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14 pages, 672 KB  
Article
Medical Nutrition Therapy with Meal Sequence and Divided Carbohydrate Intake: Associations with Ketonuria Resolution and Neonatal Outcomes in Gestational Diabetes Mellitus
by Saeko Imai, Shizuo Kajiyama, Yuki Higuchi, Shintaro Kajiyama, Yoshitaka Hashimoto and Michiaki Fukui
Nutrients 2026, 18(16), 2665; https://doi.org/10.3390/nu18162665 (registering DOI) - 14 Aug 2026
Abstract
Background/Objectives: Ketonuria is frequently observed in women with gestational diabetes mellitus (GDM), particularly when energy and carbohydrate intake is inadequate. This retrospective study evaluated nutritional status and neonatal outcomes following dietitian-led medical nutrition therapy (MNT) in 517 Japanese women with GDM with and [...] Read more.
Background/Objectives: Ketonuria is frequently observed in women with gestational diabetes mellitus (GDM), particularly when energy and carbohydrate intake is inadequate. This retrospective study evaluated nutritional status and neonatal outcomes following dietitian-led medical nutrition therapy (MNT) in 517 Japanese women with GDM with and without ketonuria. Methods: Dietary counseling emphasized a meal sequence in which vegetables were consumed before protein-rich foods and carbohydrates were consumed last, together with divided carbohydrate intake (4–5 meals/day), to attenuate postprandial glucose excursions while ensuring adequate energy and carbohydrate intake. Clinical characteristics, dietary intake, and neonatal outcomes were compared between women with and without ketonuria. Results: Among the participants, 143 (27.7%) exhibited ketonuria. The 60-min plasma glucose concentration during the OGTT was significantly higher in the ketonuria-positive group, whereas age, pre-pregnancy BMI, HbA1c, and glycated albumin did not differ between groups. Energy and carbohydrate intakes were significantly lower in the ketonuria-positive group before and after GDM diagnosis. Following GDM diagnosis, dietary intake decreased further in both groups; however, after MNT, energy and carbohydrate intakes increased significantly, and ketonuria resolved in all affected women. Birth weight, cesarean section rates, and the prevalence of congenital anomalies did not differ significantly between groups. None of the participants subsequently required insulin therapy during pregnancy. Conclusions: These findings suggest that dietitian-led MNT incorporating meal sequence and divided carbohydrate intake was associated with improved nutritional adequacy and resolution of ketonuria, with favorable neonatal outcomes observed in Japanese women with GDM regardless of urinary ketone status. Full article
13 pages, 202 KB  
Article
Ethnic Differences in Pregnancy Complications Among Women with Gestational Diabetes
by Tiziana Filardi, Paola Galoppi, Stefania Gorini, Ilenia Mappa, Giuseppe Rizzo and Susanna Morano
Med. Sci. 2026, 14(4), 482; https://doi.org/10.3390/medsci14040482 - 14 Aug 2026
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a metabolic disorder associated with an amplified risk of unfavorable pregnancy outcomes. This study aimed to compare clinical characteristics and pregnancy outcomes among GDM patients belonging to different ethnic groups. Patients and Methods: This retrospective [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a metabolic disorder associated with an amplified risk of unfavorable pregnancy outcomes. This study aimed to compare clinical characteristics and pregnancy outcomes among GDM patients belonging to different ethnic groups. Patients and Methods: This retrospective analysis included n = 466 women with GDM (n = 167 Asian; n = 299 European). The impact of ethnicity on pregnancy outcomes was evaluated using multivariable logistic regression models, adjusting for confounding factors. Results: Asians were younger than Europeans (p < 0.001) and more frequently multiparous (p = 0.003). Fasting glucose at OGTT was higher in Asians, as well as HbA1c values at the end of pregnancy (p = 0.010 and p = 0.001, respectively). Asian ethnicity was associated with an increased likelihood of insulin therapy (OR = 3.36 [1.72–6.58] 95% CI, p < 0.001), in the adjusted model. The gestational week of delivery was lower in Asians compared to Europeans (p = 0.007). The Asian group had a higher occurrence of cesarean section (p = 0.048) and emergency cesarean section (p = 0.006) compared to the European group. Delivery complications were more frequent in the Asian cohort, adjusting for confounders (OR = 2.19 [1.11–4.32] 95% CI, p = 0.023). Newborns of the Asian group were more frequently small for gestational age (SGA) in adjusted models (OR = 2.36 [1.08–5.15] 95% CI, p = 0.031). Conclusions: Worse GDM outcomes were observed in the Asian cohort compared to the European cohort. Identifying risk factors for GDM-related complications is crucial for developing tailored interventions and reducing the overall disease burden. Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
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25 pages, 2354 KB  
Review
The Lectin Pathway of Complement as a Sentinel for Nutritional and Metabolic Status: From Molecular Immunomodulation by Nutrients to Public Health Perspectives
by Tomasz Olszowski and Dariusz Chlubek
Nutrients 2026, 18(16), 2635; https://doi.org/10.3390/nu18162635 - 12 Aug 2026
Abstract
The lectin pathway (LP) of complement activation functions as a crucial effector of innate immunity and a homeostatic sensor operating at the intersection of systemic metabolism, nutritional status, and endothelial integrity. This review provides a comprehensive synthesis of current molecular, clinical, and epidemiological [...] Read more.
The lectin pathway (LP) of complement activation functions as a crucial effector of innate immunity and a homeostatic sensor operating at the intersection of systemic metabolism, nutritional status, and endothelial integrity. This review provides a comprehensive synthesis of current molecular, clinical, and epidemiological literature regarding the environmental and metabolic regulation of this pathway. First, we summarize the biophysical, structural, and stoichiometric requirements for divalent cations in fluid-phase activation and macromolecular assembly, integrating the contrasting roles of calcium (Ca2+) and zinc (Zn2+) into an explanatory Dual-Cation Dichotomy Framework. Second, we evaluate the transcriptomic mechanisms of nutrigenetic licensing, reviewing how fat-soluble vitamins sustain endoplasmic reticulum chaperone networks and mucosal barrier competence. We discuss how these micronutrient-driven axes interact with host genetic diversity, presenting a Nutrigenetic Rescue Framework to contextualize the environmental modulation of low-expressing MBL2 alleles. Third, the LP responds to metabolic and endocrine shifts, focusing on its biomarker value in gestational diabetes and its clinical patterns in type 1 diabetes. These connections to metabolic disease and related microvascular complications are further integrated into a broader Somatotropic-Gestational Sentinel Hypothesis. Fourth, we connect these metabolic profiles with public health challenges, reviewing LP hyperactivation in viral infections and discussing localized surface plasmon resonance (LSPR) biosensors, at present a conceptual, preclinical technology, as a candidate approach for future point-of-care population screening. In conclusion, bridging nutritional biochemistry with metabolic endocrinology and diagnostic technologies that remain largely preclinical outlines a potential shift from empiric management toward biomarker-driven, point-of-care stratification, which could help mitigate both infectious thromboinflammation and chronic microvascular failure once these technologies undergo further mechanistic and clinical validation. Full article
(This article belongs to the Section Nutrition and Metabolism)
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20 pages, 1053 KB  
Article
Development of Thai-Specific Gestational Weight Gain Targets Using Asian BMI Cut-Points: Implications for Nursing and Midwifery Practice in Preventing Gestational Diabetes Mellitus
by Piyanut Xuto, Daniel Bressington, Lawitra Khiaokham, Patompong Khaw-on, Nantarat Matayaboon, Suraphan Sangsawang, Nantawan Janta, Pradab Sungplipan, Suratsawadee Wiangsuwan, Sujitra Chaiwatthanakorn, Ampaporn Phiwon, Kamonchanok Khetwang and Ratchaneewan Charuloedphong
Nurs. Rep. 2026, 16(8), 274; https://doi.org/10.3390/nursrep16080274 - 4 Aug 2026
Viewed by 142
Abstract
Background: Thai obstetric nurses follow WHO gestational weight gain (GWG) guidelines to prevent gestational diabetes mellitus (GDM). However, these Western-derived guidelines misclassify approximately 16% of Thai pregnant women, who carry excess metabolic risk at lower BMI values than Western populations. Objectives: [...] Read more.
Background: Thai obstetric nurses follow WHO gestational weight gain (GWG) guidelines to prevent gestational diabetes mellitus (GDM). However, these Western-derived guidelines misclassify approximately 16% of Thai pregnant women, who carry excess metabolic risk at lower BMI values than Western populations. Objectives: To derive and validate Thai-specific GWG targets using Thai BMI cut-points across five BMI subgroups and assess implications for nursing practice in GDM prevention. Methods: Retrospective cohort study of 1396 Thai singleton pregnancies at a maternal and child hospital (2023–2025). GWG targets were derived as interquartile ranges (P25–P75) from a healthy-outcomes subgroup (n = 706), with validity confirmed by multivariable logistic regression and a 70:30 derivation/validation split. Results: GDM prevalence was 15.8%, with a rising crude trend that was attenuated after accounting for a mid-study change in screening protocol. Provisional Thai-specific GWG targets were underweight/normal weight 11.5–18.0 kg, overweight 9.7–18.0 kg, obesity class I 9.1–16.0 kg, and obesity class II+ 5.8–12.1 kg. Inadequate GWG in obesity class I was associated with a 3.92-fold GDM risk increase (aOR 3.92, 95% CI 2.12–7.24, p < 0.001). Adherence improved from 34.7% (IOM 2009) to 50.2% with Thai-specific targets. Conclusions: These Thai-specific GWG targets are provisional, single-centre pilot estimates. They appear clinically safe and are substantially more achievable than IOM 2009 criteria and are offered to inform BMI-appropriate antenatal counselling and to justify a multi-centre validation study, rather than as ranges that are ready for immediate national adoption. Full article
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15 pages, 509 KB  
Article
Association Between Maternal Protein Intake and the Risk of Adverse Pregnancy Outcomes
by Suzette Rosas-Rogers, Ronald Anguzu, Alyssa M. Hernandez and Anna Palatnik
Nutrients 2026, 18(15), 2543; https://doi.org/10.3390/nu18152543 - 4 Aug 2026
Viewed by 387
Abstract
Background/Objectives: This study examined the association between low protein intake and pregnancy outcomes to test whether low protein intake was associated with higher rates of small for gestational age (SGA), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP), and lower [...] Read more.
Background/Objectives: This study examined the association between low protein intake and pregnancy outcomes to test whether low protein intake was associated with higher rates of small for gestational age (SGA), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP), and lower rates of large for gestational age (LGA). Methods: A secondary analysis was performed using the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (NuMoM2b). Participants missing diet data or pregnancy outcomes and whose pregnancy ended <20 weeks were excluded. Protein intake was calculated in grams per kilogram of bodyweight per day and stratified into quartiles. Multi-variable analyses were done to assess the association between protein intake quartiles and rates of HDP, GDM, SGA, and LGA, adjusting for relevant covariates. Results: Participants (n = 7067) were categorized into quartiles by daily protein intake: Q1 (<0.6 g/kg), Q2 (0.6–<0.8 g/kg), Q3 (0.8–<1.1 g/kg), and Q4 (≥1.1 g/kg). Lower protein intake was common among Black women (p = 0.001), women with less than a high school education (p < 0.001), unemployment (p = 0.004), lower income (p = 0.003), or government insurance (p = 0.04). After adjusting for age, insurance, education, income, chronic hypertension, and dietary kcal, protein intake resulted in significantly lower odds of developing SGA < 10th percentile for women in Q3 (aOR 0.78, 95% CI 0.61–0.99 for Q3). Protein in-take was not significantly associated with HDP, GDM or LGA. Conclusions: Moderate to high protein intake in the first trimester was associated with reduced SGA risk; however, these findings are exploratory and require confirmation in future studies. Full article
(This article belongs to the Section Nutrition in Women)
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16 pages, 1539 KB  
Article
Marked Third-Trimester Placental Thickening Is Associated with Maternal Infectious, Hormonal, and Metabolic Burden: A Matched Case-Control Study
by Julia Murlewska, Maria Respondek-Liberska and Iwona Strzelecka
J. Clin. Med. 2026, 15(15), 5990; https://doi.org/10.3390/jcm15155990 - 1 Aug 2026
Viewed by 200
Abstract
Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study [...] Read more.
Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case–control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch’s t-test and the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch’s t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann–Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m2 was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case–control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes. Full article
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9 pages, 250 KB  
Article
Association Between Maternal Serum 25-Hydroxyvitamin D Concentrations and Gestational Diabetes Mellitus in Women Undergoing Diagnostic 100-g Oral Glucose Tolerance Testing
by Hüseyin Karakaya, Gökhan Doğukan Akarsu, Taylan Onat and Rukiye Höbek Akarsu
J. Clin. Med. 2026, 15(15), 5977; https://doi.org/10.3390/jcm15155977 - 31 Jul 2026
Viewed by 233
Abstract
Background: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy. Vitamin D has been implicated in glucose metabolism; however, its association with GDM remains controversial. Objective: The objective was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and [...] Read more.
Background: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy. Vitamin D has been implicated in glucose metabolism; however, its association with GDM remains controversial. Objective: The objective was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and GDM in pregnant women referred for diagnostic 100 g oral glucose tolerance testing following a positive 50 g glucose challenge test. Methods: This retrospective study included 92 pregnant women (44 with GDM and 48 without GDM) who underwent diagnostic 100 g oral glucose tolerance testing between January 2016 and June 2025 at a tertiary-care hospital. Demographic characteristics and biochemical parameters, including serum 25(OH)D concentrations, were obtained from medical records. Logistic regression analysis was performed to identify factors independently associated with GDM. Results: Women with GDM were significantly older than those without GDM (37.55 ± 6.06 vs. 29.21 ± 4.29 years, p < 0.001) and had lower serum vitamin D concentrations (14.08 ± 9.88 vs. 19.06 ± 10.30 ng/mL, p = 0.003). In multivariable logistic regression analysis, advanced maternal age (OR 1.404, 95% CI 1.217–1.620; p < 0.001) and lower serum vitamin D concentrations (OR 0.933, 95% CI 0.880–0.989; p = 0.020) were independently associated with GDM. Conclusion: Lower maternal serum 25(OH)D concentrations were independently associated with GDM in women referred for diagnostic 100 g oral glucose tolerance testing. These findings should be interpreted as observational and hypothesis-generating. Larger prospective studies are needed to confirm these results. Full article
(This article belongs to the Section Obstetrics & Gynecology)
23 pages, 21263 KB  
Article
MMP8 Promotes NETosis in Gestational Diabetes Mellitus
by Nan Li, Tong Zhou, Kun Yang, Wen-Jun Yang, Gui Yang, Yong-Wei Duan, Ying Yang, Huan-Yu Liu and Song-Mei Liu
Antioxidants 2026, 15(8), 955; https://doi.org/10.3390/antiox15080955 - 30 Jul 2026
Viewed by 277
Abstract
Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and [...] Read more.
Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and cell models to identify hub genes linked to NET formation (NETosis) and to elucidate how NETs contribute to placental injury in GDM. Results: We found that circulating NET levels were increased in pregnant women with GDM both under fasting conditions and following an oral glucose tolerance test (OGTT). Primary neutrophils isolated from healthy pregnant women produced more NETs upon high-glucose stimulation in vitro. The mRNA expression of PADI4, a key regulator of NETosis, was upregulated and positively correlated with MMP8 mRNA in patients with GDM. Inhibition of MMP8 suppressed intracellular reactive oxygen species (ROS) generation and attenuated NETosis in neutrophils. scRNA-seq analysis of placental tissues from patients with GDM identified a neutrophil subset with higher PADI4 expression. In vitro stimulation with NETs induced functional impairment of HTR8/SVneo cells. Conclusions: We uncovered that MMP8, a novel NETosis-promoting molecule, is a promising target for GDM intervention. Full article
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17 pages, 4658 KB  
Article
Altered Placental Ezrin Expression in Gestational Diabetes Mellitus: An Immunohistochemical and Bioinformatic Analysis
by Fırat Aşır, Ebru Gökalp Özkorkmaz, Nilüfer Dönmezdil, Senem Çetin Duran, Fırat Şahin, Tuğcan Korak and Elif Ağaçayak
Diagnostics 2026, 16(15), 2404; https://doi.org/10.3390/diagnostics16152404 - 30 Jul 2026
Viewed by 275
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is associated with placental structural and functional alterations that may impair trophoblast integrity and maternal–fetal exchange. Ezrin, radixin, and moesin (ERM) proteins are membrane–cytoskeleton linker proteins involved in microvillous organization, cell polarity, and signal transduction. This study [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is associated with placental structural and functional alterations that may impair trophoblast integrity and maternal–fetal exchange. Ezrin, radixin, and moesin (ERM) proteins are membrane–cytoskeleton linker proteins involved in microvillous organization, cell polarity, and signal transduction. This study aimed to investigate placental ERM protein expression in GDM and to explore ERM-associated molecular pathways through bioinformatic analysis. Methods: This prospective observational study included placental tissues obtained from 40 women with GDM and 40 healthy pregnant women. Immunohistochemical staining for ezrin, radixin, and moesin was performed on paraffin-embedded placental sections, and quantitative image analysis was conducted using QuPath software (version 0.7.0) to calculate H-scores. Correlation and receiver operating characteristic (ROC) analyses were performed to evaluate associations between ERM expression and clinical parameters. In addition, bioinformatic analyses were conducted using the publicly available GSE154414 placental transcriptomic dataset to investigate ERM-associated signaling pathways and interaction networks. Results: Ezrin immunoreactivity was significantly increased in the GDM group compared with controls (118.63 ± 20.56 vs. 107.95 ± 17.41, p = 0.026), whereas Radixin and Moesin expression levels did not differ significantly between groups (p > 0.05). Ezrin expression demonstrated significant positive correlations with maternal body mass index, birth weight, fasting glucose, and HbA1c levels. ROC analysis demonstrated modest discriminatory performance of the Ezrin H-score for distinguishing GDM from control pregnancies (AUC = 0.645, p = 0.018). Bioinformatic analyses identified enrichment of ERM-associated pathways involved in cytoskeletal remodeling, inflammatory signaling, and protein phosphorylation-related cellular processes. Conclusions: Placental Ezrin expression was significantly increased in women with GDM and was positively associated with maternal glycemic parameters. These findings suggest that altered Ezrin expression may reflect adaptive cytoskeletal remodeling in diabetic placentas. ERM-associated signaling pathways may contribute to placental responses to metabolic stress in GDM. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Gynecologic Diseases, 3rd Edition)
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15 pages, 1772 KB  
Article
Association Between HbA1c Levels and Postpartum Depressive Symptoms: Insights from Edinburgh Postnatal Depression Scale Screening After Gestational Diabetes Mellitus
by Sophia Lutz, Yvonne Lindemann, Ekkehard Schleußner, Tanja Groten and Friederike Weschenfelder
J. Clin. Med. 2026, 15(15), 5919; https://doi.org/10.3390/jcm15155919 - 29 Jul 2026
Viewed by 278
Abstract
Background/Objectives: Depressive symptoms are more frequent following pregnancies complicated by gestational diabetes mellitus (GDM), prompting postpartum depression screening recommendations in the German S3 guideline. Although GDM is associated with increased postpartum depression risk, the relationships between postpartum metabolic parameters and the Edinburgh [...] Read more.
Background/Objectives: Depressive symptoms are more frequent following pregnancies complicated by gestational diabetes mellitus (GDM), prompting postpartum depression screening recommendations in the German S3 guideline. Although GDM is associated with increased postpartum depression risk, the relationships between postpartum metabolic parameters and the Edinburgh Postnatal Depression Scale (EPDS) scores remain unclear. We investigated whether metabolic markers measured during diabetes screening 6–12 weeks postpartum are associated with depressive symptoms. Methods: We retrospectively analyzed EPDS screenings conducted during postpartum testing at our inpatient clinic between 07/2021 and 02/2024. The EPDS is a validated 10-item tool (score range 0–30), with scores ≥10 indicating potential depression. Metabolic parameters included HbA1c, the 75 g oral glucose tolerance test (oGTT), insulin, and the Homeostasis Model Assessment index (HOMA index). Group comparisons were performed using non-parametric tests and receiver operating characteristic (ROC) analyses, with the Youden index identifying optimal cutoffs. Results: Among the 102 women presenting for postpartum testing, 43.1% had normal glucose tolerance, 54.9% prediabetes, and 2.0% diabetes. A total of 13.7% (n = 14) screened positive for potential depression, including two who reported suicidal ideations. Women with positive EPDS scores had significantly higher HbA1c [5.7% (38.3 mmol/mol) vs. 5.4% (35.5 mmol/mol), p = 0.013]. An HbA1c cutoff of 5.42% (35.75 mmol/mol) showed discriminatory ability for depressive symptoms with an Area Under the Curve (AUC) of 0.708 (CI 0.567–0.849). Other metabolic parameters showed no significant associations. Conclusions: Elevated postpartum HbA1c is associated with depressive symptoms after GDM pregnancies. An HbA1c threshold of 5.42% (35.75 mmol/mol) may help identify women at increased postpartum depression risk and prompt subsequent psychological assessment when depression screening is otherwise omitted. Full article
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27 pages, 1362 KB  
Article
Body Roundness Index and A Body Shape Index as First-Trimester Risk-Stratification Markers for Gestational Diabetes in Overweight Pregnant Women Without Established Major Risk Factors: A Prospective Single-Center Cohort Study
by Ömer Osman Eroğlu, Cansın Eroğlu, Sait Erbey, Murat Polat, Bilge Erbey, Mehmet Alican Sapmaz and Çağanay Soysal
Diagnostics 2026, 16(15), 2384; https://doi.org/10.3390/diagnostics16152384 - 29 Jul 2026
Viewed by 271
Abstract
Background/Objectives: Universal screening for gestational diabetes mellitus (GDM) is performed at 24–28 gestational weeks, but recommendations for earlier risk stratification differ across guidelines. Overweight pregnant women (body mass index [BMI] 25.0–29.9 kg/m2) without established major GDM risk factors constitute a clinical [...] Read more.
Background/Objectives: Universal screening for gestational diabetes mellitus (GDM) is performed at 24–28 gestational weeks, but recommendations for earlier risk stratification differ across guidelines. Overweight pregnant women (body mass index [BMI] 25.0–29.9 kg/m2) without established major GDM risk factors constitute a clinical gray zone for which current guidelines provide no explicit directive. We evaluated the first-trimester diagnostic performance of two composite anthropometric indices—the Body Roundness Index (BRI) and A Body Shape Index (ABSI)—for subsequent IADPSG-defined GDM within this specific clinical niche. Methods: This prospective single-center cohort study enrolled 198 consecutive overweight pregnant women without major GDM risk factors at 11 + 0 to 13 + 6 gestational weeks; 186 participants completed the 75 g OGTT at 24–28 weeks and were analyzed. Anthropometric measurements were obtained by trained nurses blinded to outcome. Glucose was assayed by hexokinase enzymatic reference method (intra-assay CV ≤ 1.5%). Discrimination, calibration, reclassification (NRI, IDI), decision curve analysis, and three independent internal validation procedures were performed. Results: GDM prevalence was 18.28% (34/186). BRI achieved an AUC of 0.905 (95% CI 0.835–0.974) and ABSI an AUC of 0.889 (95% CI 0.815–0.963), both significantly greater than BMI (AUC 0.705; DeLong p < 0.001). The optimal BRI cutoff of 4.45—interpreted as a cohort-specific analytic anchor rather than a transferable clinical threshold—yielded 85.3% sensitivity and 90.8% specificity. Adding BRI to BMI improved discrimination by 45.6% (IDI). Bootstrap optimism remained below 0.01 across all models. Conclusions: Following internal validation through bootstrap optimism correction and cross-validation, first-trimester BRI and ABSI provided strong supplementary risk stratification for GDM in overweight pregnant women without major risk factors. External validation in independent populations is required before clinical implementation. Full article
(This article belongs to the Special Issue Advanced Diagnostics in Women's Health: From Biomarkers to Imaging)
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11 pages, 271 KB  
Article
Public Health-Relevant Factors Associated with Gestational Diabetes Mellitus and Obstetric Outcomes: A Case–Control Study from Kazakhstan
by Togzhan Serbatyrova, Gulnar Shalgumbayeva, Assel Tukinova, Gulnara Sarsebayeva and Laura Danyarova
Int. J. Environ. Res. Public Health 2026, 23(8), 959; https://doi.org/10.3390/ijerph23080959 - 25 Jul 2026
Viewed by 516
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with adverse maternal and neonatal outcomes. Data on GDM in Central Asian populations remain limited. This study aimed to identify factors associated with GDM and evaluate selected obstetric outcomes among [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with adverse maternal and neonatal outcomes. Data on GDM in Central Asian populations remain limited. This study aimed to identify factors associated with GDM and evaluate selected obstetric outcomes among pregnant women in Kazakhstan. Methods: A retrospective case–control study based on medical record data was conducted among 256 pregnant women, including 106 women with GDM and 150 women with normal glucose tolerance. GDM was diagnosed using a 75 g oral glucose tolerance test according to the International Association of Diabetes and Pregnancy Study Groups criteria. Demographic, clinical, anthropometric, laboratory, and obstetric data were obtained from medical records. Multivariable logistic regression was used to identify factors statistically associated with GDM. Obstetric outcomes were compared using unadjusted analyses. Results: Women with GDM were older than controls (31.6 ± 5.8 vs. 28.6 ± 5.3 years, p < 0.001) and had a higher pre-pregnancy body mass index (BMI) (29 [25–33] vs. 26 [23–29] kg/m2, p < 0.001). Thyroid-stimulating hormone levels were also higher in the GDM group (p = 0.026). In multivariable analysis, pre-pregnancy obesity (adjusted OR 4.54, 95% CI 2.08–9.91; p < 0.001) and educational level (overall p = 0.001) remained associated with GDM, whereas maternal age was not independently associated after adjustment. Hypertension (24.5% vs. 2.0%; p < 0.001), eclampsia (3.8% vs. 0%; p = 0.028), cesarean delivery (52.8% vs. 28.0%; p < 0.001), and fetal macrosomia (21.7% vs. 12.0%; p = 0.037) were more frequent among women with GDM. No significant difference was observed in neonatal birth weight. Conclusions: Pre-pregnancy obesity and educational level were independently associated with GDM. Women with GDM more frequently experienced hypertensive complications, cesarean delivery, and fetal macrosomia; however, these findings were based on unadjusted analyses and should be interpreted cautiously. Further multicenter prospective studies are needed to confirm these findings in Central Asian populations. Full article
15 pages, 514 KB  
Article
Migraine Symptom Progression During Pregnancy and Associations with Fetal Growth Patterns and Placental-Mediated Complications in Women with Pre-Existing Migraine: A Prospective Cohort Study
by Milan Lackovic, Dejan Nikolic, Jovana Kuzmanovic Pficer and Sladjana Mihajlovic
Biomedicines 2026, 14(8), 1655; https://doi.org/10.3390/biomedicines14081655 - 23 Jul 2026
Viewed by 349
Abstract
Background: Migraine has been associated with vascular dysfunction and adverse pregnancy outcomes. However, the relationship between changes in migraine manifestations during pregnancy and fetal growth remains incompletely understood. This prospective study aimed to investigate whether migraine symptom progression during pregnancy is associated with [...] Read more.
Background: Migraine has been associated with vascular dysfunction and adverse pregnancy outcomes. However, the relationship between changes in migraine manifestations during pregnancy and fetal growth remains incompletely understood. This prospective study aimed to investigate whether migraine symptom progression during pregnancy is associated with abnormal fetal growth patterns and placental-mediated pregnancy complications among women with pre-existing migraine. Methods: This prospective cohort study included 400 pregnant women with a pre-pregnancy diagnosis of migraine who received antenatal care at the Department of Obstetrics and Gynecology, University Hospital “Dr Dragiša Mišović”, Belgrade, Serbia, between 2024 and 2026. Maternal migraine characteristics, pregnancy complications, and fetal growth assessments were evaluated. Fetal growth was categorized according to estimated fetal weight percentiles adjusted for gestational age. Univariable and multivariable logistic regression analyses were performed to identify factors associated with abnormal fetal growth. Because of the relatively small number of events, Firth’s penalized logistic regression was additionally performed as a sensitivity analysis. Results: Persistent or worsening migraine symptoms during pregnancy were more frequently observed among pregnancies complicated by impaired fetal growth, pregnancy-induced hypertension, gestational diabetes mellitus, abnormal gestational weight gain, and preterm birth. In univariable analyses, migraine worsening was associated with increased odds of abnormal fetal growth. However, after adjustment for maternal and obstetric factors, migraine worsening was no longer independently associated with abnormal fetal growth. Pregnancy-induced hypertension and inadequate gestational weight gain remained the strongest independent predictors. Findings were confirmed in sensitivity analyses using Firth’s penalized logistic regression. Conclusions: Among women with pre-existing migraine, persistent or worsening migraine manifestations during pregnancy were associated with a higher burden of placental-mediated complications and abnormal fetal growth patterns in unadjusted analyses. However, migraine worsening was not independently associated with abnormal fetal growth after adjustment for maternal and obstetric factors, suggesting that migraine symptom progression may represent a clinical marker of shared vascular, inflammatory, endothelial, and metabolic processes rather than an independent causal factor. Further prospective multicenter studies incorporating non-migraine control groups and detailed migraine phenotyping are warranted. Full article
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24 pages, 1543 KB  
Review
Fermented Foods, Functional Nutrition, and Maternal Gut Microbiota During Pregnancy: Molecular Mechanisms and the Maternal–Infant Microbiome Axis
by Tuğba Küçükkasap, Asmin Yavuz and Özde Kuran
Int. J. Mol. Sci. 2026, 27(14), 6488; https://doi.org/10.3390/ijms27146488 - 21 Jul 2026
Viewed by 409
Abstract
Pregnancy is associated with profound metabolic, hormonal, and immunological adaptations accompanied by dynamic alterations in maternal gut microbiota composition and function. Emerging evidence suggests that maternal diet is a major regulator of these microbiota-related changes and may influence maternal–fetal health through microbial metabolites [...] Read more.
Pregnancy is associated with profound metabolic, hormonal, and immunological adaptations accompanied by dynamic alterations in maternal gut microbiota composition and function. Emerging evidence suggests that maternal diet is a major regulator of these microbiota-related changes and may influence maternal–fetal health through microbial metabolites and host signaling pathways. Fermented foods and functional dietary components, including prebiotics, probiotics, synbiotics, and polyphenols, have gained increasing attention because of their potential to modulate gut microbial diversity, intestinal barrier integrity, inflammatory responses, and metabolic homeostasis. Mechanistically, these effects are mediated through pathways involving short-chain fatty acids, G protein-coupled receptors, nuclear factor kappa B signaling, histone deacetylase inhibition, and immune cell regulation. Altered microbiota-associated signaling has been linked to gestational metabolic disorders such as obesity, gestational diabetes mellitus, and preeclampsia, as well as fetal immune and metabolic programming. Particular emphasis is placed on the maternal–infant microbiome axis, highlighting how maternal nutrition and microbiota-mediated signaling may influence microbial transmission, fetal programming, and early-life microbiome development. This review summarizes current evidence regarding pregnancy-associated gut microbiota alterations and discusses the molecular mechanisms through which fermented foods and functional nutrition may influence maternal and fetal health outcomes. Full article
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25 pages, 833 KB  
Perspective
Gestational Diabetes Mellitus and Polycystic Ovary Syndrome: A Proposed Intergenerational Metabolic Continuum Within the DOHaD Framework
by Miroslava Gojnić, Stefan Dugalić, Katarina Ivanović, Miloš Milinčić and Maja Macura
Healthcare 2026, 14(14), 2204; https://doi.org/10.3390/healthcare14142204 - 21 Jul 2026
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Abstract
Background: Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are clinically distinct disorders that share important metabolic features. This Perspective proposes a non-causal intergenerational framework linking maternal PCOS-related metabolic vulnerability, susceptibility to GDM, intrauterine metabolic exposure, and later reproductive-metabolic risk in [...] Read more.
Background: Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are clinically distinct disorders that share important metabolic features. This Perspective proposes a non-causal intergenerational framework linking maternal PCOS-related metabolic vulnerability, susceptibility to GDM, intrauterine metabolic exposure, and later reproductive-metabolic risk in female offspring. Methods: A narrative synthesis of evidence from reproductive endocrinology, obstetrics, diabetology, developmental biology, and public health was undertaken. The strength of evidence supporting individual components of the proposed continuum was qualitatively appraised. Separately, aggregated surveillance data from Belgrade for 2015–2024 were used as a registry-based illustration of ICD-10 O24.4-coded GDM diagnoses. No formal time-series analysis, causal modeling, or forecasting was performed. Results: Evidence was strongest for the increased risk of GDM among women with PCOS and for the association between intrauterine exposure to maternal diabetes and later offspring metabolic susceptibility. Evidence linking maternal PCOS with offspring metabolic vulnerability was less definitive, while direct evidence that GDM exposure leads to clinically diagnosed PCOS in female offspring remained weak and indirect. Registry-recorded GDM rates varied across years, but this variability may reflect differences in screening, diagnostic criteria, coding, reporting completeness, and healthcare access rather than true changes in prevalence. Conclusions: The proposed GDM–PCOS continuum is a hypothesis-generating and probabilistic framework, not an established causal pathway. Its clinical value lies in connecting prevention opportunities before conception, during pregnancy, after delivery, and across the life course. Longitudinal maternal–offspring studies are required to test the proposed relationships. Full article
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