Association between maternal body mass index and increased fetal pancreatic circumference in normoglycemic pregnancies: a prospective cross-sectional study

Abstract

Objective

To evaluate the association between maternal body mass index (BMI) and fetal pancreatic circumference (PC) in singleton pregnancies without gestational diabetes mellitus (GDM), and to determine whether maternal obesity is related to pancreatic changes independent of conventional fetal growth parameters.

Methods

This prospective multicenter cross-sectional study included normoglycemic singleton pregnancies assessed in the second (n = 142) and third (n = 154) trimesters. All participants underwent a 75-g oral glucose tolerance test (OGTT), and GDM cases were excluded. Maternal BMI was categorized according to World Health Organization (WHO) criteria. Fetal PC was measured using a standardized freehand tracing technique, and the mean of three measurements was recorded. Comparisons among BMI groups were performed using ANOVA and ANCOVA adjusted for fetal abdominal circumference (AC). Correlation and multivariable logistic regression analyses were conducted to assess associations with composite adverse neonatal outcomes (CANO).

Results

Maternal, fetal, and neonatal characteristics, including estimated fetal weight, AC percentile, birth weight, and Apgar scores, were similar across maternal BMI categories. However, fetal PC differed significantly by maternal BMI in both trimesters. In the second trimester, mean PC was 6.44 ± 0.86 cm in normal-weight women, 7.10 ± 0.94 cm in overweight women, and 7.11 ± 0.98 cm in obese women (p = 0.008), remaining significant after AC adjustment (p = 0.021). In the third trimester, PC increased progressively (6.84 ± 0.48 cm, 7.64 ± 0.78 cm, and 7.93 ± 1.04 cm; p = 0.004), persisting after adjustment (p = 0.003). PC correlated positively with maternal BMI, gestational age, and AC. Neither BMI nor PC independently predicted adverse neonatal outcomes.

Conclusion

Higher maternal BMI is associated with increased fetal PC independent of conventional growth parameters, suggesting organ-specific intrauterine effects even without GDM. Short-term neonatal outcomes were unaffected.

Background

Maternal obesity has become increasingly prevalent worldwide and is associated with a wide range of adverse maternal and fetal outcomes. Although these adverse effects are often evaluated in relation to the presence of gestational diabetes mellitus (GDM), obesity is also characterized by glycemia-independent metabolic disturbances, including insulin resistance, chronic low-grade inflammation, and altered lipid metabolism [1, 2]. These obesity-related metabolic changes may influence fetal development even in the absence of overt maternal hyperglycemia.

Traditionally, fetal effects of maternal obesity have been assessed using global growth parameters such as estimated fetal weight, birth weight, and the risk of large-for-gestational-age (LGA) infants. However, these conventional biometric indices may not fully reflect obesity-related intrauterine effects. Recent data suggest that maternal obesity may affect fetal development through selective, organ-specific pathways that are not necessarily accompanied by generalized fetal overgrowth, including placental dysfunction and alterations in fetal cardiac structure and function [3, 4]. These findings raise the possibility that other metabolically active fetal organs may also be affected. In this context, the fetal pancreas is considered an important metabolic target organ. In pregnancies complicated by GDM, fetal pancreatic alterations, including changes in size and volume as well as related functional parameters, have been reported and are largely attributed to maternal hyperglycemia [5, 6].

In contrast, data regarding the impact of maternal obesity on fetal pancreatic development in normoglycemic pregnancies are limited. In many studies investigating maternal obesity, GDM has not been adequately excluded, or the glycemia-independent effects of obesity have not been clearly distinguished [7, 8]. Consequently, whether maternal obesity alone leads to measurable changes in fetal pancreatic size remains unclear. Although animal studies suggest that maternal obesity can influence fetal pancreatic development independently of overall fetal growth, corresponding evidence in human pregnancies remains scarce [9].

The aim of this study was to evaluate the association between maternal body mass index (BMI) and fetal pancreatic circumference (PC) in singleton pregnancies in which GDM was excluded. By assessing fetal PC in both the second and third trimesters, we sought to determine whether maternal obesity is associated with organ-specific alterations in fetal pancreatic development independent of conventional fetal growth parameters.

Materials and methods

Study design and population

This prospective multicenter cross-sectional study was conducted at the Department of Perinatology, University of Health Sciences Izmir City Hospital and Department of Perinatology, Izmir Katip Celebi University Ataturk Training and Research Hospital, both tertiary referral centers. The study protocol was approved by the Izmir Katip Celebi University Health Research Institutional Review Board (Decision No: 0111), and institutional approval was also obtained from Izmir City Hospital. The study was conducted in accordance with the principles of the Declaration of Helsinki (October 2024 revision), and written informed consent was obtained from all participants prior to enrollment.

Singleton pregnancies evaluated in the second or third trimester were eligible for inclusion. The second trimester was defined as gestational weeks 14 + 0 through 27 + 6, and the third trimester as gestational weeks 28 + 0 onwards, consistent with internationally adopted standards. Gestational age was confirmed in all cases based on first-trimester crown–rump length (CRL) measurements. Analyses were performed as two independent cross-sectional cohorts (second- and third-trimester), and no longitudinal follow-up between trimesters was performed. Inclusion criteria were maternal age ≥ 18 years, singleton pregnancy, reliable ultrasonographic visualization of the fetal pancreas, and availability of complete maternal clinical data allowing calculation of BMI. All participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation, and pregnancies diagnosed with GDM or pregestational diabetes mellitus were excluded from the study. Additional exclusion criteria included multiple gestations, fetuses with major structural or chromosomal anomalies, maternal systemic conditions known to significantly affect metabolism (such as uncontrolled thyroid disease or chronic hypertension), pregnancies complicated by hypertensive disorders of pregnancy or intrahepatic cholestasis of pregnancy, and inadequate image quality precluding reliable pancreatic assessment. Pancreatic visualization was unsuccessful in 12 s-trimester and 9 third-trimester cases (predominantly due to unfavorable fetal positioning or inadequate acoustic window) and these were excluded from the final analysis.

Maternal BMI was calculated at the time of ultrasound examination and classified according to World Health Organization (WHO) criteria into normal-weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obesity (≥ 30.0 kg/m²) categories [10]. GDM was defined according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting ≥ 92 mg/dL, 1-hour ≥ 180 mg/dL, or 2-hour ≥ 153 mg/dL), with the presence of any abnormal value considered diagnostic [11]. Participants meeting the diagnostic criteria for GDM were excluded from the final analysis. For participants initially evaluated before completion of the OGTT, eligibility was confirmed after test results became available.

Ultrasonographic assessment

All ultrasonographic examinations were performed by experienced perinatologists at each participating center using a GE Voluson E8 ultrasound system (GE Healthcare, Zipf, Austria), following a standardized imaging protocol. Routine fetal biometry, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), was obtained, and estimated fetal weight (EFW) was calculated using the Hadlock formula [12].

Following routine biometric assessment, fetal pancreatic measurements were obtained. The pancreas was identified in an axial or mildly oblique upper-abdominal plane, using the stomach and surrounding vascular structures as anatomical landmarks. It appeared as an elongated structure located posterior to the stomach and anterior to the aorta and vertebral column (Fig. 1). Fetal PC was measured by manually tracing the outer contour of the gland using a freehand technique. Three consecutive measurements were obtained during the same examination, and the mean value was used for analysis. All measurements were performed according to a predefined standardized protocol to ensure consistency across examinations. PC values were evaluated in relation to gestational age and fetal biometric parameters.

Fig. 1.

Sonographic visualization of the fetal pancreas. Axial upper-abdominal ultrasound image demonstrating the fetal pancreas (outlined) posterior to the stomach. Pancreatic circumference was measured using a standardized freehand tracing technique

Data collection and outcomes

Maternal demographic and clinical data, including age, BMI, parity and gestational age were recorded. Neonatal outcomes, including birth weight, Apgar scores, and need for neonatal intensive care unit (NICU) admission, were collected from hospital records.

The primary outcome of the study was fetal PC measured during the second and third trimesters. Secondary outcomes included the associations between fetal PC and maternal BMI categories, gestational age at measurement, and fetal biometric parameters. Composite adverse neonatal outcomes (CANO) include presence of at least one of the adverse outcomes; respiratory distress syndrome, hyperbilirubinemia, infection or sepsis and, neonatal intensive care unit admission.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or standard error (SE), while categorical variables were presented as frequencies and percentages. Comparisons among three groups were performed using one-way analysis of variance (ANOVA) test, followed by Bonferroni post-hoc correction where appropriate. Categorical variables were compared using the χ² test or Fisher’s exact test, depending on expected cell counts. Analysis of covariance (ANCOVA) was used to evaluate pancreatic circumference values adjusted for fetal AC. The relationships between fetal pancreatic circumference and selected maternal and fetal parameters were evaluated using Pearson’s correlation coefficient. To identify independent prenatal predictors of CANO, multivariable logistic regression analyses were performed separately for the second- and third-trimester cohorts. Only prenatal variables available at the time of ultrasound examination were included in the regression models to avoid postnatal and overadjustment bias. These variables comprised maternal age, parity, BMI at ultrasound, and fetal pancreatic circumference. Results were reported as regression coefficients (B), odds ratios (ORs), and 95% confidence intervals (CIs). A two-sided p value < 0.05 was considered statistically significant.

Use of artificial intelligence tools

A large language model (ChatGPT, OpenAI) was used only for language editing and translation. The authors independently verified all scientific content, analyses, interpretations, and approved the final version of the manuscript.

Results

The study population consisted of 142 pregnant women evaluated in the second trimester and 154 pregnant women evaluated in the third trimester. In the second trimester cohort, participants were classified into normal-weight (n = 54), overweight (n = 62), and obesity (n = 26) groups. In the third trimester cohort, participants were similarly classified into normal-weight (n = 44), overweight (n = 70), and obesity (n = 40) groups.

Maternal, fetal, and neonatal characteristics according to maternal BMI categories in the second and third trimesters are summarized in Tables 1 and 2. In both trimesters, maternal age, parity, gestational age at measurement, AC percentile, EFW percentile, gestational age at birth, birth weight, and Apgar scores did not show significant differences among BMI categories. As expected, BMI measured at the time of ultrasound was significantly different between groups in both the second and third trimesters (p < 0.001, for all comparisons). To further assess the potential contribution of subclinical maternal glycemia, fasting, 1-hour, and 2-hour 75 g OGTT values were compared across maternal BMI categories. No statistically significant differences were observed in any OGTT parameter between groups in either trimester cohort (p > 0.05, for all comparisons). The rates of neonatal outcomes (including respiratory distress syndrome, hyperbilirubinemia, and infection or sepsis), NICU admission, and CANO were similar across maternal BMI categories in both the second and third trimesters, with no statistically significant differences observed.

Table 1.

Maternal, fetal, and neonatal characteristics according to maternal body mass index categories in the second trimester

	BMI at the time of ultrasound healthy weight range 18.5–24.9 (kg/m2) (n = 54)	BMI at the time of ultrasound overweight range 25.0–29.9 (kg/m2) (n = 62)	BMI at the time of ultrasound obesity ≥ 30 (kg/m2) (n = 26)	p
Maternal age (years) (mean ± SD)	29 ± 7	31 ± 5	31 ± 5	0.385
Parity (n,%)				0.192
Nulliparous	30 (53.6%)	24 (38.7%)	12 (46.1%)
Multiparous	24 (46.4%)	38 (61%)	14 (53.9%)
BMI at the time of ultrasound (kg/m2) (mean ± SD)	22.8 ± 1.9	27.2 ± 1.2	33.8 ± 3.6	< 0.001a
Fasting glucose (mg/dL)	77 ± 8	80 ± 9	80 ± 9	0.468
1-hour glucose (mg/dL)	119 ± 23	124 ± 27	131 ± 30	0.237
2-hour glucose (mg/dL)	102 ± 19	107 ± 20	105 ± 17	0.625
Gestational age at measurement (weeks) (mean ± SD)	25 ± 2	25.1 ± 1.8	26.1 ± 1.6	0.327
AC percentile (%) (mean ± SD)	43.5 ± 22.3	40.1 ± 18.5	46.4 ± 23.5	0.514
EFW percentile (%) (mean ± SD)	47.1 ± 20.9	46.7 ± 21.1	50.3 ± 20.8	0.773
Gestational age at delivery (weeks) (mean ± SD)	37.7 ± 2.2	38.2 ± 1.9	37.4 ± 1.8	0.417
Birth weight (g) (mean ± SD)	2959 ± 562	3208 ± 499	3185 ± 652	0.226
1st minute APGAR score (mean ± SD)	8 ± 1	8 ± 0	8 ± 1	0.743
5th minute APGAR score (mean ± SD)	9 ± 0	9 ± 0	9 ± 1	0.236
Neonatal Complications (n,%)
RDS	0 (0%)	1 (1.6%)	1 (3.8%)	0.386
Hyperbilirubinemia	0 (0%)	1 (1.6%)	1 (3.8%)	0.386
Infection and/or sepsis	1 (1.8%)	0 (0%)	0 (0%)	0.440
NICU admission (n,%)	1 (1.8%)	2 (3.2%)	2 (7.7%)	0.408
* Composite adverse neonatal outcomes (n,%)	1 (1.8%)	2 (3.2%)	2 (7.7%)	0.408
Perinatal mortality (n,%)	0 (0%)	0 (0%)	0 (0%)	N/A

BMI: body mass index, AC: abdominal circumference, EFW: estimated fetal weight, RDS: respiratory distress syndrome, NICU: neonatal intensive care unit

* Composite adverse neonatal outcomes include presence of at least one of the adverse outcome; respiratory distress syndrome, hyperbilirubinemia, infection or sepsis and, neonatal intensive care unit admission

^a Significant differences were found between all groups

Table 2.

Maternal, fetal, and neonatal characteristics according to maternal body mass index categories in the third trimester

	BMI at the time of ultrasound healthy weight range 18.5–24.9 (kg/m2) (n = 44)	BMI at the time of ultrasound overweight range 25.0–29.9 (kg/m2) (n = 70)	BMI at the time of ultrasound obesity ≥ 30 (kg/m2) (n = 40)	p
Maternal age (years) (mean ± SD)	30 ± 5	28 ± 5	30 ± 4	0.522
Parity (n,%)				0.292
Nulliparous	24 (54.5%)	32 (45.7%)	15 (37.5%)
Multiparous	20 (45.5%)	38 (54.3%)	25 (62.5%)
BMI at the time of ultrasound (kg/m2) (mean ± SD)	23.1 ± 1.3	27.1 ± 1.5	32.2 ± 1.2	< 0.001a
Fasting glucose (mg/dL)	79 ± 9	81 ± 9	82 ± 10	0.352
1-hour glucose (mg/dL)	121 ± 24	126 ± 29	134 ± 32	0.241
2-hour glucose (mg/dL)	100 ± 19	105 ± 19	107 ± 20	0.425
Gestational age at measurement (weeks) (mean ± SD)	33.6 ± 2.4	35.3 ± 2.6	34.3 ± 1.6	0.191
AC percentile (%) (mean ± SD)	30.6 ± 21.1	41.2 ± 26.9	49.8 ± 24.3	0.216
EFW percentile (%) (mean ± SD)	29.1 ± 15.1	37.6 ± 21.7	43.9 ± 22.5	0.230
Gestational age at delivery (weeks) (mean ± SD)	37.4 ± 2.6	38.8 ± 1.2	38.8 ± 1.4	0.380
Birth weight (g) (mean ± SD)	2839 ± 439	3149 ± 315	3350 ± 518	0.065
1st minute APGAR score (mean ± SD)	9 ± 0	9 ± 0	9 ± 0	0.947
5th minute APGAR score (mean ± SD)	10 ± 0	10 ± 0	10 ± 0	0.756
Neonatal Complications (n,%)
RDS	1 (2.2%)	1 (1.4%)	1 (2.5%)	0.910
Hyperbilirubinemia	0 (0%)	1 (1.4%)	1 (2.5%)	0.595
Infection and/or sepsis	1 (2.2%)	0 (0%)	0 (0%)	0.284
NICU admission (n,%)	2 (4.5%)	2 (2.8%)	2 (5%)	0.826
* Composite adverse neonatal outcomes (n,%)	2 (4.5%)	2 (2.8%)	2 (5%)	0.826
Perinatal mortality (n,%)	0 (0%)	0 (0%)	0 (0%)	N/A

BMI: body mass index, AC: abdominal circumference, EFW: estimated fetal weight, RDS: respiratory distress syndrome, NICU: neonatal intensive care unit

* Composite adverse neonatal outcomes include presence of at least one of the adverse outcome; respiratory distress syndrome, hyperbilirubinemia, infection or sepsis and, neonatal intensive care unit admission

^a Significant differences were found between all groups

In contrast to the largely similar baseline characteristics, fetal PC showed a clear association with maternal BMI. In the second trimester, mean PC differed significantly among BMI categories (p = 0.008), with fetuses of overweight and obese mothers demonstrating larger measurements compared with those of normal-weight mothers. This difference remained statistically significant after adjustment for fetal AC (p = 0.021), and adjusted mean PC values were higher in both the overweight and obesity groups (Table 3; Fig. 2). Consistent findings were observed in the third trimester. Unadjusted fetal PC increased progressively across maternal BMI categories (p = 0.004), and this association persisted following adjustment for AC (p = 0.003). As illustrated in Table 3; Fig. 3, adjusted PC values were significantly higher in the overweight and obesity groups compared with the normal-weight group. Post-hoc analyses further clarified these differences, demonstrating that the observed increases in PC were significant between the normal-weight group and both the overweight and obesity groups, whereas no statistically significant difference was detected between the overweight and obesity groups in either trimester.

Table 3.

Comparison of fetal pancreatic measurements according to maternal body mass index categories in the second and third trimester

	BMI at the time of ultrasound healthy weight range 18.5–24.9 (kg/m2)	BMI at the time of ultrasound overweight range 25.0–29.9 (kg/m2)	BMI at the time of ultrasound obesity ≥ 30 (kg/m2)	p
Second trimester	(n = 54)	(n = 62)	(n = 26)
Pancreatic circumference (cm) (mean ± SD)	6.44 ± 0.86	7.10 ± 0.94	7.11 ± 0.98	0.008a
Pancreatic circumference adjusted for AC (cm) (mean ± SE)	6.45 ± 0.12	7.02 ± 0.14	7.01 ± 0.16	0.021a
Third trimester	(n = 44)	(n = 70)	(n = 40)
Pancreatic circumference (cm) (mean ± SD)	6.84 ± 0.48	7.64 ± 0.78	7.93 ± 1.04	0.004a
Pancreatic circumference adjusted for AC (cm) (mean ± SE)	6.81 ± 0.10	7.64 ± 0.12	7.96 ± 0.15	0.003a

AC: abdominal circumference

^a Significant differences were found between Groups 1–2 and 1–3

Fig. 2.

Adjusted mean fetal pancreatic circumference according to maternal BMI categories in the second trimester after adjustment for fetal abdominal circumference (AC, cm). Values are adjusted for fetal abdominal circumference (AC, cm) using ANCOVA. Error bars represent standard error of the mean

Fig. 3.

Adjusted mean fetal pancreatic circumference according to maternal BMI categories in the third trimester after adjustment for fetal abdominal circumference (AC, cm). Values are adjusted for abdominal circumference (AC, cm) using ANCOVA. Error bars represent standard error of the mean

Correlation analyses supported these findings by revealing positive associations between fetal PC and maternal BMI, gestational age at measurement, and fetal AC in both trimesters. In the second trimester, PC correlated with maternal BMI (r = 0.320, p = 0.002), gestational age (r = 0.326, p = 0.001), and AC (r = 0.333, p = 0.001). Similar correlations were observed in the third trimester, including maternal BMI (r = 0.357, p = 0.004), gestational age (r = 0.328, p = 0.009), and AC (r = 0.313, p = 0.003), as shown in Table 4.

Table 4.

The correlation between fetal pancreatic measurements and selected maternal, and fetal parameters

	BMI	Gestational age at measurement (weeks)	AC
Second trimester
Pancreatic circumference (cm)	r = 0.320, p = 0.002	r = 0.326, p = 0.001	r = 0.333, p = 0.001
Third trimester
Pancreatic circumference (cm)	r = 0.357, p = 0.004	r = 0.328, p = 0.009	r = 0.313, p = 0.003

BMI: body mass index, AC: abdominal circumference

Finally, multivariable logistic regression analyses were conducted to assess whether fetal PC was independently associated with CANO. In both second- and third-trimester models, maternal age, parity, maternal BMI, and fetal PC were not independently associated with adverse neonatal outcomes (p > 0.05, for all comparisons), as detailed in Table 5.

Table 5.

Prenatal multivariable logistic regression analysis of factors associated with composite adverse neonatal outcomes

Variable	B	OR	CI_low	CI_high	p
Second trimester
Maternal age (years)	0.060	1.062	0.949	1.188	0.293
Parity	-0.408	0.665	0.337	1.310	0.238
BMI at the time of ultrasound (kg/m2)	-0.015	0.985	0.864	1.122	0.817
Pancreatic circumference (cm)	-0.301	1.351	0.927	1.968	0.117
Third trimester
Maternal age (years)	-0.032	0.969	0.845	1.110	0.648
Parity	-0.121	0.886	0.441	1.778	0.733
BMI at the time of ultrasound (kg/m2)	0.153	1.165	0.953	1.425	0.137
Pancreatic circumference (cm)	-0.105	0.900	0.702	1.153	0.404

BMI: body mass index

Discussion

In this prospective multicenter study of normoglycemic singleton pregnancies, we demonstrated that increasing maternal BMI was significantly associated with larger fetal PC in both the second and third trimesters, whereas conventional growth parameters, including EFW and birth weight, did not differ across BMI categories. Importantly, the association between maternal BMI and fetal PC persisted after adjustment for fetal AC. These findings suggest that the fetal effects of maternal obesity may occur not only through changes in overall fetal growth, but also via organ-specific and metabolic pathways.

Fetal pancreatic size has primarily been investigated in pregnancies affected by GDM. Previous studies have shown that fetal pancreatic volume or circumference is increased in GDM pregnancies and that this enlargement is associated with fetal hyperinsulinemia and increased glucose exposure [6, 13, 14]. Gilboa et al. reported that fetal PC measured between 20 and 25 weeks of gestation was increased in the presence of GDM and had a moderate discriminatory ability for predicting GDM (AUC: 0.71) [13]. Similarly, Keven et al. demonstrated that PC measured at 24–28 weeks was significantly larger in GDM pregnancies compared with controls (7.0 cm vs. 6.4 cm; p < 0.001) [15]. Golbasi et al. also reported a significant increase in PC during the third trimester in pregnancies complicated by GDM (72.8 ± 14.7 mm vs. 66.7 ± 10 mm; p = 0.001) [6]. In these studies, pancreatic enlargement was predominantly interpreted as a consequence of maternal hyperglycemia. Normative reference data for fetal PC have been established in prior studies. Our values in the normal-weight group are concordant with the gestational age-specific nomograms reported by Liao et al. and Li et al., supporting the methodological validity of the present measurements [16, 17]. However, many studies evaluating the fetal effects of maternal obesity did not exclude GDM or failed to adequately distinguished accompanying metabolic disturbances, making it difficult to assess the independent effect of obesity on the fetal pancreas [18, 19]. Studies that specifically examine the relationship between maternal obesity and fetal pancreatic size in normoglycemic pregnancies are extremely limited. In this respect, our study addresses a clear gap in the literature. The consistent association observed between maternal BMI and fetal PC in normoglycemic pregnancies suggests that maternal obesity may influence fetal pancreatic development even in the absence of impaired glycemic control, and may be mediated by obesity-related metabolic factors.

Evidence from animal models strongly supports these hypotheses. Using an ovine animal model, Zhang et al. demonstrated that maternal obesity led to increased fetal pancreatic weight and β-cell proliferation during early gestation, followed by β-cell loss and increased apoptosis in later stages of pregnancy [9]. Notably, despite significant changes in fetal pancreatic structure and function during late gestation, no significant differences were observed in fetal growth parameters or birth weight between groups. Similarly, studies by Ford et al. using the same model reported time-dependent, biphasic effects of maternal obesity on fetal pancreatic development that were not consistently paralleled by conventional fetal biometric measurements [20]. These findings suggest that evaluating the fetal effects of maternal obesity solely through general growth patterns may be insufficient. Our study is important in that it demonstrates, in human fetuses and in the absence of GDM, an association between maternal obesity and fetal PC. These findings indicate that obesity-related intrauterine effects may occur independently of overt hyperglycemia.

The association between maternal obesity and increased birth weight has been widely reported in the literature. Large cohort studies and systematic reviews have shown that obesity in pregnancy is associated with an increased risk of macrosomia and LGA infants. In a systematic review by Weir et al., maternal obesity was reported to increase the risk of macrosomia by approximately three-fold and the risk of LGA by nearly two-fold (OR ≈ 2.5–3.0 for macrosomia; OR ≈ 1.9–2.0 for LGA) [19]. However, a substantial proportion of these studies included pregnancies complicated by GDM or other metabolic disturbances. In contrast, studies excluding GDM or adequately controlling for metabolic disorders have reported more heterogeneous findings with respect to birth weight. Moreno-Estrada et al. suggested that pregestational BMI may have a stronger influence on fetal growth than gestational weight gain, but that increases in birth weight were not consistent in GDM-excluded populations [21]. In this context, the finding of similar birth weights across maternal BMI groups in our GDM-excluded cohort is consistent with the heterogeneity reported in the literature.

In our cohort, EFW measured in both the second and third trimesters did not differ across maternal BMI categories, and this finding was consistent with the absence of significant differences in birth weight. To our knowledge, there are no previous studies evaluating trimester-specific EFW differences related to maternal obesity in a population from which GDM has been excluded. Although fetal PC showed a positive correlation with AC, this relationship reflects an expected anatomical and biometric association given the pancreatic location within the fetal abdomen. However, despite this correlation, no significant differences in EFW were observed across maternal BMI groups. These findings indicate that maternal obesity may be associated with organ-specific effects rather than generalized fetal overgrowth.

The effects of maternal obesity on neonatal outcomes have been extensively investigated. Systematic reviews and large cohort studies have reported associations between maternal obesity and adverse neonatal outcomes, including low Apgar scores, increased rates of NICU admission, and metabolic adaptation difficulties. However, these associations appear to be strongly influenced by the presence of concomitant metabolic conditions. For instance, a systematic review reported an increased risk of NICU admission among obese mothers, particularly in pregnancies complicated by GDM or other metabolic disorders [19]. Similarly, Reed et al. reported that the relationship between maternal obesity and adverse neonatal outcomes is heterogeneous and largely dependent on accompanying metabolic conditions [18]. In studies focusing on GDM pregnancies, fetal pancreatic enlargement has been linked to neonatal metabolic disturbances, but these observations were predominantly made in the context of maternal hyperglycemia [5]. The absence of significant adverse neonatal outcomes in our GDM-excluded population is consistent with these observations and suggests that the neonatal effects of maternal obesity may not always be reflected in short-term clinical outcomes. Nevertheless, the observed increase in fetal pancreatic size may represent an early metabolic adaptation that precedes overt clinical manifestations. However, these findings should be interpreted with caution, as the number of adverse neonatal events was limited and the regression analyses were exploratory. Alternatively, the absence of differences in neonatal outcomes despite increased pancreatic size may suggest that this enlargement represents a compensatory or protective metabolic adaptation rather than a pathological process.

Several limitations of this study should be acknowledged. First, the sample size may limit the generalizability of the findings. Second, the absence of detailed neonatal metabolic assessments and long-term childhood metabolic outcomes limits the ability to directly assess the clinical implications of the prenatal pancreatic changes observed. Third, due to the cross-sectional design, longitudinal changes in pancreatic size within the same fetus could not be assessed. In addition, maternal BMI was calculated at the time of ultrasound rather than before pregnancy, and gestational weight gain was not separately evaluated; therefore, the potential effect of pregnancy-related weight changes cannot be excluded. Despite these limitations, the study has several notable strengths. The multicenter design enhances external validity, and the rigorous exclusion of GDM using standardized OGTT criteria reduces metabolic confounding. In addition, the evaluation of two distinct gestational windows provides trimester-specific insights, and the focus on the fetal pancreas, an underexplored yet metabolically relevant organ, addresses a meaningful gap in the current literature.

In conclusion, this study demonstrates that maternal obesity in GDM-excluded pregnancies is associated with increased fetal PC, while EFW and birth weight remain unaffected. These findings suggest that maternal obesity may influence intrauterine development of fetal metabolic organs independently of classical biometric growth parameters and that routine fetal assessments may not fully capture obesity-related intrauterine metabolic effects. Prenatal evaluation of the fetal pancreas may contribute to a better understanding of the early metabolic consequences of maternal obesity. Larger studies with long-term follow-up are needed to clarify the relationship between these prenatal findings and neonatal as well as long-term metabolic outcomes.

Abbreviations

AC

Abdominal circumference

ANCOVA

Analysis of covariance

ANOVA

Analysis of variance

AUC

Area under the curve

BMI

Body mass index

CANO

Composite adverse neonatal outcomes

CI

Confidence interval

CRL

Crown–rump length

EFW

Estimated fetal weight

GDM

Gestational diabetes mellitus

IADPSG

International Association of Diabetes and Pregnancy Study Groups

LGA

Large for gestational age

LLM

Large language model

NICU

Neonatal intensive care unit

OGTT

Oral glucose tolerance test

OR

Odds ratio

PC

Pancreatic circumference

RDS

Respiratory distress syndrome

SD

Standard deviation

SE

Standard error

WHO

World Health Organization

Author contributions

IGA conceptualized the study, developed the project, collected and interpreted the data, and drafted the manuscript. HG contributed to study design, data interpretation, and critical revision of the manuscript. CSP collected data and revised the manuscript. HAA and ZEC contributed to manuscript revision and editing. BB performed statistical analysis, data management, and methodological support. MC and EST contributed to data collection and clinical verification. AE supervised the study, oversaw the project, and critically revised the manuscript. All authors read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The data that support the findings of this study are not publicly available due to ethical considerations and participant confidentiality but are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study protocol was approved by the Izmir Katip Celebi University Health Research Institutional Review Board (Decision No: 0111). Institutional approval was also obtained from Izmir City Hospital. The study was conducted in accordance with the Declaration of Helsinki (revised in 2024). Written informed consent was obtained from all participants prior to enrollment.

Consent for publication

Not applicable.

Authors’ information

Ilayda Gercik Arzik is a specialist in perinatology at Izmir City Hospital, Turkey. The authors are affiliated with tertiary referral centers specializing in maternal–fetal medicine.

Competing interests

The authors declare no competing interests.