Healthcare interventions for the prevention and control of gestational diabetes mellitus in China: a scoping review

Every pregnancy is associated with a certain degree of hyperinsulinemia and insulin resistance, but in some women these physiological changes lead to Gestational Diabetes Mellitus (GDM) [1]. GDM is a condition in which women without previously diagnosed glucose intolerance exhibit high blood glucose levels during pregnancy, particularly during their third trimester [2]. Over the past 20 years, the prevalence of GDM has increased world-wide, and across China [3]. According to the latest diagnostic criteria established by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) in 2010 [4, 5] the GDM prevalence was estimated at 9.8–25.5% worldwide and 9.3–18.9%% in China [6, 7].

GDM has a significant impact on the health of both the mother and the baby. Women with GDM are at greater risk of pregnancy complications, such as pre-eclampsia, pre-term birth and macrosomia [8], as well as post-partum complications, such as a higher risk of GDM in subsequent pregnancies and the development of type II diabetes up to 25 years after the childbirth [9, 10]. Of greatest concern, however, are the profound epigenetic changes that GDM has, through the intrauterine environment, on the offspring, who display a increased risk of short- and long-term health effects. In the post-natal period, potential adverse outcomes include neonatal hypoglycemia, macrosomia, hyperbilirubinemia and respiratory distress syndrome [9]. In later life, babies born from mothers with GDM have a higher risk of type II diabetes, obesity, and metabolic syndrome [11‐13]. In turn, these traits are transmitted to the next generation, further perpetuating the vicious cycle of metabolic diseases [14, 15].

Recent evidence indicates that GDM treatments can effectively improve some maternal and newborn health outcomes [16, 17]. In 2014, the Department of Obstetrics and Gynecology and the Department of Perinatal Medicine within the Chinese Medical Association developed a joint recommendation for the diagnosis and treatment of GDM in China [18]. The guideline is similar to the American Diabetes Association and International Association of Diabetes and Pregnancy Study Group (IADPSG) guideline [19, 20] and recommends that all non-diabetic women undergo diagnostic testing with a 75 g Oral Glucose Tolerance Test (OGTT) at the 24-28th weeks of pregnancy. GDM is defined as an OGTT fasting glucose level higher than 5.1 mmol/L (92 mg/dl), 1 h post-OGTT higher than 10.0 mmol/L (180 mg/dl), or 2 h post-OGTT higher than 8.5 mmol/L (153 mg/dl). Women diagnosed with GDM should receive lifestyle interventions (including intensive diet, exercise, and/or health education). Medication interventions (e.g., insulin therapy) may be recommended for women who do not respomnd to lifestyle interventions or with diabetic ketoacidosis. There are minor differences between China and Western guidelines in lifestyle treatment recommendations. For example, the exercise time and intensity recommended in China are lower than those in the United States, Canada, and Australia [18, 21].

Considering the rising rate of GDM-related morbidity and adverse outcomes in mothers and babies in China, there is an impending and great need for effective GDM treatment strategies along with GDM prevention programs. Despite a large number of GDM clinical trials conducted over past 20 years in China, there has been no systematic search of the literature describing the types of healthcare interventions targeting GDM and examining comparative effectiveness. Therefore, the objective of this review was to identify and provide a descriptive overview of healthcare interventions aimed at the prevention and control of GDM in China. The secondary objective was to examine the effectiveness of these treatment strategies in reducing the risk of adverse health outcomes.

Social changes combined with decades of economic reform in China have resulted in a transition from the traditional Chinese lifestyle and dietary patterns being replaced by with “Western” lifestyle habits and dietary patterns. These changes have had a dramatic impact on the demographics of China’s health and diseases. Over the past 20 years, China has seen a sharp rise in obesity and related non-communicable diseases, including type II diabetes mellitus and GDM. Aside from the increased health risks to the mother, the offspring born from mothers with GDM are more prone to obesity and related metabolic disorders such as cardiovascular diseases in later life [27]. Therefore, the detection and treatment of GDM is necessary to identify women at risk of short- and long-term complications, and ameliorate the health outcomes in the offspring.

Thus far, several systematic reviews have been published on various interventions, either single [28] or different interventions [29], for the management of GDM in other countries, and only a few have evaluated preventive intervention programs [30‐32]. The goal of this study was to review the most widely-used GDM healthcare interventions in China and to the best of our knowledge, this is the first study to do so. We selected 802 published articles that reported the outcomes of independent studies evaluating various healthcare treatment interventions in pregnant women with GDM. The first GDM healthcare intervention study in China was published in 1997; from that time onwards, the number of published articles on GDM healthcare interventions in China rapidly increased. This not only reflects the rising incidence of GDM in China over the last 20 years, but it also highlights a growing awareness among researchers and healthcare practitioners on the importance of addressing this problem.

In our analysis, indeed, we observed that a wide variety of intervention strategies used to address GDM in China. Almost half of the reviewed studies reported combination interventions that combined different types of interventions with the goal of managing GDM [33]. Among all the possible combination interventions, dietary + exercise + medication + health education + psychological (DEMHP) interventions accounted for highest percentage (27.4%) of these studies. The initial treatment interventions with the greatest number of studies was found to be either diet alone or diet in combination with another intervention. It is estimated that the majority of women with GDM can achieve target glycemic control through diet and exercise (DE) [34, 35] and this is consistent with the recommendations by American Diabetic Association, according to which all pregnant women with GDM need an individual dietary plan tailored to the individual’s health status (including height and weight) [36, 37]. However, DE interventions are less common in China compared with other Western countries, highlighting a need to gain a better understanding of the comparative and cost-effectiveness of such programs in China [38]. When dietary interventions were shown to be ineffective at controlling GDM, medication was added to the treatment regimen. Consistent with professional guidelines insulin was the most frequently-used medication [39, 40]. Surprisingly, only a few studies examined the use of traditional Chinese medicines [41, 42] or the integration of Chinese traditional medicine and Western medicine. Given the long history of the use of traditional Chinese medicine and concomitant Chinese therapies, a better understanding is needed of the efficacy of these therapies and their roles as part of an integrated healthcare solutions in China. The least frequent approach to the control of GDM was found to be with the use of some form of psychological interventions [43]. Finally, a few studies employed combined DEMHP interventions to control GDM in early stages in China, which showed very high positive effects [44, 45].

The results obtained suggest that the interventions studied may be effective in reducing the risk of several adverse maternal and short-term neonatal outcomes in China. However care needs to be taken in interpreting these results. The observed protective effects could have been overestimated considering the low quality of the evidence included in this analysis. Nevertheless, scientific findings from other countries indicates that even if glycaemic control is achieved through lifestyle or therapy interventions, there is a clear impact on a limited number of maternal and offspring short term outcomes. Treatment of GDM has been found to significantly reduce the risk of pre-eclampsia and macrosomia [46]. While dietary interventions for women with GDM, have been studied for their efficacy against a variety of short and long-term maternal and offspring outcomes, and have only been associated with less frequent insulin use and a lower birthweight [47], or with a reduction in caesarean sections [30]. In contrast, the current study identified a considerable effect of dietary interventions on the majority of maternal and infant health outcomes in China.

This study also evaluate the effects of pharmacological interventions. Evidence supports the use of oral antidiabetic drugs in China, particularly metformin alone or in combination with insulin to reduce the risk of adverse maternal and neonatal outcomes, including pregnancy induced hypertension, neonatal hypo glycemia, and the need for NICU admission [48]. Our data showed that the combination of metformin and insulin performed better than insulin alone. To date no evidence exists for evidence-based psychological interventions, and neither do guidelines addressing the psychosocial management of GDM patients [49]. In this review, the studies incorporating this dimension did not show a greater effects than the lifestyle or pharmacological interventions.

The first limitation of this study was that all studies were included in the review without regards to the criteria used for randomizing participants, study methodology, treatment dose, or duration. For these reasons, it is likely that some low-quality studies were included in the full text extractions and data analysis. Second, we did not perform any power analyses nor statistical analyses to evaluate the effectiveness of interventions, as this was out of the scope: most of the identified studies were small and heterogeneous, especially in regards to maternal age, weight status, risk for GDM and treatment periods. Thus, a comparison of the effectiveness of the different types of GDM treatment interventions is challenging and all comparisons should be reviewed with caution. Third, the over-restrictive inclusion criteria may have limited our ability to identify GDM prevention studies. Four, the majority of the studies were based in urban areas in Eastern China; further data would be needed from rural China to have a more complete national overview. Fifth, the meta-analysis may be subject to publication bias with only studies with positive finding published and may not necessarily reflect the true practice in China. Finally, we only considered published original research articles, excluding reports, agency work, dossiers, and other types of documents that may also be used by clinicians and decision makers.

Our study is a synthesis of the existing healthcare interventions to control GDM in China and shows objective data supporting an increasing interest in GDM and research efforts to identify the best approach to control this condition. The growing prevalence of GDM and its associated adverse maternal and neonatal outcomes among China’s huge population suggests a substantial economic cost; more data are urgently needed to inform national healthcare policies in order to facilitate the prevention and treatment of GDM. Further research and clinical evidence is particularly needed with regards to GDM prevention programs in China which appear to be missing and may not be implemented at a national level. Although lots of treatment interventions have been employed in China, the most important item is create a good environment to implement these treatment strategies [50]. Although we identified 6 major types of interventions in China, we failed to find interventions utilizing digital technology or cellphones to monitor glucose levels and implementations of GDM treatments. Well-designed clinical trials are also needed to determine the most effective control and prevention treatments, incorporating cost effectiveness evaluations.