Abstract
Objective
To establish reference ranges for fetal gastric parameters via two-dimensional (2D) and three-dimensional (3D) ultrasound virtual organ computer-aided analysis (VOCAL) technology and assess fetal gastric development and function in normal and hyperglycemia in pregnancy (HIP) cases.
Methods
A prospective cross-sectional study was conducted with 457 normal fetuses (11–40 gestational weeks) via 2D and 3D ultrasound VOCAL techniques to measure gastric parameters (maximum length, transverse diameter, anteroposterior diameter, circumference, area, and volume) and calculate the gastric circumference-to-abdominal circumference (GC/AC), gastric area-to-abdominal area (GA/AA), and gastric emptying rate (GER). Nomograms were developed according to gestational age (GA). Intra- and inter-observer reliability were assessed in 50 randomly selected cases. Additionally, 126 HIP cases (90 well-controlled, 36 poorly-controlled) were analyzed via these nomograms.
Results
Comprehensive nomograms for 2D and 3D gastric parameters were established. The gastric dimensions (maximum length, transverse diameter, anteroposterior diameter, circumference, area, and volume) and GER increased with increasing GA (p < 0.05), whereas the GC/AC and GA/AA ratios were not correlated (p > 0.05). The measurements revealed high intra- and inter-observer reliability. Compared with both the well-controlled HIP and normal groups, the poorly-controlled HIP group had significantly greater gastric parameters and lower GERs (p < 0.05), with no significant differences between the well-controlled HIP and normal groups (p > 0.05). Both HIP groups had lower GC/AC and GA/AA ratios than that in the normal group (p < 0.05), with significant differences between the poorly-controlled and well-controlled HIP groups (p < 0.05).
Conclusions
Fetal gastric parameter nomograms using 2D and 3D ultrasound VOCAL technology provide valuable tools for assessing fetal gastric development and function in normal and HIP pregnancies, highlighting the impact of glycemic control.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12884-025-07986-2.
Keywords: Fetal development, Gastrointestinal tract, Reference range, Ultrasonography, Gestational diabetes mellitus
Introduction
Hyperglycemia in pregnancy (HIP) includes pregestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM), and diabetes first identified during pregnancy (DIP) [1–3]. Globally, HIP affects approximately 16.7% of pregnancies, posing significant risks to maternal and fetal health [1]. HIP increases the risk of maternal complications such as diabetic gastroparesis, hypertension, and preeclampsia, and fetal risks including macrosomia, stillbirth, and neonatal hypoglycemia [4–6]. Furthermore, in utero exposure to hyperglycemia can also lead to long-term metabolic issues such as obesity and cardiometabolic abnormalities in childhood and beyond [7, 8] (Fig. 1).
Fig. 1.
Risks of HIP to pregnant mothers and fetuses. HIP Hyperglycemia in pregnancy, NRDS Neonatal respiratory distress syndrome
However, whether HIP-related fetal hyperglycemia affects fetal gastric development and motility remains unclear, but it is critical to assess fetal gastric parameters because of their role in nutrient absorption and metabolic regulation. Impaired gastric development or function might affect fetal growth and health. The advent of advanced imaging technologies, particularly two-dimensional (2D) and three-dimensional (3D) ultrasound via the virtual organ computer-aided analysis (VOCAL) technique, is potentially important for assessing fetal gastric development and gastric emptying. While VOCAL has been applied to study various fetal organs [9–11] and gastric emptying in gastroparesis [12, 13], its application to fetal gastric parameters and the gastric emptying rate (GER) in both normal and HIP patients is limited, necessitating further investigation.
Thus, this study aims to establish reference ranges for fetal gastric parameters via 2D and 3D ultrasound VOCAL technology and assess fetal gastric development and function in normal and HIP cases.
Methods
Study design and participants
This study involving humans was conducted with ethical approval from the Ethics Committee of Fujian Medical University Second Affiliated Hospital (approval number: 2024 [067]) and in accordance with the ethical principles outlined in the Declaration of Helsinki. All participants provided informed consent prior to inclusion in the study.
This prospective study enrolled 502 singleton pregnancies (Nov 2022-Nov 2024), with 45 excluded due to maternal comorbidities (endocrine/cardiovascular/rheumatic autoimmune, n = 15), gestational age (GA) dating discrepancies (n = 5), maternal adiposity (n = 12), poor fetal positioning (n = 8), or amniotic fluid abnormalities (n = 5). Final normal controls included 457 fetuses with clear abdominal imaging.
A parallel HIP cohort initially comprised 148 pregnancies, with 22 excluded for systemic diseases (n = 12), abdominal adiposity (n = 4), positioning issues (n = 2), or amniotic fluid anomalies (n = 4). The remaining 126 HIP cases were stratified by glycemic control into well-controlled (n = 90) and poorly-controlled (n = 36) subgroups based on their glycemic control status (Fig. 2).
Fig. 2.
Study design. HIP Hyperglycemia in pregnancy, GA: Gestational age, BMI: Body mass index, AFI: Amniotic fluid index, GER: Gastric emptying rate, GC/AC: The ratio of gastric circumference to abdominal circumference, GA/AA The ratio of the gastric area to the abdominal area
Inclusion criteria for the normal control group: (1) singleton pregnancies between 11 and 40 gestational weeks; (2) accurate GA based on last menstrual period and estimated by ultrasound; (3) absence of fetal abnormalities; (4) low-risk pregnancy without additional maternal or placental complications; (5) Normal maternal plasma glucose levels. Exclusion criteria for the normal control group: (1) Multiple pregnancies; (2) Presence of fetal malformations; (3) Pregnancy concurrent any diseases; (4) poor ultrasonography imaging. Postnatal follow-up was conducted for neonates in the normal control group to ensure the absence of gastrointestinal or respiratory anomalies. None of the neonates exhibited feeding or defecation problems, structural gastrointestinal abnormalities, or pulmonary infections, thereby validating their classification as physiologically normal.
In this study, HIP included pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). The diagnostic criteria for PGDM [5]: (1) fasting plasma glucose (FPG) ≥ 7.0 mmol/L (126 mg/dL); (2) 2-h plasma glucose (2-h PG) value during a 75-g oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L (200 mg/dL); (3) a random plasma glucose ≥ 11.1 mmol/L (200 mg/dL) accompanied by classic symptoms of hyperglycemia or hyperglycemic crisis. A diagnosis of PGDM was confirmed if any of these criteria were met. The diagnostic criteria for GDM [5]: (1) FPG during pregnancy ≥ 5.1 mmol/L (92 mg/dL); (2) 1-h plasma glucose (1-h PG) during an OGTT ≥ 10.0 mmol/L (180 mg/dL); (3) 2-h PG during an OGTT ≥ 8.5 mmol/L (153 mg/dL). Meeting any one of these criteria qualified for a GDM diagnosis. The case group included singleton pregnancies without concurrent pregnancy-related complications or fetal malformations.
The target glycemic levels for managing HIP were defined as follows: fasting plasma glucose < 5.3 mmol/L (95 mg/dL ), and either 1-h postprandial glucose < 7.8 mmol/L (140 mg/dL ) or 2-h postprandial glucose < 6.7 mmol/L (120 mg/dL) [5].
Measurements
A GE Voluson E8 or E10 Expert device (General Electric Healthcare, Milwaukee, MI, USA) equipped with a three-dimensional curvilinear transducer operating at frequencies of 4–9 MHz was used to measure all ultrasonographic parameters in this study.
Prior to the ultrasonographic assessment, each participant underwent a thorough medical history review and physical examination, and essential information such as maternal age, height, pre-pregnancy weight, blood pressure, past medical history, and date of the last menstrual period was collected. A routine obstetric examination was performed to evaluate fetal position, fetal biometry, the amniotic fluid index (AFI), and fetal morphology to ensure comprehensive obstetric assessment.
Fetal gastric 2D measurements were conducted on the abdominal circumference (AC) plane while the fetus remained at rest. Images were saved, and offline analyzes were performed to measure the gastric transverse diameter, anteroposterior diameter, circumference, and area, as well as the AC and abdominal area (AA) (Fig. 3). Additionally, the maximum cross-section of the fetal stomach, including the pylorus, was obtained through transverse or oblique scanning, and the maximum gastric length and 3D gastric volume were measured on this plane (Figs. 4 and 5). Pregnant participants were asked to hold their breath briefly to maintain fetal stillness, after which the automatic scanning window was activated to capture the full image of the fetal stomach. All the images were saved for further detailed offline analysis.
Fig. 3.
Transabdominal ultrasound image and schematic diagram of measurements of gastric transverse diameter, anterior-posterior diameter, circumference and area on the abdominal circumference plane. UV: Umbilical vein, PV: Portal vein, ST: Stomach, SP: Spleen, AG: Adrenal glands, IVC: Inferior vena cava, AO: Abdominal aorta
Fig. 4.
Transabdominal ultrasound image and schematic diagram of maximum gastric length on the plane of the maximum stomach, including the pylorus. GB: Gallbladder, ST: Stomach, SP: Spleen, AG: Adrenal gland, IVC: Inferior vena cava, AO: Abdominal aorta
Fig. 5.
Measurement of gastric volume via the transabdominal 3D ultrasound VOCAL technique in sections of the maximum stomach, including the pylorus
On the AC plane, the gastric anteroposterior diameter was defined as the line extending between the inner gastric walls parallel to the mid-sagittal plane. A line drawn perpendicular to this line within the gastric wall was designated the transverse diameter. The inner wall of the stomach was traced manually to calculate its circumference and area, and the outer edge of the abdominal wall was similarly traced for the AC and AA (Fig. 3). The maximum gastric length was defined as the longest distance along the inner wall on the largest section of the stomach that included the pylorus (Fig. 4).
The 3D gastric volume was measured via VOCAL technology as described previously, with some minor changes [9]. In brief, stored images were accessed within the ultrasound system, and VOCAL software (General Electric Medical Systems, KretzTechnik) was used to calculate the gastric volume. The initial cross-section (plane A) was selected with a rotation angle of 30° along the z-axis (six planes). The inner wall contour of the gastric cavity was manually traced across each of these sections. The system then automatically generated a 3D reconstruction of the fetal stomach and calculated the volume (Fig. 5).
Calculation of the gastric emptying rate
Changes in the gastric cavity result from fetal swallowing and gastric motility, which cause fluctuations in stomach size, allowing for the calculation of the gastric emptying rate (GER). Specifically, after the initial measurement of gastric volume, the pregnant participant was instructed to perform light activity for 20–30 min before the second measurement was taken. The method for measuring gastric volume was consistent with the above-described approach. The GER was subsequently calculated via the following formula:
 |
where x was the time interval (in minutes) between the two volume measurements. If the second volume measurement exceeded the initial one, it was redefined as the initial volume, followed by another measurement after an additional 20–30 min. In instances where the gastric volume did not decrease, three measurements were taken at 20–30-minute intervals, with the average of the two resulting GER values used as the final GER for that case.
To assess intra- and inter-observer measurement reliability, 50 normal fetuses were randomly selected for analysis. The primary sonographer (X.L.) conducted all gastric parameter measurements twice to determine intra-observer reliability. Additionally, an independent sonographer (X.W.) performed a separate set of measurements to assess inter-observer agreement. Both examiners independently conducted their evaluations and were blinded to each other’s results, ensuring unbiased comparisons.
Statistical analysis
Statistical analysis was performed via SPSS software (version 22.0) and MedCalc software (version 20.0). Reliability and consistency of measurements were assessed via intraclass correlation coefficients (ICCs) and Bland‒Altman plots for both the intra-sonographer and inter-sonographer variations. Quantitative data were expressed as the means ± standard deviations (‾x ± SDs). The correlation between each gastric parameter and GA was evaluated via regression models. The coefficient of determination (R2) was employed to assess model fit. Based on the best-fit equation, predictive values for the mean, SD, and 5th, 50th, and 95th percentile ranges of each fetal gastric parameter were established between 11 and 40 gestational weeks. To control for GA effects, Z scores were calculated when comparing measurements between the HIP groups and the normal control group, as certain gastric parameters increased with advancing GA. The Z score was calculated as follows:
 |
The Kolmogorov-Smirnov test and Levene’s test were used to assessed data normality and homogeneity of variance. One-way ANOVA was used for normally distributed data with homogeneous variance, while the nonparametric Kruskal-Wallis test was applied for nonnormally distributed or heterogeneous variance data. A p value of < 0.05 was considered statistically significant.
Results
Demographic characteristics of the participants
Comparisons of GA, maternal age, body height, pre-pregnancy body weight, pre-pregnancy body mass index (BMI), blood pressure, and AFI among the normal group, the well-controlled HIP group, and the poorly-controlled HIP group are presented in Table 1. No statistically significant differences were observed in these general clinical characteristics, suggesting that these groups were comparable.
Table 1.
Demographic characteristics of participants in different groups
| Variable | Normal (n = 457) | Case group 1 (n = 90) | Case group 2 (n = 36) | p value |
|---|---|---|---|---|
| GA (weeks) | 26.79 ± 7.82 | 26.81 ± 5.58 | 27.97 ± 5.31 | 0.734 |
| Age (years) | 30.57 ± 4.77 | 30.67 ± 4.55 | 29.58 ± 4.73 | 0.464 |
| Height (cm) | 158.80 ± 5.45 | 159.01 ± 3.40 | 159.51 ± 4.12 | 0.711 |
| Pre-pregnancy body weight (kg) | 57.26 ± 5.21 | 57.79 ± 4.11 | 58.87 ± 5.71 | 0.151 |
| Pre-pregnancy BMI (kg/m2) | 22.79 ± 2.62 | 22.88 ± 2.00 | 23.18 ± 2.51 | 0.658 |
| Blood pressure (mmHg) | ||||
| Systolic blood pressure | 106.23 ± 9.09 | 107.54 ± 8.90 | 107.08 ± 8.62 | 0.425 |
| Diastolic blood pressure | 75.79 ± 8.10 | 75.53 ± 8.81 | 77.33 ± 9.28 | 0.525 |
| AFI | 12.29 ± 2.68 | 12.17 ± 2.71 | 11.99 ± 2.82 | 0.776 |
Case group 1: Well-controlled hyperglycemia in pregnancy; Case group 2: Poorly-controlled hyperglycemia in pregnancy
GA: Gestational age, BMI: Body mass index, AFI: Amniotic fluid index
Feasibility analysis of the intra-observer and inter-observer results
The reliability and agreement for intra- and inter-observer measurements were good, with ICC exceeding 0.80 for the maximum length, transverse diameter, anteroposterior diameter, circumference, area, and volume of the stomach. The maximum gastric length showed the highest reliability, with ICC values of 0.9691 for intra-observer and 0.9415 for inter-observer measurements. Measurements by the same ultrasonographer had higher ICC values compared to different ultrasonographers (Table 2). Bland-Altman analysis revealed that over 95% of measurements for all parameters were within the limits of agreement, with no outliers. The limits were narrower for the same operator compared to different operators (Supplementary Figure S1).
Table 2.
Intra-observer and inter-observer reliability and agreement
| Parameters | Intra-observer | Inter-observer | ||
|---|---|---|---|---|
| ICC | 95%CI | ICC | 95%CI | |
| Gastric maximum length (cm) | 0.9691 | 0.9461 ~ 0.9823 | 0.9415 | 0.8992 ~ 0.9664 |
| Gastric transverse diameter (cm) | 0.9205 | 0.8641 ~ 0.9541 | 0.8426 | 0.7383 ~ 0.9075 |
| Gastric anteroposterior diameter (cm) | 0.9324 | 0.8838 ~ 0.9611 | 0.8417 | 0.7370 ~ 0.9070 |
| Gastric circumference (cm) | 0.9498 | 0.9132 ~ 0.9712 | 0.8821 | 0.8012 ~ 0.9314 |
| Gastric area (cm2) | 0.9251 | 0.8716 ~ 0.9568 | 0.8122 | 0.6911 ~ 0.8889 |
| Gastric volume (cm3) | 0.9573 | 0.9260 ~ 0.9756 | 0.8900 | 0.8139 ~ 0.9360 |
ICC: Intraclass correlation coefficients, 95%CI: 95% confidence interval
Normal reference range of fetal gastric measurements
A total of 457 normal fetuses were divided into 10 groups based on GA, each representing a three-week interval. Significant correlations were observed between GA and the fetal gastric maximum length, transverse diameter, anteroposterior diameter, circumference, area, volume, and GER (p < 0.05). However, no significant correlation was found between GA and GC/AC or GA/AA (p > 0.05). In addition, the parameters of maximum gastric length, transverse diameter, anteroposterior diameter, circumference, area, volume and GER increased with GA, as modelled by linear or quadratic regression equations, whereas the ratios of GC/AC and GA/AA did not significantly change with increasing GA (Fig. 6). Supplementary Table S1 shows the reference range of the gastric 2D and 3D measurements for each GA group. Figure 6 shows the scatterplot of fetal gastric parameters with respect to GA, and Table 3 shows the regression equations and correlation coefficients (R2) of fetal gastric parameters to GA.
Fig. 6.
Scatterplot of fetal gastric parameters and gestational age. Panel a: Gastric maximum length, Panel b: Gastric transverse diameter, Panel c: Gastric anteroposterior diameter, Panel d: Gastric circumference, Panel e: Gastric area, Panel f: Gastric volume, Panel g: GC/AC, Panel h: GA/AA, Panel i: GER. GC/AC: gastric circumference to abdominal circumference ratio, GA/AA Gastric area to abdominal area ratio, GER Gastric emptying rate. The three curves represent the 2.5th centile, mean and 97.5th centile, respectively. Gestational age group 1: 11–13 weeks, gestational age group 2: 14–16 weeks, gestational age group 3: 17–19 weeks, gestational age group 4: 20–22 weeks, gestational age group 5: 23–25 weeks, gestational age group 6: 26–28 weeks, gestational age group 7: 29–31 weeks, gestational age group 8: 32–34 weeks, gestational age group 9: 35–37 weeks, and gestational age group 10: 38–40 weeks
Table 3.
Regression equations and correlation coefficients (R2) of fetal gastric parameters with gestational age
| Gastric parameter | Regression equation | R 2 |
|---|---|---|
| Gastric maximum length | y = 0.1573 + 0.4650x | 0.8824 |
| Gastric transverse diameter | y = 0.2218 + 0.1782x | 0.8135 |
| Gastric anteroposterior diameter | y = 0.1475 + 0.2503x | 0.7959 |
| Gastric circumference | y = 0.2465 + 0.7949x | 0.8006 |
| Gastric area | y = -0.1671 + 0.203x + 0.0219x 2 | 0.8174 |
| Gastric volume | y = -0.1342 + 0.0571x + 0.0633x 2 | 0.8689 |
| GC/AC | y = 0.2162 + 0.00116x | 0.0072 |
| GA/AA | y = 0.0401 + 0.00038x | 0.0064 |
| GER | y = 1.0916– 0.8353x + 0.2188x 2 | 0.8249 |
GC/AC: Gastric circumference to abdominal circumference ratio, GA/AA: Gastric area to abdominal area ratio, GER: Gastric emptying rate, R2: correlation coefficient
Comparison of fetal gastric parameters between the hyperglycemia in pregnancy group and the normal control group
Table 4 presents a comparative analysis of fetal gastric parameters among the well-controlled HIP group, the poorly-controlled HIP group, and the normal control group. The maximum gastric length, gastric transverse diameter, gastric anteroposterior diameter, gastric circumference, gastric area and gastric volume in the poorly-controlled HIP group were significantly greater than those in both the well-controlled HIP group and normal group (p < 0.05). In contrast, no statistically significant differences were observed between the well-controlled HIP group and the normal control group (p > 0.05) except for the gastric volume. Furthermore, the ratios of GC/AC and GA/AA in the poorly-controlled HIP group were lower than those in both the well-controlled HIP group and the normal control group (p < 0.05). Notably, the ratios in the well-controlled HIP group were also lower than those in the normal group (p < 0.05). In addition, the gastric emptying rate (GER) in the poorly-controlled HIP group was lower than that in both the well-controlled HIP group and the normal group (p < 0.05), and the GER in the well-controlled HIP group was lower than that in the normal group (p < 0.05).
Table 4.
Comparison of fetal gastric parameters between normal control group and HIP case groups
| Group (n) | Normal (457) | Case group 1 (90) | Case group 2 (36) |
|---|---|---|---|
| GA (weeks) | 26.79 ± 7.83 | 26.79 ± 5.62 | 27.97 ± 5.31 |
| Gastric maximum length (cm) | 2.91 ± 1.30 | 2.99 ± 0.94 | 3.81 ± 0.92*‡ |
| Gastric transverse diameter (cm) | 1.28 ± 0.52 | 1.31 ± 0.41 | 1.64 ± 0.42*‡ |
| Gastric anteroposterior diameter (cm) | 1.63 ± 0.73 | 1.67 ± 0.50 | 2.07 ± 0.56*‡ |
| Gastric circumference (cm) | 4.96 ± 2.32 | 5.10 ± 1.49 | 6.31 ± 1.41*‡ |
| Gastric area (cm2) | 1.96 ± 1.30 | 2.08 ± 0.85 | 2.78 ± 0.85*‡ |
| Gastric volume (cm3) | 2.86 ± 2.18 | 3.32 ± 1.60† | 4.79 ± 1.72*‡ |
| GER (mL/h) | 0.364 ± 0.305 | 0.251 ± 0.140† | 0.162 ± 0.113*§ |
| GC/AC | 0.223 ± 0.036 | 0.210 ± 0.018* | 0.190 ± 0.014*‡ |
| GA/AA | 0.042 ± 0.013 | 0.038 ± 0.004† | 0.034 ± 0.003*§ |
* p < 0.001 versus normal group; †p < 0.05 versus normal group; ‡p < 0.01 versus case group 1; §p < 0.05 versus case group 1.
GC/AC: Gastric circumference to abdominal circumference ratio, GA/AA: Gastric area to abdominal area ratio, Case group 1: well-controlled hyperglycemia in pregnancy, Case group 2: poorly-controlled hyperglycemia in pregnancy
Discussion
This study successfully established comprehensive nomograms of 2D and 3D fetal gastric parameters from 11 to 40 gestational weeks. Further analysis revealed that 2D and 3D gastric parameters and the gastric emptying rate (GER) increased with increasing GA, whereas the GC/AC and GA/AA ratios were not correlated. In addition, this study demonstrated the high reliability and consistency of all the measurements for both the intra-observer and inter-observer reliability. Importantly, the poorly-controlled HIP group demonstrated significantly greater gastric parameters and a lower GER than both the well-controlled HIP and normal groups did. No differences were found in the gastric parameters between the well-controlled HIP group and the normal group; however, the GER was lower in the well-controlled HIP group than in the normal group. Additionally, the GC/AC and GA/AA ratios were lower in both HIP groups than in the normal group.
Fetal stomach could be visualized by ultrasound as early as 11 weeks in this study, which is one week earlier than in a previous study [14]. Although prior studies have measured gastric longitudinal, transverse, and anteroposterior dimensions, as well as the gastric area or volume, to evaluate fetal stomach size across gestational ages, these studies have generally involved a limited number of normal fetuses, focusing only on correlations between gastric parameters and GA or the AFI [12, 14, 15]. Additionally, they focused on fewer gastric parameters in one study rather than a more comprehensive assessment, incorporating both 2D and 3D gastric parameters, as we conducted. The GER, which calculates the change in gastric volume over time during ultrasound examination on the basis of peristaltic activity, provides a more precise estimation of gastric function without the need to monitor a complete gastric emptying cycle over 60 min or more [14, 16]. The latter method is time-consuming and unacceptable for some pregnant mothers, resulting in a lack of enough participants to establish the reference range. The nomograms of fetal gastric parameters, derived from a large cohort across various gestational ages, provide valuable references for assessing normal fetal gastric development and function, and for identifying abnormalities that may indicate pathophysiological changes, especially in HIP cases.
The results indicate that most fetal gastric parameters, including maximum gastric length, transverse diameter, anteroposterior diameter, circumference, area, volume, and GER, were positively correlated with GA, steadily increasing as pregnancy progressed. This growth pattern aligns with the expected development of the fetal gastrointestinal system. Notably, GER remained relatively stable until approximately 19 weeks, then gradually increased from 20 to 28 weeks, rising significantly after 28 weeks, consistent with previous research indicating minimal gastric emptying prior to 27 gestational weeks and a marked increase thereafter [16]. However, the ratios of GC/AC and GA/AA did not significantly correlate with gestational age, suggesting that these metrics remain relatively stable throughout pregnancy. This stability is a novel finding of this study, highlighting that GC/AC and GA/AA could serve as reliable reference values for assessing conditions affecting gastric or abdominal measurements, unaffected by natural fetal growth.
Our analysis of the HIP groups showed that fetal gastric measurements in the poorly-controlled HIP group were significantly higher than in the well-controlled HIP and normal groups. 2D and 3D volume parameters were markedly elevated in the poorly-controlled HIP group, suggesting that poor glycemic control may contribute to fetal gastric enlargement. Research indicates that hyperglycemia increases fetal glucose exposure, leading to hyperinsulinemia and accelerated organ growth, including the gastrointestinal system [4]. This may account for the observed increase in gastric dimensions in patients with poorly-controlled HIP. The absence of significant differences in 2D gastric parameters and significant differences in gastric volume between the well-controlled HIP and normal group suggest that 3D gastric volume measurements are more sensitive for monitoring the effect of glycemic control on the fetal stomach. These findings emphasize the importance of effective glycemic management in preventing abnormal gastric development.
The GER was the lowest in the poorly-controlled HIP group, followed by the well-controlled HIP and normal groups. The reduced GER in the poorly-controlled HIP group likely reflects impaired gastric motility, possibly due to hyperglycemia-induced changes in fetal gastrointestinal function. HIP can disrupt fetal gastrointestinal hormone regulation (insulin and glucagon) essential for gastric motility [17–19] and may also impair the vagus nerve, affecting the function of interstitial cells of Cajal, which coordinate smooth muscle contractions [20, 21]. This reduced GER could cause gastric distension and further enlargement in the poorly-controlled group. The intermediate GER in the well-controlled group suggests partial improvement in gastric motility due to glycemic management, though no such effect was observed in the normal group.
Interestingly, the GC/AC and GA/AA ratios in two HIP groups were significantly lower than those in normal group, even though gastric measurements were elevated in the poorly-controlled HIP group. This suggests that while gastric size increases in poorly-controlled HIP pregnancies, the abdominal size does not increase proportionally, resulting in lower GC/AC and GA/AA ratios [4]. These ratios may serve as potential markers for monitoring blood glucose levels in HIP patients.
Both 2D and 3D ultrasound measurements showed high reliability and consistency, supporting the use of the VOCAL technique for routine fetal gastric evaluation. However, this study has several limitations. First, the operator dependence of the VOCAL technique may introduce variability, particularly in cases where the examiner has limited experience, potentially affecting measurement accuracy and reproducibility. Second, its cross-sectional design restricts tracking fetal gastric parameter changes over time, whereas longitudinal analysis would better reveal progression. Finally, future research should explore potential long-term neonatal and pediatric health effects.
Conclusion
In conclusion, this study established comprehensive fetal gastric reference ranges using 2D and 3D ultrasound VOCAL techniques. Fetal gastric parameter nomograms provide valuable tools for assessing fetal gastric development and function in normal and HIP pregnancies, highlighting the impact of glycemic control.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
We would like to extend our sincere gratitude to all the staff members at the Department of Ultrasound Medicine at the Second Hospital of Fujian Medical University, as well as to all the participants in the study who generously contributed their data for our research.
Abbreviations
- 1-h PG
1-h plasma glucose
- 2D
Two-dimensional
- 2-h PG
2-h plasma glucose
- 3D
Three-dimensional
- AC
Abdominal circumference
- AFI
Amniotic fluid index
- AIUM
American institute of ultrasound in medicine
- BMI
Body mass index
- FPG
Fasting plasma glucose
- GA/AA
The ratio of gastric area to abdominal area
- GA
Gestational age
- GC/AC
The ratio of gastric circumference to abdominal circumference
- GDM
Gestational diabetes mellitus
- GER
Gastric emptying rate
- HIP
Hyperglycemia in pregnancy
- ICC
Intraclass correlation coefficients
- OGTT
Oral glucose tolerance test
- PGDM
Pregestational diabetes mellitus
- SD
Standard deviation
- VOCAL
Virtual organ computer-aided analysis
Author contributions
X.L., X.W. and Z.Z. participated in study design, methodology, data collection, analysis and interpretation, funding acquisition, and writing - review and editing. X.L. wrote the first draft of the manuscript. P.L., J.B. and H.Z. collected data and reviewed the manuscript. S.H. applied for funding acquisition and reviewed the manuscript; G.L. reviewed the manuscript. Z.X. and S.L. conceptualized and designed the study and reviewed the manuscript, and provided supervision. All authors have read and approved the final version of the manuscript.
Funding
This work was supported by the Quanzhou City Science and Technology Project (No. 2024NY037) and the Joint Funds for the Innovation of Science and Technology, Fujian province (No. 2023Y9264, 2024Y9410 and 2024Y9392). The funders provided financial support for the research work but did not involve in the study design, data collection, analysis and interpretation, or manuscript writing and revision.
Data availability
Data is provided within the manuscript or supplementary information files.
Declarations
Ethics approval and consent to participate
This study involving humans was conducted with ethical approval from the Ethics Committee of Fujian Medical University Second Affiliated Hospital (approval number: 2024 [067]) and in accordance with the ethical principles outlined in the Declaration of Helsinki. All participants provided informed consent prior to inclusion in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Xihua Lian, Xiaoying Wang and Zhixing Zhu have equally contributed to this work.
Contributor Information
Zhenhong Xu, Email: 18905953959@qq.com.
Shunlan Liu, Email: 85443785@fjmu.edu.cn.
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