Abstract:

This study estimates gestational diabetes mellitus prevalence in Brazil. A systematic review was conducted with articles published between 2010 and 2021 on the PubMed, Scopus, Google Scholar, SciELO, LILACS and Virtual Health Library databases, as well as gray literature. Data were extracted using a standardized instrument together with the risk of bias assessment tool proposed by Hoy et al. A meta-analysis with robust variance and random effects was developed. Heterogeneity was verified using I² and publication bias was assessed using funnel plot and Egger’s test. Prevalence according to risk of bias, diagnostic criteria and country’s regions was determined by subgroup analyses. A total of 32 studies were included, representing 21,942 women. gestational diabetes mellitus pooled prevalence was 14% (95%CI: 11.0; 16.0), considerably higher than estimates from previous studies. Regarding risk of bias, studies with low, medium, and high risk showed a pooled prevalence of 12%, 14% and 14%, respectively. Overall GRADE certainty of evidence rating was low. Most studies used the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria or the adapted IADPSG, showing a pooled prevalence of 15% and 14%, respectively. As for region, the pooled prevalence was higher in the Southeast (14%) and lower in the Central-West (9%). This is the first systematic review to provide evidence on gestational diabetes mellitus prevalence at a national level and to demonstrate considerable heterogeneity among articles and the influence of region, diagnostic criteria and study quality on the referred indicator.

Keywords:
Gestational Diabetes Mellitus; Prevalence; Meta-Analysis; Systematic Review

Resumo:

Este artigo estimou a prevalência da diabetes gestacional no Brasil. Foi realizada uma revisão sistemática e metanálise com artigos publicados de 2010 até 2021 nas bases de dados PubMed, Scopus, Google Scholar, SciELO, LILACS e Biblioteca Virtual em Saúde, além de literatura cinzenta. Os dados foram extraídos usando um instrumento padronizado juntamente com o instrumento de avaliação de risco de viés de Hoy et al. Posteriormente, foi desenvolvida uma metanálise com variância robusta e efeitos aleatórios. A heterogeneidade foi verificada pelo uso do I² e o viés de publicação foi avaliado pelo gráfico de funil e pelo teste de Egger. Análises de subgrupos foram realizadas para determinar a prevalência de acordo com o risco de viés, critérios diagnósticos e regiões do país. Ao todo, 32 estudos foram incluídos nesta metanálise, totalizando 21.942 mulheres. A prevalência combinada de diabetes gestacional no Brasil foi de 14% (IC95%: 11,0; 16,0), consideravelmente superior às estimativas de estudos anteriores. Em relação ao risco de viés, estudos com baixo, médio e alto risco mostraram prevalência combinada de 12%, 14% e 14%, respectivamente. Em relação à certeza da evidência (abordagem GRADE), a classificação geral foi baixa. A maioria dos estudos utilizou os critérios do Grupo de Estudo da Associação Internacional de Diabetes na Gravidez (IADPSG) e do IADPSG adaptado, mostrando uma prevalência combinada de 15% e 14%, respectivamente. Em relação às regiões, a prevalência combinada foi maior no Sudeste (14%) e menor no Centro-oeste (9%). Esta foi a primeira revisão sistemática a fornecer evidências sobre a prevalência de diabetes gestacional em nível nacional, demonstrando considerável heterogeneidade entre os artigos e a influência da região, dos critérios diagnósticos e da qualidade dos estudos sobre o referido indicador.

Palavras-chave:
Diabetes Mellitus Gestacional; Prevalência; Metanálise; Revisão Sistemática

Resumen:

Este artículo estimó la prevalencia de diabetes gestacional en Brasil. Se realizó una revisión sistemática y metaanálisis con artículos publicados del 2010 al 2021 en las bases de datos PubMed, Scopus, Google Scholar, SciELO, LILACS y Biblioteca Virtual en Salud, además de literatura gris. Los datos se extrajeron usando un instrumento estandarizado junto con el instrumento de evaluación del riesgo de sesgo de Hoy et al. Posteriormente, se desarrolló un metaanálisis con varianza robusta y efectos aleatorios. La heterogeneidad se verificó mediante el I², y el sesgo de publicación se evaluó por medio del gráfico en embudo y la prueba de Egger. Se realizaron análisis de subgrupos para determinar la prevalencia según el riesgo de sesgo, criterios diagnóstico y regiones del país. En total, se incluyeron 32 estudios en este metaanálisis, con un total de 21.942 mujeres. La prevalencia combinada de diabetes gestacional en Brasil fue del 14% (IC95%: 11,0; 16,0), considerablemente más alta que las estimaciones de estudios anteriores. Con relación al riesgo de sesgo, los estudios con riesgo bajo, medio y alto mostraron una prevalencia combinada del 12%, del 14% y del 14%, respectivamente. En cuanto a la certeza de la evidencia (enfoque GRADE), la clasificación general fue baja. La mayoría de los estudios utilizó los criterios del Grupo de Estudio de la Asociación Internacional de Diabetes en el Embarazo (IADPSG) y del IADPSG adaptado, lo que muestra una prevalencia combinada del 15% y del 14%, respectivamente. Con relación a las regiones, la prevalencia combinada fue mayor en el Sudeste (14%) y menor en el Centro-Oeste (9%). Esta fue la primera revisión sistemática que proporcionó evidencias sobre la prevalencia de diabetes gestacional en el ámbito nacional, lo que demuestra una considerable heterogeneidad entre los artículos y la influencia de la región, los criterios diagnósticos y la calidad de los estudios sobre este indicador.

Palabras-clave:
Diabetes Mellitus Gestacional; Prevalencia; Metaanálisis; Revisión Sistemática

Introduction

Gestational diabetes mellitus consists in the state of hyperglycemia during pregnancy with glycemic levels that indicate no previous diabetes mellitus diagnosis ¹1. Organização Pan-Americana da Saúde; Ministério da Saúde; Federação Brasileira das Associações de Ginecologia e Obstetrícia; Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Brasília: Organização Pan-Americana da Saúde; 2016.. Its development involves factors such as a state of insulin resistance and hormonal and metabolic changes caused by the body’s adaptation to the fetal needs, as well as nutritional and genetic factors ²2. Sociedade Brasileira de Diabetes. Diretrizes da Sociedade Brasileira de Diabetes 2019-2020. São Paulo: Clannad; 2019.. Gestational diabetes mellitus is one of the leading causes of morbidity and mortality in pregnant women and newborns, representing a global public health issue with repercussions for the maternal-fetal binomial ³3. Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, et al. Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2018; 18:494., such as childhood obesity or type 2 diabetes mellitus. Consequently, it results in higher public health expenses which could be avoided with early diagnoses and effective interventions to aid pregnant women during this period ³3. Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, et al. Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2018; 18:494.^,44. International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33:676-82..

Gestational diabetes mellitus has several diagnostic criteria resulting in a high diversity for its estimated prevalence. The American Diabetes Association (ADA) and the World Health Organization (WHO) recommend adopting the International Association of Diabetes in Pregnancy Study Group (IADPSG) diagnostic criteria for gestational diabetes mellitus diagnosis, confirmed by testing the levels of fasting blood glucose or using oral glucose tolerance test (OGTT) 75g between 24-28 weeks of pregnancy, period in which insulin resistance is significantly increased ⁵5. Durnwald C. Gestational diabetes mellitus: screening, diagnosis, and prevention. https://medilib.ir/uptodate/show/6797 (accessed on 05/Jan/2023).
https://medilib.ir/uptodate/show/6797... . In 2013, WHO extended the IADPSG criterion validity for any gestational age and established OGTT values after 2 hours up to 199mg/dL, thus avoiding convergence with the diabetes mellitus criteria ¹1. Organização Pan-Americana da Saúde; Ministério da Saúde; Federação Brasileira das Associações de Ginecologia e Obstetrícia; Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Brasília: Organização Pan-Americana da Saúde; 2016..

Globally, gestational diabetes mellitus prevalence varies between 0.3% and 28% ⁶6. Jiwani A, Marseille E, Lohse N, Damm P, Hod M, Kahn JG. Gestational diabetes mellitus: results from a survey of country prevalence and practices. J Matern Fetal Neonatal Med 2011; 25:600-10.. In 2015, approximately 17.8 million deliveries with neonates born alive to pregnant women between 20 and 49 years old were affected by this condition ⁷7. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group's Criteria. Diabetes Res Clin Pract 2022; 183:109050.. In Brazil, prevalence data show considerable variability as shown by a multicenter cohort study with 5,564 pregnant women that estimated a 18% prevalence (95% confidence interval - 95%CI: 16.9; 19.0) ⁸8. Trujillo J, Vigo A, Reichelt A, Duncan BB, Schmidt MI. Fasting plasma glucose to avoid a full OGTT in the diagnosis of gestational diabetes. Diabetes Res Clin Pract 2014; 105:322-6., whereas a cohort research with 4,131 participants observed a 2.6% prevalence (95%CI: 2.1; 3.1) ⁹9. Buffarini R, Barros AJD, Matijasevich A, Loret de Mola C, Santos IS. Gestational diabetes mellitus, pre-gestational BMI and offspring BMI z-score during infancy and childhood: 2004 Pelotas Birth Cohort. BMJ Open 2019; 9:e024734., despite being based on self-reported answers.

The lack of systematic reviews and meta-analyses on gestational diabetes mellitus in Brazil, as well as the impact of this clinical outcome on national health, justifies an in-depth investigation of observational studies conducted in the country. In this context, this article estimated the gestational diabetes mellitus pooled prevalence in Brazil, a relevant data to subsidize planning and administration of interventions such as public policies, health services and programs aimed at reducing the level of gestational diabetes mellitus impact and improving mother and child health ¹⁰10. Muche AA, Olayemi OO, Gete YK. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: a systematic review and meta-analysis. Arch Public Health 2019; 77:36.^,1111. Pereira MG. Epidemiologia: teoria e prática. Rio de Janeiro: Guanabara Koogan; 1995.. Additionally, it categorized the pooled prevalence evaluation according to country region, the gestational diabetes mellitus diagnostic criteria used and the risk of bias in the analyzed articles.

Methods

This systematic review and meta-analysis was developed according to the Cochrane Handbook for Systematic Reviews guidelines and the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) precepts. It was registered on the PROSPERO platform (code CRD42022293743).

Search strategy and databases

Intending to access all eligible studies for inclusion in the data set, we performed a systematic search for articles in the PubMed, Scopus, Google Scholar, SciELO, LILACS and Virtual Health Library databases, as well as the analysis of gray literature researched in annals and works published in Brazilian and Latin-American congresses in the fields of Gynecology and Obstetrics, Endocrinology, and Metabology. For each database a search strategy was developed using sensitive terms to the subject (Supplementary Material - Box S1; https://cadernos.ensp.fiocruz.br/static//arquivo/suppl-e00064919_9189.pdf). Articles in Portuguese, Spanish and English were considered.

Study eligibility

This systematic review included observational or diagnostic studies on gestational diabetes mellitus that presented data about the prevalence of this disease in Brazil published between 2010 and 2021. The year 2010 represents the milestone of adherence to the IADPSG diagnostic criteria for gestational diabetes mellitus, adopted by WHO and the Brazilian Ministry of Health ⁴4. International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33:676-82.. Exclusion criteria consisted of studies that did not address the research question, duplicated studies, qualitative studies, article reviews, case reports, narrative reviews and conference abstracts with incomplete information or that did not answer the investigators, editorials, commentaries, letters to the editor, author responses and other publications that did not include quantitative data.

Study selection

Studies identified in each database were imported into Microsoft Word (https://products.office.com/). After removing duplicates using the Copyspider tool (https://copyspider.com.br/), the title, abstract and full text of the articles were analyzed based on the established inclusion and exclusion criteria. Pairs independently performed this analysis and, in case of disagreement, a third evaluator was responsible for the final decision.

Data extraction

Data on authors, title, year of publication, journal, database, language, location, region of the country and state, year of investigation, study design and main objective were extracted from the selected studies using Google Forms (https://docs.google.com/forms). Inclusion and exclusion criteria, size of total and studied samples, lost sample size, diagnostic criteria, gestational period at time of diagnosis, gestational diabetes mellitus prevalence and respective confidence interval and risk factors for the mother and child were also observed. Pairs independently performed the extraction and, in case of disagreement, a third evaluator made the final decision.

Outcomes and diagnostic criteria

Gestational diabetes mellitus prevalence was obtained by calculating the ratio between the number of pregnant women diagnosed with gestational diabetes mellitus and the total number of pregnant women in the studied sample. Gestational diabetes mellitus diagnostic criteria varied between articles. IADPSG criterion was attributed when the study followed the definition below or cited its use: fasting blood glucose ≥ 92mg/dL and ≤ 125mg/dL at the first prenatal visit or at least one of the OGTT with 75g values of ≥ 92mg/dL in fasting, ≥ 180mg/dL after one hour and ≥ 153mg/dL after two hours, performed between 24 and 28 weeks of gestation ¹1. Organização Pan-Americana da Saúde; Ministério da Saúde; Federação Brasileira das Associações de Ginecologia e Obstetrícia; Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Brasília: Organização Pan-Americana da Saúde; 2016.. Adapted IADPSG was considered when the article adopted the specifications above with some alteration in the testing period or blood glucose values. The 2010 ADA criterion was met if gestational diabetes mellitus diagnosis was confirmed with an OGTT 100g value greater than or equal to at least two of the values: 95mg/dL in fasting, 180mg/dL after one hour, 155mg/dL after two hours, and 140mg/dL after three hours ¹²12. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 34:62-9.. Studies that made the diagnosis using fasting plasma glucose ≥ 126mg/dL and/or OGTT 75g ≥ 140mg/dL after two hours followed the 1999 WHO guidelines ¹1. Organização Pan-Americana da Saúde; Ministério da Saúde; Federação Brasileira das Associações de Ginecologia e Obstetrícia; Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Brasília: Organização Pan-Americana da Saúde; 2016.. The Brazilian Diabetes and Pregnancy Task Force (GTDG, acronym in Portuguese) 2001 criterion corresponds to diagnosis based on fasting glucose ≥ 110mg/dL or OGTT 75g ≥ 140mg/dL after two hours ¹³13. Reichelt AJ, Oppermann MLR, Schmidt MI. Recomendações da 2ª Reunião do Grupo de Trabalho em Diabetes e Gravidez. Arq Bras Endocrinol Metabol 2002; 46:574-81.. Finally, articles that did not inform or that did not specify the adopted diagnostic criteria were listed as not informed and non-accurate criteria, respectively.

Quality evaluation

Study quality was assessed by analyzing risk of bias based on a tool developed by Hoy et al. ¹⁴14. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol 2012; 65:934-9. which has been used in systematic reviews aiming to assess the prevalence of a health problem or event ¹⁰10. Muche AA, Olayemi OO, Gete YK. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: a systematic review and meta-analysis. Arch Public Health 2019; 77:36.^,1515. Badakhsh M, Daneshi F, Abavisani M, Rafiemanesh H, Bouya S, Sheyback M, et al. Prevalence of gestational diabetes mellitus in Eastern Mediterranean region: a systematic review and meta-analysis. Endocrine 2019; 65:505-14.^,1616. Mwanri AW, Kinabo J, Ramaiya K, Feskens EJM. Gestational diabetes mellitus in sub-Saharan Africa: systematic review and metaregression on prevalence and risk factors. Trop Med Int Health 2015; 20:983-1002.. The instrument consists of ten items that address four different bias domains and an overall summary assessment based on the responses to the previous items. Their topics correspond to external (items 1 to 4, whose domains are selection and non-response bias) and internal (items 5 to 10, whose domains are measurement and analysis) study validity dimensions ¹⁴14. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol 2012; 65:934-9.. Each article was classified according to the answers to individual items: “yes”, if the item was answered or “no”, if the information was insufficient or not contemplated, resulting in a final classification depending on the added result: 8 or more “yes” answers indicated low risk of bias; 6 to 7 “yes” answers, moderate; and 5 or less “yes” answers a high risk of bias. Similar categorization was used in other systematic review studies ¹⁰10. Muche AA, Olayemi OO, Gete YK. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: a systematic review and meta-analysis. Arch Public Health 2019; 77:36.^,1616. Mwanri AW, Kinabo J, Ramaiya K, Feskens EJM. Gestational diabetes mellitus in sub-Saharan Africa: systematic review and metaregression on prevalence and risk factors. Trop Med Int Health 2015; 20:983-1002.. Some conventions were adopted to standardize the risk of bias classification. Regarding external validity, study of local population, exclusion criteria selective to a certain population or use of a convenience sample were considered high risk. As for internal validity, information obtained from only one source (e.g., only from medical records), unspecified diagnostic criteria, different data collection between individuals in the sample, unspecified time of diagnosis (gestational week) or no information on the numerator and denominator used to calculate prevalence indicated high risk.

The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) assessment tool for prognosis studies was used to rate the certainty of the evidence generated ¹⁷17. Iorio A, Spencer FA, Falavigna M, Alba C, Lang E, Burnard B, et al. Use of GRADE for assessment of evidence about prognosis: rating confidence in estimates of event rates in broad categories of patients. BMJ 2015; 350:h870.. A summary of findings was developed, explaining the decision regarding the five criteria (risk of bias, inconsistency, imprecision, indirectness and publication bias).

Data analysis

All eligible studies were included in the systematic review for constructing a database based on the collection instrument. We developed a meta-analysis with robust variance and random effects using the Stata software, version 16 (https://www.stata.com), in which we prepared the forest plot and estimated the summary measure for the pooled prevalence data together with its confidence interval. Heterogeneity between studies was verified by calculating I² variability (low < 25%, moderate 25-50% and high > 50%). Gestational diabetes mellitus pooled prevalence for each country region and according to risk of bias was estimated by subgroup analyses. Pooled prevalence was also analyzed according to the gestational diabetes mellitus diagnostic criteria used. Publication bias was verified by a funnel plot, Egger’s test and trim-and-fill sensibility analysis. Finally, a meta-regression analysis for random effects was performed to verify trends over time considering the years of data collection. The first year was considered when the study presented a data collection longer than one year. Articles lacking this information were excluded from the meta-regression analysis.

Results

Figure 1 summarizes the selection process for the studies included in this systematic review. A total of 3,121 articles were identified, 3,120 from five different databases and 1 retrieved from gray literature. By reading the titles and abstracts, 273 duplicates were identified resulting in 2,848 studies for screening. Of these, 2,776 articles were excluded in a later evaluation for not addressing the research topic, not presenting prevalence data, and not considering Brazil as the source of analysis. Of the 71 articles pre-selected for reading, 39 were removed for meeting the exclusion criteria thus totaling 32 studies included in the review.

Total sample consisted of 21,942 women from four different Brazilian regions. Seven studies were conducted in the Northeast, two in the Central-West, 11 in the Southeast and ten in the Southern region (Table 1). Regarding study design, 17 were cross-sectional studies, 13 were prospective cohort studies and four were retrospective cohort studies.

Gestational diabetes mellitus prevalence ranged from 1.6% to 40.2%. As for the gestational diabetes mellitus diagnostic criteria, 14 studies used the IADPSG adapted, five used the IADPSG, two the WHO 1999, two the ADA 2010, one the GTDG 2001, and one failed to specify the criterion used. Additionally, seven studies failed to report the criteria used for gestational diabetes mellitus diagnosis (Table 1).

Risk of bias analysis based on the instrument by Hoy et al. ¹⁴14. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol 2012; 65:934-9. found that five studies (15.6%) had a low risk of bias, 13 (37.5%) had a moderate risk of bias and 15 (46.8%) a high risk (Table 2). As 28 (82.4%) out of the 34 articles were characterized as moderate or high risk of bias, this indicates a vulnerability of the studies. The item with the highest frequency of “no” answers referred to the use of a representative sample (84.3%), whereas the item with the most “yes” answers concerns the use of the same diagnostic method for all evaluated pregnant women (96.9%). Only the study by Renz et al. ¹⁸18. Renz PB, Cavagnolli G, Weinert LS, Silveiro SP, Camargo JL. HbA1c test as a tool in the diagnosis of gestational diabetes mellitus. PLoS One 2015; 10:e0135989. had all risk of bias criteria contemplated for avoidability, thus presenting the highest number of positive responses. Conversely, the study by Siqueira et al. ¹⁹19. Siqueira F, Ferreira EM, de Matos Calderon I, Dias A. Prevalence of colonisation by group B streptococcus in pregnant patients in Taguatinga, Federal District, Brazil: a cross-sectional study. Arch Gynecol Obstet 2019; 299:703-11. met none of the criteria, having the highest number of negative answers.

Overall certainty of evidence rating was low. Quality assessment showed weaknesses in inconsistency and indirectness (Box 1).

The meta-analysis included all 32 articles to estimate the gestational diabetes mellitus pooled prevalence of 14% (95%CI: 11.0; 16.0) with a heterogeneity between studies (I²) of 97.9% (p < 0.001) (Figure 2). Regarding publication bias, the Egger’s test with a p-value of 0.003 and the funnel plot indicate its presence (Figure 3). To estimate the potential impact of publication bias on the gestational diabetes mellitus pooled prevalence, we performed a trim-and-fill test imputing two studies on the left side of the funnel plot, resulting in a pooled prevalence of 12.3% (95%CI: 8.8; 15.9).

Other meta-analyses stratified by some characteristics were conducted to analyze their influence on the gestational diabetes mellitus pooled prevalence (Table 3) (forest plots are presented in Supplementary Material - Figures S1, S2 and S3; https://cadernos.ensp.fiocruz.br/static//arquivo/suppl-e00064919_9189.pdf). Risk of bias analysis classified five (15.6%) studies as low risk of bias, which analyzed 1,645 individuals and 12% (95%CI: 3.0; 20.0) pooled prevalence; 12 articles (37.5%) as moderate risk of bias, totaling 7,515 women and 14% (95%CI: 10.0; 19.0) pooled prevalence, and 15 studies as high risk of bias, with 14% of gestational diabetes mellitus pooled prevalence (95%CI: 10.0; 18.0) and a population of 11,460 participants.

As for diagnostic criteria, the gestational diabetes mellitus pooled prevalence was 15% (95%CI: 10.0; 20.0), 14% (95%CI: 11.0; 18.0), 15% (95%CI: 6.0; 24.0) and 10% (95%CI: 5.0; 15.0), respectively, for the IADPSG, IADPSG adapted, other criteria and unspecified criteria. Analysis by country region showed that most studies were conducted in the Southeast and South regions, with 14% (95%CI: 0.09; 0.18) and 13% (95%CI: 9.0; 16.0) gestational diabetes mellitus pooled prevalences, respectively. Northeast presented a pooled prevalence of 11% (95%CI: 5.0-18.0) and the Central-West, 9% (95%CI: 7.0; 11.0).

Finally, the results of the meta-regression analysis for random effects (Figure 4) showed that the variable “year of data collection” did not significantly contribute to heterogeneity, presenting a coefficient equal to -0.002 (95%CI: -0.009; 0.004) and a p-value of 0.439.

Discussion

This systematic review and meta-analysis estimated the gestational diabetes mellitus pooled prevalence in Brazil at 14% (95%CI: 11.0; 16.0) from analyzing 32 studies, totaling a sample of 21,942 pregnant women. Moreover, it assessed the pooled prevalence according to country region, the diagnostic criteria used and the risk of bias.

Brazil’s estimated gestational diabetes mellitus pooled prevalence is similar to that is found in mainland China (14.8%; 95%CI: 12.8; 16.7) ²⁰20. Gao C, Sun X, Lu L, Liu F, Yuan J. Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis. J Diabetes Investig 2018; 10:154-62., Australia (14%) ²¹21. Laurie JG, McIntyre HD. A review of the current status of gestational diabetes mellitus in Australia: the clinical impact of changing population demographics and diagnostic criteria on prevalence. Int J Environ Res Public Health 2020; 17:9387. and Africa (13.6%; 95%CI: 10.99; 16.23) ¹⁰10. Muche AA, Olayemi OO, Gete YK. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: a systematic review and meta-analysis. Arch Public Health 2019; 77:36.. Pooled prevalence was 11.7% (95%CI: 10.7; 12.6) in Eastern Mediterranean ¹⁵15. Badakhsh M, Daneshi F, Abavisani M, Rafiemanesh H, Bouya S, Sheyback M, et al. Prevalence of gestational diabetes mellitus in Eastern Mediterranean region: a systematic review and meta-analysis. Endocrine 2019; 65:505-14. and 11.5% (95%CI: 10.9; 12.1) in Asia ³3. Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, et al. Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2018; 18:494., specifically reaching 10.07% (95%CI: 6.47; 15.68) in East and Southeast Asia ²²22. Nguyen CL, Pham NM, Binns CW, Duong DV, Lee AH. Prevalence of gestational diabetes mellitus in Eastern and Southeastern Asia: a systematic review and meta-analysis. J Diabetes Res 2018; 2018:6536974.. In Europe, the value was 10.9% (95%CI: 10; 11.8) ²³23. Paulo MS, Abdo MN, Bettencourt-Silva R, Al-Rifai RH. Gestational diabetes mellitus in Europe: a systematic review and meta-analysis of prevalence studies. Front Endocrinol 2021; 12:691033.; 8.2% (95%CI: 7.5; 8.9) in the United States ²⁴24. Zhou T, Du S, Sun D, Li X, Heianza Y, Hu G, et al. Prevalence and trends in gestational diabetes mellitus among women in the United States, 2006-2017: a population-based study. Front Endocrinol 2022; 13:868094.; 7.7% (95%CI: 1.9; 27.9) in Turkey ²⁵25. Karaçam Z, ÇelIk D. The prevalence and risk factors of gestational diabetes mellitus in Turkey: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2021; 34:1331-41.; 3.4% (95%CI: 18.6; 1.3) in Iran ²⁶26. Jafari-Shobeiri M, Ghojazadeh M, Azami-Aghdash S, Naghavi-Behzad M, Piri R, Pourali-Akbar Y, et al. Prevalence and risk factors of gestational diabetes in Iran: a systematic review and meta-analysis. Iran J Public Health 2015; 44:1036-44.; and 2.3% in Japan ²⁷27. Mizuno S, Nishigori H, Sugiyama T, Takahashi F, Iwama N, Watanabe Z, et al. Association between social capital and the prevalence of gestational diabetes mellitus: an interim report of the Japan Environment and Children's Study. Diabetes Res Clin Pract 2016; 120:132-41..

According to the Diabetes Atlas of the International Diabetes Federation (IDF) ⁷7. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group's Criteria. Diabetes Res Clin Pract 2022; 183:109050., in 2021 the estimated gestational diabetes mellitus prevalence in South and Central America was 10.4% (95%CI: 10.1; 10.7), below the pooled prevalence found in this systematic review. A study conducted in Chile found an even lower prevalence, 7.6% (95%CI: 7.5; 7.8) ²⁸28. Garmendia ML, Mondschein S, Montiel B, Kusanovic JP. Trends and predictors of gestational diabetes mellitus in Chile. Int J Gynaecol Obstet 2020; 148:210-8.. Studies in countries like Argentina and Peru, in turn, observed a higher prevalence than those found in Brazil, 24.9% and 16%, respectively ²⁹29. Gorban de Lapertosa S, Sucani S, Salzberg S, Alvariñas J, Faingold C, Jawerbaum A, et al. Prevalence of gestational diabetes mellitus in Argentina according to the Latin American Diabetes Association (ALAD) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria and the associated maternal-neonatal complications. Health Care Women Int 2021; 42:636-56.^,3030. Larrabure-Torrealva GT, Martinez S, Luque-Fernandez MA, Sanchez SE, Mascaro PA, Ingar H, et al. Prevalence and risk factors of gestational diabetes mellitus: findings from a universal screening feasibility program in Lima, Peru. BMC Pregnancy Childbirth 2018; 18:303..

A Brazilian study conducted with greater robustness (larger sample and low risk of bias) showed a prevalence of 20.8% ³¹31. Alves AS, Coutinho I, Mendes-Segatto JC, Silva LA, Sousa-Silva MD, Katz L. Evaluation of the adequacy of tracking and diagnosis of gestational diabetes mellitus in pregnant women attending a hospital unit in two municipalities in the São Francisco Valley Region - Northeast Brazil. Rev Bras Saúde Matern Infant 2014; 14:39-46.. Other studies with comparatively larger samples, but with a moderate risk of bias, presented greater variability, probably due to the sources of heterogeneity discussed later: 3.3% ³²32. Guttier MC, Barcelo RS, Ferreira RW, Bortolotto CC, Dartora WJ, Schmidt MI, et al. Repeated high blood pressure at 6 and 11 years at the Pelotas 2004 birth cohort study. BMC Public Health 2019; 19:1260., 10.8% ³³33. Nascimento GR, Alves LV, Fonseca CL, Figueiroa JN, Alves JG. Dietary patterns and gestational diabetes mellitus in a low income pregnant women population in Brazil - a cohort study. Arch Latinoam Nutr 2016; 66:301-8. and 18,1% ³⁴34. de Lima MC, Santos IS, Crivellenti LC, Sartorelli DS. A better quality of maternal dietary fat reduces the chance of large for gestational age infants: a prospective cohort study. Nutrition 2021; 91-92:111367..

Importantly, this was the first systematic review and meta-analysis on gestational diabetes mellitus in the country. Previously, based on a cohort study ³⁵35. Schmidt MI, Duncan BB, Reichelt AJ, Branchtein L, Matos MC, Costa e Forti A, et al. Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes. Diabetes Care 2001; 24:1151-5. from 1991 to 1995, the 2006 Brazilian guidelines ³⁶36. Sociedade Brasileira de Endocrinologia e Metabologia. Diretrizes em foco. Diabetes mellitus gestacional. Rev Assoc Méd Bras 2008; 54:471-86. cited a prevalence between only 2.4% (95%CI: 2.0; 2.9) and 7.2% (95%CI: 6.5; 7.9) according to 2000 ADA and 1999 WHO criteria, respectively. Conversely, the 2017 Brazilian consensus ¹1. Organização Pan-Americana da Saúde; Ministério da Saúde; Federação Brasileira das Associações de Ginecologia e Obstetrícia; Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Brasília: Organização Pan-Americana da Saúde; 2016. points to a prevalence of around 18% (95%CI: 16.9; 19.0) based on a cohort study ⁸8. Trujillo J, Vigo A, Reichelt A, Duncan BB, Schmidt MI. Fasting plasma glucose to avoid a full OGTT in the diagnosis of gestational diabetes. Diabetes Res Clin Pract 2014; 105:322-6. using IADPSG criteria. Our study presents a considerably higher estimate than older investigations founded on previous diagnostic criteria and a similar, but lower, estimate to a newer research using the updated criteria.

Regarding pooled prevalences analyzed by region, the Northeast showed a pooled prevalence of 11%, due to the disparity between the studies with 20.8% ³⁰30. Larrabure-Torrealva GT, Martinez S, Luque-Fernandez MA, Sanchez SE, Mascaro PA, Ingar H, et al. Prevalence and risk factors of gestational diabetes mellitus: findings from a universal screening feasibility program in Lima, Peru. BMC Pregnancy Childbirth 2018; 18:303. and 1.6% ³⁷37. Pereira DO, Ferreira TLS, de Araújo DV, Melo KDF, de Andrade FB. Evaluation of prenatal consultations: prenatal access and complications in maternal-child health. Rev Ciênc Plur 2017; 3:2-15. values, and the Central-West of 9%, given the 28.2% ¹⁸18. Renz PB, Cavagnolli G, Weinert LS, Silveiro SP, Camargo JL. HbA1c test as a tool in the diagnosis of gestational diabetes mellitus. PLoS One 2015; 10:e0135989. and 4.3% ³⁸38. Ayach W, Paranhos-Calderon IM, Rudge MVC, Araújo-Costa RAA. Comparison between two gestational diabetes screening tests and the perinatal outcome. Rev Bras Ginecol Obstet 2010; 32:222-8. values. A possible explanation for data variability is the asymmetry in socioeconomic conditions and access to health services between Brazilian regions, influencing the number of diagnoses. Screening is made difficult by factors such as housing conditions, family income, schooling level, urbanization, water supply and sanitation thus increasing the chances of complications during pregnancy ³⁷37. Pereira DO, Ferreira TLS, de Araújo DV, Melo KDF, de Andrade FB. Evaluation of prenatal consultations: prenatal access and complications in maternal-child health. Rev Ciênc Plur 2017; 3:2-15.. This hypotheses aligns with in a study conducted in India ³⁹39. Swaminathan G, Swaminathan A, Corsi DJ. Prevalence of gestational diabetes in India by individual socioeconomic, demographic, and clinical factors. JAMA Netw Open 2020; 3:2025074., which pointed to a considerable variation in gestational diabetes mellitus prevalence by state, socioeconomic level and demographic factors, as well as the correlation of areas with few economic resources allocated to gestational diabetes mellitus screening with lower prevalence levels. Hence, socioeconomic and care factors may influence this decrease in regional prevalence.

As for the diagnostic criteria used, we observed a weakness in the studies homogeneity. A total of five different diagnostic criteria were identified in the analyzed articles, in addition to those lacking this information. IADPSG (five studies) and the adapted IADPSG (14 studies) were the most used, frequently performing the OGTT 75g in a period different from that established in the original instrument. The stratified meta-analysis found a higher pooled prevalence (15%; 95%CI: 10.0; 20.0) in articles that employed the original criterion and a lower pooled prevalence (14%; 95%CI: 11.0; 18.0), in those with some adaptation, showing a possible decrease in diagnostic sensitivity. Similarly, when comparing the IADPSG criterion with the 2010 ADA, other studies have found higher diagnostic rates with the former ⁴⁰40. González-González NL, González-Dávila E, Megía A, Pintado P, Vega B, Padrón E, et al. The NDDG criteria versus the IADPSG or the ADA criteria for diagnosing early-onset gestational diabetes mellitus or abnormal glucose tolerance. Int J Gynaecol Obstet 2023; 160:906-14.^,4141. Shang M, Lin L. IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes. J Perinatol 2014; 34:100-4.^,4242. Tonguc M, Tayyar AT, Müderris I, Bayram F, Muhtaroglu S, Tayyar M. An evaluation of two different screening criteria in gestational diabetes mellitus. J Matern Fetal Neonatal Med 2018; 31:1188-93., confirming its greater sensitivity.

Regarding risk of bias, although most of the articles (82.4%) analyzed presented moderate or high risk, proportional values were obtained among low, moderate and high risk. A gestational diabetes mellitus pooled prevalence of 12% was found among low-risk studies; of 14% among moderate-risk studies, and of 14% among high-risk studies. Representative sample (27 studies) and random or census selection (26 studies) were the most frequent risks of bias, whereas using different diagnostic methods for all participants occurred only once. Despite the importance of study quality for selecting the best evidence, the risk of bias was not a factor of great influence on distorting the results found.

Study limitations include the disparity in the number of studies from different regions and the lack of detailed information about methodology and gestational diabetes mellitus measurement criteria in some articles. Thus, threshold value changes in identifying gestational diabetes mellitus would inevitably cause high heterogeneity in the results. Additionally, the meta-analysis included studies with small sample sizes, which may result in data with high analytical variability, and different designs (whether prospective or retrospective cohort, cross-sectional study, diagnostic or descriptive test).

Despite achieving the main study objective, we did not evaluate the factors that may influence gestational diabetes mellitus prevalence. Most studies have not evaluated the gestational diabetes mellitus effects on maternal and fetal outcomes and were conducted in Southeastern and Southern municipalities, causing a great risk of bias in data interpretation and generalization for other locations which were not included in the meta-analysis or had few articles analyzed in comparison. Similarly, none of the studies included in this systematic review used a national population base pointing to the need for new nationally representative research.

Despite these limitations, this is the first meta-analysis conducted in Brazil about gestational diabetes mellitus prevalence stratified by region and with analysis of risk of bias and methodological quality of the publications, helping with data interpretation.

Conclusion

This study provided evidence on estimated gestational diabetes mellitus occurrence in Brazil between 2010 and 2021. Data summarized in the meta-analysis showed a gestational diabetes mellitus pooled prevalence of 14%. Country region, the diagnostic criteria used and study quality influenced the resulting pooled prevalence indicator. However, the high heterogeneity between the studies hindered to summarize the findings.

To the best of our knowledge, this meta-analysis is the first to provide evidence on the national gestational diabetes mellitus pooled prevalence, a key factor in understanding and characterizing the epidemiology of the condition. Given the evidence generated, the issue may trigger greater interest in health managers to address the disease. The current national scenario requires planning to manage the condition. Screening and diagnosis, based on standardized criteria, as well as preventive actions for gestational diabetes mellitus control and adequate patient management could potentially reduce this disease’s burden.

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