Ido Solt

Objective: Gestational diabetes mellitus (GDM) is more prevalent in twin pregnancies, yet screening strategies remain largely based on singleton data. In the present study, we aimed to evaluate whether the mid‐trimester sum of estimated fetal weights (sum‐EFW) at the anatomy scan is associated with subsequent GDM in twin pregnancies. Methods: We conducted a retrospective cohort study of twin pregnancies undergoing routine mid‐trimester ultrasound (2010–2025) at a tertiary center. Sum‐EFW was calculated as the combined estimated fetal weight of both fetuses. The primary outcome was GDM. Receiver operating characteristic (ROC) analysis assessed discriminative performance and multivariable logistic regression identified independent predictors. Results: Among 728 women, 70 (9.6%) developed GDM. Sum‐EFW was higher in GDM pregnancies (1177 ± 187.9 vs. 1103 ± 178.8 g; P = 0.001). ROC analysis demonstrated modest discriminative ability (area under the curve [AUC] 0.62; 95% confidence interval [CI]: 0.55–0.69; P = 0.001). After adjustment for gestational age, discrimination was similar (AUC 0.586; 95% CI: 0.518–0.655; P = 0.013), with sensitivity 67.1%, specificity 47.6%, positive predictive value (PPV) 12.1%, and negative predictive value (NPV) 93.1% at the optimal threshold. A cutoff of 1130 g identified a higher‐risk subgroup (14.3% vs. 6.3%; P = 0.001). In multivariable analysis, maternal age ≥ 30 years (adjusted odds ratio [aOR] 2.45; 95% CI: 1.10–5.45), body mass index (BMI) ≥30 (aOR 5.48; 95% CI: 2.33–12.85), and sum‐EFW ≥1130 g (aOR 3.21; 95% CI: 1.41–7.34) were independently associated with GDM. Conclusion: In twin pregnancies, a higher mid‐trimester sum‐EFW is independently associated with subsequent GDM. These findings suggest that combined fetal growth may reflect early metabolic alterations in twin gestations. Discrimination remains modest, limiting use as a screening or risk‐stratification tool.

Background: Whether a fetus can experience pain remains scientifically and clinically contested, particularly as invasive fetal procedures become more common. Objectives: To review fetal nociceptive development, the evidence and uncertainties relevant to pain perception, and the clinical rationale for fetal analgesia during invasive procedures. Methods: We performed a targeted narrative search of PubMed/MEDLINE, Google Scholar, the Cochrane Library, reference lists, and professional society websites. The final synthesis comprised 34 core sources. Results: Functional nociceptive and neuroendocrine responses to noxious stimuli are documented from the mid-second trimester and can be attenuated by fetal opioids. Early thalamic and subplate circuitry may challenge the claim that mature cortical architecture is required for all pain-related processing, but this circuitry has not been shown to be sufficient for conscious pain. Continuous endogenous fetal sedation is not supported by behavioral evidence, although the fetal neurochemical environment may modulate arousal and sensory processing. Maternal anesthesia, especially regional anesthesia, may not provide reliable fetal analgesic exposure. Professional guidance differs on the gestational age at which pain perception becomes possible. Conclusions: The clinical case for fetal analgesia should be separated from the unresolved question of conscious pain. Potential rationales include preventing possible suffering, attenuating documented physiological stress responses, and facilitating procedural stability. Decisions should therefore be based on a proportionate, procedure-specific maternal-fetal risk-benefit assessment rather than a universal precautionary default.

Background: Preeclampsia (PE), a multisystem and complex disorder diagnosed when maternal hypertension manifests after 20 weeks of gestation with proteinuria, is one of the direct causes of maternal morbidity and mortality, in addition to bleeding and infection. Despite its critical impact, effective preventive dietary interventions are scarce. Oxidative stress and microvascular damage are central to PE pathophysiology. Extra virgin olive oil (EVOO), particularly early harvested EVOO (EVOOEH), is rich in antioxidant compounds and may mitigate these issues. Methods: This randomized, single-masked (investigator and data analysis) interventional pilot study protocol will enroll 156 high-risk pregnant women (8 to 16 weeks of gestation) at Barzilai University Medical Center. Participants will be allocated to two parallel arms: the EVOOEH arm (n=78), receiving 42 mL/day (three tablespoons) of EVOOEH in addition to general Ministry of Health (MOH) dietary recommendations for 4 weeks; and the Control arm (n=78), receiving MOH dietary recommendations only. Low-dose aspirin prophylaxis will be co-administered, if indicated. Adherence will be monitored via phone calls and assessment of maternal whole blood and plasma hydroxytyrosol (HT) at recruitment and approximately four weeks post-intervention initiation. Primary outcomes are incidence of gestational diabetes mellitus (GDM), PE, Cesarean section, preterm birth, and small for gestational age (SGA) newborns. Secondary outcomes include post-intervention maternal 1-hour glucose challenge test (GCT) and serum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF), as well as maternal blood pressure, gestational age at delivery, and newborn percentile. Blood samples will be analyzed for serum 25-hydroxyvitamin D [25(OH)D], sFlt-1/PlGF ratio and HT. Statistical analysis will include use of JMP Pro software, with compared by chi-squared or Fisher’s exact tests for categorical variables and Student’s t-tests or Wilcoxon rank-sum tests for continuous variables when appropriate. Multivariate analyses will be performed for significant variables. Discussion: This pilot study will provide crucial insights into the potential of EVOOEH as a dietary intervention for reducing PE risk in high-risk pregnancies, addressing a significant gap in current preventive strategies. This protocol study findings can inform larger-scale trials and contribute to evidence-based nutritional recommendations for PE prevention. Trial Registration: This study was registered on ClinicalTrials.gov (NCT06759545).

Recent advances in single-cell transcriptomics have provided significant insights into the pathophysiology of preeclampsia, uncovering cell-type–specific gene expression changes at the maternal-fetal interface. Key discoveries include dysregulated angiogenic factors, such as elevated sFlt-1 (soluble fms-like tyrosine kinase-1) and reduced PlGF (placental growth factor), predominantly in syncytiotrophoblasts, alongside inflammatory and stress-related signatures in stromal and immune cells. These findings reinforce the clinically observed concept of 2 distinct preeclampsia subtypes: a placenta-dominant form and a maternal cardiovascular–dominant form, each characterized by unique etiologies, clinical presentations, and therapeutic implications. Ongoing genomic research has the potential to identify novel biomarkers and therapeutic targets, paving the way for improved screening and management strategies for this multifaceted condition.

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies.Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated.Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC.Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

To compare approval rates of late termination of pregnancy (LTOP) requests before and after a policy change in Israel in late 2007. In a retrospective study, LTOP requests and board decisions from 2002-2007 (group 1) were compared with those from 2007-2012 (group 2) at 3 university-affiliated medical centers in Israel. Reasons for application, approval, or rejection were compared between the groups. There were 552 applications for LTOP. The overall approval rate for LTOP and the specific approval rate per medical indication did not differ significantly between the groups. The rate of requests due to confirmed genetic anomalies decreased from 18.4% in group 1 to 11.3% in group 2 (P=0.03). Compared with group 1, the rate of rejection for intrauterine infection increased from 8.3% to 26.3% (P=0.2), and that for pregnancy complications decreased from 62.5% to 35.0% (P=0.2) in group 2 but these differences were not statistically significant. Requests due to structural anomalies were declined because they were considered to be minor cardiac, renal, cerebral, or skeletal anomalies. The more stringent 2007 criteria for approving requests for LTOP did not affect the rate of rejection of requests due to structural anomalies between the 2 time periods.

Objectives The purpose of this study was to examine the efficacy of nonvisualization of the fourth ventricle for first‐trimester detection of spina bifida. Methods A total of 250 digitally stored sonographic examinations at gestational ages of 11 weeks to 13 weeks 6 days (245 normal and 5 randomly interspersed spina bifida cases) were retrospectively analyzed by 4 blinded reviewers for the presence or absence of the fourth ventricle followed by an anteroposterior ventricular dimension measurement. The ventricle size was related to the crown‐rump length and gestational age by linear regression analysis and Pearson correlation. Results The fourth ventricle was identified in 971 of 1000 image readings (97.1%). False‐negative and false‐positive readings occurred in 11 of 20 (55.0%) and 20 of 980 (2.0%) cases, respectively (sensitivity, 0.45; specificity, 0.98.). False‐negative and false‐positive readings were evenly distributed throughout the gestational age range. When the ventricular size was measurable, its mean dimensions increased linearly with gestational age and were below the fifth percentile in 10 of 245 (4.0%) normal and 0 of 4 spina bifida cases, respectively. Intraclass correlation coefficient estimates were calculated based on the 2‐way analysis of variance model and found to be 0.30 for a single rater and 0.64 for the mean of 4 raters. Conclusions Nonvisualization of the first‐trimester fourth ventricle is a less robust screening parameter for spina bifida than previously published.