Current status of screening and management of gestational diabetes in early pregnancy: a questionnaire survey in Japan

Abstract

Our aim is to investigate the obstetric practices in Japan regarding the screening and management of gestational diabetes mellitus (GDM) diagnosed before 20 weeks of gestation (early-GDM). A web-based questionnaire survey was administered to 991 teaching hospitals between November 2021 and February 2022, and 602 responses were received (a response rate of 61%). Screening tests for all pregnant women in the first trimester were conducted in 553 (92%) hospitals, and nearly all of these hospitals (535/553 [97%]) adhered to an individual protocol, predominantly relying on random plasma glucose measurements (488/535 [91%]). A quarter (139 [26%]) implemented a risk profile assessment for GDM screening, taking into account factors such as previous gestational diabetes, prior macrosomia, and family history of diabetes. A small number (23 [4%]) targeted only women at high risk of GDM using the risk profile assessment. The majority of hospitals (501 [94%]) employed a 75 g oral glucose tolerance test as a diagnostic measure, and glycemic control for early-GDM was established in most hospitals (429 [80%]). Of the 535 hospitals that maintained an individual management protocol, 356 [67%] facilitated dietary management, self-monitoring of blood glucose, and insulin administration if needed to meet glycemic targets. Our survey revealed a widespread adoption of universal screening and subsequent treatment for early-GDM in Japan.

Introduction

In accordance with the guidelines from the Japan Society of Obstetrics and Gynecology (JSOG), screening for glucose intolerance during pregnancy is strongly recommended in Japan [1]. To elaborate, the JSOG guidelines recommend a screening test for all pregnant women in the first trimester and, for those without a diagnosis of overt diabetes or gestational diabetes mellitus (GDM), an additional screening at 24–28 weeks of gestation. If the screening result is positive, GDM is diagnosed by a 75 g oral glucose tolerance test (75 g OGTT) at any time during pregnancy [1]. However, due to the lack of evidence supporting the benefits of therapeutic intervention for GDM diagnosed before 20 weeks of pregnancy (early-GDM) [2], the JSOG guideline also suggest priority is given to the detection of overt diabetes in pregnancy, not early-GDM, in early pregnancy. Consequently, clinical practices regarding early-GDM may vary among obstetric facilities in Japan. In this context, we investigated the obstetric practices pertaining to the screening and management of early-GDM in Japan.

Materials and methods

We conducted a web-based questionnaire survey targeting 991 teaching hospitals specializing in obstetrics and gynecology across Japan between November 2021 and February 2022. The surveys gathered information on the screening and management of early-GDM in each hospital. The focal points of the questionnaires included: (1) The screening test for glucose intolerance in early pregnancy, (2) The protocol for the screening of glucose intolerance, (3) The screening and diagnostic tests for early-GDM, and (4) The management of early-GDM post-diagnosis (Table 1). This study received approval from the Ethics Committee of the International Catholic Hospital (approval date: Nov. 10, 2021, approval number: 21-5).

Table 1.

Contents of this survey questionnaire

Question 1	Is the screening test of glucose intolerance performed in early pregnancy (before 20 weeks of gestation)?
Answer	Yes or no
Question 2	Do you use the institutional protocol for screening of glucose intolerance in early pregnancy?
Answer	Yes or no
Question 3	Please select the method for screening of glucose intolerance employed in your hospital (multiple answers allowed)
Answer	(1) Random plasma glucose (2) Fasting plasma glucose (3) HbA1c (4) Glycated albumin (5) Glycosuria (6) 50-g glucose challenge test (7) Risk profile assessment
Question 4	If risk profile assessment is employed, is it considered equal to biochemical examination results?
Answer	(1) When the patient has one of the known risk factors or abnormal values of biochemical examinations, a diagnostic test is performed (2) When the patient has one of the known risk factors and abnormal values of biochemical examinations, a diagnostic test is performed (3) When the patient has one of the known risk factors, biochemical examinations are performed. Thereafter, if values of biochemical examinations are abnormal, a diagnostic test is performed
Question 5	If risk profile assessment is employed, please select the factors utilized for assessing risk profiles in early pregnancy (Multiple answers allowed)
Answer	(1) Advanced maternal age (≧35 years) (2) Pregestational obesity (body mass index ≧25 kg/m2) (3) Previous GDM (4) Prior macrosomia (5) Family history of diabetes (6) History of glucose intolerance (7) History of unexplained stillbirth
Question 6	Please select a diagnostic test for early-GDM
Answer	(1) 75 g OGTT only (2) 75 g OGTT and HbA1c measurement (3) HbA1c measurement only
Question 7	Please select the criteria for initiating treatment of early-GDM
Answer	(1) All women with early-GDM (2) Only women with 2/3-AV values (3) Women with obesity or 2/3-AV values (4) Judgement based on the levels of fasting plasma glucose, HbA1c, glycated albumin, etc (5) Entrustment of treatment to diabetologists or in the secondary/tertiary obstetric care institutions (6) No treatment for early-GDM
Question 8	Please select the management for early-GDM post-diagnosis
Answer	(1) Weight management only (2) Dietary management only (3) Dietary management, self-monitoring of blood glucose, and insulin administration if needed

HbA1c hemoglobin A1c, GDM gestational diabetes mellitus, OGTT oral glucose tolerance test, 2/3-AV two or three abnormal OGTT

Results

Out of the 991 hospitals, 602 completed and returned the survey (response rate: 61%). Almost all hospitals (553/602 [92%]) conducted screening for glucose intolerance in early pregnancy, and the majority (535/553 [97%]) had established protocols for screening and managing glucose intolerance within their individual hospitals. The majority of hospitals utilized universal testing involving biochemical examinations: random plasma glucose (PG) (488/535 [91%]), glycosuria (108/535, 20%), HbA1c (93/535 [17%]), fasting PG (61/535 [11%]), a 50 g glucose challenge test (51/535 [10%]), and glycated albumin (2/535 [0.4%]) (Fig. 1). A quarter (139/535 [26%]) employed risk profile assessments of GDM, incorporating factors such as previous GDM, prior macrosomia, history of glucose intolerance, pregestational obesity (body mass index ≧25 kg/m²), family history of diabetes, and advanced maternal age (≧35 years)) (Fig. 2). These assessments were predominantly combined with biochemical examination results. A total of 23 facilities (23/535 [4%]) conducted targeted screening only for women presenting the aforementioned GDM risk profiles.

Fig. 1.

Methods for screening glucose intolerance in early pregnancy. The methods used for the initial screening of glucose intolerance in 535 hospitals are presented. Note that that respondents could select more than one method. HbA1c hemoglobin A1c

Fig. 2.

Risk factors utilized for risk profile assessment in early pregnancy. The risk factors employed by 139 hospitals to assess risk profiles in early pregnancy are depicted here. Note that multiple selections of risk factors were allowed in this quarry. GDM gestational diabetes mellitus

In nearly all hospitals (501/535 [94%]), women with positive screening results underwent a 75 g OGTT, and GDM diagnoses were made in accordance with the JSOG recommendations [1]. Approximately half (247/535 [46%]) also evaluated HbA1c levels in conjunction with the 75 g OGTT. The remaining hospitals (34/535 [6%]) relied exclusively on HbA1c levels to detect overt diabetes in women with a positive screening.

In the majority of the hospitals (429/535 [80%]), women with early-GDM were treated immediately after the diagnosis. However, in 32 hospitals (6%), treatment was reserved only for women with two or three abnormal OGTT (2/3-AV) values. Additionally, 12 hospitals (2%) adopted a policy to treat women with early-GDM who presented with obesity or 2/3-AV values. In six hospitals (1%), therapeutic intervention for early-GDM was not performed until a diagnostic 75 g OGTT was repeated at 24–28 weeks of gestation. A small proportion of the hospitals (24/535 [4%]) arbitrarily determined the treatment of early-GDM according to levels of fasting plasma glucose, HbA1c, glycated albumin, and risk factors such as obesity and family history of diabetes alone or in combination. In 32 hospitals (6%), the treatment of early-GDM was performed by diabetologists or in the secondary/tertiary care institutions. Regarding early-GDM treatment approaches, approximately two-thirds of the hospitals (356/535 [67%]) facilitated dietary management, self-monitoring of blood glucose, and insulin administration if needed to meet glycemic targets.

Discussion

Our survey revealed that in Japan, universal screening for glucose intolerance in early pregnancy was more prevalent than risk-based screening. Although, the method of screening varied, the random PG measurement was a common approach. Nearly all hospitals diagnosed early-GDM using the 75 g OGTT. Additionally, this survey indicated most facilities immediately implemented glycemic control for women diagnosed with early-GDM.

Most globally recognized clinical guidelines strongly recommend screening for GDM at 24–28 weeks of gestation. However, a consensus regarding the preferred testing approach or diagnostic glycemic thresholds for early-GDM is lacking [3, 4]. Thus, most guidelines emphasize the importance of detecting overt diabetes in the first trimester. Regarding the candidates for early screening, the majority of health organizations including the American Diabetes Association and the National Institute for Health and Care Excellence recommend selective testing based on risk factors from the view of cost-effectiveness [5, 6], although the International Federation of Gynecology and Obstetrics supports recommends for all pregnant women (i.e. universal screening) [7]. Consequently, the prevalent practice of universal screening for early-GDM in most Japanese facilities diverges from the global trend [4]. The International Association of Diabetes in Pregnancy Study Groups posits that the decision to screen all pregnant women or only high-risk women at the first prenatal visit should be dependent on the characteristics of each population and local circumstances [8]. Given the high prevalence of glucose intolerance in Asians, universal screening seems appropriate for Japanese pregnant women.

In our survey, 49 hospitals did not perform the screening for glucose intolerance in early pregnancy. Of 49 hospitals, 35 were facilities specific for fertility or cancer treatment and did not provide prenatal checkup. In the remaining 14 facilities, the survey respondents from 5 facilities commented that they did not perform early testing because of a lack of evidence supporting the detection and treatment of early-GDM as well as the limited human resources for the diagnostic test. In other facilities, the reason was not answered. Although there is no consensus regarding diagnosing and treating early-GDM, early detection of hyperglycemia in pregnancy (i.e. overt diabetes) is highly recommended. For the appropriate obstetric practice, therefore, the importance of the screening for glucose intolerance in early pregnancy should be noticed in all teaching hospitals.

In Japan, due to its cost advantages, corroborated by a previous Japanese multicenter prospective cohort study [9], the random PG measurement has been extensively employed for early-GDM screening. Similarly, the German Diabetes Association and the German Association of Gynecology and Obstetrics endorse the use of random PG measurement at the initial visit during pregnancy for the screening of glucose intolerance in early pregnancy [10]. However, the random PG level in early pregnancy might demonstrate poor sensitivity in detecting glucose intolerance, particularly in patients experiencing hyperemesis, thereby increasing the number of false negatives. Thus, the reevaluation of the efficacy of screening with the random PG measurement might be required.

A principal concern in the management of early-GDM is the lack of high-quality evidence demonstrating that intervention improves perinatal outcomes. A previous meta-analysis has indicated an increased risk of adverse perinatal outcomes in early-GDM compared to late-GDM, diagnosed after 24 weeks of gestation, even with treatment [11]. A retrospective study from Japan revealed that early-GDM presents a higher risk of maternal complications, including hypertensive disorders in pregnancy and cesarean section, compared to late-GDM [12]. The most recent randomized trial involving women at risk of glucose intolerance during pregnancy showed that immediate treatment for early-GDM could modestly reduce the prevalence of adverse neonatal outcomes [13]. Conversely, no notable differences were observed in maternal pregnancy outcomes and neonatal birthweight between immediate-treatment and control groups. Another concern for the management of early-GDM is the possibility of overdiagnosis and overtreatment. It is demonstrated that one third to nearly half of women with early-GDM showed normal 75 g OGTT values at 24–28 weeks of pregnancy [13, 14]. Furthermore, information is scarce regarding potential risks and economic burden associated with the treatment of early-GDM. Therefore, the cost-effectiveness of treating all women with early-GDM warrants meticulous examination.

This study has several limitations. With a response rate of 61%, our findings may not fully represent the practices of all obstetric hospital in Japan. When the analysis was limited to the hospitals participating in the perinatal registry of JSOG, the response rate was 73%. This suggests that the survey respondents were probably more aware of the management of abnormal glucose tolerance during pregnancy. This could have introduced a selection bias. Moreover, the limited and simplified nature of the survey meant that detailed clinical information on the screening and management of early-GDM could not be obtained. Despite these limitations, this is the first nationwide survey regarding the screening and management of early-GDM, and our data will contribute to the understanding of the current obstetric practices in Japan.

In conclusion, the universal screening and detection of early-GDM, primarily using random PG measurements, along with immediate therapeutic interventions, are prevalent in Japan. Currently, there is no data available on the effectiveness of such interventions in Japanese women with early-GDM. Further research is warranted to determine the appropriate management for early-GDM.

Author contributions

All authors contributed to the concept and design of the study and the interpretation of the results. MY: researched data, wrote the manuscript, contributed to discussion, and reviewed/edited the manuscript. KM: wrote the manuscript, contributed to discussion, and reviewed/edited the manuscript. SN, NI, SA, IY and TS: contributed to discussion and reviewed the manuscript. All authors approved the final version of the manuscript and agreed to be responsible for all aspects of the work.

Funding

This survey was conducted using the research funding from the Japan Society of Obstetrics and Gynecology.

Data availability

Not applicable to this paper.

Declarations

Conflict of interest

The authors have no potential conflict of interest to disclose.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the Ethics Committee of the International Catholic Hospital/approval date: Nov. 10, 2021/approval number: 21-5) and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from the staffs of the teaching hospitals who completed and returned the questionnaires.