult Treatment Panel.

*NA- Not available.

Majority of the studies used a simple random sampling strategy to select the study participants, used mercury sphygmomanometer to measure the blood pressure, performed multiple BP recordings, and used NHBPEP criteria to determine the prevalence of hypertension. Kumar [47] did not mention details about the criteria used to classify hypertension; Reddy and Vamsheedar [49] used self-determined cut-off; Gupta et al. [53] used modified ATP classification for classifying hypertension. Majority of the studies (22 of 25 studies) were school based; Savitha [33] and Mujumdar [19] were community-based. Except the studies by Rai [52] and Kumar [50], remaining studies were done in urban setting. All the studies measured blood pressure using mercury sphygmomanometer except the study done by George [44] and Kumar [47] who had used digital blood pressure apparatus. All the studies collected data prospectively. None of the studies were multisite or nationally representative.

Risk of bias assessment

Out of 25 studies, six studies were of high quality, eighteen were of moderate quality and one study was low quality (S2 Table). Among the included studies, 14 studies had used validated tool, acceptable non-response rate and robust sampling strategy.

Prevalence of hypertension among adolescents in India

Prevalence of hypertension for both sexes combined (n = 25 studies) ranged from 2% in a cross-sectional study done by Mujumdar [19] in Southern India, to 20.5% by Gupta et al. [53] conducted in Northern India.

Random effects pooled estimate

The random effects pooled estimate for prevalence of hypertension among adolescent in India was 7.6% (95% CI: 6.1 to 9.1%) (Fig 2). There was significant heterogeneity between the studies. Heterogeneity test showed I2 = 96.7%, Q = 723.8 and p-value <0.001.

Fig 2. Forest plot of pooled prevalence of hypertension among adolescents in India.

Fig 2

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Subgroup analysis

Prevalence of hypertension based on geographical region

Based on the zonal divisions of India, places of study were grouped into five regions: north, south, east, central, and west (Fig 3). Studies conducted in west region demonstrated a small heterogeneity (I2 = 18.3%, p-value = 0.294). There was significant difference in the prevalence in the studies conducted among the various regions in India (p-value<0.001). The prevalence of hypertension among various sub-groups is shown in Table 2.

Fig 3. Forest plot of region wise prevalence of hypertension among adolescents in India.

Fig 3

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Table 2. Prevalence of hypertension among adolescents by sub-groups.
Sub-group No. of studies Total no. of participants Prevalence (%) 95% CI Heterogeneity test p-value* (subgroup difference)
I2 Q
Region
Central 1 404 15.3 11.8–18.8 - - <0.001
West 3 2,627 10.0 8.8–11.3 18.3 2.5
North 13 18,366 8.6 6.3–10.8 97.1 413.7
East 2 1,210 6.0 -0.9–13.0 85.9 7.1
South 6 5,075 3.7 2.6–4.8 77.4 22.1
No. of readings
Two readings 6 7,985 9.9 5.1–14.7 97.9 243.4 <0.001
Three readings 15 16,873 7.0 5.3–8.7 95.6 317.0
Study setting
Rural 5 5,794 3.8 2.9–4.7 60.6 10.2 <0.001
Urban 20 19,105 8.8 6.7–10.8 96.5 542.7
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*Null hypothesis for this test is that there is no difference in the subgroups and the test of significance carried was out by chi square test.

Prevalence of hypertension based on number of blood pressure readings

Out of 25 studies, three studies did not mention about the number of readings and one study with only one reading was excluded from the analysis. There was significant difference in the prevalence between the studies that used two and three readings to classify hypertension as shown in Fig 4 (p-value<0.001).

Fig 4. Forest plot of prevalence of hypertension with two and three blood pressure readings among adolescents in India.

Fig 4

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Prevalence of hypertension based on study setting

Out of 25 studies, three studies were conducted in both urban and rural regions of which one study did not mention details on sample size and prevalence of hypertension based on the setting. There was significant difference in the prevalence between the studies of rural and urban setting as shown in Fig 5 (p-value<0.001).

Fig 5. Forest plot of prevalence of hypertension among adolescents in India based on study setting.

Fig 5

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Publication bias

Funnel plot demonstrated a mild asymmetry (Fig 6). However, the p-value for Egger’s test was observed to be 0.288, implicating no or undetected publication bias.

Fig 6. Funnel plot to check for publication bias.

Fig 6

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Sensitivity analysis

Sensitivity analysis was performed by removing one low quality study by Mohan et al. and the prevalence of hypertension showed no substantial change from 7.6% (95% CI: 6.1 to 9.1%) to 7.7% (95% CI: 6.1 to 9.4%). The pooled estimate after removal of three studies that used criteria other than NHBPEP criteria to diagnose hypertension was 7.3% (95%CI: 5.9 to 8.6%) The pooled estimate after removing 10 studies based on number of blood pressure readings, (3- no. of readings not mentioned, 1- with single reading and 6- with only two readings) was 7.0% (95% CI: 5.3 to 8.7%) as shown in Table 3.

Table 3. Results for sensitivity analysis for the prevalence of hypertension among adolescents.

S. No Sensitivity analysis Prevalence of hypertension (%) with 95% CI Heterogeneity test p-value
I2 Q
1. Removing one low quality study 7.7 (6.1–9.4) 96.7 723.8 <0.001
2. Removing studies that have used criteria, other than NHBPEP, to diagnose hypertension 7.3 (5.9–8.6) 95.1 428.6 <0.001
3. Removing studies that included only one and two readings of blood pressure 7.0 (5.3–8.7) 95.6 317.0 <0.001
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Meta regression

In the univariate meta-regression, we observed that change in diagnostic criteria caused a decrease in the effect size with the beta-coefficient value -4.33(-7.532, -1.134). The multivariate model with year of study, number of BP readings, and diagnostic criteria were included in which none of the covariates came out to be statistically significant (Table 4). The R2 value for meta-regression was 23%. Monte Carlo permutation test was conducted with 50,000 permutations and the adjustment for type 1 error did not change the result.

Table 4. Results for meta-regression for the prevalence of hypertension among adolescents.

S.No Covariate (No. of studies included) Univariate model Multivariate model
Meta-regression coefficient (95%CI) p-value Meta-regression coefficient (95%CI) p-value
1. Year of publication (25) 0.321(-0.139, 0.692) 0.148 0.239(-0.203, 0.681) 0.271
2. Sample size (25) 0.000(-0.001, 0.002) 0.833 -
3. Mean age (11) -0.511 (-3.184, 2.163) 0.676 -
4. No. of BP reading (22) -2.478 (-5.770, 0.813) 0.132 -2.053 (-5.064, 0.958) 0.169
5. Diagnostic criteria (24) -4.33 (-7.532, -1.134) 0.010 -3.423 (-7.354, 0.508) 0.084
6. Proportion of females (23) 0.000 (-0.372, 0.373) 0.984 -
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Discussion

We did a systematic review and meta-analysis of data from 25 studies involving 27,682 participants and found a pooled prevalence of hypertension of 7.6% (95% CI: 6.1 to 9.1%) among adolescents in India. The studies had significant statistical heterogeneity between them, which we could partly explain by subgroup analysis. The studies included from Western India demonstrated quite small heterogeneity.

A systematic review and meta-analysis done by de Moraes [54], reported prevalence of hypertension of 11.2% among adolescents from developed and developing countries which was higher that the pooled prevalence in our study (7.6%). The possible reason for disparity in the estimate of hypertension prevalence might be due to the inclusion of hypertension estimates from regions like North America, Oceania, Africa, Europe and Latin America in their meta-analysis. They also included studies using a cut-off of more than 90th percentile for elevated blood pressure which might have overestimated the prevalence of elevated blood pressure in their study [55] whereas, the studies included in this systematic review and meta-analysis have used a cut-off of more than 95th percentile. The difference might also be attributed to the race of the population studied. The former study mainly consisted of Mongoloid race, whereas the present study included population belonging to Mongoloid, Dravidian and Caucasoid [56, 57]. A systematic review and meta-analysis conducted by Noubiap JJ et al. [4] among African children and adolescents of age group 2–19 years, estimated the prevalence of hypertension as 5.5% (95% CI: 4.2 to 6.9%) which is lower from the current estimate of 7.6%, which might be due to the age group considered in the previous study. Genetic factors have been documented to play a major role in determining hypertension prevalence. One such factor is the Gly460Trp allele, which is implicated in being responsible for a higher prevalence of hypertension in Asians [58–60].

Another systematic review and meta-analysis of hypertension prevalence done among the Brazilian adolescents (10–19 years) by Goncalves [61] reported a pooled estimate of prevalence of 8.0% (95% CI 5.0 to 11.0%). This estimate is similar to our study finding which might be due to Asian contribution to the Brazilian population [62].

Existing information on prevalence of hypertension has methodological issues like different criteria used for diagnosis of hypertension, number of readings and instrument used to record blood pressure. Majority of the studies did not mention any details about the calibration of the blood pressure apparatus. According to the criteria of the European Hypertension Society, and the American Academy of Pediatrics recommended that difference between averages of the measure’s mercury column and tested monitor for a device to be validated should be ≤ 5 mmHg [63, 64]. Also, that the standard deviation of the differences of the averages should not be larger than 8 mmHg. The differences in the prevalence can introduce misclassification of individuals and may cause underestimation or overestimation of the true prevalence [65].

Majority of the studies were school based and the pooled prevalence of hypertension among school-based studies was higher than the community-based studies. Some factors may influence the blood pressure levels when it is measured in school setting. Talking or active listening is considered as one major factor that increases the level of blood pressure [66]. Full bladder tends to increase the blood pressure by 10-15mmHg [67]. The stress and anxiety (due to tests and assessments in school) in students could be responsible for the increased blood pressure [68]. Also, the school enrolment ratio is less especially in the rural parts of India and a school-based study will not be representative of the population [69]. Hence with all these factors community-based studies appear to be superior than school-based studies.

Most of the studies were from the urban area and only three studies were from the rural areas. Urban studies revealed higher prevalence of hypertension compared to the studies from rural parts of India which might be due to the sedentary lifestyle of urban participants. Higher prevalence of hypertension was seen in studies conducted in North and West part of India than in the studies conducted in South India.

High heterogeneity was present in the pooled as well subgroup analyses, which requires caution in extrapolating the results. In sub-group analysis, west region showed a small heterogeneity (I2 = 18%). Other sub-groups on various variables showed high heterogeneity. The reasons for high heterogeneity could be different sampling strategy, methodology of blood pressure measurement, regional variations and varied cut-off used to diagnose hypertension (e.g. NHBPEP criteria, modified ATP criteria and cut-off arbitrarily decided by authors [49, 52, 53]). Other reasons could be natural differences among the individuals included in the studies since states and cities are socioeconomically and culturally different from each other. In meta-regression, none of covariate was statistically significant.

One of the potential limitations was the blood pressure measurement methods used in the studies included in the review. Measurements varied significantly among the various studies and in relation to their adaptations and interpretations, which may influence the summarization of the prevalence. The NHBPEP criteria recommends that at least three blood pressure readings should be recorded and for diagnosis, this should be repeated for at three different occasions [70]. But majority of the studies had not adhered to this recommendation.

NHBPEP includes overweight children in the blood pressure distribution data and uses data of the first blood pressure reading only. Some studies have found that inclusion of overweight/obese children raised the cutoff points for elevated blood pressure [71–75]. Xi et al. have now established an international blood pressure reference, based on data from seven large cross-sectional surveys consisting of non-overweight children and adolescents. When compared with the US fourth report at median height, systolic BP of the corresponding percentiles of these international references was lower, whereas diastolic BP was similar [76].

The various factors that are related to blood pressure measurement were cuff size (small cuff-size overestimates blood pressure [77, 78]), technique used to determine the DBP (choice of fourth or fifth Korotkoff sound), the number of BP measurements, and type of instruments used (oscillometric or mercury sphygmomanometer). In a systematic review and meta-analysis conducted among children showed that higher SBP readings were recorded by oscillometric devices as compared to a standard mercury sphygmomanometer with a pooled effect estimate of 2.53 mmHg, 95% CI 0.57 to 4.5 mmHg) [79]. Another comparative study conducted by Shahbabu to estimate the accuracy of readings of aneroid and digital sphygmomanometers in reference to mercury sphygmomanometers showed that more than 89% of aneroid readings and less than 44% of the readings by digital device had absolute difference of 5mm Hg when compared with the mercury readings for both systolic and diastolic blood pressure. Sensitivity and specificity of aneroid device was higher (86.7% and 98.7%) than digital device (80% and 67.7%) [80]. In a multicentric study conducted among children with chronic kidney disease (CKD), oscillometric SBP and DBP measurements were constantly higher than the readings obtained by auscultation (median elevations of 9 and 6 mm for SBP and DBP) [81]. So, this overestimation of both systolic and diastolic blood pressure leads to frequent misclassification of blood pressure values with false-positive diagnosis of hypertension. Moreover, oscillometric devices require regular maintenance and repeated calibration for accurate BP measurements. Hence these factors should be given due attention for the accurate diagnosis of hypertension which plays a pivotal role in the blood pressure measurement and to prevent overdiagnosis.

A study done by Raj M et al., published in 2010, a cross sectional study in Kerala among 5–16 years of age, to determine blood pressure distribution in schoolchildren and to derive population specific reference values appropriate for age, gender, and height status. They found that these children exhibited higher diastolic blood pressures for both boys and girls than the US children across all age groups and for systolic blood pressure, girls showed higher values than the international standard while for boys, there was a minimal difference [82]. But this study has considered only for school going children and was not a community-based study which might not be representative of all the children of that age group.

Cost-effectiveness study conducted in United States published in 2011, about the blood pressure screening in adolescents showed that the population-wide strategies such as salt reduction (cost-saving [boys] and $650/ QALY [girls]) and increasing physical education ($11 000/QALY [boys] and $35 000/QALY [girls]) and treating the adolescents at highest risk was most cost-effective [83]. Hence population-based high-risk screening should be undertaken which would be an effective solution to prevent hypertension and future burden of cardiovascular diseases.

Also, studies show that oscillometeric devices overestimates blood pressure when compared with mercury sphygmomanometer [84]. NHBPEP reference blood pressure tables were based on mercury sphygmomanometer so; the prevalence of hypertension increases if NHBPEP criteria was followed when other oscillometeric devices were used to measure the blood pressure. All the children above 3 years of age should have an annual blood pressure examination. The confirmatory diagnosis and appropriate management should be not be made by automatic blood pressure apparatus as per the guidelines [70].

Differences in study setting and the lack of method standardization reflected in different equipment and different intervals between measurements, may have contributed to the observed heterogeneity. The heterogeneity could not be explained by subgroup analyses or meta-regression. It is possible that other subject characteristics such as nutritional status, stages of adolescence and sexual maturity may have a role to play in determining prevalence of hypertension. However, the absence of this information in most original studies prevented further analysis. Signs and symptoms in the early stages of hypertension do not present unless micro or macrovascular complications occur, thus it is also called as ‘silent killer’ [85]. Hence, health promotion is more relevant today in addressing NCDs. Health educational programmes should be implemented across all the schools and basic awareness on prevention of hypertension should be imparted to the adolescents in school. It will not only educate the adolescent and modify their behaviors; it would also have an impact over the knowledge on hypertension of their parents who might be in the early stages of development of hypertension. So, health promotion for school students through school health programme and through Anganwadi constitutes an important strategy for behavior change communication. School based aerobic exercise programmes that are proven effective in reducing risk may be implemented [86]. A familial tendency for developing high blood pressure is well known, which suggests a genetic role in the development of hypertension [87]. Hence, adolescents having a positive family history of hypertension, should be screened which helps in early diagnosis and appropriate management which in turn helps in reducing the burden and complications of hypertension.

Strengths and limitations

To the best of our knowledge, our’s is a first systematic review and meta-analysis that estimated the prevalence of hypertension among adolescents in India. We used a standard search strategy, risk of bias assessment for individual studies, and explored heterogeneity using subgroup analysis, and meta-regression. But a few limitations were there in our study. We did not consider, studies reported in language other than in English, and grey literature. We believe this not to affect our findings since in India, almost all medical literature is published in English language. The pooled estimate of hypertension emerging from this study needs to be interpreted along with the considerable heterogeneity observed between the studies. The number of studies conducted in rural settings that were included in this review were less in number and hence it limits the generalizability of the results as it is an important determinant.

Conclusion

The pooled prevalence of hypertension among adolescent in India is 7.6% with substantial heterogeneity between the studies. Hypertension in adolescents poses an important issue in public health and clinical medicine. Due attention should be given to this growing concern. Future studies should evaluate the use of a screening programme for hypertension in schools and community. Randomized Control Trails (RCTs) evaluating the effect of screening on relevant outcomes like CVD events and mortality would be instrumental in guiding future policy. A uniform criterion to classify hypertension in children and adolescents ought to be developed through large community-based studies in India rather than classifying hypertension based on US reference population. Early detection by screening for hypertension among students under school health programme and opportunistic screening at Paediatric OPD should be implemented by Policy makers.

Perspectives

There is no country wide information from India on adolescent hypertension. This review provides the pooled estimate on the prevalence of hypertension but also highlights the heterogeneity in the studies conducted across India, which to needs to be interpreted with caution.

Supporting information

S1 Checklist. PRISMA 2009 checklist.

(DOC)

Click here for additional data file. (65.5KB, doc)
S1 Table. Search strategy.

(DOCX)

Click here for additional data file. (13.6KB, docx)
S2 Table. Risk of bias assessment for all the selected studies for systematic review and meta-analysis.

(DOCX)

Click here for additional data file. (16.9KB, docx)

Abbreviations

BP

Blood pressure

CI

Confidence interval

NCD

Non communicable disease

NHBPEP

National High Blood Pressure Education Program

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

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10 Mar 2020

PONE-D-20-01922

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of observational studies

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Reviewer #1: Partly

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Title

1) I suggest to the authors to replace in the title the term “observational” by “cross-sectional” since in inclusion criteria, they considered only cross-sectional studies.

Introduction

2) The sutdy is well justify and the objective is clear.

Methods

3) The authors should update the stage of the review in PROSPERO. For instance, “Preliminary searches” are not “completed”.

4) Inclusion. It is not clear whether the authors only considered population/community-based studies (including school-based) studies. Only this kind of studies should be considered to have reliable epidemiological data.

5) Data extraction. Cochrane do not recommend scoring quality assessment (https://handbook-5-1.cochrane.org/chapter_8/8_assessing_risk_of_bias_in_included_studies.htm).

6) Statistical analysis. Consider reporting all prevalence estimates with 95% prediction intervals that better measure uncertainty.

Results

7) Characteristics of included studies. The sentence “All included studies were cross-sectional studies.” is not necessary since in the Inclusion criteria, the authors stated that they will consider only cross-sectional studies.

8) Table 1 should include diagnostic criteria for hypertension.

9) Table 2. The signification of 0, 1, 2, 3, 4 for Selection, Comparability, and Outcome is not clear. This was not described any part in manuscript.

10) Please report all prevalence with only one decimal.

11) Results. Line 285: “a little increase”. I’m not sure it is adequate to write a little increase. I would suggest changing to “no substantial change”.

12) Results. Line 286-289: “Analysis repeated after removing two studies that reported the hypertension prevalence of more than 15% and the prevalence of hypertension decreased from 7.64% (95% CI: 6.13% to 9.14) to 6.75% (95% CI: 5.55 to 7.96%) with more precise estimate.” It is not a correct methodological practice to exclude studies based on the outcome of outcome (here prevalence). Sensitivity analyses are carried out on methodological criteria, criteria for inclusion of participants and methodological quality (risk of bias). The authors may explore why these studies had higher prevalence when looking at participants characteristics, method (example sampling method), setting (urban vs rural for example)… Authors can conduct leave-one-out sensitivity analysis to assess the effect on the overall pooled estimate of removing each study.

13) Results. Line 289-290: “We also reran the main analysis by removing two community-based study and one hospital-based study”. The authors should not pool community-based and hospital-based studies. In addition, in term of epidemiology only community-based studies should be considered to have reliable hypertension prevalence in the adolescent populations. In general, burden of diseases is higher in hospital-based studies and do not represent the “real” face of the epidemiology in the population. In conclusion, hospital-based studies should be removed from this meta-analysis.

14) Results. Line 289-290: “We also reran the main analysis by removing two community-based study and one hospital-based study”. It is not clear why the authors removed both community-based and hospital-based studies.

15) Results. Line 291-293. “The analysis was repeated after removing the study done by Maiti & Bandyopadhyay with sample size of less than 200 and the pooled estimate came out to be 7.57%, 95% CI: 6.04 to 9.09%.” The authors should give a strong rationale on the reason for choosing a threshold of 200.

16) Results. Table 5.

a. It is not whether the findings in this table are for univariable or multivariable meta-regression. Both models (uni- and multivariable) should be reported.

b. I do not understand why some variance are reported with “(-)”. Variance is never negative.

c. P value less than 0.05 should be reported with at least three decimals.

d. Meta-regression should include methods to diagnose hypertension i.e. diagnostic criteria.

e. For total no. of males and females, only the proportion of males or females should be considered since the no. can vary among studies, but the proportion is a comparable measure of the representativeness of sex distribution.

f. How many studies were included in final multivariable model?

g. How many studies were included in each univariable model?

h. It is not clear why for the “Age group” variable, the authors reported only one coefficient since there would be n-1 coefficients according to the number age groups.

Discussion

17) Line 318-320. “The possible reason for disparity in the estimate of hypertension prevalence might be due to the race and ethnicity of the developed and developing countries and the criteria used to classify hypertension”. What is the difference in term of ethnicity and race that explain this difference; i.e. what is the race/ethnicity in India and the race/ethnicity in the study by Moraes et al. In addition, also describe criteria to classify hypertension in both studies. And then discuss the mechanisms of these differences.

18) The comparison with the study by Noubiap and colleagues should be more detailed. The authors suggested Black Africans children in Africa had lower prevalence compared to Indian Adolescents. Authors may report prevalence data on hypertension in adults, and compare Indians and Black Africans to support this hypothesis (consider using global burden of diseases data) [https://jamanetwork.com/journals/jama/fullarticle/2596292]. Also add sentences on the mechanism of this difference: genetics? Dietary habits (with more details)?

Reviewer #2: General comment

Thanks for this review which brings new information. However, there are some concerns raised below. In addition, the paper should be thoroughly proofread: there are many grammatical errors and the style used makes sometimes the message hard to capture.

Specific comments

Lines 102-3: hard to understand what the authors are meaning

Line 105: This should be the beginning of a new paragraph, starting with “Adolescents…”

Line 109: The authors explain the rationale of their study by indicating that most studies that were carried out in India were school based, and that their review would help solving such inconsistencies. I totally disagree, as the review is just a summary of existing literature; limitations of individual studies constitute limitations of the review…

Lines 129-31: These sentences relate to study selection, not literature search strategy

Line 138: why only cross sectional studies were included? Baseline or end-of-study data of cohort studies could present prevalence estimates, as well as control arms of RCTs…

Line 138: The title is about a study in adolescents, but here the authors say they have included children and ados up to 19yo

Line 139: please what do you mean by enough data was available?

Line 140: why papers written in Hindi were not considered? All these exclusions may have tended to increase the probability of publication bias

Line 143-4: why were studies within which parents had specific conditions rather than their kids excluded?

The authors do not mention to have excluded studies like in pregnant ados, or those with other conditions capable of biasing the prevalence of HTN? Nevertheless, they could still have included those studies and present them n subgroup analysis

Lie 150: I do not align with eliminating duplicates without verifying which is the more recent and complete version before ruling out…

Line 176: I would have suggested to add age groups, setting (urban/rural), sex (male/female), and year of publication as other variables for subgroup analysis; social d; social development index/human development index or quintile of life are other parameters to consider, to know if poorer ados have more or less HTN than richer ones

Fig 1: there is a problem in this figure: records excluded should be linked with records after duplicates removed instead of records screened; in fact, it is after exclusion that the remaining records are screened

What do you mean by non-relevant articles, n=92? Does it mean that your first round of exclusion was too sensitive?

Table 1: Is putting the study area more informative than for eg the setting: urban vs rural? It is also important to know how HTN was defined in each of these studies; was the study multisite/national representative?

Line 209: majority is how many?

Line 217: how many studies were national representative, data were they collected prospectively or retrospectively?

Line 223; risk of bias should precede data on HTN

Table 2 can be sent as supplementary table or the final score can be included in table 1

Line 237: what guided the breakdown into 4 regions? This was not presented and clearly explained in methodology

Line 247: this is hard to understand: what was the region of reference, for the others to have significant different prevalence estimates?

Line 278: the reason given to justify why publication bias was not assessed in the whole sample of studies is not clear to me. Should this bias be assessed only when there is low heterogeneity?

Table 3: I would have appreciated to see more variables in the subgroup analysis; see comment above

Line 299 & table 5: how can males and females be included in the same model? This is to be the same variable, sex with two modalities male and female

Study setting, region, method of sampling, method of HTN definition, etc could be explored in the model

Line 323: no reference is given to support the statement on HTN and race; I am not sure the comparison between Noubiap and the authors is suitable, as Noubiap included children in their review

Line 328: what is the pertinence in this statement?

Lines 337-44: this should be also discussed as limitations of the review; refer to the above comment in the introduction

Lines 345-7: I have not seen this result earlier

Lines 411-12; these lines are very insufficient as limitations of this study; please see comments above; in addition, discuss the generalizability of finding to the entire country, heterogeneity, etc

Further, I think the discussion is insufficient: little was discussed about clinical implications of this study in terms of harmonizing the way of measuring BP and defining HBP among ados in the country; public health implications in terms of what strategies could be put in place to raise awareness on the issue and preventive measures/programs that could be introduced in school programs, etc

Some refs could be updated, eg ref 9 published in 2006

**********

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Reviewer #1: Yes: Jean Joel Bigna

Reviewer #2: No

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PLoS One. 2020 Oct 6;15(10):e0239929. doi: 10.1371/journal.pone.0239929.r002

Author response to Decision Letter 0

19 Apr 2020

I have updated the search till 1st March 2020.

Captions for supporting information is added now.

Reply to the reviewers’ comment

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies.

Reviewer Number Original comments of the reviewer Reply by the author(s) Changes done on (manuscript with track changes) page number and line number

1 I suggest to the authors to replace in the title the term “observational” by “cross-sectional” since in inclusion criteria, they considered only cross-sectional studies. We thank the reviewer for this correction. This is corrected now Page- 1, line-3

1 Methods: The authors should update the stage of the review in PROSPERO. For instance, “Preliminary searches” are not “completed” This is addressed now Page-7, line-138

1 Inclusion: It is not clear whether the authors only considered population/community-based studies (including school-based) studies. Only this kind of studies should be considered to have reliable epidemiological data This is addressed now Page-7, line-144.

1 Data extraction: Cochrane do not recommend scoring quality assessment We agree, sir. However, there are instances where Cochrane reviewers have used Newcastle Ottawa Scale in systematic reviews of observational studies. The following is one example of a Cochrane review where NOS has been used.

Reference:

1. Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis. Read Online: Critical Care Medicine | Society of Critical Care Medicine [Internet]. 2020 [cited 2020 Apr 17];48: e98. Page-8, line-168-175

1 Statistical analysis: Consider reporting all prevalence estimates with 95% prediction intervals that better measure uncertainty We believe confidence intervals are better suited for the present study, considering that the purpose of using prediction intervals is primarily for predicting future unobserved observation and for other reasons mentioned in the following citation:

Reference:

Chiolero A, Santschi V, Burnand B, Platt RW, Paradis G. Meta-analyses: with confidence or prediction intervals? Eur J Epidemiol [Internet]. 2012 [cited 2020 Apr 17]; 27:823–5. Page-8

1 Results: Characteristics of included studies. The sentence “All included studies were cross-sectional studies.” is not necessary since in the Inclusion criteria, the authors stated that they will consider only cross-sectional studies This is addressed now Page-9, line-206

1 Table 1 should include diagnostic criteria for hypertension This is addressed now Page 11,12,13, Table 1.

1 Table 2: The signification of 0, 1, 2, 3, 4 for Selection, Comparability, and Outcome is not clear. This was not described any part in manuscript. This is addressed now Page-8, line-171-714

1 Please report all prevalence with only one decimal This is addressed now Entire document

1 “a little increase”. I’m not sure it is adequate to write a little increase. I would suggest changing to “no substantial change”. This is addressed now Page-21, line-320

1 “Analysis repeated after removing two studies that reported the hypertension prevalence of more than 15% and the prevalence of hypertension decreased from 7.64% (95% CI: 6.13% to 9.14) to 6.75% (95% CI: 5.55 to 7.96%) with more precise estimate.” It is not a correct methodological practice to exclude studies based on the outcome of outcome (here prevalence). Sensitivity analyses are carried out on methodological criteria, criteria for inclusion of participants and methodological quality (risk of bias). The authors may explore why these studies had higher prevalence when looking at participants characteristics, method (example sampling method), setting (urban vs rural for example)… Authors can conduct leave-one-out sensitivity analysis to assess the effect on the overall pooled estimate of removing each study. This is addressed now Page-21, line-321-328

1 “We also reran the main analysis by removing two community-based study and one hospital-based study”. It is not clear why the authors removed both community-based and hospital-based studies. This is addressed now Page-21, line-321-328

1 “The analysis was repeated after removing the study done by Maiti & Bandyopadhyay with sample size of less than 200 and the pooled estimate came out to be 7.57%, 95% CI: 6.04 to 9.09%.” The authors should give a strong rationale on the reason for choosing a threshold of 200. This is addressed now Page-21, line-321-328

1 Table 5.

a. It is not whether the findings in this table are for univariable or multivariable meta-regression. Both models (uni- and multivariable) should be reported. b. I do not understand why some variance are reported with “(-)”. Variance is never negative. c. P value less than 0.05 should be reported with at least three decimals. d. Meta-regression should include methods to diagnose hypertension i.e. diagnostic criteria. e. For total no. of males and females, only the proportion of males or females should be considered since the no. can vary among studies, but the proportion is a comparable measure of the representativeness of sex distribution. f. How many studies were included in final multivariable model? g. How many studies were included in each univariable model? h. It is not clear why for the “Age group” variable, the authors reported only one coefficient since there would be n-1 coefficients according to the number age groups. All points raised for this table are addressed now Table 4, Page-22

1 Discussion: “The possible reason for disparity in the estimate of hypertension prevalence might be due to the race and ethnicity of the developed and developing countries and the criteria used to classify hypertension”. What is the difference in term of ethnicity and race that explain this difference; i.e. what is the race/ethnicity in India and the race/ethnicity in the study by Moraes et al. In addition, also describe criteria to classify hypertension in both studies. And then discuss the mechanisms of these differences. This is addressed now Page-23, line-355-361

1 The comparison with the study by Noubiap and colleagues should be more detailed. The authors suggested Black Africans children in Africa had lower prevalence compared to Indian Adolescents. Authors may report prevalence data on hypertension in adults and compare Indians and Black Africans to support this hypothesis (consider using global burden of diseases data) [https://jamanetwork.com/journals/jama/fullarticle/2596292]. Also add sentences on the mechanism of this difference: genetics? Dietary habits (with more details)? This is addressed now Page 23, line:365-372

2 hard to understand what the authors are meaning This is addressed now Page-5, line- 105.

2 This should be the beginning of a new paragraph, starting with “Adolescents…” This is addressed now Page-5, line-109

2 The authors explain the rationale of their study by indicating that most studies that were carried out in India were school based, and that their review would help solving such inconsistencies. I totally disagree, as the review is just a summary of existing literature; limitations of individual studies constitute limitations of the review… This is addressed now Page-6, line-113-116

2 These sentences relate to study selection, not literature search strategy This is addressed now Page-7, line:140-141.

2 why only cross-sectional studies were included? Baseline or end-of-study data of cohort studies could present prevalence estimates, as well as control arms of RCTs… We thank the reviewer for this comment. However, we believe that large cross-sectional studies would be the best design for this question, as even control arm of RCTs or cohort study population would not be representative. A cross-sectional study would be able to yield the best estimate for baseline risk.

Reference:

Kesmodel US. Cross-sectional studies – what are they good for? Acta Obstetricia et Gynecologica Scandinavica [Internet]. 2018 [cited 2020 Apr 7]; 97:388–93. Page-7, line:142

2 The title is about a study in adolescents, but here the authors say they have included children and ados up to 19yo This is addressed now Page-7, line:142-143

2 please what do you mean by enough data was available? This is addressed now Page-7, line:144-145

2 why papers written in Hindi were not considered? All these exclusions may have tended to increase the probability of publication bias There are no databases for Hindi studies and all the Indian papers are written in English. The following is the reference for all papers from India being published in English. For these reasons we believe that this will not be a source of publication bias.

Reference:

Medical Journals of India [Internet]. [cited 2020 Apr 17]. Available from: http://medind.nic.in/ Page-7, line:146

2 why were studies within which parents had specific conditions rather than their kids excluded? This is addressed now Page-7, line:120-152

2 I do not align with eliminating duplicates without verifying which is the more recent and complete version before ruling out This is addressed now Page-7, line:158-159

2 I would have suggested to add age groups, setting (urban/rural), sex (male/female), and year of publication as other variables for subgroup analysis; social d; social development index/human development index or quintile of life are other parameters to consider, to know if poorer ados have more or less HTN than richer ones This is addressed now Page-9, line:186-187

2 Figure1: there is a problem in this figure: records excluded should be linked with records after duplicates removed instead of records screened; in fact, it is after exclusion that the remaining records are screened What do you mean by non-relevant articles, n=92? Does it mean that your first round of exclusion was too sensitive? This is addressed now Figure 1

2 Table1: Is putting the study area more informative than for eg the setting: urban vs rural? It is also important to know how HTN was defined in each of these studies; was the study multisite/national representative? This is addressed now Table1, Page-11

2 majority is how many? This is addressed now Page-15, line:223

2 how many studies were national representative, data were they collected prospectively or retrospectively? This is addressed now Page-15,

line-230-231

2 Table 2 can be sent as supplementary table or the final score can be included in table 1 This is addressed now Table S2 (Supplement)

2 what guided the breakdown into 4 regions? This was not presented and clearly explained in methodology This is addressed now Page-9, line:186-187

2 this is hard to understand: what was the region of reference, for the others to have significant different prevalence estimates? This is addressed now Page-19, Line-286-287

2 the reason given to justify why publication bias was not assessed in the whole sample of studies is not clear to me. Should this bias be assessed only when there is low heterogeneity? This is addressed now Page-20, line:310-311

2 Table5: how can males and females be included in the same model? This is to be the same variable, sex with two modalities male and female Study setting, region, method of sampling, method of HTN definition, etc could be explored in the model This is addressed now Table 4, page-22

2 Discussion: no reference is given to support the statement on HTN and race; I am not sure the comparison between Noubiap and the authors is suitable, as Noubiap included children in their review This is addressed now Page-23, line-365-373

2 Discussion: what is the pertinence in this statement? This is addressed now Page-24, line:377-378

2 these lines are very insufficient as limitations of this study; please see comments above; in addition, discuss the generalizability of finding to the entire country, heterogeneity, etc This is addressed now Page-28, line:480-485

2 Further, I think the discussion is insufficient: little was discussed about clinical implications of this study in terms of harmonizing the way of measuring BP and defining HBP among ados in the country; public health implications in terms of what strategies could be put in place to raise awareness on the issue and preventive measures/programs that could be introduced in school programs, etc This is addressed now Page-27-28, line-458-472

Attachment

Submitted filename: Response to reviewers.docx

Click here for additional data file. (515.9KB, docx)

Decision Letter 1

Simeon-Pierre Choukem

24 Jun 2020

PONE-D-20-01922R1

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies

PLOS ONE

Dear Dr. Haldar,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Among the major issues you should address is the age range of participants in the studies included in the metaanalysis. For studies in which the age range falls beyond the range indicated in the study, you should either extract data of eligible participants or exclude the study if extraction is not possible.  

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We look forward to receiving your revised manuscript.

Kind regards,

Simeon-Pierre Choukem

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I thank the authors for this important work. I appreciated their responses to queries. However, this review and meta-analysis should be extensively revised. The authors should perform what they stated they will perform in Methods section. There are two major concerns and this study should not be considered for publication until strict respect to the methodology.

1) The authors stated that they will included studies conducted among adolescents, 10 to 19 years. However, among studies included, some of them included participants < 10 years old: Anjana 2005 (6-14 years), Buch 2011 (6-18 years), Mujumdar 2012 (6-15 years), Yuvaraj 2014 (9-16 years), George 2014 (9-18 years), Kumar 2017 (5-14 years), and Rai 2018 (8-17 years). Definitively, this is not a study a meta-analysis of data from adolescents since the authors included data from children/infants. The authors should exclude these studies from the review or when possible extract data from adolescents only (> or = 10 years) (if not possible, then exclude).

2) The authors stated that they will include only population/community-based (including school-based) studies. This is an important criteria and I agree with this. However, the authors included a hospital-based study: Soundarssanane 2006.

Reviewer #3: 1. This manuscript describes a systematic review and meta-analysis which aims to calculate the pooled prevalence of hypertension among adolescents (10-19 years) in India. The research is valuable given the well-known short-term and long-term ill effects of high blood pressure diagnosed in adolescence. I believe this study could be a useful contribution to the literature examining the global burden of hypertension in adolescents.

2. The main title clearly identifies the report as a systematic review and meta-analysis; it also indicates the target population as well as the epidemiological measure (“prevalence”) that will be pooled. However, the running title does not contain the world “prevalence”. We suggest that “prevalence” should be added to the running title to fully match with the main title.

3. The abstract summarizes the rationale for the study and the analytic methods used, as well as the key findings.

#Background (line 43): The authors are right that there are concerns on the threat of elevated blood pressure in children and adolescents. It is also known that these concerns originate from existing evidence on the short-term and long-term ill effects of high blood pressure diagnosed in adolescence. This suggests that the authors could replace the expression “…considerable concerns on the threat…” by something like “… the well-known short-term and long-term ill effects…”.

#Methods: The processes of study search and selection were described. However, there is no mention that the study only included manuscripts written in English language (lines 48-50); it is a detail worth mentioning. Further, it is not stated that a meta-regression analysis was carried out, whereas the authors took great care to do it; this should be added to the abstract to accurately reflect the analyses performed during the research.

#Results: The abstract contains the value of the pooled prevalence. It would have been interesting if it also contained the range of the prevalence across studies, so that readers could have an idea of the variability of such measure. Besides, the value of the heterogeneity of subgroup analyses was described as “acceptable” (line 59). It is understandable that a low level of heterogeneity can be deemed acceptable. However, it might be preferable to use the established thresholds of heterogeneity which will qualify an I-square = 18.3% as “small”.

#Conclusion: The authors proposed legitimate policy measures that should be put in place to control hypertension in adolescents. These recommendations could have been stronger if they were preceded by a comment describing the value of that pooled prevalence as “high”.

#Key words (line 65): The abstract contains the key words that will facilitate future bibliographical searches. “Systematic review” and “prevalence” are other important key words that were omitted and ought to be added.

4. The introduction includes important information about the global burden of elevated blood pressure, the rising trend of hypertension in the adolescent population contrasted by the paucity of evidence on its burden and the low level of awareness, the considerable proportion of India’s population that is adolescent, and the lack of information on the national prevalence of hypertension in that population.

# (lines 88-90) The authors supported their point by raising awareness about the burden of cardiovascular diseases (CVD) in developing countries. The expression “…which is now being recognized as a major killer in developing countries” conveys the same information as the first part of the sentence and thus should be removed. Furthermore, the argument about high BP in adolescents of developing countries could have been strengthened by providing factual evidence such as the value of 5.5% that represents the pooled prevalence of elevated blood pressure in children and adolescents in Africa computed by Noubiap JJ et al.

# (lines 100-104) An attempt was made to provide evidence of the link between blood pressure in adolescence and hypertension in adulthood, which is commendable. We believe that more detailed information on this link should be presented to further support the rationale of this study.

# (lines 104-106) Childhood blood pressure (BP) was presented as the ”best” indicator of adult BP. The quality of the reference used is not contested. However, the use of the word “best” is questionable, because it supposes that in this reference, measures of association were used to quantify the predictive value of childhood BP; it also suggests that a comparison was made with other potential predictive factors. In their report, Xiaoli Chen and Youfa Wang did a meta-regression analysis of correlation coefficients rather than measures of association. Further, they did not make a comparison with the predictive value of other potential predictive factors such as diet, family history, etc… Therefore, it would be more accurate to rather describe childhood BP as a “strong” indicator of adult BP.

# (lines 116-123) The importance of the current research is justified by arguing that there is a lack of studies reporting on the prevalence of hypertension among adolescents; it is also claimed that there exists no national survey investigating that issue. It is important to remind that the current work is not an original research but rather a review of existing studies; furthermore, it is not a national survey. Therefore, alternate arguments should be found to justify the relevance of the present study.

5. The methods provides details about the literature search strategy, the study selection criteria and selection process, the data extraction, and the statistical analyses.

# (lines 163-167) The process used to extract data was presented clearly. However, it is not possible to know if there were attempts made to contact the authors of publications that had missing information on key variables. This is critical given that 3,326 participants had missing information on sex (line 208), and 3 studies did not mention the number of BP readings (line 291).

# (lines 168-174) The quality of each included study was assessed using an established scale. The 2 sentences spanning from line 168 to line 174 convey the same information and hence should be combined.

# (lines 182-183) There was an attempt to measure the heterogeneity between the included studies. The only metric used was the I-square. Although we do not contest that the I-square must be presented, using it solely is not convenient for several reasons:

(1) the I-square is not a test statistic but rather a scale;

(2) the I-square does not measure the heterogeneity itself but rather provides the percentage of variation

across studies that is due to their heterogeneity rather than chance;

(3) there is much uncertainty about the I-square when there are few studies such as is the case here

(https://training.cochrane.org/handbook/current/chapter-10#section-10-10-2);

(4) the established test statistic to confirm the presence of heterogeneity is the Cochrane's Q statistic.

Therefore, in addition to the I-square, a Cochrane's Q statistic test of heterogeneity should also be performed, and the results presented and discussed.

# (line 183) The result of the pooled analysis is referred to as the “mean” percent prevalence. It is agreed that the pooled analysis uses a sort of average across studies, but it is in no case a simple mean since there are specific weights that are applied. Therefore, the term “mean” should be replaced by “pooled”.

# (lines 198-192) A meta-regression analysis was carried out to identify the causes of heterogeneity. Two important information were not provided:

(1) how the model fit was assessed;

(2) how the researchers controlled for false-positive findings (type I error) when performing meta-

regression with multiple covariates.

This information should be provided to reinforce the robustness of the analyses seen throughout the paper.

6. The data appear to be sound and the results section presents the output of the processes described in the methods section.

# (line 212) Table 1 presents the characteristics of the studies included in the systematic review and meta-analysis. It appears that several of these studies included participants with an age that fell outside the target range of 10-19 years. This raises several questions about the following:

(1) the accuracy of the study selection process, especially whether the inclusion criteria were respected;

(2) the rationale of restricting the meta-analysis to the adolescent population given the rarity of studies

treating about hypertension in the youth of India; this further raises concerns about the main title of the

systematic review.

# (line 206-207) It should be written: “The total number …was 28,355…”

# (line 250) As stated above, the term “mean” should be replaced by “pooled”.

# (line 252) As stated above, the I-square is not a heterogeneity test but rather a simple scale. The Cochrane's Q statistic test should be performed, and the results presented and discussed.

7. The discussion and conclusion are well balanced and adequately supported by the data.

# (Paragraph starting on line 352) There are valuable arguments presented to explain why the value of the pooled estimate is different from what other authors had found. It would have been easier for the readers to follow the trend of thoughts if there was first a formal comparison made between these values, before presenting the reasons for any difference observed.

# (line 392-393) Community-based studies were described as “superior” to school-based studies. The manuscript lacks the criteria on which this superiority was assessed as well as the references.

# (line 380-381) Specific references should be provided for the criteria of the European Hypertension society and the American Academy of Pediatrics, respectively.

# (line 411-428) The authors did well by highlighting that some of the differences observed might be due to the difference in blood pressure measurement methods used in various studies. However, a more thorough discussion on these methods is warranted because of the great influence that they might have on the accuracy of the diagnosis of hypertension.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: Jean Joel Bigna

Reviewer #3: No

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PLoS One. 2020 Oct 6;15(10):e0239929. doi: 10.1371/journal.pone.0239929.r004

Author response to Decision Letter 1

10 Aug 2020

Dear Sir,

We have responded to all the comments given by the reviewers and the manuscript has been revised.

Response to reviewers

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies.

Reviewer number Original comments of the reviewer Reply by the Author(s) Changes done on page number and line number

1 The authors stated that they will be included studies conducted among adolescents, 10 to 19 years. However, among studies included, some of them included participants < 10 years old: Anjana 2005 (6-14 years), Buch 2011 (6-18 years), Mujumdar 2012 (6-15 years), Yuvaraj 2014 (9-16 years), George 2014 (9-18 years), Kumar 2017 (5-14 years), and Rai 2018 (8-17 years). Definitively, this is not a study a meta-analysis of data from adolescents since the authors included data from children/infants. The authors should exclude these studies from the review or when possible extract data from adolescents only (> or = 10 years) (if not possible, then exclude). Thank you for the comments. Yes, indeed as per inclusion criteria, we did include only the studies where it was possible to abstract data for ages 10 to 19 years. Page 7, line 126-128.

1 The authors stated that they will include only population/community-based (including school-based) studies. This is an important criterion and I agree with this. However, the authors included a hospital-based study: Soundarssanane 2006 Thank you so much. We have addressed this issue now. One hospital-based study is removed.

Accordingly, we updated our meta-analysis. Page 10, updated table 1. After excluding study author Soundarssanane et al

3 The main title clearly identifies the report as a systematic review and meta-analysis; it also indicates the target population as well as the epidemiological measure (“prevalence”) that will be pooled. However, the running title does not contain the world “prevalence”. We suggest that “prevalence” should be added to the running title to fully match with the main title. Thank you so much. This was an oversight from us. We have added the word ‘prevalence in title’ Page 1, line 4.

3 Abstract- Background (line 43): The authors are right that there are concerns on the threat of elevated blood pressure in children and adolescents. It is also known that these concerns originate from existing evidence on the short-term and long-term ill effects of high blood pressure diagnosed in adolescence. This suggests that the authors could replace the expression “…considerable concerns on the threat…” by something like “… the well-known short-term and long-term ill effects…”. Thank you for this suggestion. We have done correction accordingly in the abstract. Page 3, line 39.

3 Methods: The processes of study search and selection were described. However, there is no mention that the study only included manuscripts written in English language (lines 48-50); it is a detail worth mentioning. Further, it is not stated that a meta-regression analysis was carried out, whereas the authors took great care to do it; this should be added to the abstract to accurately reflect the analyses performed during the research. Thank you for this comment. This is addressed now Page 3, line 46 & 51.

3 Results: The abstract contains the value of the pooled prevalence. It would have been interesting if it also contained the range of the prevalence across studies, so that readers could have an idea of the variability of such measure. Besides, the value of the heterogeneity of subgroup analyses was described as “acceptable” (line 59). It is understandable that a low level of heterogeneity can be deemed acceptable. However, it might be preferable to use the established thresholds of heterogeneity which will qualify an I-square = 18.3% as “small”. Thank you for this suggestion. We have done correction accordingly in the abstract. Page 3, line 54-57.

3 Conclusion: The authors proposed legitimate policy measures that should be put in place to control hypertension in adolescents. These recommendations could have been stronger if they were preceded by a comment describing the value of that pooled prevalence as “high”. This is addressed now. We have now removed this recommendation from the manuscript. Page 4, line 60-61.

3 #Key words (line 65): The abstract contains the key words that will facilitate future bibliographical searches. “Systematic review” and “prevalence” are other important key words that were omitted and ought to be added. Thank you for this suggestion. We have done correction accordingly in the keywords. Page 4, line 62.

3 (lines 88-90) The authors supported their point by raising awareness about the burden of cardiovascular diseases (CVD) in developing countries. The expression “…which is now being recognized as a major killer in developing countries” conveys the same information as the first part of the sentence and thus should be removed. Furthermore, the argument about high BP in adolescents of developing countries could have been strengthened by providing factual evidence such as the value of 5.5% that represents the pooled prevalence of elevated blood pressure in children and adolescents in Africa computed by Noubiap JJ et al. Thank you for this comment. This is corrected now in the introduction. Page 5, line 79 and line 86-87.

3 (lines 100-104) An attempt was made to provide evidence of the link between blood pressure in adolescence and hypertension in adulthood, which is commendable. We believe that more detailed information on this link should be presented to further support the rationale of this study. Thank you so much for this comment. This is addressed now. Page 5, line 94-97.

3 (lines 104-106) Childhood blood pressure (BP) was presented as the” best” indicator of adult BP. The quality of the reference used is not contested. However, the use of the word “best” is questionable, because it supposes that in this reference, measures of association were used to quantify the predictive value of childhood BP; it also suggests that a comparison was made with other potential predictive factors. In their report, Xiaoli Chen and Youfa Wang did a meta-regression analysis of correlation coefficients rather than measures of association. Further, they did not make a comparison with the predictive value of other potential predictive factors such as diet, family history, etc… Therefore, it would be more accurate to rather describe childhood BP as a “strong” indicator of adult BP. Thank you for this comment. This is addressed now. Page 5, line 98

3 (lines 116-123) The importance of the current research is justified by arguing that there is a lack of studies reporting on the prevalence of hypertension among adolescents; it is also claimed that there exists no national survey investigating that issue. It is important to remind that the current work is not an original research but rather a review of existing studies; furthermore, it is not a national survey. Therefore, alternate arguments should be found to justify the relevance of the present study Thank you so much for this comment. This is addressed now in the rationale part. Page 6, line 105.

3 (lines 163-167) The process used to extract data was presented clearly. However, it is not possible to know if there were attempts made to contact the authors of publications that had missing information on key variables. This is critical given that 3,326 participants had missing information on sex (line 208), and 3 studies did not mention the number of BP readings (line 291). Authors were not contacted.

-

3 (lines 168-174) The quality of each included study was assessed using an established scale. The 2 sentences spanning from line 168 to line 174 convey the same information and hence should be combined. Thank you for this comment. This is addressed now. Page 8, line 150-156.

3 (lines 182-183) There was an attempt to measure the heterogeneity between the included studies. The only metric used was the I-square. Although we do not contest that the I-square must be presented, using it solely is not convenient for several reasons: (1) the I-square is not a test statistic but rather a scale; (2) the I-square does not measure the heterogeneity itself but rather provides the percentage of variation across studies that is due to their heterogeneity rather than chance; (3) there is much uncertainty about the I-square when there are few studies such as is the case here (https://training.cochrane.org/handbook/current/chapter-10#section-10-10-2); (4) the established test statistic to confirm the presence of heterogeneity is the Cochrane's Q statistic. Therefore, in addition to the I-square, a Cochrane's Q statistic test of heterogeneity should also be performed, and the results presented and discussed. Thank you so much for this suggestion. Cochrane's Q statistic test of heterogeneity is reported throughout the paper now. Page 8, line 164

3 (line 183) The result of the pooled analysis is referred to as the “mean” percent prevalence. It is agreed that the pooled analysis uses a sort of average across studies, but it is in no case a simple mean since there are specific weights that are applied. Therefore, the term “mean” should be replaced by “pooled”. Thank you for the comment. This is addressed throughout the paper now. Page 8, line 166

3 (lines 198-192) A meta-regression analysis was carried out to identify the causes of heterogeneity. Two important information were not provided: (1) how the model fit was assessed; (2) how the researchers controlled for false-positive findings (type I error) when performing meta- regression with multiple covariates. This information should be provided to reinforce the robustness of the analyses seen throughout the paper. Thank you so much for this valuable suggestion. This is addressed now.

1.) R2 value is reported for assessment of goodness of fit.

2.) Monte Carlo permutation test was conducted and the adjustment for type 1 error did not changed the result. Page 9, line 177-179.

3 (line 212) Table 1 presents the characteristics of the studies included in the systematic review and meta-analysis. It appears that several of these studies included participants with an age that fell outside the target range of 10-19 years. This raises several questions about the following: (1) the accuracy of the study selection process, especially whether the inclusion criteria were respected; (2) the rationale of restricting the meta-analysis to the adolescent population given the rarity of studies treating about hypertension in the youth of India; this further raises concerns about the main title of the systematic review. Thank you for the comments. Yes,

1.) As we have stated before we have included only those studies where it was possible to abstract data for ages 10 to 19 years. Thus, this suggestion is already incorporated in our review.

2.) We intended for results to be applicable to the adolescent age group since it represents a distinct demographic and a unique stage of development. For this reason, we included studies from which we could abstract data specific to this age group, and the title reflects this. -

3 (line 206-207) It should be written: “The total number …was 28,355…” Thank you for this comment. This is addressed now Page 9, line 189

3 (line 250) As stated above, the term “mean” should be replaced by “pooled”. Thank you for this comment. This is addressed now Page 15, line 216

3 (line 252) As stated above, the I-square is not a heterogeneity test but rather a simple scale. The Cochrane's Q statistic test should be performed, and the results presented and discussed. Thank you for this comment. As mentioned above we have addressed this throughout the manuscript. Page 15 and page 17 – Table 2 and 3.

3 (Paragraph starting on line 352) There are valuable arguments presented to explain why the value of the pooled estimate is different from what other authors had found. It would have been easier for the readers to follow the trend of thoughts if there was first a formal comparison made between these values, before presenting the reasons for any difference observed. Thank you for this comment. This is addressed now. Page 19, line 282.

3 (line 392-393) Community-based studies were described as “superior” to school-based studies. The manuscript lacks the criteria on which this superiority was assessed as well as the references. Thank you so much for this comment. This is addressed now. Page 20, line 316-318.

3 (line 380-381) Specific references should be provided for the criteria of the European Hypertension society and the American Academy of Pediatrics, respectively. Thank you for this comment. The references have been added now. Page 20, line 307.

3 (line 411-428) The authors did well by highlighting that some of the differences observed might be due to the difference in blood pressure measurement methods used in various studies. However, a more thorough discussion on these methods is warranted because of the great influence that they might have on the accuracy of the diagnosis of hypertension. Thank you so much for suggestion. This is addressed now. Page 21, Line 347-367.

Attachment

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Click here for additional data file. (25.2KB, docx)

Decision Letter 2

Simeon-Pierre Choukem

16 Sep 2020

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies.

PONE-D-20-01922R2

Dear Dr. Haldar,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Simeon-Pierre Choukem

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I thank you for the revision of the paper. All my queries have been adressed. The paper is now acceptable for publication.

Reviewer #3: General: We commend the authors for the extensive work that was done to fully address our concerns.

Line 274: We suggest that the authors replace the word "countries" by "regions".

Lines 275-277: The authors indicate the cut off percentile (90th) used as a reason of the difference between that results obtained by Moraes and theirs. We suggest that the authors also indicate the cut off that was used in their study so that the readers will be able to do a direct comparison.

Lines 401-410: The authors might also want to add to their limitations the fact that it is a very small number of studies conducted in rural settings that was included in their study, as this is an important determinant of the generalizability of their results.

Lines 59-60 and 412-413: We believe that the authors should maintain the recommendations that were in the previous version, for two reasons: (1) our comments did not judge the said recommendations as invalid, but rather proposed that the recommendations be backed by a description of the results; (2) the said recommendations are warranted given the fact that the pooled estimate obtained might actually be an underestimate of the true figure.

**********

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Jean Joel Bigna

Reviewer #3: No

Acceptance letter

Simeon-Pierre Choukem

24 Sep 2020

PONE-D-20-01922R2

Prevalence of hypertension among adolescents (10-19 years) in India: A systematic review and meta-analysis of cross-sectional studies.

Dear Dr. Haldar:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Kind regards,

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on behalf of

Dr. Simeon-Pierre Choukem

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PLOS ONE

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