Article Text

Economic burden of IADPSG gestational diabetes diagnostic criteria in China: propensity score matching analysis from a 7-year retrospective cohort
1. Zonglin He1,2,
2. Yuan Tang1,
3. Huatao Xie1,
4. Yuchen Lin1,
5. Shangqiang Liang1,
6. Yuyuan Xu3,
7. Zhili Chen4,
8. Liang-zhi Wu5,
9. Jie Sheng6,
10. Xiaoyu Bi6,
11. Muyi Pang6,
12. Babatunde Akinwunmi7,8,
13. Xiaomin Xiao5,
14. Wai-kit Ming2
1. 1Faculty of Medicine, International School, Jinan University, Guangzhou, China
2. 2Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
3. 3Out-patient Department, Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
4. 4Department of Nursing, Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
5. 5Department of Obstetrics and Gynaecology, Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China
6. 6College of Economics, Jinan University, Guangzhou, China
7. 7Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
8. 8Maternal-Fetal Medicine Unit, Brigham and Women’s Hospital, Boston, Massachusetts, USA
1. Correspondence to Professor Wai-kit Ming; wkming{at}connect.hku.hk

## Abstract

Introduction The International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) increased the morbidity significantly, but the cost and effectiveness of its application are still unclear. This study aimed to analyze the impact of the IADPSG criteria for diagnosing GDM in China on the perinatal outcomes, and medical expenditure of GDM women versus those with normal glucose tolerance (NGT).

Research design and methods We conducted a retrospective cohort study involving 7794 women admitted at the First Affiliated Hospital of Jinan University (Guangzhou, China), from November 1, 2010 to October 31, 2017. The perinatal outcomes and medical expenditure were retrieved from the electronic medical records in the hospital. Propensity score matching (PSM, in a 1:1 ratio) algorithm was used to minimize confounding effects on the difference in the two cohorts.

After the PSM, the median total medical expenditure of the GDM women throughout the hospitalization was ¥3018.1 (US$465.1), which is ¥912.9 (US$140.7) more than that of the NGT women, who spent ¥2105.2 (US$324.4) (p=0.09, online supplementary table 5). After PSM, only the laboratory tests differed significantly between the NGT and the GDM women (¥456.6 (US$70.4) vs ¥572.0 (US$88.1), p<0.01, online supplementary table 5). Moreover, the NGT women spent more on the examination and blood transfusion than the GDM women (online supplementary table 5). We further analyzed the medical expenditures in the missed diagnosis GDM women and definite GDM women (online supplementary table 5). There was a stepwise increase in the total medical expenditure across the NGT, missed GDM and definite GDM groups. An increase of expenditure for western medicine (¥664.5 (US$102.4), p=0.02) and surgery (¥800.0 (US$123.3), p=0.87) were found among the missed GDM women relative to the other two groups, while the blood transfusion cost (¥1060.0 (US$163.3), p=0.08) was considerably lower in the missed GDM women (online supplementary table 5). Moreover, the definite GDM group had a much greater laboratory test cost (¥714.0 (US$110.0), p<0.01, online supplementary table 5). ### Matrix correlation of occupation and payment method with the medical expenditure The correlation of the occupations of the GDM women with the methods of payment were further analyzed (figure 2). We found except for the three occupations (clerical support workers, managers and professionals) who had the possibilities of free medical service, most people tended to pay their medical expenditure by self-paying or mixed-method, especially the NGT women (figure 2A,B). A large number of pregnant women self-paid the whole amount of medical expenditure, especially the GDM women (figure 2C). Figure 2 The matrix heat map of mean medical expenditure associated with occupation and payment type. (A) All women; (B) women with normal glucose tolerance; (C) women with gestational diabetes mellitus. The occupations were recoded according to the International Standard Classification of Occupations 2008 versions (ISCO-o8) structure. ## Discussion In the present study, we applied PSM to counterbalance confounding effects of maternal age, height and weight at delivery, as well as the duration of pregnancy. The implementation of the IADPSG criteria improved the perinatal outcomes, but the incidence of GDM increased by 3.95-times after implementing the IADPSG criteria, and the medical expenditure also increased, causing an economic burden of ¥912.9 (US$140.7).

We observed that the GDM women diagnosed according to the IADPSG criteria, despite their higher medical expenditures, showed better perinatal outcomes than the NGT women, after PSM of baseline differences using one-to-one matching. This finding indicates that the IADPSG criteria are beneficial from the clinician’s perspectives. And the results were also proven by the linear regression (online supplementary tables 4 and 5). Many scholars have stressed untreated GDM might lead to higher rates of maternal and perinatal morbidity and mortality,20 21 and we found that the adverse perinatal outcomes can be reversed through proper management and treatment of GDM (table 2). Besides, the overall occurrences of adverse perinatal outcomes of the GDM women were significantly less than that of the NGT women, both maternal and neonatal outcomes (table 2), or in other words, the NGT women and their neonates were more susceptible to adverse outcomes. This might be accounted for by more attention and the better obstetric care of the GDM women, by both themselves and the clinicians. There may also be a remote possibility that the NGT women may have had a false negative result and underdiagnosed.

Nevertheless, the neonates of GDM women tended to be more susceptible to pulmonary pathologies, patent foramen ovale and macrosomia, which are the diseases more congenital in nature than the other outcomes (p<0.05 for all, table 2). This finding is as expected following a general knowledge of influence of maternal hyperglycemia on developing fetuses and it coincides with the studies by Boney et al, who reported that macrosomic offsprings were exposed to a hyperglycemic intrauterine environment are at increased risk of developing metabolic disorders in childhood.22–24 del Rosario et al found that due to the intrauterine exposure to hyperglycemia, the neonates might have an increased risk of developing T2DM through DNA methylation, causing epigenetic changes via an effect on β-cell function in the offspring.25 Moreover, owing to the mitotic stability of DNA methylation, the effects can be long-standing as time passes, producing long-term changes in the gene expression.25

However, we cannot dismiss the potential role of social determinants of health, especially socioeconomic factors—such as the access to medical care, income and education level.26 In our study, we found that the total medical expenditure of the GDM women spent throughout the hospitalization was ¥583.2 (US$89.9) more than the NGT women (¥912.9 (US$140.7) after the PSM) (p=0.14 before PSM and p=0.09 after PSM, table 3), which does not coincide with the findings by Xu et al, who found that, on average, the medical expenditure of a GDM woman was ¥6677.37 (US\$1929.87 in 2015) more than an NGT women.13 And Xu et al estimated the economic burden of GDM to be ¥19.36 billion.13

Table 3

Comparison of medical expenditures in NGT and GDM women, and the medical expenditures in women with NGT, GDM and the missed diagnosed group†

The inconsistencies might be a result of variation in management plans and algorithms for different types of GDM, and the follow-up expenditure (viz. pharmaceutical and ambulatory services, as well as the lifestyle management). Xu et al only calculated the direct medical expenditure using insulin, dismissing other hyperglycemic drugs for GDM, including metformin. The percentage of patients with GDM needing pharmacological treatment varies from 20% to 60% in various studies, not to mention that the use of insulin therapy itself clinically is seldom.27–29 According to the 2011 National Diabetes Fact Sheet of Center of Disease Control, only 12% of adults diagnosed with diabetes are receiving treatment with insulin in the USA, and this number could be much lower in low-income and middle-income countries like China.30 Therefore, this result might infer that the actual capacities or willingness of the residents to pay for the management of GDM might remain far below the present economic burden of GDM care brought on by the introduction of the IADPSG criteria in China.

Also, after relegating the GDM women diagnosed under the IADPSG criteria to the missed diagnosed group (missed GDM, n=1087) and GDM (definite GDM, n=368) according to the previous Chinese guidelines, we inferred that the incidence of GDM increased 3.95-times after implementing the IADPSG criteria (online supplementary table 2). These results were consistent with our previous data, where the incidence of GDM was 22.94% when implementing the IADPSG criteria.11 However, under the previous Chinese criteria (the Textbook guidelines), the occurrence rate of GDM was only 8.9%, and Zhu et al found that in Beijing, the prevalence rate of GDM is 18.9% after the implementation of the IADPSG diagnostic criteria in 2015.12

We further analyzed the medical expenditures in the missed diagnosed GDM women and definite GDM women (table 3). There was a stepwise increase in total medical expenditure across the NGT, missed and definite GDM groups. Moreover, in order to evaluate how medical expenditure was influenced, we correlated the occupations of the GDM women with the payment methods (figure 2). Despite the introduction and application of social basic medical insurance, a large number of pregnant women, especially GDM women, self-paid the total amount of the medical expenditure, or in fact they paid less money with the basic medical insurance (figure 2C).

Some global qualitative studies report that one of the barriers to GDM treatment is the financial barriers related to healthcare and unaffordability, which accounts for the non-adherence to treatment among women with GDM in low-income and middle-income countries and in high-income countries like the USA.31–33 However, in low-income and middle-income countries, this situation could be much worse, as not all of the rural primary health centers are accessible to insulin treatment or the early screening for GDM.34

In this regard, ambulatory management of GDM might be feasible. In theory, the blood glucose level of most pregnant women with GDM can be controlled merely by dietetic treatment, indicating that the adoption of the IADPSG criteria in China may be reasonable. Some studies also point out there is no strict difference in glycemic control and perinatal outcomes in women with GDM between the hospitalization and the ambulatory management. 31 35 Therefore, ambulatory management, including telemedicine, diet and exercise management, as well as preconception education, can be considered feasible to lessen the current economic burdens of GDM management.31 In 80% of cases, interventions were shown to significantly reduce GDM complications and their final costs, and only 20% of women with GDM needed additional medications.36 37

Recently, Ming et al performed a meta-analysis, finding a modest but statistically significant improvement in hemoglobin A1c associated with the use of a telemedicine technology.38 Overall, the clinicians should pay greater attention to the preconception counseling, weight management prior to and during pregnancy, self-monitoring of blood glucose levels, medication, medical nutrition therapy and exercise, especially in low-income and middle-income cities and countries.38

An important strength of our study is the utilization of PSM algorithm to reduce the selection bias. By measuring and adjusting for all known and measurable confounding variables, this approach yields efficient estimates for observational studies. Nevertheless, we cannot exclude some bias due to residual confounding.39 Moreover, owing to the nature of the retrospective study, we failed to follow-up the conditions of glycemic control in the women with GDM and to distinguish the medical expenditure of different GDM managements undertaken, which are the limitations of this study.

## Conclusion

In sum, this study has shown that by applying the IADPSG criteria for diagnosing the GDM in China, despite the increasing medical expenditure, improvements were found for both short-term and long-term maternal and neonatal outcomes. And the increased medical costs may be offset by the benefits gained in the long run.

## Acknowledgments

The authors would like to thank the First Affiliated Hospital of Jinan University for providing the platform and resources needed for the conduction of this study.

## Footnotes

• ZH, YT and HX are joint first authors.

• Contributors XX and W-kM conceptualized the design of the study, and drafted and revised the manuscript. ZH and YT conceptualized and drafted the article, with the assistance of XX and W-kM. HX and SL collected the clinical data from the First Affiliated Hospital of Jinan University. YX, ZC, JS, XB, MP and L-zW helped collect and analyze the data regarding the medical expenditure in the Department of the Obstetrics and Gynecology of the First Affiliated Hospital of the Jinan University and drafted the manuscript. All authors have contributed significantly, and all authors have approved the final version of the manuscript.

• Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

• Competing interests None declared.

• Patient consent for publication Not required.

• Ethics approval This study design was approved and waived from ethical application abiding by the regulation of the Ethics Committee of the First Affiliated Hospital of Jinan University. This study was conducted in accordance with the principles of the Declaration of Helsinki.

• Provenance and peer review Not commissioned; externally peer reviewed.

• Data availability statement Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. Data were obtained from a Tertiary Hospital, and in view of the protection of the privacy of the patients, the data are not publicly available, but on reasonable request, the data are available.