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Keywords = singleton pregnancies

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18 pages, 289 KB  
Article
Physical Activity During Pregnancy, Dietary Adequacy, and Energy-Dense, Nutrient-Poor Food and Beverage Intake: Associations with Preterm Birth
by Oana Liliana Atomei, Petronela Vicoveanu, Dragos Vicoveanu and Monica Tarcea
Nutrients 2026, 18(12), 2030; https://doi.org/10.3390/nu18122030 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: Maternal nutrition and physical activity are modifiable behaviours relevant to pregnancy outcomes, but higher activity may coexist with both favourable and unfavourable dietary patterns. This study examined associations between pregnancy physical activity, individualised fruit–vegetable adequacy, energy-dense, nutrient-poor (EDNP) food and beverage intake, [...] Read more.
Background/Objectives: Maternal nutrition and physical activity are modifiable behaviours relevant to pregnancy outcomes, but higher activity may coexist with both favourable and unfavourable dietary patterns. This study examined associations between pregnancy physical activity, individualised fruit–vegetable adequacy, energy-dense, nutrient-poor (EDNP) food and beverage intake, and preterm birth. Methods: This cross-sectional study included 1048 postpartum women with singleton live births recruited consecutively at a tertiary maternity hospital in Romania. Physical activity during the last three months of pregnancy was assessed using the Pregnancy Physical Activity Questionnaire and categorised into quartiles of total MET-hours/week. Dietary intake was assessed using an adapted food frequency questionnaire. Fruit–vegetable adequacy was evaluated against individualised recommendations, and EDNP intake was summarised using a composite score derived from fast food, sweets, chocolate, and sugar-sweetened beverages. Preterm birth was defined as delivery before 37 completed weeks of gestation. Results: Preterm birth occurred in 118 cases (11.3%). Higher physical activity categories showed greater fruit–vegetable intake and adequacy, but also higher EDNP intake. After adjustment for maternal age, pregestational BMI, parity, education, and income, physical activity category remained associated with all modelled dietary outcomes. Category 4 had higher odds of fruit–vegetable adequacy than category 1 (OR 2.24, 95% CI 1.55–3.24). In diet-informed models, category 3 had the lowest odds of preterm birth (OR 0.38, 95% CI 0.21–0.68). Conclusions: Total physical activity during pregnancy was associated with a complex dietary profile rather than a uniformly favourable lifestyle pattern. The lowest odds of preterm birth were observed in the third activity category, suggesting a non-linear association. Full article
13 pages, 976 KB  
Article
Beyond Diagnostic Cut-Offs: Associations Between the sFlt-1/PlGF Ratio and Perinatal Outcomes in Low-Risk Term Pregnancies
by Karolina Bednarz, Maisa Manasar-Dyrbuś, Marcin Sadłocha, Magdalena Bednarek-Jędrzejek, Rafał Stojko and Jakub Staniczek
J. Clin. Med. 2026, 15(12), 4679; https://doi.org/10.3390/jcm15124679 - 16 Jun 2026
Viewed by 182
Abstract
Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical [...] Read more.
Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical placental dysfunction even in otherwise low-risk pregnancies. To investigate associations between the sFlt-1/PlGF ratio and maternal and neonatal outcomes in a low-risk term obstetric population, beyond established diagnostic cut-offs. Methods: This prospective cohort study included 87 women with singleton term pregnancies. Serum sFlt-1 and PlGF concentrations were measured at hospital admission before delivery, and the sFlt-1/PlGF ratio was calculated. The primary outcome was estimated blood loss at delivery. Secondary maternal outcomes included postpartum hemoglobin decline, uterine atony, and fibrinogen concentration. Neonatal outcomes included birthweight, umbilical artery pH, and bilirubin concentration. Multivariable regression models were used to evaluate associations between the ln-transformed sFlt-1/PlGF ratio and outcomes after adjustment for prespecified maternal and obstetric covariates. Results: Each doubling of the sFlt-1/PlGF ratio was associated with greater estimated peripartum blood loss (+78.0 mL, 95% CI 42.1–113.9; p < 0.001), a larger postpartum hemoglobin decline (+0.078 g/dL, 95% CI 0.008–0.148; p = 0.030), lower fibrinogen concentration (−20.7 mg/dL, 95% CI −30.5 to −10.9; p < 0.001), and lower neonatal birthweight (−64.6 g, 95% CI −102.0 to −27.2; p = 0.001). No significant associations were observed for uterine atony, premature rupture of membranes, or umbilical artery pulsatility index above the 75th centile. Conclusions: In low-risk term pregnancies, higher sFlt-1/PlGF ratios were associated with greater estimated peripartum blood loss, lower fibrinogen concentrations, and lower neonatal birthweight. These findings support the hypothesis that variation in angiogenic balance may reflect subclinical placental dysfunction even in apparently uncomplicated pregnancies. Further prospective studies are needed to validate these exploratory observations and determine their clinical relevance. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Prenatal Diagnosis)
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10 pages, 352 KB  
Article
Preliminary Comparison of a Modified cfDNA Extraction Protocol for Y-Chromosome Marker Detection in Maternal Plasma
by Tugba Elgun, Yasemin Musteri Oltulu, Burcin Erkal Cam, Halil Ibrahim Arslan, Fulya Ozkal Molla, Pınar Ata and Asiye Gok Yurttas
Diagnostics 2026, 16(12), 1849; https://doi.org/10.3390/diagnostics16121849 - 15 Jun 2026
Viewed by 162
Abstract
Objectives: Noninvasive prenatal testing relies on the analysis of total cell-free DNA (cfDNA) in maternal plasma, where fetal-derived DNA constitutes only a minor fraction. This study aimed to preliminarily compare a modified TPY cfDNA extraction protocol with two commercial extraction kits for [...] Read more.
Objectives: Noninvasive prenatal testing relies on the analysis of total cell-free DNA (cfDNA) in maternal plasma, where fetal-derived DNA constitutes only a minor fraction. This study aimed to preliminarily compare a modified TPY cfDNA extraction protocol with two commercial extraction kits for the downstream detection of Y-chromosome-specific markers in pregnancies carrying male fetuses. Methods: Plasma samples were obtained from 52 singleton pregnancies between 10 and 30 weeks of gestation with male fetal sex confirmed by ultrasonography. Total cfDNA was extracted from aliquots of the same maternal plasma samples using the modified TPY protocol, the QIAamp DSP Virus Kit, and the MagMAX™ Cell-Free DNA Isolation Kit. Quantitative real-time PCR was performed for the Y-chromosome-specific markers SRY and DYS14. At the same time, GLO was used as a reference marker to reflect the total cfDNA background. Extraction performance was assessed primarily using total cfDNA concentration and Ct values obtained from amplification of fetal-specific Y-chromosome markers. Results: Total cfDNA concentrations varied among the extraction methods, with the commercial kits yielding higher total cfDNA concentrations than the modified TPY protocol. In contrast, the TPY protocol yielded slightly lower mean Ct values for SRY and DYS14 than the commercial kits. SRY and DYS14 amplification was detected in 90.4% and 94.2% of samples, respectively. However, these Ct differences should be interpreted cautiously because fetal fraction, maternal DNA contamination, extraction recovery, and fragment size distribution were not directly measured. Conclusions: The modified TPY protocol showed preliminary technical feasibility for extracting total cfDNA from maternal plasma and enabling downstream amplification of Y-chromosome-specific markers in male pregnancies. Nevertheless, the observed lower Ct values do not establish selective fetal DNA enrichment, reduced maternal DNA contamination, or clinical superiority over commercial methods. Further analytical validation using standardized fetal fraction measurement, recovery efficiency testing, fragment size analysis, fetal-to-maternal DNA ratio assessment, and larger cohorts including both male and female pregnancies is required before broader clinical applicability can be determined. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 1000 KB  
Article
Effect of Previous Cesarean Section on Ultrasound Doppler Studies of Placental Circulation and Pregnancy Outcome
by Threebhorn Kamlungkuea, Woraluk Moradokkasem, Nareenun Chansriniyom, Chayada Tangshewinsirikul, Sommart Bumrungphuet and Theera Tongsong
J. Clin. Med. 2026, 15(12), 4412; https://doi.org/10.3390/jcm15124412 - 7 Jun 2026
Viewed by 227
Abstract
Objectives: To primarily determine the effect of a previous cesarean section on Doppler studies of the uterine artery, umbilical artery, and umbilical vein. Patients and Methods: This prospective study was conducted on singleton pregnancies between 18 and 22 weeks of gestation, including both [...] Read more.
Objectives: To primarily determine the effect of a previous cesarean section on Doppler studies of the uterine artery, umbilical artery, and umbilical vein. Patients and Methods: This prospective study was conducted on singleton pregnancies between 18 and 22 weeks of gestation, including both women with and without a previous cesarean section. Doppler studies of the uterine artery, umbilical artery, and umbilical vein indices were performed during mid-trimester fetal ultrasound scans. Doppler indices and pregnancy outcomes were compared between the two groups. Results: A total of 351 pregnancies, including 74 women with a previous cesarean section and 277 women with an unscarred uterus, underwent Doppler studies. The uterine artery pulsatility index (PI) and resistance index (RI) were significantly higher in women with a previous cesarean section (p < 0.001). Moreover, both univariate and multivariate analyses demonstrated that a previous cesarean section was significantly associated with an increase in uterine artery PI, RI, and the rate of abnormal uterine artery PI, defined as values above the 95th percentile (p = 0.034). Other Doppler study results, as well as pregnancy outcomes, were comparable between the two groups. Conclusions: Pregnant women with a previous cesarean section have significantly higher uterine artery resistance, and a higher rate of abnormal uterine artery PI during mid-pregnancy. Therefore, a cesarean section may be detrimental to uterine arterial health. However, no significant adverse clinical outcomes were observed. Full article
(This article belongs to the Special Issue Clinical Insights in Maternal–Fetal Medicine)
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15 pages, 3980 KB  
Article
Serum sPD-L1 Levels in Early Pregnancy Predict Fetal Growth Restriction and Its Subtypes: A Prospective Nested Case–Control Study
by Yao Wang, Yue Shi, Ruqun Zheng, Xiaoyi Bai, Maran Bo Wah Leung, Lai Kwan Lam, Chi Chiu Wang and Tak Yeung Leung
Int. J. Mol. Sci. 2026, 27(11), 5037; https://doi.org/10.3390/ijms27115037 - 2 Jun 2026
Viewed by 236
Abstract
Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, yet reliable first-trimester biomarkers for early prediction remain lacking. Growing evidence suggests that placental dysfunction is a central pathological driver of FGR. Therefore, placenta-derived proteins in maternal circulation may serve [...] Read more.
Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, yet reliable first-trimester biomarkers for early prediction remain lacking. Growing evidence suggests that placental dysfunction is a central pathological driver of FGR. Therefore, placenta-derived proteins in maternal circulation may serve as mechanistically informative biomarkers for early detection. Here, we aimed to evaluate several placenta-relevant molecules as biomarkers for predicting isolated FGR and its subtypes. In this prospective nested case–control study, we included singleton pregnancies that underwent Down screening in the first trimester and were subsequently diagnosed with FGR (n = 50, including early-onset FGR [EFGR] and late-onset FGR [LFGR]) and healthy pregnancies (n = 100). Pregnancies with maternal comorbidities or fetal anomalies were excluded. Maternal serum protein concentrations were measured using ELISA kits. There were no significant differences in placenta-specific protein 1 (PLAC1) or netrin-1 between the two groups. By contrast, maternal soluble programmed death-ligand 1 (sPD-L1) levels were significantly lower in overall FGR (p < 0.001) and FGR subtypes (p = 0.002) than in controls. Circulating sPD-L1 levels were positively correlated with gestational age at delivery and birth weight Z score. Each one-unit increase in sPD-L1 was associated with lower odds of overall FGR (Odd ratio, OR 0.33), EFGR (OR 0.17), LFGR (OR 0.43), birth weight Z score 3–10% (OR 0.30), and neonatal intensive care unit (NICU) admission (OR 0.38). Moreover, first-trimester sPD-L1 predicted overall FGR (area under the receiver operating characteristic curve, AUC 0.75), EFGR (AUC 0.84), LFGR (AUC 0.70), birth weight Z score 3–10% (AUC 0.75), and NICU admission (AUC 0.67). Collectively, decreased maternal circulating sPD-L1 in early pregnancy may serve as a potential biomarker for isolated FGR, warranting validation in larger multicenter mechanistic studies. Full article
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13 pages, 3226 KB  
Article
Factors Associated with Cesarean Delivery Due to Intrapartum Fetal Compromise in Late-Onset Fetal Growth Restriction: A Retrospective Cohort Study
by Dinçer Sümer, Ahmet Arif Filiz, Özgür Volkan Akbulut, Kubilay Çanga, Büşra Seçilir, Hilal Dönmez, Gülten Çirkin Tekeş and Kadriye Yakut Yücel
J. Clin. Med. 2026, 15(11), 4298; https://doi.org/10.3390/jcm15114298 - 2 Jun 2026
Viewed by 233
Abstract
Objective: To investigate clinical, ultrasonographic, and hematological factors associated with cesarean delivery due to intrapartum fetal compromise in pregnancies complicated by isolated late-onset fetal growth restriction (FGR) undergoing induction of labor at 37 weeks of gestation. Methods: This retrospective cohort study included singleton [...] Read more.
Objective: To investigate clinical, ultrasonographic, and hematological factors associated with cesarean delivery due to intrapartum fetal compromise in pregnancies complicated by isolated late-onset fetal growth restriction (FGR) undergoing induction of labor at 37 weeks of gestation. Methods: This retrospective cohort study included singleton pregnancies with isolated late-onset FGR undergoing elective induction of labor between 37 + 0 and 37 + 6 weeks of gestation. Patients who underwent cesarean delivery due to intrapartum fetal compromise constituted the study group (n = 44), whereas those who achieved vaginal delivery formed the control group (n = 100). Maternal demographic characteristics, fetal ultrasonographic findings, and systemic inflammatory indices were evaluated. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Gravidity, parity, induction-to-birth interval, cervical dilatation at admission, femur length, and platelet count differed significantly between the groups. In multivariable logistic regression analysis, parity remained the only independent predictor of cesarean delivery due to intrapartum fetal compromise (adjusted OR 0.421, 95% CI 0.191–0.926, p = 0.031). Systemic inflammatory indices and most fetal ultrasonographic parameters did not demonstrate independent predictive value. The combined multivariable model demonstrated acceptable discriminative performance (AUC 0.731, 95% CI 0.636–0.827, p < 0.001). Neonatal outcomes were comparable between the groups. Conclusions: In pregnancies complicated by isolated late-onset FGR undergoing induction of labor at 37 weeks, parity was the only independent predictor of cesarean delivery due to intrapartum fetal compromise. Routine clinical, ultrasonographic, and hematological inflammatory markers demonstrated limited independent predictive value. These findings suggest that intrapartum fetal compromise in FGR pregnancies may primarily reflect reduced fetoplacental reserve rather than isolated antenatal parameters. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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15 pages, 3350 KB  
Article
Placental Heat Shock Protein (HSP) Expression in Fetal Growth Restriction (FGR) Pregnancies: A Case–Control Immunohistochemistry Study
by Athina A. Samara, Michel B. Janho, Konstantina Zacharouli, Theodoros Floros, Maria Ioannou, Antonios Garas, Sofia Karachrysafi, Theodora Papamitsou, Christina I. Messini, Alexandros Daponte and Sotirios Sotiriou
Int. J. Mol. Sci. 2026, 27(11), 4841; https://doi.org/10.3390/ijms27114841 - 27 May 2026
Viewed by 355
Abstract
Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case–control immunohistochemistry study is to evaluate the expression [...] Read more.
Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case–control immunohistochemistry study is to evaluate the expression of HSP90 and HSP70 in the placentas of pregnancies complicated with FGR and compare their levels with the control placentas of normal-growth pregnancies. A prospective case–control study was conducted including people undergoing singleton pregnancies who gave birth in a tertiary university hospital in Central Greece. Participants were divided into two equal groups: an FGR pregnancy group and a control group with normal growth. Immunohistochemistry of placental samples was assessed using anti-HSP90 alpha/beta antibody (clone F-8, Santa Cruz Biotechnology, Dallas, TX, USA) and anti-HSC70/HSP70 antibody (clone W27, sc-24, Santa Cruz Biotechnology, Dallas, TX, USA). A scoring system was created to quantify the expression of HSP90 and HSP70 in each sample, and the grade of staining was measured at four points. A total of 80 pregnant people were prospectively enrolled in our study, with 40 in each group. Both constitutive (HSP90β and HSC70/HSPA8) and stress-inducible (HSP90α and HSP70/HSPA1A/B) isoforms were analyzed. When comparing the total score of HSP expression, a statistically significant difference was observed for both HSP90 and HSP70. For HSP90 expression, only the Hofbauer cell’s stain was identified as a statistically significant independent factor, meaning that its positive expression was observed in Hofbauer cells. For HSP70 expression, only the staining of syncytiotrophoblasts was identified as an independent factor. FGR is a common pregnancy complication and a leading cause of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide. Based on our findings, the lower expression levels of both HSP90 and HSP70 are associated with FGR, revealing a possible association with stress response in FGR pathophysiology. However, more robust data from larger-scale prospective studies are needed to elucidate the possible role of HSPs as potential FGR biomarkers. Full article
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19 pages, 3791 KB  
Article
A Fetal Fraction Optimized 106-Plex Digital PCR Assay for Non-Invasive Prenatal Testing of Fetal Trisomy
by Songchang Chen, Xiaorui Luan, Xianling Cao, Cong Liu, Li Zhang, Wu Shang, Yiliang Zhang, Zhijie Yang and Chenming Xu
Diagnostics 2026, 16(11), 1642; https://doi.org/10.3390/diagnostics16111642 - 27 May 2026
Viewed by 319
Abstract
Background/Objectives: Non-invasive prenatal testing (NIPT) for fetal aneuploidy requires accurate trisomy detection together with reliable fetal fraction assessment. This study evaluated the clinical feasibility of a 106-plex digital PCR (dPCR) NIPT assay for trisomies 13, 18, and 21 with internal fetal fraction quantification. [...] Read more.
Background/Objectives: Non-invasive prenatal testing (NIPT) for fetal aneuploidy requires accurate trisomy detection together with reliable fetal fraction assessment. This study evaluated the clinical feasibility of a 106-plex digital PCR (dPCR) NIPT assay for trisomies 13, 18, and 21 with internal fetal fraction quantification. Methods: We consecutively recruited 470 women with high-risk singleton pregnancies. Fetal trisomies were detected using dPCR-NIPT and confirmed by invasive prenatal diagnosis. Pregnancies with negative prenatal diagnostic results were followed to birth. Analytical performance and quality control were assessed using trisomic DNA. The euploid cut-off and diagnostic performance were evaluated in two independent maternal plasma sample sets, using invasive diagnosis and clinical outcome as the reference standard. Results: dPCR-NIPT measured fetal fraction irrespective of fetal sex and detected trisomies at fetal fractions ≥3% using 5 ng DNA. A total of 12 of 470 plasma samples failed cell-free DNA quality control and were excluded before dPCR testing. Of the remaining 458 samples, 5 had fetal fractions below 3% and were classified as failed tests, yielding a nonreportable rate of 1.1%. Using a cut-off of 6.9 established in 103 training samples, no false-positive or false-negative trisomy calls were observed in the 350-sample testing set, corresponding to 100% sensitivity (95% confidence interval [CI], 85.18–100%) and 100% specificity (95% CI, 98.88–100%) for 23 confirmed trisomies. Conclusions: This proof-of-principle study supports the feasibility of fetal fraction-informed dPCR-NIPT for trisomy detection in high-risk singleton pregnancies. Larger prospective studies in average-risk and earlier-gestation populations are required. Full article
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13 pages, 550 KB  
Article
Temporal Dynamics of Catestatin Across Gestation: Links to Metabolic and Hemodynamic Adaptation
by Zdenka Sunjic Lovric, Jasminka Resic Karara, Vedran Stefanovic, Bianka Mimica, Marko Kumric, Daniela Supe-Domic, Roko Santic and Josko Bozic
Life 2026, 16(6), 896; https://doi.org/10.3390/life16060896 - 27 May 2026
Viewed by 419
Abstract
Catestatin is a chromogranin A–derived peptide involved in sympathetic, cardiovascular, inflammatory, and metabolic regulation, but its longitudinal profile during pregnancy remains insufficiently defined. This prospective cohort study aimed to evaluate changes in serum catestatin concentrations from the first to the third trimester and [...] Read more.
Catestatin is a chromogranin A–derived peptide involved in sympathetic, cardiovascular, inflammatory, and metabolic regulation, but its longitudinal profile during pregnancy remains insufficiently defined. This prospective cohort study aimed to evaluate changes in serum catestatin concentrations from the first to the third trimester and to explore their associations with blood pressure and metabolic parameters in initially low-risk singleton pregnancies. Fifty pregnant women were followed longitudinally from 11–13 + 6/7 to 30–41 + 5/7weeks of gestation. Clinical and biochemical parameters were assessed at both visits, and serum catestatin concentrations were measured using a commercial enzyme immunoassay. Serum catestatin concentrations were significantly lower in the third trimester than in the first trimester (median [IQR]: 9.4 [4.9–15.5] vs. 13.4 [9.9–24.6] ng/mL; p < 0.001). Longitudinal changes in catestatin were positively associated with third-trimester insulin concentrations after adjustment for selected covariates. Third-trimester catestatin concentrations were positively correlated with systolic blood pressure (r = 0.356, p = 0.011) and remained associated with systolic blood pressure in a limited multivariable model. These findings suggest that catestatin concentrations decline from early to late pregnancy and may reflect selected metabolic and hemodynamic changes. Larger longitudinal studies including pathological pregnancy cohorts are needed to clarify its clinical relevance. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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13 pages, 535 KB  
Article
Maternal Methyl-Group Donor Intake and Neonatal Birth Size in Singleton IVF Pregnancies
by Szilvia Bokor, Regina Felső, Ildikó Csölle, Tícia Oláh, Noémi Szabó, Róbert Herczeg, Attila Gyenesei, Reka Anna Vass, Simone Funke, Tibor Ertl and Dénes Molnár
Nutrients 2026, 18(11), 1693; https://doi.org/10.3390/nu18111693 - 26 May 2026
Viewed by 308
Abstract
Background/Objectives: Maternal intake of methyl-group donors (MGD) during pregnancy may influence fetal development, yet its role in in vitro fertilization (IVF) pregnancies remains poorly understood. The aim of the present study was to investigate maternal intake of MGDs during late pregnancy and [...] Read more.
Background/Objectives: Maternal intake of methyl-group donors (MGD) during pregnancy may influence fetal development, yet its role in in vitro fertilization (IVF) pregnancies remains poorly understood. The aim of the present study was to investigate maternal intake of MGDs during late pregnancy and its association with neonatal outcomes in IVF versus spontaneously (S) conceived pregnancies. Methods: We assessed third-trimester, daily maternal intake of MGD (folate, betaine, choline, methionine, and folic acid) using a validated food-frequency questionnaire, and maternal supplement intake using a structured questionnaire. Methyl-donor nutrient score (MDNS) was calculated based on deciles of MGD intake. Serum folic acid and vitamin B12 concentrations were measured using standardized immunochemical assay. Predefined inclusion and exclusion criteria were applied. Anthropometric data were measured from singleton newborns (weight, length, head- and waist circumference, body composition) and mothers (height, weight, body composition) after delivery. Statistical analysis was conducted using R (4.1.2v). Results: 265 mother–child pairs were included in the study (IVF n = 83). Daily dietary intake of MGDs was similar between groups, but IVF mothers reported significantly higher daily folic acid (668.7 ± 1050.9 vs. 418.8 ± 419.2 µg, p = 0.0034) and vitamin B12 (11.07 ± 31.58 vs. 7.95 ± 29.00 µg, p = 0.0078) supplementation. Serum analyses were available in a subgroup (n = 131, IVF n = 61) of mothers, showing higher postpartum folate (IVF: 10.96 ± 5.54 vs. S: 8.29 ± 4.72 µg/L, p = 0.0064) and vitamin B12 (IVF: 288.22 ± 113.82 vs. S: 233.70 ± 78.23 ng/L, p = 0.0053). Maternal daily dietary choline intakes were significantly below recommendations (IVF: 251.9 ± 98.5 mg, S: 243.8 ± 106.8 mg). Among 151 singleton neonates (IVF n = 57), anthropometric parameters did not differ between IVF and spontaneously conceived groups and were not associated with MDNS tertiles. Conclusions: Maternal MGD intake during third trimester of pregnancy was not associated with neonatal anthropometric outcomes in singleton pregnancies. Consistently low dietary choline intake highlights a potential nutritional gap warranting improved dietary guidance and supplementation strategies. 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 231
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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22 pages, 5320 KB  
Article
Comparison of Machine Learning Models and the FMF Competing-Risks Algorithm for First-Trimester Preeclampsia Screening in a Romanian Cohort
by Alexandra-Elena Cristofor, Alexandru Carauleanu, Ingrid-Andrada Vasilache, Iustina Condriuc, Ovidiu Bica and Dragos Nemescu
Diagnostics 2026, 16(10), 1540; https://doi.org/10.3390/diagnostics16101540 - 19 May 2026
Viewed by 317
Abstract
Background/Objectives: First-trimester preeclampsia (PE) screening is most widely implemented using the Fetal Medicine Foundation (FMF) algorithm, which combines maternal factors with biophysical and biochemical markers via a competing-risks/Bayes framework to produce individualized risks and guide prophylaxis decisions. We aimed to compare commonly [...] Read more.
Background/Objectives: First-trimester preeclampsia (PE) screening is most widely implemented using the Fetal Medicine Foundation (FMF) algorithm, which combines maternal factors with biophysical and biochemical markers via a competing-risks/Bayes framework to produce individualized risks and guide prophylaxis decisions. We aimed to compare commonly used machine-learning (ML) classifiers (logistic regression, random forest, XGBoost) against FMF a priori and a posteriori risk estimates in a Romanian screening cohort. Methods: We analyzed 1583 singleton pregnancies screened at 11–14 weeks’ gestation. Primary analyses excluded aspirin-treated women to reduce treatment-induced outcome modification. We evaluated two feature sets mirroring FMF structure: (1) a maternal-factor “a priori” set and (2) a “a posteriori” set additionally incorporating mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and Pregnancy-Associated Plasma Protein A (PAPP-A). Models were trained using stratified repeated cross-validation (5-fold × 10 repeats) and evaluated using AUC-ROC, DeLong tests, and sensitivity at 10% false-positive rate. Calibration of the model, sensitivity analyses and decision-curve analysis (DCA) were also assessed. Results: In the a priori comparison, the best ML model was logistic regression (AUC 0.796) versus FMF prior risk AUC 0.841 (DeLong p = 0.349). The sensitivity at 10% false positive rate (FPR) was 33.3% for the model versus 50.0% for FMF model. In the a posteriori comparison, the best ML model was random forest (AUC 0.844) versus FMF posterior risk AUC 0.929 (DeLong p = 0.087), with sensitivity at 10% FPR of 57.1% for ML and 71.4% for FMF. Random undersampling did not improve ML performance. Including aspirin-treated pregnancies did not significantly change our results. Conclusions: In this study, the FMF competing-risks outputs outperformed or matched ML classifiers in both maternal-only and biomarker-augmented screening, and DCA favored FMF particularly for the a posteriori model. Full article
(This article belongs to the Special Issue Advanced Diagnostics in Women's Health: From Biomarkers to Imaging)
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16 pages, 1953 KB  
Article
Arterial and Venous Doppler Parameters in Fetal Growth Restriction: A Comparative Evaluation of Early- and Late-Onset Subtypes
by Hale Ankara Aktas, Ilayda Gercik Arzik, Zubeyde Emiralioglu Cakir, Burak Bayraktar, Bahar Konuralp Atakul, Emre Bayram, Eyyup Suer Timur, Ibrahim Omeroglu, Atalay Ekin and Hakan Golbasi
Diagnostics 2026, 16(10), 1488; https://doi.org/10.3390/diagnostics16101488 - 14 May 2026
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Abstract
Objective: To evaluate and compare fetal arterial and venous Doppler parameters in early-onset (EO) and late-onset (LO) fetal growth restriction (FGR), and to assess their performance within the study cohort and their association with composite adverse neonatal outcome (CANO). Methods: This [...] Read more.
Objective: To evaluate and compare fetal arterial and venous Doppler parameters in early-onset (EO) and late-onset (LO) fetal growth restriction (FGR), and to assess their performance within the study cohort and their association with composite adverse neonatal outcome (CANO). Methods: This prospective observational cohort study included 184 singleton pregnancies between 24 and 37 weeks of gestation, comprising 91 FGR cases and 93 appropriate-for-gestational-age controls. FGR was defined according to Delphi consensus criteria and classified as EO-FGR (<32 weeks) or LO-FGR (≥32 weeks). All fetuses underwent standardized Doppler assessment of the umbilical artery (UA), middle cerebral artery (MCA), uterine artery (UtA), and ductus venosus (DV). The cerebroplacental ratio (CPR) was calculated. Multivariable logistic regression models were constructed separately for EO-FGR and LO-FGR. Classification performance was evaluated using receiver operating characteristic analysis. CANO was defined as at least one of the following: 5-min Apgar score <7, respiratory distress syndrome, neonatal intensive care unit admission, or preterm birth. Results: In both EO-FGR and LO-FGR, UA PI values were significantly higher, whereas MCA PI and CPR were significantly lower than in controls. CPR demonstrated the highest discriminative performance among arterial parameters in both subgroups. DV Doppler indices were not significantly different in EO-FGR. In LO-FGR, DV S-wave and v-wave velocities were independently associated with FGR. No significant associations were observed between Doppler parameters and CANO in subgroup analyses. Conclusions: Arterial Doppler parameters, particularly CPR, showed consistent alterations in both EO- and LO-FGR. The contribution of venous Doppler parameters differed according to clinical subtype, with additional value observed in LO-FGR. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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14 pages, 1755 KB  
Article
Integrating Clinical Factors and Parity-Specific Models with Molecular Biomarkers to Better Predict the Risk of Preterm Birth in Asymptomatic Women
by Ashoka Polpitiya, Charles Cox, Heather Butler, Md. Bahadur Badsha, Laura J. Sommerville, J. Jay Boniface, George Saade and Paul Kearney
Diagnostics 2026, 16(10), 1487; https://doi.org/10.3390/diagnostics16101487 - 14 May 2026
Viewed by 339
Abstract
Background/Objectives: Prior spontaneous preterm birth (sPTB) and short cervical length predict the occurrence of sPTB with low sensitivity, highlighting the need for better detectors of at-risk pregnancies. PreTRM® is a validated, biomarker-based sPTB predictor that we aimed to improve in this [...] Read more.
Background/Objectives: Prior spontaneous preterm birth (sPTB) and short cervical length predict the occurrence of sPTB with low sensitivity, highlighting the need for better detectors of at-risk pregnancies. PreTRM® is a validated, biomarker-based sPTB predictor that we aimed to improve in this study by developing models that incorporate parity and key risk factors. Methods: A Model was developed and validated through retrospective analysis of a cohort of singleton pregnancies that resulted in a live term or preterm birth (PTB) (n = 976). The Model’s ability to predict sPTB and PTB was assessed and its clinical utility compared to PreTRM. Results: The Model predicted sPTB with 77.1% sensitivity, 74.4% specificity, 21.4% positive predictive value (PPV) and 97.3% negative predictive value (NPV), an improvement over PreTRM’s sensitivity (75.0%) and PPV (14.6%), and a higher PPV than short cervix (16.2%). PTB was predicted by the Model with 76.8% sensitivity, 74.6% specificity, 31.6% PPV and 95.5% NPV. Relative to PreTRM, the Model achieved significantly higher area under the receiver operating characteristic curve (AUC) results when predicting whether a PTB or sPTB would be associated with a neonatal hospital stay ≥5 days (p = 0.001 for PTB; p = 0.044 for sPTB). The Model also achieved significantly higher sensitivity than PreTRM in predicting a ≥5 day hospital stay associated with PTB (p = 0.009) and higher sensitivity for a ≥5 day hospital stay associated with sPTB, showing improved clinical utility over PreTRM. Conclusions: The Model achieved substantially higher performance than standard of care risk predictors, and an improvement in clinical utility over PreTRM, demonstrating the robustness of the Model as a sPTB and PTB predictor. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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18 pages, 723 KB  
Article
BMI-Stratified Risk of Cesarean Delivery Following Labor Induction: A Robson Classification-Based Cohort Study with Predictive Modeling
by Sait Erbey, Gizem Aktemur, Mehmet Alican Sapmaz, Ömer Osman Eroğlu, Murat Polat, Bilge Erbey, Betül Tokgöz Çakır and Nazan Vanlı Tonyalı
J. Clin. Med. 2026, 15(10), 3603; https://doi.org/10.3390/jcm15103603 - 8 May 2026
Viewed by 274
Abstract
Objectives: Maternal obesity is associated with adverse labor induction outcomes, but real-world data stratified by the full WHO body mass index (BMI) classification and adjusted for parity remain limited. We evaluated BMI-stratified induction outcomes using the Robson Ten-Group Classification System and developed a [...] Read more.
Objectives: Maternal obesity is associated with adverse labor induction outcomes, but real-world data stratified by the full WHO body mass index (BMI) classification and adjusted for parity remain limited. We evaluated BMI-stratified induction outcomes using the Robson Ten-Group Classification System and developed a combined multivariable model integrating BMI, Bishop score, and parity for pre-induction risk stratification. Methods: This single-center retrospective cohort study included 501 singleton term pregnancies undergoing labor induction in Ankara, Turkey (March–August 2023), stratified by five WHO BMI categories. The primary outcome was cesarean delivery. Analyses included Cochran–Armitage trend tests, multivariable logistic regression, and ROC analysis with DeLong comparison and bootstrap optimism-corrected internal validation. The study followed STROBE guidelines. Results: The overall cesarean rate was 30.3%, rising from 17.1% (normal weight) to 52.2% (Obese class III; Cochran–Armitage Z = 6.099, p < 0.001), with consistent trends across Robson Groups 2 and 4 (both p < 0.001). Failed induction increased from 2.9% to 15.2% (p < 0.001). The cervical ripening requirement rose from 32.4% to 60.9% (p = 0.003). BMI (adjusted odds ratio [aOR] = 1.489, 95% confidence interval [CI] 1.254–1.767) and Bishop score (aOR = 0.807, 95% CI 0.718–0.906) were independent predictors; nulliparity showed a non-significant trend (p = 0.090). The combined model (BMI + Bishop + nulliparity) achieved an apparent AUC of 0.715 (optimism-corrected 0.709), outperforming both Bishop score alone (DeLong p = 0.010) and BMI alone (p = 0.012). Calibration was adequate (Hosmer–Lemeshow p = 0.632). Conclusions: Higher BMI independently predicts increased cesarean risk following labor induction across parity subgroups. The combined multivariable model provides practical bedside pre-induction risk stratification superior to either individual predictor, though external validation is warranted before widespread clinical implementation. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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