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14 pages, 635 KB  
Article
Maternal Consumption of Fruits, Vegetables and Fruit Juices in Relation to Offspring Weight at 4 Years
by Lucía Riggioni-Saborío, Cristina Jardí, Nerea Becerra-Tomás, Josué Cruz-Rodríguez and Victoria Arija
Nutrients 2026, 18(17), 2918; https://doi.org/10.3390/nu18172918 - 6 Sep 2026
Viewed by 160
Abstract
Background/Objectives: Maternal diet plays a crucial role in fetal development and may influence offspring weight development. Although fruits and vegetables provide nutritional and metabolic benefits during pregnancy, evidence regarding their specific role on childhood overweight/obesity remains limited. This study aimed to examine [...] Read more.
Background/Objectives: Maternal diet plays a crucial role in fetal development and may influence offspring weight development. Although fruits and vegetables provide nutritional and metabolic benefits during pregnancy, evidence regarding their specific role on childhood overweight/obesity remains limited. This study aimed to examine the association between maternal intake of fruits, vegetables, and fruit juices during pregnancy and the risk of overweight/obesity in children at 4 years of age. Methods: We analyzed 252 mother–child pairs from the Mediterranean ECLIPSES cohort in a prospective observational study. Maternal dietary intake was assessed at 12, 24 and 36 weeks of gestation using a semiquantitative food frequency questionnaire previously validated in a Spanish population. Childhood overweight/obesity was defined as a BMI z-score above the 85th percentile for age and sex at age 4. Multivariable-adjusted logistic regression models estimated ORs and 95% CIs. Results: Higher maternal consumption of fruits and vegetables was inversely associated with overweight/obesity in children (OR: 0.31 [0.13–0.74]). No associations were observed for total or natural fruit juice, whereas higher consumption of commercial fruit juice was associated with increased odds of overweight/obesity (OR: 2.48 [1.06–5.78]). Conclusions: Higher maternal combined consumption of fruits and vegetables during pregnancy was associated with lower odds of overweight or obesity in offspring at 4 years of age, whereas the opposite association was observed for commercial, but not natural, fruit juice. These associations may involve both prenatal biological and postnatal behavioral and family dietary pathways; however, the commercial fruit juice finding should be considered exploratory and requires confirmation in larger prospective studies. Full article
(This article belongs to the Special Issue Maternal Nutrition: Developmental Origins of Health and Disease)
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14 pages, 731 KB  
Article
Excessively High Maternal Total Cell-Free DNA Concentration and Fetal Growth Restriction in Singleton Pregnancies: A Retrospective Cohort Study
by Lingling Xing, Xiaosha Jing, Ting Bai, Sha Liu, Jianlong Liu, Cechuan Deng, Tianyu Xia, Yunyun Liu, Xiang Wei, Yuan Luo, Quanfang Zhou, Qian Zhu and Hongqian Liu
J. Clin. Med. 2026, 15(17), 6798; https://doi.org/10.3390/jcm15176798 - 2 Sep 2026
Viewed by 183
Abstract
Background/Objectives: Noninvasive prenatal screening (NIPS) fails in approximately 0.2% of cases due to high maternal plasma total cell-free DNA (t-cfDNA) concentration (≥0.6 ng/µL) confirmed after two DNA extraction attempts. The clinical implications of this quality control metric for fetal growth restriction (FGR) remain [...] Read more.
Background/Objectives: Noninvasive prenatal screening (NIPS) fails in approximately 0.2% of cases due to high maternal plasma total cell-free DNA (t-cfDNA) concentration (≥0.6 ng/µL) confirmed after two DNA extraction attempts. The clinical implications of this quality control metric for fetal growth restriction (FGR) remain unknown. Methods: This retrospective cohort study, conducted in a major prenatal diagnosis center in China, involved pregnant women who underwent noninvasive prenatal screening (NIPS) between 2019 and 2024. From a total of 73,636 pregnancies, 102 singleton pregnancies with excessively high t-cfDNA concentration (≥0.6 ng/µL upon retesting) leading to NIPS failure were compared with 396 matched controls (t-cfDNA < 0.6 ng/µL) after propensity score matching. The primary outcome was FGR, defined as estimated fetal weight or abdominal circumference below the 10th percentile for gestational age. Results: In the matched cohort, FGR occurred in 26.47% of the high-concentration group versus 9.60% of controls (OR = 3.27, 95% CI: 1.45–7.41, p = 0.004). The high-concentration group also had lower gestational age at delivery (37.44 vs. 38.48 weeks, p < 0.001) and higher preterm birth rates (18.63% vs. 7.57%, p = 0.025). Subgroup analyses for severe and FGR first detected before 32 weeks were exploratory and limited by statistical power, warranting cautious interpretation. Conclusions: An excessively high maternal t-cfDNA concentration in early pregnancy shows a significant association with FGR and adverse pregnancy outcomes. These findings suggest that t-cfDNA could potentially serve as an early biomarker for identifying pregnancies at elevated risk of FGR. Further validation of our findings in prospective studies is required to establish its clinical utility. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 1329 KB  
Article
Fentanyl Exposure Is Associated with Adverse Respiratory Outcomes in Ventilated Preterm Neonates: A Retrospective Matched Cohort Study
by Maria Di Chiara, Gianluigi Laccetta, Maria Chiara De Nardo, Lucia Dito and Gianluca Terrin
J. Clin. Med. 2026, 15(16), 6457; https://doi.org/10.3390/jcm15166457 - 20 Aug 2026
Viewed by 228
Abstract
Background/Objectives: Fentanyl is widely used in ventilated preterm neonates, but respiratory safety evidence is limited. We assessed the association between fentanyl exposure during mechanical ventilation and respiratory outcomes in preterm neonates <34 weeks and explored a candidate exposure-duration threshold, defined as the duration [...] Read more.
Background/Objectives: Fentanyl is widely used in ventilated preterm neonates, but respiratory safety evidence is limited. We assessed the association between fentanyl exposure during mechanical ventilation and respiratory outcomes in preterm neonates <34 weeks and explored a candidate exposure-duration threshold, defined as the duration of continuous fentanyl infusion beyond which the risk of adverse respiratory outcomes rises sharply. Methods: Single-centre retrospective cohort study at Policlinico Umberto I, Sapienza University, Rome (2015–2022). Fentanyl-exposed neonates were 1:2 matched to unexposed neonates on gestational age and birth-weight z-score. Primary outcome: bronchopulmonary dysplasia at 36 weeks postmenstrual age (multivariable logistic regression); secondary outcome: duration of invasive ventilation. A composite outcome (bronchopulmonary dysplasia or invasive ventilation ≥ 7 days) was used for threshold analysis with restricted cubic splines, maximally selected Wald χ2, and segmented logistic regression. Results: Of 315 eligible neonates, 50 fentanyl-exposed neonates were matched with 92 unexposed neonates (n = 142). Fentanyl exposure was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia (adjusted odds ratio 5.49, 95% CI 1.72–17.54) and longer invasive ventilation (adjusted exp(β) 2.25, 95% CI 1.54–3.29). Three complementary threshold methods were consistent with an exploratory signal around 3 days of continuous infusion, beyond which composite-outcome odds rose, although the breakpoint estimate was imprecise. Conclusions: Fentanyl exposure during mechanical ventilation was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia and longer invasive ventilation in preterm neonates <34 weeks. A possible signal around 3 days of continuous infusion is proposed as a hypothesis-generating stewardship prompt, not as a decision rule. Full article
(This article belongs to the Section Clinical Pediatrics)
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24 pages, 564 KB  
Article
Longitudinal Assessment of Third-Trimester Fetal Biometry and Cerebroplacental Ratio for Predicting Adverse Perinatal Outcomes in an Unselected Obstetric Population: A Prospective Cohort Study
by Emine Merve Turhan, Mustafa Koçar, Cenk Soysal and Yasemin Taşcı
J. Clin. Med. 2026, 15(16), 6316; https://doi.org/10.3390/jcm15166316 - 15 Aug 2026
Viewed by 290
Abstract
Background: The clinical value of the cerebroplacental ratio (CPR) for predicting adverse perinatal outcomes in unselected obstetric populations remains uncertain. We aimed to evaluate the prognostic performance of serial third-trimester fetal biometry and Doppler-derived CPR and to compare their ability to identify [...] Read more.
Background: The clinical value of the cerebroplacental ratio (CPR) for predicting adverse perinatal outcomes in unselected obstetric populations remains uncertain. We aimed to evaluate the prognostic performance of serial third-trimester fetal biometry and Doppler-derived CPR and to compare their ability to identify adverse perinatal outcomes and neonatal growth abnormalities. Methods: In this prospective longitudinal cohort study, 100 consecutive pregnancies from an unselected obstetric population underwent standardized ultrasonographic examinations at both 28 and 37 weeks of gestation. Fetal biometric measurements, estimated fetal weight (EFW), amniotic fluid index, umbilical and middle cerebral artery Doppler indices, and CPR were recorded. Maternal, obstetric, delivery, and neonatal data were collected prospectively. Receiver operating characteristic (ROC) curve analyses and parsimonious multivariable regression models, accompanied by 1000-sample bootstrap internal validation, were performed to evaluate the independent predictive capacity of fetal biometry and CPR metrics. Results: Gestational age-specific CPR percentiles were associated with expected physiological Doppler changes but showed limited associations with obstetric and neonatal outcomes. In separate parsimonious regression models optimized for event-per-variable ratios, neither 28-week nor 37-week CPR independently predicted composite adverse perinatal outcomes, NICU admission, low Apgar scores, or abnormal umbilical cord blood pH. Rigorous bootstrap internal validation confirmed that optimism-corrected area under the curve (AUC) values for CPR models remained close to chance (range: 0.463–0.507). In contrast, 37-week EFW independently predicted neonatal birth weight, while both 37-week EFW and EFW percentile demonstrated good discriminatory performance for identifying small-for-gestational-age neonates (AUC = 0.812 and 0.833, respectively; both p < 0.001). Maternal body mass index and late-pregnancy fetal biometry also showed moderate discriminatory performance for predicting large-for-gestational-age neonates. Overall, late-pregnancy biometry outperformed CPR for identifying growth abnormalities, whereas neither modality alone accurately predicted composite adverse perinatal outcomes. Conclusions: In an unselected obstetric population, serial third-trimester CPR provided limited additional prognostic information beyond routine fetal biometry. Late-pregnancy fetal biometry, particularly 37-week estimated fetal weight, demonstrated superior performance for identifying neonatal growth abnormalities. These findings support the continued use of conventional fetal biometry as the primary component of routine third-trimester surveillance, with CPR serving as a complementary rather than standalone Doppler parameter. Full article
(This article belongs to the Special Issue AI in Maternal Fetal Medicine and Perinatal Management)
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18 pages, 1957 KB  
Article
Prenatal Exposure to Size-Fractionated Particulate Matter and Fetal Growth Trajectories: Mediation by Maternal Glucose Metabolism in a Birth Cohort
by Qian Chen, Bijun Shi, Yu Liu, Xin Wang, Li Cai, Qiliang Cui, Xiaohua Tan and Yujing Chen
Toxics 2026, 14(8), 709; https://doi.org/10.3390/toxics14080709 - 12 Aug 2026
Viewed by 389
Abstract
The metabolic mechanisms linking prenatal particulate matter (PM) to fetal growth remain unclear. A prospective cohort of 616 mother–fetus pairs in Guangzhou had ultrasound-based fetal growth parameters repeatedly measured from mid to late pregnancy. Fetal head circumference (HC), abdominal circumference (AC), femur length [...] Read more.
The metabolic mechanisms linking prenatal particulate matter (PM) to fetal growth remain unclear. A prospective cohort of 616 mother–fetus pairs in Guangzhou had ultrasound-based fetal growth parameters repeatedly measured from mid to late pregnancy. Fetal head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD) were standardized as z-scores. Estimated fetal weight (EFW) trajectories were classified as average, slow, and rapid growth. Residential PM1, PM2.5, and PM10 were assessed with 1 km spatiotemporal models. Multinomial logistic regression analyzed PM-EFW trajectory associations. Generalized estimating equations evaluated PM–fetal growth z-score relationships. Maternal plasma glucose and insulin levels at mid-pregnancy were examined as intermediate factors. Each 5 μg/m3 increase in PM was associated with higher odds of rapid EFW growth versus average growth (OR PM1 = 1.56, 95% CI: 1.03, 2.37; OR PM2.5 = 1.44, 95% CI: 1.10, 1.88; OR PM10 = 1.28, 95% CI: 1.05, 1.56). Positive associations were also observed for BPD, HC, and AC z-scores, with PM1 showing the numerically larger effect estimates. Maternal fasting plasma glucose and insulin resistance may partly explain the observed associations of PM exposure with rapid EFW growth and fetal growth parameters, with estimated proportions of 5.0–29.4%. This study highlights the potential risk of accelerated fetal growth associated with maternal PM exposures, and maternal glucose metabolism may represent a plausible pathway. Full article
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14 pages, 2641 KB  
Article
Cord Blood DNA Methylation and Large-for-Gestational-Age Birth: A Pilot Epigenome-Wide Study in the GROW Cohort
by Xiaoyu Liang, Christopher Doumith, Dawn P. Misra and Vinod K. Misra
Epigenomes 2026, 10(3), 51; https://doi.org/10.3390/epigenomes10030051 - 4 Aug 2026
Viewed by 497
Abstract
Background/Objectives: Large-for-gestational-age (LGA) birth is associated with adverse perinatal outcomes and increased risk of metabolic disease later in life. Despite these risks, epigenetic studies of LGA remain limited, particularly those using umbilical cord blood DNA methylation (DNAm) as the tissue of interest. Methods: [...] Read more.
Background/Objectives: Large-for-gestational-age (LGA) birth is associated with adverse perinatal outcomes and increased risk of metabolic disease later in life. Despite these risks, epigenetic studies of LGA remain limited, particularly those using umbilical cord blood DNA methylation (DNAm) as the tissue of interest. Methods: We conducted an epigenome-wide association study of cord blood DNAm in a nested case–control sample from the Gestational Regulators of Weight (GROW) cohort. The analysis included 28 term LGA infants and 63 term appropriate-for-gestational-age (AGA) controls. DNAm was measured using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analyses were performed with adjustment for residual principal components and estimated cord blood cell-type proportions. Results: No CpG sites reached statistical significance after false discovery rate correction. Twenty-four CpGs showed nominal associations with LGA status at p-value < 1.00 × 10−4, including five CpGs with absolute methylation differences greater than 0.05. Among annotated loci, the strongest interpretable signals included cg06750897 in PBX1 (Δβ = 0.110, p-value = 1.70 × 10−5) and two nearby CpGs in SMAD3, cg23731272 (Δβ = 0.111, p-value = 4.31 × 10−5) and cg02486855 (Δβ = 0.109, p-value = 9.45 × 10−5). These two SMAD3 CpGs showed concordant hypermethylation in LGA infants and formed a candidate regional methylation signal in exploratory targeted regional analysis. Conclusions: In this pilot study, LGA was associated with modest cord blood DNAm differences, although no CpG sites reached genome-wide significance. The strongest interpretable signals involved PBX1 and SMAD3, suggesting candidate loci for further evaluation in larger studies of fetal overgrowth. Full article
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16 pages, 2313 KB  
Article
The Effect of Using Hypotension Prediction Index to Reduce Intraoperative Hypotension in Elective Cesarean Sections: A Randomized Controlled Trial
by Nadhirah Abd Halim, Azlina Masdar, Syarifah Noor Nazihah Sayed Masri, Iskandar Khalid, Maryam Budiman and Saw Kian Cheah
Medicina 2026, 62(8), 1486; https://doi.org/10.3390/medicina62081486 - 1 Aug 2026
Viewed by 546
Abstract
Background and Objectives: The Hypotension Prediction Index (HPI) is a predictive algorithm that enables proactive management of intraoperative hypotension (IOH) and has been integrated into finger cuff devices for practical use in obstetric settings. This study aims to evaluate the effectiveness of HPI [...] Read more.
Background and Objectives: The Hypotension Prediction Index (HPI) is a predictive algorithm that enables proactive management of intraoperative hypotension (IOH) and has been integrated into finger cuff devices for practical use in obstetric settings. This study aims to evaluate the effectiveness of HPI in reducing IOH during elective cesarean sections (CS). Materials and Methods: This randomized controlled trial enrolled parturients undergoing elective CS under spinal anesthesia. The parturients were randomized to either the HPI or the control group using non-invasive blood pressure (NIBP) monitoring. The primary outcome was the time-weighted average mean arterial pressure below 65 mmHg (TWA-MAP < 65 mmHg). Secondary outcomes included maternal nausea and vomiting, intraoperative fluid and vasopressor requirements, incidences of hypertension and bradycardia, estimated blood loss, duration of high-dependency unit admission, fetal Apgar scores, umbilical cord pH, and length of neonatal intensive care unit (NICU) stay. Results: A total of 100 parturients were enrolled in the study, with 96 included in the analysis. Baseline demographic characteristics were similar between the groups. The TWA-MAP < 65 mmHg was significantly lower in the HPI group (0.24 [0, 0.70] vs. 1.67 [0.71, 2.57] mmHg; p < 0.001). The incidence of intraoperative and postoperative nausea and vomiting were significantly reduced in the HPI group (p < 0.01). Incidence of intraoperative hypertension and bradycardia, fetal Apgar scores, umbilical cord pH, and length of NICU stay did not differ between the two groups (p > 0.05). Conclusions: HPI-guided management was associated with a reduction in hypotension burden and perioperative nausea and vomiting. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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19 pages, 3399 KB  
Systematic Review
Listeriosis in Pregnant Women and Neonates in China: A Systematic Review
by Baorong Gao, Yali Miao, Rui Miao and Hui Ye
J. Clin. Med. 2026, 15(15), 5915; https://doi.org/10.3390/jcm15155915 - 29 Jul 2026
Viewed by 447
Abstract
Background: Pregnancy-related listeriosis typically causes mild, self-limited maternal symptoms but can lead to severe fetal and neonatal outcomes, posing a significant public health concern given its rising incidence. However, data on the epidemiology of this infection and its impact on maternal and neonatal [...] Read more.
Background: Pregnancy-related listeriosis typically causes mild, self-limited maternal symptoms but can lead to severe fetal and neonatal outcomes, posing a significant public health concern given its rising incidence. However, data on the epidemiology of this infection and its impact on maternal and neonatal outcomes in China remain scarce and fragmented. Methods: A systematic search was conducted in the following three Chinese-language databases (CNKI, Wanfang, and CBM) and two English-language databases (PubMed and Embase) for studies performed in China from 1 January 2018 to 14 March 2026. Relevant studies published before 2018 were identified from two previous systematic reviews. Information on the epidemiology, clinical manifestations, and outcomes of pregnancy-related listeriosis was extracted. For inclusion in pooled incidence estimates for pregnant women, studies were required to have the number of pregnant women or pregnancies as the denominator; for pooled neonatal case fatality risk estimates, studies were required to report the total number of neonatal listeriosis cases. The methodological quality of each included study was appraised using the Joanna Briggs Institute critical appraisal tool. Heterogeneity among the studies was quantified by the I2 statistic. All statistical analyses were performed using STATA version 12 and Microsoft Excel 365 (PROSPERO: CRD420261326136). Results: Of 389 abstracts initially identified, 160 full-text articles were retrieved for detailed evaluation, and 73 studies (including two previous systematic reviews) ultimately met the inclusion criteria. These studies, which were conducted across 19 provinces, provided sufficient data for analysis, encompassing 956 pregnant women and 749 neonates. Pregnancy-related listeriosis showed regional variation, with Beijing (n = 215), Zhejiang (n = 143), and Shaanxi (n = 142) contributing the most cases. The pooled incidence of obstetric listeriosis was 11.57 per 100,000 pregnancies (95% CI, 7.63–15.50; I2 = 73%) based on nine studies, and the pooled incidence of neonatal listeriosis was 7.55 per 100,000 live births (95% CI, 4.44–10.67; I2 = 60%) based on six studies. Fever (53.7%, 513/956) was the most common symptom among pregnant women, whereas respiratory distress (34.8%, 261/749) predominated in neonates. For empirical therapy, only 6.0% (57/956) of pregnant women received a penicillin-based regimen, whereas 32.5% (311/956) received cephalosporins. Two maternal deaths were recorded, whereas major adverse outcomes (miscarriage, stillbirth, prematurity, or low birth weight) occurred in 58.3% of pregnancies. Among neonates, 27.5% (206/749) received empirical penicillin therapy and 15.6% (117/749) received cephalosporins. The neonatal case fatality rate was 11% (95% CI, 0.06–0.17; I2 = 60%). Conclusions: Pregnancy-related listeriosis in China carries a substantial burden, with high rates of adverse fetal and neonatal outcomes. Suboptimal surveillance and inappropriate empirical antibiotic therapy likely contribute to these poor outcomes, highlighting the urgent need for enhanced surveillance, prompt recognition, and appropriate antibiotic use when Listeria infection is suspected. Full article
(This article belongs to the Section Epidemiology & Public Health)
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15 pages, 6443 KB  
Article
Integrated Single-Strand DNA Capture and Haplotype-Guided Variant Calling Platform for Non-Invasive Prenatal Testing of Monogenic Disorders
by Jie Shen, Wei Liu, Li Lu, Li Yu, Yin Wang, Ningyuan Zhang, Fei Lin, Zhenyu Diao, Huijun Li, Rui Xiao, Xiangyu Zhu and Jun Zhang
Diagnostics 2026, 16(15), 2344; https://doi.org/10.3390/diagnostics16152344 - 27 Jul 2026
Viewed by 408
Abstract
Background/Objectives: Non-invasive prenatal testing for monogenic disorders (NIPT-MD) provides a safe alternative to invasive procedures. However, its clinical utility is often limited by challenges such as low fetal fractions (FF), technical artifacts, and the difficulty in resolving maternally inherited pathogenic variants from [...] Read more.
Background/Objectives: Non-invasive prenatal testing for monogenic disorders (NIPT-MD) provides a safe alternative to invasive procedures. However, its clinical utility is often limited by challenges such as low fetal fractions (FF), technical artifacts, and the difficulty in resolving maternally inherited pathogenic variants from the overwhelming background of maternal cell-free DNA (cfDNA). This study aimed to develop and validate a robust NIPT-MD platform for monogenic disorders, applicable across major common Mendelian inheritance patterns, by enhancing the accuracy of fetal variant detection in cfDNA. Methods: We developed a novel NIPT-MD platform validated using both simulated samples and a retrospective clinical cohort. The workflow involves a single-strand capture library preparation incorporating unique molecular identifiers (UMIs) to mitigate amplification artifacts. FF was precisely quantified using a fixed panel of high-minor-allele-frequency single-nucleotide polymorphisms (SNPs). Fetal genotypes were then inferred by resolving parental haplotypes through a statistical model that integrates weighting of variant allele frequency (VAF) and haplotype-informative SNP counts. Results: The single-strand capture protocol incorporating UMIs significantly reduced amplification biases. Validation of the fetal DNA fraction estimation algorithm revealed strong concordance with a Y-chromosome-derived method and expected spike-in samples. Optimization of the FF estimation panel conferred greater experimental stability. The platform reliably detected both paternally and maternally inherited pathogenic variants. In a retrospective cohort of 35 clinical cases, the NIPT-MD platform achieved high concordance with genotypes determined by invasive testing. Conclusions: These findings present an accurate and robust NIPT-MD platform for monogenic disorders, with high concordance to invasive testing validated in a retrospective cohort of 35 clinical cases. This method holds promise for clinical application in managing families at high risk of monogenic diseases. Full article
(This article belongs to the Special Issue Advancements in Maternal–Fetal Medicine: 3rd Edition)
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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 427
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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11 pages, 3922 KB  
Article
Effect of Maternal Obesity on Fetal Interventricular Septum Volume: A Three-Dimensional Ultrasound STIC and VOCAL Study
by Stefano Raffaele Giannubilo, Camilla Grelloni, Elisa Carboni, Dayana Quintili, Mariarosaria Motta, Dario Colacurci, Chiara Murolo, Alessandro Cecchi, Giuseppe Maria Maruotti and Andrea Ciavattini
J. Clin. Med. 2026, 15(14), 5555; https://doi.org/10.3390/jcm15145555 - 15 Jul 2026
Viewed by 341
Abstract
Objective: To assess correlations between maternal obesity and fetal interventricular septum (IVS) volume measured by means of spatiotemporal image correlation and Virtual Organ Computer-Aided Analysis (STIC-VOCAL), after adjustment for gestational age. Methods: This cross-sectional observational study included 88 consecutive singleton pregnancies [...] Read more.
Objective: To assess correlations between maternal obesity and fetal interventricular septum (IVS) volume measured by means of spatiotemporal image correlation and Virtual Organ Computer-Aided Analysis (STIC-VOCAL), after adjustment for gestational age. Methods: This cross-sectional observational study included 88 consecutive singleton pregnancies undergoing routine obstetric ultrasound at our center between January 2024 and December 2025. Fetal IVS volume was assessed using STIC-VOCAL, and its association with maternal characteristics was evaluated by means of univariate and multivariable regression analyses adjusted for gestational age. Results: Fetal IVS volume increased with estimated fetal weight (r = 0.860, p < 0.0001) and gestational age (r = 0.891, p < 0.0001), which represented the main determinant of absolute fetal cardiac volume. The association between maternal obesity and fetal IVS volume was not evident on univariate analysis (U = 987.5, p = 0.874) but became significant after adjustment for gestational age in multivariable regression models (β = +89.1 mm3, p < 0.0001). At comparable gestational ages, maternal obesity was associated with an adjusted increase in fetal IVS volume of approximately 22.6 mm3. Conclusions: Maternal obesity was independently associated with a modest increase in fetal IVS volume after adjustment for gestational age. STIC-VOCAL volumetry may provide a sensitive tool for detecting subtle fetal cardiac structural changes, although these findings remain exploratory. Full article
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22 pages, 3316 KB  
Article
Temporal External Validation of a Customized Fetal Body Mass Index Percentile Model for Neonatal Nutritional Status Assessment
by Juan Jesús Fernández Alba, María Castillo Lara, Laura Gutiérrez Palomino, José Castro Peñas, Rocío Quintero Prado and Carmen González Macías
Diagnostics 2026, 16(11), 1584; https://doi.org/10.3390/diagnostics16111584 - 22 May 2026
Viewed by 388
Abstract
Background/Objectives: Accurate identification of neonatal malnutrition is essential for optimizing perinatal care and reducing adverse outcomes. Traditional birthweight-based methods fail to account for body proportionality, limiting their ability to distinguish constitutionally small or large neonates from those with true nutritional abnormalities. We [...] Read more.
Background/Objectives: Accurate identification of neonatal malnutrition is essential for optimizing perinatal care and reducing adverse outcomes. Traditional birthweight-based methods fail to account for body proportionality, limiting their ability to distinguish constitutionally small or large neonates from those with true nutritional abnormalities. We previously developed a customized fetal body mass index (cFBMI) percentile model that incorporates both weight and length, adjusted for maternal and fetal characteristics. This study aims to perform a temporal external validation of the cFBMI model following the Riley et al. framework, comparing its performance against the GROW customized birthweight model and the INTERGROWTH-21st population-based standard. Methods: A temporal validation study was conducted using singleton deliveries from Hospital Universitario de Puerto Real, Cádiz, Spain. The development cohort comprised 7864 deliveries (2002–2021); the validation cohort comprised 4441 deliveries (2022–2025). Inclusion criteria: singleton pregnancy, gestational age of 33–42 + 6 weeks, birthweight of 500–6000 g, known neonatal sex and length, and complete maternal data. The Ponderal Index (PI = weight/length3 × 100) stratified by sex and gestational age served as the gold standard (undernutrition: PI < p10; overnutrition: PI > p90). Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) with bootstrap 95% confidence intervals (2000 iterations) and DeLong tests. Calibration was evaluated by comparing observed versus expected proportions across percentile categories. Clinical utility was assessed using decision curve analysis (DCA). Temporal stability was quantified by comparing AUCs and Brier scores between the development and validation cohorts. Results: In the validation cohort (n = 4441), cFBMI demonstrated superior discrimination for both undernutrition (AUC: 0.962) and overnutrition (AUC: 0.961) compared with GROW (AUC: 0.751 and 0.676, respectively) and INTERGROWTH-21st (AUC: 0.756 and 0.682, respectively); all DeLong comparisons p < 0.0001. The cFBMI exhibited excellent temporal stability (ΔAUC = −0.004 for undernutrition, +0.002 for overnutrition) and superior calibration (observed proportions: 9.6%/81.7%/8.8% vs. expected 10%/80%/10%; χ2 = 9.22, p = 0.010). The decision curve analysis confirmed the superior net benefit of cFBMI across all threshold probabilities. Conclusions: The customized fetal BMI percentile model demonstrates excellent and temporally stable discriminative performance in this single-institution temporal validation study, with superior calibration and apparent advantages in clinical utility as determined by decision curve analysis compared with existing methods. Its integration of body proportionality provides conceptual alignment with the Ponderal Index gold standard. These findings are promising but require confirmation through external multicenter validation before clinical implementation can be recommended. Although the mathematical relationship between the index test (weight/length2) and the reference standard (weight/length3) should be considered when interpreting the magnitude of discrimination metrics, validation against independent clinical outcomes is an essential next step. The cFBMI thus provides a proportionality-aware nutritional metric whose primary discriminative advantage over weight-based methods is realized at and beyond the moment of birth, and which is forward-compatible with emerging modalities for independent prenatal fetal length estimation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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12 pages, 1126 KB  
Article
Cerebroplacental Ratio in Monochorionic Diamniotic Twin Pregnancies with and Without Gestational Diabetes: A Longitudinal Cohort Study
by Gülen Yerlikaya-Schatten, Marija Adamovic, Anja Catic, Kitana Hendling, Vivien Sauer, Stephanie Springer, Florian Heinzl and Theresa Reischer
J. Clin. Med. 2026, 15(10), 3864; https://doi.org/10.3390/jcm15103864 - 17 May 2026
Viewed by 469
Abstract
Objective: To investigate whether gestational diabetes mellitus (GDM), including insulin-treated GDM, affects cerebroplacental ratio (CPR) values in monochorionic diamniotic (MCDA) twin pregnancies. Methods: This retrospective single-center cohort study included a total of 262 MCDA twin pregnancies managed at a tertiary referral center, comprising [...] Read more.
Objective: To investigate whether gestational diabetes mellitus (GDM), including insulin-treated GDM, affects cerebroplacental ratio (CPR) values in monochorionic diamniotic (MCDA) twin pregnancies. Methods: This retrospective single-center cohort study included a total of 262 MCDA twin pregnancies managed at a tertiary referral center, comprising pregnancies without GDM (n = 120), with diet-controlled GDM (n = 80), and with insulin-treated GDM (n = 62). Doppler ultrasound examinations were performed at three gestational time points between 24 and 36 weeks of gestation. CPR, umbilical artery pulsatility index (UA-PI), and middle cerebral artery pulsatility index (MCA-PI) were compared longitudinally between groups. Doppler indices were compared between groups without adjustment for baseline differences such as BMI and parity Results: Maternal body mass index was significantly higher in pregnancies complicated by GDM, particularly in those requiring insulin therapy (p < 0.001). Estimated fetal weight was higher in the insulin-treated GDM group at mid-gestation (28–32 weeks; p = 0.01). However, CPR values remained within normal ranges throughout all screening points across all three groups. No relevant differences in UA-PI, MCA-PI, gestational age at delivery, Apgar scores, or umbilical cord pH were observed between groups. Conclusions: In MCDA twin pregnancies, gestational diabetes—regardless of insulin treatment—does not appear to significantly influence cerebroplacental ratio values throughout gestation. No statistically significant differences in CPR values were observed between groups. No statistically significant differences in CPR values were detected between groups. However, given the exploratory design and lack of adjustment for confounders, subtle effects cannot be excluded. The clinical utility of CPR in this population requires further investigation. Full article
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12 pages, 1116 KB  
Article
Gestational Age-Specific Biometric and Estimated Fetal Weight Curves in Gastroschisis: A Brazilian Multicenter Cohort Study
by Karina Felippe Monezi Pontes, Liliam Cristine Rolo, Gustavo Yano Callado, Alberto Borges Peixoto, Manoel Sarno, Alex Sandro Rolland Souza, Francisco Herlânio Costa Carvalho, Antonio Braga and Edward Araujo Júnior
Diagnostics 2026, 16(9), 1402; https://doi.org/10.3390/diagnostics16091402 - 6 May 2026
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Abstract
Objective: This study aimed to describe gestational age-specific biometric and estimated fetal weight (EFW) patterns derived from a multicenter cohort of fetuses with gastroschisis and to evaluate the agreement between prenatal EFW and birth weight. Methods: This retrospective study included singleton [...] Read more.
Objective: This study aimed to describe gestational age-specific biometric and estimated fetal weight (EFW) patterns derived from a multicenter cohort of fetuses with gastroschisis and to evaluate the agreement between prenatal EFW and birth weight. Methods: This retrospective study included singleton pregnancies with a prenatal diagnosis of gastroschisis and at least two ultrasound evaluations between 20 and 37 weeks. Data were collected from four Brazilian tertiary centers between 2010 and 2024. Biometric parameters (biparietal diameter, head circumference [HC], abdominal circumference, and femur length) and EFW were recorded. EFW was calculated using Hadlock IV and Siemer formulas. Polynomial regression models were applied to generate gestational age-specific curves for HC, femur length (FL), and EFW. Agreement between prenatal EFW and birth weight (in cases assessed within 14 days of delivery) was analyzed using Bland–Altman plots and the concordance correlation coefficient (CCC). Results: A total of 116 pregnancies and 355 ultrasound tests were included. Polynomial models showed a strong association between gestational age and EFW (R2 = 0.837 for Siemer; R2 = 0.728 for Hadlock), HC (R2 = 0.849), and FL (R2 = 0.877). The 50th percentile curves for gastroschisis were consistently lower than those from standard growth charts. In the birthweight concordance analysis (n = 46), the Siemer formula showed low agreement (CCC = 0.55), while the Hadlock formula showed even lower concordance (CCC = 0.44), with both formulas underestimating actual birth weight. Conclusions: Fetuses with gastroschisis have distinct growth patterns not captured by standard references. Tailored growth curves and careful interpretation of EFW are essential to improve prenatal assessment in this population. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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21 pages, 2757 KB  
Article
Amino Acid Dysregulation in the Mother–Fetus Unit: Multi-Compartment Metabolomic Signatures of Gestational Diabetes Mellitus and Fetal Macrosomia
by Natalia A. Frankevich, Alisa O. Tokareva, Anna A. Derenko, Vitaliy V. Chagovets, Anastasia V. Novoselova, Vladimir E. Frankevich and Gennadiy T. Sukhikh
Int. J. Mol. Sci. 2026, 27(8), 3346; https://doi.org/10.3390/ijms27083346 - 8 Apr 2026
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Abstract
The role of amino acid disturbances in the mother–fetus system remains poorly understood, despite their critical involvement in gestational diabetes mellitus (GDM), fetal macrosomia (FM) and offspring metabolic programming. This study included 62 mother–newborn dyads stratified by GDM and FM status. An analysis [...] Read more.
The role of amino acid disturbances in the mother–fetus system remains poorly understood, despite their critical involvement in gestational diabetes mellitus (GDM), fetal macrosomia (FM) and offspring metabolic programming. This study included 62 mother–newborn dyads stratified by GDM and FM status. An analysis of the association of amino acids with clinical parameters was performed using the Spearman test. Amino acid markers of GDM were identified using the mutual information index and the Mann–Whitney test. A random forest method was used to identify amino acid markers, with the SHAP value used to estimate the contribution of each amino acid. In maternal serum, GDM was associated with significantly lower levels of glycine, 1-methylhistidine, γ-aminobutyric acid, lysine, and tryptophan. Umbilical cord serum from GDM pregnancies showed reduced concentrations of glutamine, glycine, asparagine, methionine, and proline. In amniotic fluid, GDM with FM was characterized by elevated lysine and 1-methylhistidine. Cord blood exhibited increased lysine, proline, leucine, and allo-isoleucine, while amniotic fluid showed low homocitrulline, asparagine, and lysine, together with high histidine. Fetal weight correlated directory with lysine and isoleucine and inversely with homocitrulline. Pathway analysis linked maternal serum markers to disturbances in biotin, glutamate, and carnitine metabolism, whereas cord blood markers involved broader alterations in amino acid, purine, and amino sugar metabolism. In amniotic fluid from GDM with FM, the methylhistidine pathway was specifically enriched, suggesting changes in neonatal muscle protein turnover. GDM induces distinct alterations in the amino acid profiles of all three compartments, and the combination with FM yields unique metabolic signatures. These findings identify candidate biomarkers for prediction of GDM and its complications and point to potential targets for metabolic intervention. Full article
(This article belongs to the Special Issue Latest Advances in Diabetes Research and Practice)
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