Abstract
Aims
To compare the effect on maternal and neonatal outcomes of 75-g oral glucose tolerance test (75-g OGTT) versus 50-g glucose challenge test (GCT) plus 75-g OGTT for diagnosis of gestational diabetes mellitus (GDM).
Materials and methods
A non-randomized trial was conducted in a tertiary hospital between January and December 2020. Participants were assigned into the one-step (i.e., 75-g OGTT) and two-step screening (50-g GCT plus 75-g OGTT) groups. Primary outcomes were GDM, hypertensive disorder in pregnancy (HDP), macrosomia, and Cesarean section.
Results
2265 eligible participants were enrolled in the trial, including 1130 in the one-step group and 1135 in the two-step group. GDM was diagnosed in 197 (17.4%) participants in the one-step group and 123 (10.8%) in the two-step group (OR, 1.94; 95% CI, 1.49, 2.54). There was only borderline statistical significance in the difference of HDP between two groups (OR, 0.64; 95% CI, 0.40, 1.01), while all other outcomes showed no statistically significant differences. In pregnant women with high risk factors for GDM (maternal age ≥ 35 years, pre-pregnancy BMI ≥ 24 kg/m2, multipara, history of GDM, or family history of diabetes), the incidence of GDM was higher (OR, 1.74; 95% CI, 1.19, 2.56) for the one-step versus two step-step screening, while the incidences of HDP (OR, 0.51; 95% CI, 0.29, 0.90) and macrosomia (OR, 0.62; 95% CI, 0.39, 0.97) were lower.
Conclusions
The one-step screening at least performs as well as the two-step screening, potentially more suitable for Chinese pregnant women with high risk factors for GDM.
The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100054505) on Dec 18th, 2021.
Keywords: Gestational diabetes mellitus, Screening, Trial, Oral glucose tolerance test, Glucose challenge test
Introduction
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy [1]. GDM is associated with higher risks of short- and long-term adverse outcomes such as pre-eclampsia and type 2 diabetes mellitus for the mothers and macrosomia and obesity for the offspring [2]. Timely GDM diagnosis during pregnancy is essential for glucose control to minimize these adverse outcomes.
There is no consensus on GDM diagnostic criteria worldwide. The American College of Obstetricians and Gynecologists (ACOG) and the National Institutes of Health recommend a two-step screening approach for GDM diagnosis [1], including a 50-g glucose challenge test (GCT), followed by a 100-g oral glucose tolerance test (OGTT). The two-step approach has a relatively high acceptance among pregnant women because the first step used to triage pregnant women can be done without fasting. However, the American Diabetes Association endorses both the two-step approach and the one-step approach using the 75-g OGTT, of which the latter could increase the prevalence of GDM by 1–3 times [3]. In China, the one-step approach for GDM diagnosis is recommended [4], although rigorous evidence is lacking in the Chinese populations.
Controversies have been noted over differential impact on the adverse outcomes for mothers and their offspring for the two screening approaches for GDM [5]. However, the two approaches have rarely been compared in trials in Chinese pregnant women. In addition, there is a lack of such studies on specific populations of pregnant women, particularly those at high risk for GDM. Whether those with high risk factors for GDM, such as advanced maternal age, pre-pregnancy body mass index (BMI) ≥ 24 kg/m2 (based on Chinese BMI classification guidelines, which define overweight as BMI ≥ 24 kg/m²), multipara, previous GDM, and family history of diabetes, should receive a modified screening and diagnosis algorithm, is uncertain.
To address the knowledge gap, we conducted a nonrandomized trial to compare major maternal and child outcomes between the one-step and two-step screening approaches for GDM among Chinese pregnant women. In addition, we exploratively examined whether the two approaches showed differential effects among those with high risk factors for GDM.
Materials and methods
Study participants
Pregnant women who visited the Chengdu First People’s Hospital for prenatal care at 24–28 weeks of pregnancy were included in January to December, 2020. Those with pre-pregnancy diabetes, dysfunction of vital organs, mental disorders, pregnancy termination planning for fetal abnormalities, or twin or multiple pregnancies were excluded. After enrollment, participants were given an identification number and were assigned to one of the two groups based on this number: those with odd numbers in the one-step screening group (75-g OGTT), and those with even numbers in the two-step screening group (50-g GCT plus 75-g OGTT). Standard randomization procedure was not conducted in this trial for simplified procedures. The study was approved by the Chengdu First People’s Hospital Ethics Committee, and all participants provided informed consent. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100054505).
Data collection at baseline
Participant information including basic characteristics, and maternal and neonatal outcomes was extracted from medical records. Basic characteristics included age, pre-pregnancy height and weight, parity, previous GDM, and family history of diabetes. Primary outcomes were GDM, hypertensive disorder in pregnancy (HDP), macrosomia, and Cesarean section, while secondary outcomes were intrahepatic cholestasis of pregnancy (ICP), preterm birth, low birth weight, neonatal respiratory distress, and postpartum hemorrhage.
Diagnosis of GDM
In the one-step group, 75-g OGTT was used for GDM diagnosis after fasting for at least eight hours. Fasting plasma glucose (FPG) level was tested, followed by 1-h plasma glucose (PG) and 2-h PG after participants took 75-g glucose with 150 ml water. GDM was diagnosed if any glucose value reached or exceeded the threshold: 5.1 mmol/L (91.8 mg/dl) for FPG, 10.0 mmol/L (180.0 mg/dl) for 1-h PG, and 8.5 mmol/L (153.0 mg/dl) for 2-h PG [6, 7].
In the two-step group, 50-g GCT followed by 75-g OGTT was used. Without fasting, PG was measured one hour after participants received 50-g glucose with 100 ml water. The 100-g OGTT recommended for the two-step approach was replaced by the 75-g OGTT as the former was not adopted in China [8]. Participants received 75-g OGTT within one week if their 1-h PG of 50-g GCT reached or exceeded 7.8 mmol/L (140.4 mg/dl). Equivalent criteria were used for 75-g OGTT as in the one-step group. GDM was diagnosed if both 50-g GCT and 75-g OGTT showed positive results.
At our center, all GDM patients were initially managed with lifestyle promotion. If glycemic targets were not achieved within two weeks, pharmacologic treatment (insulin usage) was initiated according to standardized guidelines. According to ADA guidelines, the glycemic control targets were: FPG < 5.3 mmol/L, and 2-h PG < 6.7 mmol/L.
PG values were measured utilizing the hexokinase method by ADVIA 2400 Chemistry System (Siemens, Germany). It had a measurement varying from 0.2–38.9 mmol/L with a reported coefficient of variation (CV) varying from 0.8–3.1%.
Diagnosis of other outcomes
Maternal outcomes other than GDM included HDP, Cesarean section, ICP, and postpartum hemorrhage. HDP was defined as gestational hypertension, pre⁃eclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed pre⁃eclampsia based on the Chinese guidelines [9], which were adapted from the guidelines from the International Federation of Obstetrics and Gynecology, and ACOG [10, 11]. ICP (including mild and severe forms) was diagnosed based on the guidelines for diagnosis and treatment of ICP (2015) [12]. Mild ICP is defined as total bile acid ≥ 10–40 μmol/L with skin pruritus, but without other obvious symptoms. Severe ICP is characterized by 1) total bile acid ≥ 40 μmol/L; 2) severe pruritus; 3) other concomitant conditions, such as multiple pregnancy, HDP, recurrent ICP, or previous ICP causing fetal death; or 4) early-onset ICP. Postpartum hemorrhage is defined as blood loss ≥ 500 mL for vaginal delivery or ≥ 1000 mL for cesarean delivery within 24 h postpartum.
Neonatal outcomes included preterm birth, macrosomia (birth weight ≥ 4000 g), low birth weight (birth weight < 2500 g), and neonatal respiratory distress.
The primary composite outcome was defined as the presence of any of the following: GDM, HDP, macrosomia, Cesarean section. The secondary composite outcome was defined as the presence of any of the following: ICP, preterm birth, low birth weight, neonatal respiratory distress, postpartum hemorrhage.
Statistical analysis
Baseline characteristics were summarized as mean (standard deviation, SD) for continuous variables, and frequencies (percentages) for categorical variables. These characteristics were compared by t test (for continuous variables), and chi-square test (for categorical variables) between the one-step group and the two-step group. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) of primary and secondary outcomes were estimated using logistic regression after adjustment for age (continuous, years), pre-pregnancy BMI (continuous, kg/m2), parity (nulliparous and multiparous), family history of diabetes (yes and no), and history of GDM (yes and no) between two approaches. Subgroup analyses were conducted to examine the risk of other maternal and neonatal outcomes between two approaches by GDM status. In addition, subgroup analyses were done to compare all maternal and neonatal outcomes between two approaches in those with and without established GDM risk factors (maternal age ≥ 35 years, pre-pregnancy BMI ≥ 24 kg/m2, multipara, history of GDM, and family history of diabetes). All data were analyzed by R version 4.0.3. A two-sided P value < 0.05 was defined as statistically significant.
Results
Of 3181 pregnant women who were approached, 907 were excluded due to major prevalent diseases or refusal to participate. 2274 were eligible for group assignment, but 9 participants withdrew during the trial. As the trial was not a randomized trial, we only included the remaining 2265 in the analyses, including 1130 in the one-step group and 1135 in the two-step group (Supplementary Figure 1). Mean age and pre-pregnancy BMI were 28.90 years (SD, 3.66) and 21.14 kg/m2 (2.86). There were no statistical differences in maternal age, pre-pregnancy BMI, family history of diabetes, and history of GDM between the two groups (P ≥ 0.716; Table 1). However, participants were more likely to be multiparous in the one-step group than in the two-step group (33.6 vs 27.9%; P = 0.004).
Table 1.
Characteristics of study participants in the one-step and the two-step groups
| Overall | One-step screening | Two-step screening | P | |
|---|---|---|---|---|
| No. | 2265 | 1130 | 1135 | |
| Age, mean (SD), years | 28.90 (3.66) | 28.90 (3.76) | 28.90 (3.57) | 0.979 |
| Pre-pregnancy BMI, mean (SD), kg/m2 | 21.14 (2.86) | 21.14 (2.99) | 21.14 (2.73) | 0.996 |
| Multiparous, n (%) | 697 (30.8) | 380 (33.6) | 317 (27.9) | 0.004 |
| Family history of diabetes, n (%) | 50 (2.2) | 25 (2.2) | 25 (2.2) | 1.000 |
| History of GDM, n (%) | 33 (1.5) | 18 (1.6) | 15 (1.3) | 0.716 |
GDM was diagnosed in 197 (17.4%) pregnant women in the one-step group, compared to the 123 (10.8%) in the two-step group (OR, 1.94; 95% CI, 1.49, 2.54; Table 2). In this study, none of the participants received oral glucose-lowering medications during pregnancy. The ratio of lifestyle intervention to insulin therapy for GDM management was approximately 9:1 in both groups, with no statistically significant difference between them. In the two-step group, 317 (27.9%) of pregnant women showed a positive result in the GCT and thus received the 75-g OGTT, of whom 123 was identified to have GDM. HDP was diagnosed in 3.0% of pregnant women in the one-step group, which seemed to be lower than the 4.4% in the two-step group. However, there was only borderline statistical significance for the HDP difference between the two groups (OR, 0.64; 95% CI, 0.40, 1.01). Our analyses did not show statistical differences in the incidences of other primary outcomes, including macrosomia (4.6 vs 6.2% for two groups; OR, 0.70; 95% CI, 0.48, 1.03), Cesarean section (45.0 vs 46.7% for two groups; OR, 0.91; 95% CI, 0.77, 1.08), and a composite of all primary outcomes (55.1 vs 53.9% for two groups; OR, 1.04; 95% CI, 0.87, 1.23) between two groups. The incidences of secondary outcomes were also similar between two groups, including ICP, preterm birth, low birth weight, neonatal respiratory distress, postpartum hemorrhage, and a composite of all secondary outcomes (Table 3).
Table 2.
Maternal and neonatal health outcomes in two groups
| Outcomes | One-step screening Cases / no. (%) |
Two-step screening Cases / no. (%) |
One-step vs. two-step | |
|---|---|---|---|---|
| Model 1: OR (95% CI) a | Model 2: OR (95% CI) b | |||
| Primary outcomes | ||||
| GDM | 197/1130 (17.4) | 123/1135 (10.8) | 1.74 (1.37, 2.22) | 1.94 (1.49, 2.54) |
| HDP | 34/1130 (3.0) | 50/1135 (4.4) | 0.67 (0.43, 1.04) | 0.64 (0.40, 1.01) |
| Macrosomia | 52/1130 (4.6) | 70/1135 (6.2) | 0.73 (0.51, 1.06) | 0.70 (0.48, 1.03) |
| Cesarean section | 509/1130 (45.0) | 530/1135 (46.7) | 0.94 (0.79, 1.10) | 0.91 (0.77, 1.08) |
| All | 623/1130 (55.1) | 612/1135 (53.9) | 1.05 (0.89, 1.24) | 1.04 (0.87, 1.23) |
| Secondary outcomes | ||||
| ICP | 68/1130 (6.0) | 75/1135 (6.6) | 0.90 (0.64, 1.27) | 0.91 (0.65, 1.28) |
| Preterm birth | 45/1130 (4.0) | 36/1135 (3.2) | 1.27 (0.81, 1.99) | 1.21 (0.78, 1.91) |
| Low birth weight | 36/1130 (3.2) | 26/1135 (2.3) | 1.40 (0.85, 2.36) | 1.36 (0.82, 2.30) |
| Neonatal respiratory distress | 17/1130 (1.5) | 27/1135 (2.4) | 0.63 (0.33, 1.15) | 0.60 (0.32, 1.10) |
| Postpartum hemorrhage | 39/1130 (3.5) | 40/1135 (3.5) | 0.98 (0.62, 1.54) | 0.95 (0.60, 1.49) |
| All | 163/1130 (14.4) | 178/1135 (15.7) | 0.91 (0.72, 1.14) | 0.91 (0.72, 1.14) |
CI confidence interval, GDM gestational diabetes mellitus, HDP hypertensive disorder of pregnancy, ICP intrahepatic cholestasis of pregnancy, OR odds ratio
aCrude model
bAdjusted for age (continuous, years), pre-pregnancy BMI (continuous, kg/m2), parity (nulliparous and multiparous), family history of diabetes (yes and no), and history of GDM (yes and no)
Table 3.
Comparison of primary outcomes by GDM status in two groups
| One-step screening Cases / no. (%) |
Two-step screening Cases / no. (%) |
One-step vs. two-step | ||
|---|---|---|---|---|
| Model 1: OR (95% CI) a | Model 2: OR (95% CI) b | |||
| For those with GDM | ||||
| HDP | 5/197 (2.5) | 14/123 (11.4) | 0.20 (0.06, 0.55) | 0.20 (0.06, 0.55) |
| Macrosomia | 17/197 (8.6) | 17/123 (13.8) | 0.59 (0.29, 1.21) | 0.67 (0.31, 1.42) |
| Cesarean section | 108/197 (54.8) | 65/123 (52.8) | 1.08 (0.69, 1.70) | 1.18 (0.73, 1.90) |
| All | 118/197 (59.9) | 73/123 (59.3) | 1.02 (0.65, 1.62) | 1.15 (0.70, 1.89) |
| For those without GDM | ||||
| HDP | 29/933 (3.1) | 36/1012 (3.6) | 0.87 (0.53, 1.43) | 0.90 (0.54, 1.51) |
| Macrosomia | 35/933 (3.8) | 53/1012 (5.2) | 0.71 (0.45, 1.09) | 0.70 (0.44, 1.09) |
| Cesarean section | 401/933 (43.0) | 465/1012 (45.9) | 0.89 (0.74, 1.06) | 0.87 (0.72, 1.05) |
| All | 426/933 (45.7) | 489/1012 (48.3) | 0.90 (0.75, 1.07) | 0.89 (0.74, 1.06) |
CI confidence interval, GDM gestational diabetes mellitus, HDP hypertensive disorder of pregnancy, OR odds ratio
aCrude model
bAdjusted for age, pre-pregnancy BMI, parity, family history of diabetes, and history of GDM
In analyses limited to pregnant women with a diagnosis of GDM, the incidence of HDP was much lower in the one-step group than in the two-step group (OR, 0.20; 95% CI, 0.06, 0.55), but other primary outcomes did not show statistical differences (Table 3). In similar analyses, no statistical differences were noted between the two groups for all secondary outcomes (Supplementary Table 1). In addition, in pregnant women with high risk factors for GDM, the incidence of GDM was higher in the one-step group (OR, 1.74; 95% CI, 1.19, 2.56), while the incidences of HDP (OR, 0.51; 95% CI, 0.29, 0.90) and macrosomia (OR, 0.62; 95% CI, 0.39, 0.97) were lower in this group (Table 4). However, in those without high risk factors, a statistical difference was noted in GDM (OR, 2.18; 95% CI, 1.50, 3.19), but not in other primary outcomes (Table 5). For all secondary outcomes, there were no statistical differences between two groups when analyses were restricted to those with or without high risk factors (Supplementary Table 2–3).
Table 4.
Comparison of primary outcomes by GDM status in two groups with established risk factors for GDMa
| Outcomes | One-step screening Cases / no. (%) |
Two-step screening Cases / no. (%) |
One-step vs. two-step | |
|---|---|---|---|---|
| Model 1: OR (95%CI) b | Model 2: OR (95%CI) c | |||
| Overall | ||||
| GDM | 112/485 (23.1) | 75/425 (17.6) | 1.40 (1.01, 1.95) | 1.74 (1.19, 2.56) |
| HDP | 22/485 (4.5) | 35/425 (8.2) | 0.53 (0.30, 0.91) | 0.51 (0.29, 0.90) |
| Macrosomia | 37/485 (7.6) | 52/425 (12.2) | 0.59 (0.38, 0.92) | 0.62 (0.39, 0.97) |
| Cesarean section | 278/485 (57.3) | 246/425 (57.9) | 0.98 (0.75, 1.27) | 1.00 (0.77, 1.31) |
| All | 326/485 (67.2) | 290//425 (68.2) | 0.95 (0.72, 1.26) | 1.01 (0.75, 1.35) |
| For those with GDM | ||||
| HDP | 4/112 (3.6) | 11/75 (14.7) | 0.22 (0.06, 0.66) | 0.21 (0.05, 0.66) |
| Macrosomia | 15/112 (13.4) | 17/75 (22.7) | 0.53 (0.24, 1.14) | 0.62 (0.28, 1.37) |
| Cesarean section | 74/112 (66.1) | 47/75 (62.7) | 1.16 (0.63, 2.13) | 1.21 (0.64, 2.29) |
| All | 84/112 (75.0) | 55/75 (73.3) | 1.09 (0.56, 2.12) | 1.23 (0.61, 2.48) |
| For those without GDM | ||||
| HDP | 18/373 (4.8) | 24/350 (6.9) | 0.69 (0.36, 1.29) | 0.75 (0.39, 1.46) |
| Macrosomia | 22/373 (5.9) | 35/350 (10.0) | 0.56 (0.32, 0.98) | 0.60 (0.34, 1.06) |
| Cesarean section | 204/373 (54.7) | 199/350 (56.9) | 0.92 (0.68, 1.23) | 0.94 (0.70, 1.27) |
| All | 214/373 (57.4) | 215/350 (61.4) | 0.85 (0.63, 1.14) | 0.88 (0.65, 1.20) |
CI confidence interval, GDM gestational diabetes mellitus, HDP hypertensive disorder of pregnancy, OR odds ratio
aRisk factors included maternal age ≥ 35 years, pre-pregnancy BMI ≥ 24 kg/m2, multipara, history of GDM, or family history of diabetes
bCrude model
cAdjusted for age, pre-pregnancy BMI, parity, family history of diabetes, and history of GDM
Table 5.
Comparison of primary outcomes by GDM status in two groups without established risk factors for GDMa
| Outcomes | One-step screening Cases / no. (%) |
Two-step screening Cases / no. (%) |
One-step vs. two-step | |
|---|---|---|---|---|
| Model 1: OR (95%CI) b | Model 2: OR (95%CI) c | |||
| Overall | ||||
| GDM | 85/645 (13.2) | 48/710 (6.8) | 2.09 (1.45, 3.05) | 2.18 (1.50, 3.19) |
| HDP | 12/645 (1.9) | 15/710 (2.1) | 0.88 (0.40, 1.89) | 0.87 (0.39, 1.87) |
| Macrosomia | 15/645 (2.3) | 18/710 (2.5) | 0.92 (0.45, 1.83) | 0.95 (0.47, 1.90) |
| Cesarean section | 231/645 (35.8) | 284/710 (40.0) | 0.84 (0.67, 1.04) | 0.85 (0.68, 1.06) |
| All | 297/645 (46.0) | 322/710 (45.4) | 1.03 (0.83, 1.27) | 1.05 (0.85, 1.31) |
| For those with GDM | ||||
| HDP | 1/85 (1.2) | 3/48 (6.2) | 0.18 (0.01, 1.44) | 0.19 (0.01, 1.55) |
| Macrosomia | 2/85 (2.4) | 0/48 (0) | – | – |
| Cesarean section | 34/85 (40.0) | 18/48 (37.5) | 1.11 (0.54, 2.32) | 1.12 (0.54, 2.38) |
| All | 34/85 (40.0) | 18/48 (37.5) | 1.11 (0.54, 2.32) | 1.12 (0.54, 2.38) |
| For those without GDM | ||||
| HDP | 11/560 (2.0) | 12/662 (1.8) | 1.09 (0.47, 2.49) | 1.07 (0.46, 2.47) |
| Macrosomia | 13/560 (2.3) | 18/662 (2.7) | 0.85 (0.40, 1.74) | 0.89 (0.42, 1.82) |
| Cesarean section | 197/560 (35.2) | 266/662 (40.2) | 0.81 (0.64, 1.02) | 0.82 (0.65, 1.04) |
| All | 212/560 (37.9) | 274/662 (41.4) | 0.86 (0.68, 1.09) | 0.88 (0.70, 1.11) |
CI confidence interval, GDM gestational diabetes mellitus, HDP hypertensive disorder of pregnancy, OR odds ratio
aRisk factors included maternal age ≥ 35 years, pre-pregnancy BMI ≥ 24 kg/m2, multipara, history of GDM, or family history of diabetes
bCrude model
cAdjusted for age, pre-pregnancy BMI, parity, family history of diabetes, and history of GDM
Discussion
In a large nonrandomized trial among Chinese pregnant women, we found that the incidence of GDM was higher in the one-step group than in the two-step group (17.4 vs 10.8%), without statistical differences in other maternal and neonatal outcomes. However, for those at high risk for GDM, while the incidence was still higher, the incidences of HDP and macrosomia were lower in the one-step group. Although data from long-term follow-up after child birth are needed, our findings imply that the one-step approach is at least as good performing as the two-step approach, but could be more appropriate for high-risk women.
The one-step approach identified more GDM cases without inducing more pregnancy-related outcomes in our study. 17.4% of pregnant women were diagnosed as having GDM based on the one-step 75-g OGTT, which was slightly higher than the national average estimate in China (14.8%) [13]. The higher incidence of GDM in the one-step group as compared to the two-step group was consistent with findings from previous randomized clinical trials [14, 15], despite differential combinations of two steps used. Such contrast could be expected as pregnant women were triaged first through GCT and diagnosed using OGTT in the two-step approach. Besides GDM, our study did not show significant differences in any of the maternal and neonatal outcomes between two groups, which agreed well with the finding from a meta-analysis of six clinical trials in the US and Turkey [16]. Consistently, a recent pragmatic multicenter randomized trial of 23,792 women in the US showed no significant between-group differences in the risks of HDP, large-for-gestational-age infants, adverse perinatal outcomes, or primary cesarean section, while more diagnoses of GDM were made using the one-step approach [5]. Although differences in glucose metabolism are reported among different ethnicities/races and OGTT values at each time point among Chinese women could be different from western populations [17], there has been limited evidence from trials to compare one-step and two-step approaches for GDM screening among Chinese pregnant women. A retrospective cohort study among 25,674 pregnant women from a single hospital compared GDM and other pregnant-related outcomes for two time periods when two-step and one-step approaches were separately used [18]. Consistent with our finding, a higher incidence of GDM was reported for those who received a one-step screening, but for the same group, low incidences of outcomes such as macrosomia, Cesarean section, neonatal hypoglycemia, and perinatal death were noted. Similar “before and after” studies in other countries that assessed the transition from the two-step to one-step approach showed reductions or at least no significant changes in maternal and neonatal outcomes [19]. Of note, our two-step screening used the 75-g OGTT instead of 100-g OGTT that followed 50-g GCT to increase acceptability in clinical practice as 75-g OGTT was already widely used in China; such an adaptation may also cause an increase of GDM cases in the two-step screening compared to the one-step screening. As collective evidence from our trial and other studies shows, a major concern for the one-step approach would be the consequences of incremental GDM cases that could be otherwise undiagnosed in the two-step approach and were thus mostly milder degree of hyperglycemia in pregnancy. A review of 8 retrospective studies of 29,983 women showed that these incremental GDM cases were more likely to have adverse maternal and neonatal outcomes such as HDP, preterm birth, macrosomia, and hypoglycemia than those whose result was negative in the one-step approach [20]. While solid evidence from clinical trials was lacking for the long-term adverse outcomes for these mild GDM cases or the benefits for treatment of these cases, exploratory analyses of the Hyperglycemia and Adverse Pregnancy Outcome trial data showed that GDM cases who were diagnosed in the one-step approach (none were treated for GDM) and their offspring had higher risks of glucose metabolism disorders such as obesity and diabetes after childbirth than non-GDM counterparts in the long run [21]. In the subgroup of women without baseline risk factors, GDM incidence was doubled in the one-step group compared to the two-step group but no difference in pregnancy outcomes were observed. Only 27.9% of women in the two-step group required OGTT after their GCT, indicating that the remaining women were able to pass the screening test by GCT alone and skip the OGTT. The two-step screening might be the preferred approach to avoid over-diagnosis or over-treatment in an otherwise low risk group. One caveat with the two-step approach is that the GCT could potentially delay the diagnosis and thus treatment of GDM, which could be associated with potential adverse pregnancy related outcomes [22]. However, the one-step screening could potentially pose a burden on the system of treating more women with GDM, which raises concerns about overtreatment and psychological burden, especially in low-risk populations, and thus cost-effectiveness analyses from the societal perspective would be needed to understand the impact on the health system. Thus our findings suggest that the one-step approach is at least as good performing as the two-step approach, and could potentially be more favorable if other considerations such as less delay in diagnosis and treatment are factored into the decision in clinical practice.
An interesting finding in our study was that the one-step approach was associated with lower risks of HDP and macrosomia in pregnant women at high risk for GDM, although GDM was 1.74 times likely to be diagnosed compared to the two-step approach. One possible explanation is indeed that the two-step group may have had more prenatal visits or more frequent blood pressure monitoring due to two steps of diagnosis of GDM, potentially increasing the chance of HDP detection. Alternatively, it is also possible that women diagnosed with GDM via the one-step approach received earlier and more consistent lifestyle interventions, which may have contributed to better blood pressure control. However, since data on the frequency and content of prenatal visits, and descriptive statistics relating to the prevalence of key HDP risk factors (e.g., pre-existing hypertension, previous preeclampsia, chronic kidney disease) were not collected in this study. More Detailed information on the demographic characteristics, baseline medical conditions, previous obstetrics complications, and delivery-related factors such as gestational age, birth weight, weight gain, and chronic hypertension allow for comprehensive subgroup analyses and adjustments. GDM and other pregnancy-related outcomes mostly share risk factors, some of which were used to define pregnant women at high risk for GDM [23, 24]; thus the one-step approach with diagnosis and management of more GDM cases would potentially help reduce risk of other pregnant-related outcomes such as macrosomia. In contrast, pregnant women with risk factors for GDM might not benefit from the GCT triaging as much as the general population of pregnant women. This may indicate that pregnant women with potential risk factors for GDM were more suitable for the one-step approach to screen GDM. To date, very few clinical guidelines have stratified pregnant women for different GDM screening approaches according to the level of risk for GDM. The Chinese Guideline for Diagnosis and Treatment of Gestational Diabetes Mellitus (2014) recommends a one-step procedure for all pregnant women not previously diagnosed with overt diabetes at 24–28 weeks of gestation, but reserve a two-step approach (fasting glucose plus 75-g OGTT) for low resource areas [8]. While our findings support the use of one-step screening for the general pregnant women, whether more nuanced screening procedures could be recommended based on characteristics of Chinese pregnant women (such as high-risk factors) would need more robust evidence from future large clinical trials and cohort studies. This could be relevant for evidence-based guidelines for GDM screening in the era of precision medicine.
While our study is one of the few trials comparing one- and two-step screening procedures for Chinese pregnant women, several limitations should be acknowledged. First, no randomization was implemented in assigning participants to two screening methods. While we attempted to control for potential confounder, residual confounding may still exist. Second, the composite outcome labeled “All” (a summary indicator) was to provide a preliminary overview of the overall burden of adverse pregnancy outcomes under each screening strategy, rather than to imply a shared pathophysiology, which has limitations and should be interpreted with caution. We did not collect data for a long-term follow up, and thus could not determine whether two screening approaches could lead to differential outcomes for mothers and their offspring after child birth. Third, the study was conducted in only a single center, and thus the findings might not necessarily be generalizable to other populations. Our findings should still be validated in other large trials in Chinese and other populations. Fourth, the stratified analyses based on risk factors for GDM were only preliminary, and future work would need to consider different sets/levels of GDM risk factors and whether adverse outcomes mediated through GDM for more precise recommendations according to the characteristics of pregnant women. Fifth, this study reports ORs for most comparisons, which might lead to overestimation of associations, particularly when outcome incidence is not rare. Alternative approaches such as Poisson regression with robust variance or risk-based metrics [e.g., risk differences (RD), number needed to screen (NNS)] may be more appropriate in future research.
The one-step screening is associated with a higher incidence of GDM without adding risk of other major adverse maternal and neonatal outcomes. While our findings should still be validated in other randomized trials and prospective cohort studies, they may suggest that the one-step approach at least performs as well as the two-step approach for Chinese pregnant women. In addition, among those with high risk factors for GDM, the one-step screening seems to be more suitable.
Supplementary information
Acknowledgements
We are grateful to the staff who have been involved in this work. All persons that contributed to this study are listed as authors and meet the criteria for authorship.
Author contributions
JYL, JNZ, XXQ, SL, CHM, XFP, and XDW initiated and designed the present study. JYL and XXQ collected the data. JYL, JNZ, SL, CHM, and XFP performed data analysis. JYL and JNZ wrote the first draft of the manuscript. XDW, XFP, and XXQ reviewed, completed, and supervised the manuscript writing. All authors contributed to its interpretation and contributed to the article and approved the submitted version.
Funding
This study was supported by the Science Foundation of Sichuan Province (grant number 2022YF0042).
Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Compliance with ethical standards
Ethics approval
The study protocol was approved by the Chengdu First People’s Hospital Ethics Committee and conformed to the provisions of the Declaration of Helsinki.
Consent to participate
All informed consent was obtained from the subjects.
Conflict of interest
The authors declare that they have no conflict of interest.
Footnotes
These authors contributed equally: Jiyuan Liu, Jiani Zhang.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Xiong-Fei Pan, Email: pxiongfei@gmail.com.
Xiaodong Wang, Email: wangxd_scu@sina.com.
Supplementary information
The online version contains supplementary material available at 10.1007/s12020-025-04366-w.
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Supplementary Materials
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.