Search Results (248)

Background/Objectives: Systematic quality review of ultrasound exams is recommended to ensure accurate diagnosis. Our primary objectives were to develop a quantitative method for quality review of estimated fetal weight (EFW) and to assess the accuracy of EFW for an entire practice and for individual personnel. A secondary objective was to evaluate the accuracy of fetal sex determination. Methods: This is a retrospective cohort study. Eligible ultrasound exams included singleton pregnancies with live birth and known birth weight (BW). A published method was used to predict BW from EFW for exams with ultrasound-to-delivery intervals of up to 12 weeks. Mean error and median absolute error (AE) were compared between different personnel. Image audits were performed for exams with AE > 30% and exams with reported fetal sex different than newborn sex. Results: We analyzed 1938 exams from 890 patients. In the last exam before birth, the median AE was 5.9%, and the predicted BW was within ±20% of the actual BW in 97.2% of patients. AE was >30% in 28 exams (1.4%); image audit found correct caliper placement in all 28. Only two patients (0.2%) had AE > 30% on the last exam before birth. One sonographer systematically over-measured head and abdominal circumferences, leading to EFWs that were overestimated. Reported fetal sex differed from newborn sex in seven exams (0.4%) and five patients (0.6%). Images in four of these patients were annotated with the correct fetal sex, but a clerical error was made in the report. In one patient, an unclear image was labeled “probably female”, but the newborn was male. Conclusions: The accuracy of EFW in this practice was similar to literature reports. The quantitative analysis identified a sonographer with outlier measurements. Time-consuming image audits could be focused on a small number of exams with large errors. We suggest some enhancements to ultrasound reporting software that may help to reduce clerical errors. We provide tools to help other practices perform similar quality reviews. Full article

Background: Alterations in maternal lipid metabolism have been elucidated by several studies in relation to macrosomia. However, the lipidome of the intrauterine compartment associated with macrosomia, particularly in early pregnancy, remains largely unknown. Objectives: (1) To compare the lipidomic profile of early 2nd trimester amniotic fluid (AF) of healthy mothers with normal body mass index who gave birth to large-for-gestational age (LGA) versus appropriate-for-gestational age (AGA) infants; and (2) to examine if insulin and glucose concentrations in AF were associated with the AF lipidomic profile. Methods: In this nested case–control study, bio-banked AF samples were collected from pregnant women undergoing routine amniocentesis at 12–22 weeks of gestation. A subsample of 15 LGA infants (cases) were contrasted with 15 AGA infants (controls). An untargeted lipidomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry was conducted. Univariate and multivariate statistical analyses (principal component analysis and partial least-squares discriminant analysis) were used to extract differentially abundant (DA) features with high variable importance in projection (VIP) scores. Results: LGA AF was characterized by elevations of 30 phosphatidic acid species. Among other DA features, sphingomyelin (SM 14:0;O2/20:1) had the highest VIP score and was markedly elevated in LGA AF. Neither insulin nor glucose was associated with 2nd trimester AF lipidomic profiles in these healthy, normal-weight mothers. Conclusion: These findings provide evidence of early dysregulated lipid metabolism in healthy, normal-weight mothers with LGA infants. Full article

Introduction: The prevalence of ductus venosus agenesis (ADV) in singleton pregnancies ranges from 0.04% to 0.15%, while its prevalence in twins remains largely unknown. To our knowledge, in the literature, there is only a single case report of a monochorionic diamniotic (MCDA) pregnancy complicated by ADV. Fetuses with ADV are at increased risk for congenital cardiac disease, heart failure, and fetal growth restriction (FGR). Consequently, these pregnancies have a heightened risk of experiencing an adverse outcome, like stillbirth and neonatal or infant death. Closer antenatal monitoring is warranted when ADV is suspected. Currently, there are no guidelines regarding the standard of care in cases of ADV and no recommendations for the timing of delivery in either singleton or twin pregnancies. Cases: This study aims to provide a comprehensive overview of the management of twin pregnancies complicated by ADV, featuring two cases of MC twins with concurrent sFGR and ADV in one twin. Discussion: These pregnancies experienced completely different outcomes, underscoring the necessity for personalized management tailored to the specific risk factors present in each pregnancy. Typically, in MCDA pregnancies with severe sFGR (type II and III), delivery represents the most reasonable option when venous Doppler abnormalities are identified. However, the absence of the DV complicates the management and the process of decision-making regarding the timing of delivery in cases of sFGR and ADV. We emphasize that effective decision-making should be guided by the presence of additional risk factors, including velamentous insertion, significant estimated fetal weight discordance, and progressive deterioration of the Doppler over time. Conclusions: Our experience suggests that these factors are strongly correlated with poorer outcomes. Given this context, could it be acceptable, in the case of MC pregnancy complicated by severe sFGR and ADV, with worsening findings and additional risk factors (e.g., velamentous insertion, severe birth weight discrepancy), to anticipate the time of delivery starting from 30 weeks of gestational age? Full article

Intraventricular hemorrhage (IVH) in preterm neonates presents a high risk for developing posthemorrhagic ventricular dilatation (PHVD), a severe complication that can impact survival and long-term outcomes. Early detection of PHVD before clinical onset is crucial for optimizing therapeutic interventions and providing accurate parental counseling. This study explores the potential of explainable machine learning models based on targeted liquid biopsy proteomics data to predict outcomes in preterm neonates with IVH. In recent years, research has focused on leveraging advanced proteomic technologies and machine learning to improve prediction of neonatal complications, particularly in relation to neurological outcomes. Machine learning (ML) approaches, combined with proteomics, offer a powerful tool to identify biomarkers and predict patient-specific risks. However, challenges remain in integrating large-scale, multiomic datasets and translating these findings into actionable clinical tools. Identifying reliable, disease-specific biomarkers and developing explainable ML models that clinicians can trust and understand are key barriers to widespread clinical adoption. In this prospective longitudinal cohort study, we analyzed 1109 liquid biopsy samples from 99 preterm neonates with IVH, collected at up to six timepoints over 13 years. Various explainable ML techniques—including statistical, regularization, deep learning, decision trees, and Bayesian methods—were employed to predict PHVD development and survival and to discover disease-specific protein biomarkers. Targeted proteomic analyses were conducted using serum and urine samples through a proximity extension assay capable of detecting low-concentration proteins in complex biofluids. The study identified 41 significant independent protein markers in the 1600 calculated ML models that surpassed our rigorous threshold (AUC-ROC of ≥0.7, sensitivity ≥ 0.6, and selectivity ≥ 0.6), alongside gestational age at birth, as predictive of PHVD development and survival. Both known biomarkers, such as neurofilament light chain (NEFL), and novel biomarkers were revealed. These findings underscore the potential of targeted proteomics combined with ML to enhance clinical decision-making and parental counseling, though further validation is required before clinical implementation. Full article

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m² based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m² were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76–18.92%), with 28.0% (95% CI: 14.0–48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2–98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3–27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3–36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7–2829.4). Additionally, 40.1% (95% CI: 23.1–60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity. Full article

Background: Gestational diabetes mellitus (GDM) is the main cause of hyperglycemia in pregnancy and is related to complications throughout the gestational and post-partum period. Objectives: To analyze the pregnancy outcomes related to the occurrence of GDM in women and their offspring. Methods: Third-trimester pregnant women were interviewed and monitored until childbirth. The diagnosis of GDM, blood glucose ≥ 92 mg/dL, was defined by the criteria of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG). Results: A total of 138 women participated, and there were 136 births (due to 2 fetal losses); 23 (16.7%) were diagnosed with GDM. The risk of complications during childbirth was higher among pregnant women with GDM (RR 3.40; 95%CI 1.65–7.00), as was the occurrence of cesarean birth (RR 1.9; 95%CI 1.46–2.59). The occurrence of preterm birth did not show a significant difference between GDM/non-GDM groups. There was a non-significant association in adjusted analyses of macrosomia (birth weight ≥ 4000 g) among newborns born to mothers with GDM (RR 1.27; 95%CI 0.67–2.38). For newborns born to pregnant women with GDM, there was a higher risk for the following outcomes: large for gestational age (LGA) (3.29 95%CI 1.62–6.64), low Apgar (4.98 95%CI 2.32–10.69), and birth asphyxia (9.51 95%CI 3.42–26.48). Conclusions: The findings reinforce that GDM is an important risk factor for adverse pregnancy outcomes for women and their offspring. Full article

Background: Understanding the potential risk factors for failure of pregnancy termination is crucial for informed clinical decision making. Such insights can assist clinicians in adjusting the dosage or route of various regimens, as well as in counseling patients and predicting the likelihood of successful outcomes. However, research on these risk factors has been limited, and existing studies have yielded inconsistent results. To address this gap, we conducted a study with a large sample size, focusing on identifying the potential risk factors for failure of second-trimester termination using misoprostol as a single agent, specifically between 14 and 28 weeks of gestation. Methods: A secondary analysis based on a database of second-trimester terminations was conducted. The inclusion criteria were a singleton pregnancy, gestational age between 14 and 28 weeks, an unfavorable cervix, no spontaneous labor pain, intact membranes, and termination with misoprostol alone. Potential risk factors for failure of termination, defined as no abortion within 48 h, were analyzed using univariate and multivariate analyses. Results: A total of 1094 cases were included in the analysis, consisting of 991 successful cases and 103 (9.4%) cases of failure. The significant risk factors for failure of termination included early gestational age, live fetuses, sublingual regimen of 400 mcg every 6 h, and high maternal pre-pregnancy BMI. Previous cesarean sections and lower Bishop scores tended to increase the risk but did not reach a significant level. Conclusions: Second-trimester termination with misoprostol as a single agent was highly effective, with a failure rate of 9.4%. The risk factors for failure included gestational age, fetal viability, misoprostol regimen, and maternal pre-pregnancy BMI, suggesting that these factors should be taken into consideration for second-trimester terminations with misoprostol. Full article

Background: Gestational diabetes mellitus (GDM) is a common endocrine disease that can occur during pregnancy, increasing the risk of fetal morbidity and mortality. Metformin is a commonly used therapeutic approach for managing GDM. However, there is controversy regarding the effects of metformin on fetal outcomes during pregnancy. This study aimed to evaluate the safety of metformin in relation to neonatal complications, compared to treatment with insulin and/or specialized diets. Method: This was a retrospective study that included pregnant women who were diagnosed with GDM and treated with specialized diets, metformin, or insulin. Data were collected from patients’ electronic medical records and analyzed to evaluate the risk of neonatal outcomes in the metformin group compared to the others. Results: The study included 234 women with GDM. There was no difference between the metformin and insulin groups in terms of the rates of neonatal outcomes, while neonatal hypoglycemia, neonatal hyperbilirubinemia, large for gestational age, and respiratory distress were higher in the metformin group when compared to the diet group. Metformin slightly increased the risk of a lower APGAR score compared to diet alone. Conclusions: Metformin was found to be a safe therapy for the fetus when used to manage GDM, compared to insulin therapy. More randomized studies are needed to confirm these findings in the Saudi population. Full article

Electronic cigarette (e-cig) use in pregnancy is common, but potential effects on fetal development are largely unknown. This study’s goal was to examine the association between e-cig exposure and fetal growth. Data were extracted from medical charts in this single-site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used e-cigs throughout pregnancy and non-e-cig user controls. Fetal size measurements from second- and third-trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for e-cig exposure compared to controls. By the third trimester, the femur length difference was 28.5 points, with the fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal e-cig exposure, becoming larger and impacting more parameters with increasing gestation. While additional studies are warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following e-cig exposure in pregnancy and suggests that e-cigs may not be a “safer” alternative to combustible cigarette smoking in pregnancy. Full article

Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction and leads to neurological developmental deficits and even a higher prevalence of respiratory diseases in the further development of premature infants. Due to the proven antioxidant effect of caffeine in early use, largely protective effects on clinical outcomes can be observed. This is also impressively observed in experimental studies of caffeine application in oxidative stress-adapted rodent models of damage to the developing brain and lungs. However, caffeine shows undesirable effects outside these oxygen toxicity injury models. This review shows the effects of caffeine in hyperoxic, hypoxic/hypoxic-ischemic, and intermittent hypoxic rodent injury models, but also the negative effects on the rodent organism when caffeine is administered without exogenous oxidative stress. The narrative analysis of caffeine benefits in cerebral and pulmonary preterm infant models supports protective caffeine use but should be given critical consideration when considering caffeine treatment beyond the recommended corrected gestational age. Full article

Background and Objectives: Although considerable research has been devoted to examining the distinctions between fresh and frozen embryo transfer regarding obstetric outcomes and rates of pregnancy success, there is still a scarcity of thorough analyses that specifically examine neonatal outcomes. The objective of our study was to provide an in-depth analysis of neonatal outcomes that occur after the transfer of fresh and frozen embryos (ET vs. FET) in IVF/ICSI cycles. Materials and Methods: Multiple databases (PubMed/MEDLINE, Cochrane Library, Web of Science, Wiley, Scopus, Ovid and Science Direct) were searched from January 1980 to February 2024. Two reviewers conducted the article identification and data extraction, meeting inclusion and exclusion criteria. The methodological quality was evaluated using the Newcastle–Ottawa Scale (NOS) or the revised Cochrane Risk of Bias Tool. The meta-analysis was performed using RevMan 5.4. Results: Twenty studies, including 171,481 participants in total, were subjected to qualitative and quantitative analyses. A significant increase in preterm birth rates was noted with fresh embryo transfer compared to FET in the overall IVF/ICSI population (OR 1.26, 95% CI 1.18–1.35, p < 0.00001), as well as greater odds of a low birth weight (OR 1.37, 95% CI 1.27–1.48, p < 0.00001) and small-for-gestational-age infants in this group (OR 1.81, 95% CI 1.63–2.00, p < 0.00001). In contrast, frozen embryo transfer can result in macrosomic (OR 0.59, 95% CI 0.54–0.65, p < 0.00001) or large-for-gestational-age infants (OR 0.64, 95% CI 0.60–0.69, p < 0.00001). No significant difference was observed regarding congenital malformations or neonatal death rates. Conclusions: This systematic review confirmed that singleton babies conceived by frozen embryo transfer are at lower risk of preterm delivery, low birthweight and being small for gestational age than their counterparts conceived by fresh embryo transfer. The data support embryo cryopreservation but suggest that elective freezing should be limited to cases with a proven indication or within the framework of a clinical study. Full article

Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers’ underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods: We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results: We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions: Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy. Full article

Background/Objectives: To evaluate the quality of an ultrasound practice, both large-scale and focused audits are recommended by professional organizations, but such audits can be time-consuming, inefficient, and expensive. Our objective was to develop a time-efficient, quantitative, objective, large-scale method to evaluate fetal biometry measurements for an entire practice, combined with a process for focused image review for personnel whose measurements are outliers. Methods: Ultrasound exam data for a full year are exported from commercial ultrasound reporting software to a statistical package. Fetal biometry measurements are converted to z-scores to standardize across gestational ages. For a large-scale audit, sonographer mean z-scores are compared using analysis of variance (ANOVA) with Scheffe multiple comparisons test. A focused image review is performed on a random sample of exams for sonographers whose mean z-scores differ significantly from the practice mean. A similar large-scale audit is performed, comparing physician mean z-scores. Results: Using fetal abdominal circumference measurements as an example, significant differences between sonographer mean z-scores are readily identified by the ANOVA and Scheffe test. A method is described for the blinded image audit of sonographers with outlier mean z-scores. Examples are also given for the identification and interpretation of several types of systematic errors that are unlikely to be detectable by image review, including z-scores with large or small standard deviations and physicians with outlier mean z-scores. Conclusions: The large-scale quantitative analysis provides an overview of the biometry measurements of all the sonographers and physicians in a practice, so that image audits can be focused on those whose measurements are outliers. The analysis takes little time to perform after initial development and avoids the time, complexity, and expense of auditing providers whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative reviews. Full article

Background/Objectives: Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. Methods: A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. Results: The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3–5.2; OR = 4.3, 95%CI = 4.1–4.6; OR = 1.9, 95%CI = 1.3–2.6; OR = 2.2, 95%CI = 2–2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). Conclusions: OD pregnancies are at increased risk for PTB, SGA and PIH. Full article

Background: Single-nucleotide polymorphisms in LIN28B, critical regulators of female growth and puberty, have been linked to age at menarche. Methods: We assessed the association of rs7759938, rs314280, and rs314276 with menarcheal age in girls of Greek descent. We reviewed the records of 248 girls who had their first menstruation before 18 years and who attended the Greek Departments of Pediatric Endocrinology from January 2021 to July 2023. Genotyping was performed by standard DNA-based methods. Association analyses involved both parametric and non-parametric tests. Results: The average age of breast and pubic hair development was 9.95 years, and the age at menarche was 11.55 years. Menarche occurred ≤11 years (mean 10.24 years) in 108 girls (43.5%) and >11 years (mean 12.55 years) in 140 (56.5%). The girls’ menarcheal age correlated significantly with that of their mothers (average 12.1 years, p-value < 0.0001, Spearman’s r 0.350). The dominant rs7759938(TT) genotype was the most common (55.2%), followed by the dominant rs314276(CC) (53.2%) and dominant rs314280(TT) (14.5%) genotypes. Conclusions: There was no association between age at menarche and any of the polymorphism genotypes/alleles or between genotypes/alleles and birth weight, gestational week, mode of delivery, and maternal age at menarche. Future large sample studies are warranted to confirm these results. Full article