The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

Decreased flow-mediated dilation in gestational diabetes in pregnancy and post-partum. A systematic review and meta-analysis.

AIMS: Gestational diabetes mellitus (GDM) is a common medical complication during pregnancy. Endothelial dysfunction is considered an early step in the progression of atherosclerosis that may contribute to subclinical target organ damage. This meta-analysis aimed to systemically review the existing data regarding endothelial dysfunction between women with and without GDM during pregnancy and post-partum using flow-mediated dilation (FMD). MATERIALS AND METHODS: Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched. RESULTS: The search yielded 2272 studies, of which 17 were fully reviewed and 12 studies (N = 740 pregnant women) were finally included. Pregnant women with GDM exhibited a significantly lower FMD compared to pregnant women without GDM (pooled mean difference -3.12; 95% CI -5.36 to -0.88). Moreover, in the immediate (1-6 months) post-partum period, women with previous GDM showed lower FMD compared to healthy women without GDM history (pooled mean difference -7.52; 95% CI -9.44 to -5.59), whereas FMD did not differ in the late post-partum period (more than 4 years). CONCLUSIONS: Flow-mediated dilation is decreased in women with GDM during pregnancy and in the immediate post-partum period, compared to women without GDM, indicating that the endothelial dysfunction noted during the pregnancy in those women persists in the immediate post-partum period too. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021283113 (www. CLINICALTRIALS: gov).

The Effect of Resolution Level and Targeted Design in the Diagnostic Performance of Prenatal Chromosomal Microarray Analysis.

INTRODUCTION: This study was performed to assess the optimal resolution for prenatal testing by array comparative genomic hybridization (aCGH), aiming to balance between maximum diagnostic yield and minimal detection of variants of uncertain significance (VOUS). METHODS: This was a prospective study using data of 2,336 fetuses that underwent invasive prenatal diagnosis, and the samples were analyzed by aCGH. In total, six different aCGH platforms were studied; four different resolutions (0.18 Mb, 0.5 Mb, 1 Mb, and 2 Mb) and two platform designs (whole-genome [WG] and targeted). The results of these designs were compared based on their diagnostic yield and VOUS rate. The performance of the different designs was further analyzed according to indication for invasive testing. RESULTS: The diagnostic yield of copy number variants increased with increasing level of analysis. The detection rates of clinically significant chromosomal abnormalities were almost the same across our targeted array designs; 7.2% with 0.18 Mb backbone/0.05 Mb versus 7.1% with 0.5 Mb backbone/0.05 Mb (p >0.05). However, a significant difference in the rate of VOUS was observed; 9.4% with 0.18 Mb backbone/0.05 Mb versus 6% with 0.5 Mb backbone/0.05 Mb (p <0.001). After analyzing the results across different indications for testing, we found that the application of non-targeted platform designs and lower levels of resolution analysis (such as 1 Mb WG or 0.5 MbL/1 MbG WG) would offer similar diagnostic yield in most cases with major congenital anomalies, with lower VOUS rates. However, the sample size for many indication groups was too small to extract robust associations. CONCLUSION: It appears that the targeted array platform with 0.5 Mb backbone resolution and 0.05 Mb on targeted gene-rich regions is optimal for routine chromosomal microarray analysis use in prenatal diagnosis. It may be beneficial to individualize the minimum resolution in specific referral indications as the indications for invasive prenatal testing may be quite heterogeneous.

Daughters of polycystic ovary syndrome pregnancies and androgen levels in puberty: a Meta-analysis.

Purpose: To provide an overview and critical analysis of the literature related to the circulating androgen levels of daughters of PCOS mothers during prepubertal and pubertal stage who have not yet been diagnosed with PCOS or precocious puberty. Methods: We critically considered and meta-analyzed observational studies comparing androgens concentration in daughters of PCOS mothers compared to daughters of mothers without PCOS. A literature search was conducted in MEDLINE, Scopus and other sources from 01/09/2021 until 01/12/2021. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The primary outcome included total testosterone levels whereas the secondary outcomes included 17a-hydroxyprogesterone (17-OHP), androstenedione (Δ4Α) and Sex Hormone Binding Globulin (SHBG) levels respectively. Results: Our search yielded 1073 studies, 9 of which were included in our analysis. The results are presented differently according to pubertal stage. Pubertal daughters of PCOS mothers exhibited significantly higher total testosterone (pooled mean difference 14.95 (95%CI: 6.98 to 22.93), higher 17-OHP (pooled mean difference 0.11 (95%CI: 0.02 to 0.20) and lower SHBG levels (pooled mean difference -10.48 (95%CI: -16.46 to -4.61). Instead, prepubertal daughters of PCOS mothers presented greater SHBG levels (pooled mean difference 7.79 (95%CI: 0.03 to 15.54) compared to controls. No difference was found in Δ4Α levels in both groups. Conclusion: The onset of puberty is a critical point in the development of the disease and an early intervention may be imperative.

Early delivery or expectant management for late preterm preeclampsia: A meta-analysis of randomized controlled trials.

INTRODUCTION: Currently, there is no consensus regarding the timing of delivery in women with non-severe preeclampsia at the late preterm period. The aim of the present meta-analysis is to compare expectant management with immediate delivery in pregnant women with preeclampsia between 34+0 and 36+6 gestational weeks, in terms of maternal and neonatal outcomes. MATERIAL AND METHODS: A search was conducted until October 1, 2020 and eligible studies were identified in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), the US Registry of clinical trials (www.clinicaltrials.gov), and sources of gray literature without limitations concerning the publication dates and languages. Randomized controlled trials, comparing planned delivery vs expectant management in women with preeclampsia at 34-37 weeks were included. The primary outcomes were neonatal intensive care unit (NICU) admission and progression to eclampsia. Secondary outcomes were HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, severe preeclampsia, composite adverse maternal outcome (defined by the presence of any of the potential preeclampsia-related complications, ranging from severe hypertension to maternal death), neonatal respiratory disease, and respiratory distress syndrome. Relative risks (RRs) and mean differences with 95% CI were used for the estimation of the effect sizes; the quality of the evidence was assessed per GRADE guidelines. RESULTS: The electronic search yielded 10 721 potential studies, of which six were fully reviewed and three (1773 participants) were included in the meta-analysis. Immediate delivery increased the risk for NICU admission, (RR 1.23, 95% CI 1.05-1.45) and decreased the risk for the composite adverse maternal outcome (RR 0.86, 95% CI 0.78-0.93). There were no differences for eclampsia (RR 0.55, 95% CI 0.16-1.85), HELLP syndrome (RR 0.58, 95% CI 0.25-1.33), severe preeclampsia (RR 0.27, 95% CI 0.02-3.52), respiratory disease of neonate (RR 1.04, 95% CI 0.75-1.44), and respiratory distress syndrome (RR 2.3, 95% CI 0.73-7.25). CONCLUSIONS: Immediate delivery of women with non-severe preeclampsia at the period of late prematurity decreases the risk of a composite adverse maternal outcome by 14%, at the cost of an increase in NICU admissions by 23%. The overall quality of the evidence for these outcomes is high, indicating a high degree of certainty for the results.

Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences.

OBJECTIVE: Cytomegalovirus infection is the most frequent congenital infection and a major cause of long-term neurologic morbidity. The aim of this meta-analysis was to calculate the pooled rates of vertical transmission and fetal impairments according to the timing of primary maternal infection. DATA SOURCES: From inception to January 2020, MEDLINE, Scopus, Cochrane Library, and gray literature sources were used to search for related studies. STUDY ELIGIBILITY CRITERIA: Cohort and observational studies reporting the timing of maternal cytomegalovirus infections and rate of vertical transmission or fetal impairments were included. The primary outcomes were vertical transmission and fetal insult, defined as either prenatal findings from the central nervous system leading to termination of pregnancy or the presence of neurologic symptoms at birth. The secondary outcomes included sensorineural hearing loss or neurodevelopmental delay at follow-up and prenatal central nervous system ultrasonography findings. STUDY APPRAISAL AND SYNTHESIS METHODS: The pooled rates of the outcomes of interest with their 95% confidence intervals (CI) were calculated for primary maternal infection at the preconception period, periconception period, first trimester, second trimester, and third trimester. RESULTS: A total of 17 studies were included. The pooled rates of vertical transmission (10 studies, 2942 fetuses) at the preconception period, periconception period, first trimester, second trimester, and third trimester were 5.5% (95% CI, 0.1-10.8), 21.0% (95% CI, 8.4-33.6), 36.8% (95% CI, 31.9-41.6), 40.3% (95% CI, 35.5-45.1), and 66.2% (95% CI, 58.2-74.1), respectively. The pooled rates of fetal insult in case of transmission (10 studies, 796 fetuses) were 28.8% (95% CI, 2.4-55.1), 19.3% (95% CI, 12.2-26.4), 0.9% (95% CI, 0-2.4%), and 0.4% (95% CI, 0-1.5), for maternal infection at the periconception period, first trimester, second trimester, and third trimester, respectively. The pooled rates of sensorineural hearing loss for maternal infection at the first, second, and third trimester were 22.8% (95% CI, 15.4-30.2), 0.1% (95% CI, 0-0.8), and 0% (95% CI, 0-0.1), respectively. CONCLUSION: Vertical transmission after maternal primary cytomegalovirus infection increases with advancing pregnancy, starting from the preconception period. However, severe fetal impairments are rare after infection in the first trimester of pregnancy.

Emergency cerclage in singleton pregnancies with painless cervical dilatation: A meta-analysis.

INTRODUCTION: Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of emergency cerclage vs expectant management on maternal and perinatal outcomes, and to assess the current status of evidence. MATERIAL AND METHODS: A search was conducted from 1 June 2019 until 1 September 2019 and eligible studies were identified in the MEDLINE, Scopus, Cochrane and US clinical trials registry without limitations concerning the publication dates and languages. Randomized controlled trials (RCTs), non-RCTs and observational studies comparing emergency cerclage with no cerclage/expectant management, in women presenting with painless cervical dilatation were included. RESULTS: The electronic search yielded 3607 potential studies, of which 38 were fully reviewed and 12 observational studies (1021 participants) were included. Cerclage was superior to expectant management for the primary outcomes of preterm birth before 28 and 32 gestational weeks, OR 0.25 (95% CI 0.16-0.39, five studies, N = 392, I2 = 41%, low quality) and 0.08 (95% CI 0.02-0.29, four studies, N = 176, I2 = 51%, low quality), respectively. Cerclage was also superior to expectant management for the secondary outcomes of fetal loss OR 0.26 (95% CI 0.12-0.56, 8 studies, N = 455, I2 = 46%, very low-quality), pregnancy prolongation in days mean difference 47.45 (95% CI 39.89-55.0, 12 studies, N = 1027 I2 = 86%, very low quality), gestational age at birth in weeks mean difference 5.68 (95% CI 4.69-6.67, 9 studies, N = 892, I2 = 73%, very low quality), admission to neonatal intensive care OR 0.21 (95% CI 0.07-0.70, two studies, N = 79, I2 = 36%, very low quality) and neonatal death OR 0.12 (95% CI 0.04-0.34, five studies, N = 130, I2 = 0%, very low quality). There were no differences between cerclage and expectant management concerning premature rupture of membranes during or after the procedure OR 0.68 (95% CI 0.31-1.48, two studies, N = 155, I2 = 85%, very low quality) and chorioamnionitis OR 1.14 (95% CI 0.31-4.25, three studies, N = 88, I2 = 33%, very low quality). CONCLUSIONS: Emergency cerclage in pregnant women with painless cervical dilatation seems to decrease preterm births, prolong the pregnancy, and decrease the neonatal deaths and fetal losses, but does not increase the risk of chorioamnionitis and premature rupture of membranes. Despite the extremely favorable estimates for cerclage, the results should be viewed with caution because, as a result of the lack of randomized control trials, the quality of evidence is low to very low.

The Effect of Maternal Diet and Physical Activity on the Epigenome of the Offspring.

The aim of this review was to examine the current literature regarding the effect of maternal lifestyle interventions (i.e., diet and physical activity) on the epigenome of the offspring. PubMed, Scopus and Cochrane-CENTRAL were screened until 8 July 2023. Only randomized controlled trials (RCTs) where a lifestyle intervention was compared to no intervention (standard care) were included. Outcome variables included DNA methylation, miRNA expression, and histone modifications. A qualitative approach was used for the consideration of the studies' results. Seven studies and 1765 mother-child pairs were assessed. The most common types of intervention were dietary advice, physical activity, and following a specific diet (olive oil). The included studies correlated the lifestyle and physical activity intervention in pregnancy to genome-wide or gene-specific differential methylation and miRNA expression in the cord blood or the placenta. An intervention of diet and physical activity in pregnancy was found to be associated with slight changes in the epigenome (DNA methylation and miRNA expression) in fetal tissues. The regions involved were related to adiposity, metabolic processes, type 2 diabetes, birth weight, or growth. However, not all studies showed significant differences in DNA methylation. Further studies with similar parameters are needed to have robust and comparable results and determine the biological role of such modifications.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.

The Impact of a Single Supervised Exercise Session in the Third Trimester of Pregnancy on the Physical Activity Levels of Pregnant Women-A Pilot Study.

BACKGROUND: Despite the numerous beneficial effects of physical exercise during pregnancy, the levels of physical activity remain low. The aim of the study is to investigate the impact of a single supervised physical exercise session on the overall physical activity levels of pregnant women. METHODS: During the third trimester, pregnant women attending our outpatient clinic were requested to assess their physical activity levels using the International Physical Activity Questionnaire (IPAQ). Additionally, they were invited to participate in a supervised 30 min mild-moderate-intensity aerobic exercise session (stationary bike ergometer) under the guidance of medical personnel. Subsequently, physical activity levels were reevaluated at the time of delivery. RESULTS: Prior to the intervention, 3 out of 50 (6%) women engaged in mild-moderate physical activity for 150 min per week, while 20 out of 50 (40%) women participated in mild-moderate activity for 15-30 min, twice a week. Following the intervention, these percentages increased to 10 out of 50 (20%) and 31 out of 50 (62%), respectively (p < 0.05). CONCLUSIONS: This pilot study suggests that a single exercise session supervised by medical personnel may significantly improve the low physical activity levels observed in pregnant women.

Prevalence of preeclampsia and uterine arteries resistance in the different phenotypes of gestational diabetes mellitus.

AIMS: This study aims to investigate the different phenotypes of Gestational Diabetes Mellitus (GDM), in correlation to preeclampsia and uterine arteries resistance. MATERIALS: This is a prospective cohort study including women with and without GDM per the IADPSG criteria. Three phenotypes of GDM emerged, women with only abnormal fasting (AF) glucose levels, women with only abnormal post-load (AP) glucose levels at 60' and/or 120' and women with abnormal combined (AC) fasting and post-load glucose values. All women underwent uterine arteries doppler examination in the three trimesters and assessed for preeclampsia development. Linear regression was used to express the trajectories of uterine arteries resistance throughout the pregnancy. RESULTS: 6928 pregnant women were included, 5274 without GDM and 1654 with GDM. 546, 781 and 327 of GDM pregnancies presented with AF, AP and AC phenotypes respectively. Prevalence of preeclampsia was 17.9%, 26.8% and 30% in the AF, AP and AC phenotypes respectively (p < 0.001). In women who developed preeclampsia, AC phenotype presented with statistically different trajectory of Uterine Arteries Pulsatility Index Percentiles b = 0.129 than women without GDM and women with AP GDM phenotype b = -0.015 and b = -0.016 respectively. CONCLUSIONS: The combined abnormal phenotype presents with the highest rate of preeclampsia and the most distinct pattern of uterine arteries resistance.

Pregnancy physical activity questionnaire: Translation and cross-cultural adaptation of a Greek version.

OBJECTIVE: The aim of this study was to translate and adapt the Pregnancy Physical Activity Questionnaire (PPAQ) into Greek culture. STUDY DESIGN: The procedure followed to translate the PPAQ included the stages: forward translation, synthesis, backward translation and an expert committee review. Members of the research team discussed ambiguities, discordances and equivalence at each stage. Then, the pre-final Greek version of the PPAQ was pre-tested on 46 pregnant women; a quantitative and qualitative analysis was conducted. RESULTS: Few modifications were done to the original PPAQ, in order to ensure cultural adaptation and clinical implementation. Appropriate changes to the international metric units were done. In addition, two items have been modified to achieve relevance with Greek culture. Two items were merged into one and three items were splitted, which maintained their initial meaning. Those changes were made to match the energy expenditure compendium update for physical activities. Participants at the pre-test had a mean age of 34,23 years, response time to the questionnaire varied between 5 and 10 min and there were no missing data. No difficulties or misunderstandings were reported by the participants during pre-testing. Thus, the research team agreed on the pre-final PPAQ Greek version. CONCLUSION: The final PPAQ Greek version indicated transcultural equivalence to the original PPAQ in English. It is also a unique questionnaire for assessing physical activity in Greek pregnant women and will be a useful tool in clinical routine.

Pregnancy outcomes in the different phenotypes of gestational diabetes mellitus based on the oral glucose tolerance test. A systematic review and meta-analysis.

AIMS: To assess the prevalence variation in pregnancy outcomes of the different phenotypes of gestational diabetes mellitus (GDM). MATERIALS: Cohort, cross sectional and case control studies grouping together pregnant women with GDM, based on the results of oral glucose tolerance test(OGTT) and reporting pregnancy outcomes in each group, were included. The primary outcomes were (i)large for gestational age and ii)hypertensive disorders of pregnancy (HDP). The secondary outcomes included (i)insulin treatment, ii)admission to neonatal intensive care unit, iii)preterm birth, iv)small for gestational age and v)caesarean section. The pooled proportions of the outcomes of interest were calculated for each phenotype. RESULTS: 8 studies (n = 20.928 women with GDM) were included. The pooled prevalence of LGA, HDP and insulin treatment were 20 %, 8 % and 24 % respectively in women with abnormal fasting plasma glucose,10 %, 6 % and 9 % respectively in women with abnormal post-load plasma glucose and 14 %,14 % and 30 % in women with abnormal combined plasma glucose. CONCLUSIONS: Pregnant women with abnormal fasting plasma glucose, present with the highest prevalence of LGA, while those with abnormal combined plasma glucose, present with the highest prevalence of HDP. Pregnant women with abnormal post-load plasma glucose present with the lowest need for insulin treatment.

The Efficacy of Probiotics, Prebiotics, and Synbiotics in Patients Who Have Undergone Abdominal Operation, in Terms of Bowel Function Post-Operatively: A Network Meta-Analysis.

BACKGROUND: Abdominal operations may lead to post-operative bowel dysfunction, while administration of probiotics, prebiotics and synbiotics may limit its manifestation. Τhe study aimed to assess the efficacy of probiotics, prebiotics and synbiotics in patients who undergone abdominal operation, in terms of bowel function post-operatively. METHODS: PubMed, Scopus, Cochrane Central Register of Controlled Trials (Central), Embase, US Registry of clinical trials, and sources of grey literature were searched. The relative effect sizes were estimated, and we obtained the relative ranking of the interventions using cumulative ranking curves. RESULTS: In total, 30 studies were included in the analysis. For the outcome of post-operative ileus, probiotics was superior to placebo/no intervention (relative risk, RR: 0.38; 95%CI: 0.14-0.98) with the highest SUCRA (surface under the cumulative ranking) value (92.1%). For time to first flatus, probiotics (MD: -0.47; 95%CI: -0.78 to -0.17) and synbiotics (MD: -0.53; 95%CI: -0.96 to -0.09) were superior to placebo/no intervention. For time to first defecation and for post-operative abdominal distension probiotics were superior to placebo/no intervention. For post-operative hospitalization days, synbiotics were superior to placebo/no intervention (MD: -3.07; 95%CI: -4.80 to -1.34). CONCLUSIONS: Administration of probiotics in patients who had undergone abdominal surgery reduced the prevalence of post-operative ileus, time to first flatus, time to first defecation, and prevalence of post-operative abdominal distension. Synbiotics reduce time to first flatus and post-operative hospitalization days.

Uterine Arteries Resistance in Pregnant Women with Gestational Diabetes Mellitus, Diabetes Mellitus Type 1, Diabetes Mellitus Type 2, and Uncomplicated Pregnancies.

BACKGROUND: The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries' pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. METHODS: This was a retrospective case-control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. RESULTS: Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). CONCLUSIONS: Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups.

Effect of Intraperitoneal Chemotherapy with Regorafenib on IL-6 and TNF-α Levels and Peritoneal Cytology: Experimental Study in Rats with Colorectal Peritoneal Carcinomatosis.

Cytoreductive surgery (CRS), combined with hyperthermic intraperitoneal chemotherapy, has significantly improved survival outcomes in patients with peritoneal carcinomatosis from colorectal cancer (CRC). Regorafenib is an oral agent administered in patients with refractory metastatic CRC. Our aim was to investigate the outcomes of intraperitoneal administration of regorafenib for intraperitoneal chemotherapy (IPEC) or/and CRS in a rat model of colorectal peritoneal metastases regarding immunology and peritoneal cytology. A total of 24 rats were included. Twenty-eight days after carcinogenesis induction, rats were randomized into following groups: group A: control group; group B: CRS only; group C: IPEC only; and group D: CRS + IPEC. On day 56 after carcinogenesis, euthanasia and laparotomy were performed. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) as well as peritoneal cytology were investigated. Groups B and D had statistically significant lower mean levels of IL-6 and TNF-α compared to groups A and C, but there was no significant difference between them. Both B and D groups presented a statistically significant difference regarding the rate of negative peritoneal cytology, when compared to the control group, but not to group C. In conclusion, regorafenib-based IPEC, combined with CRS, may constitute a promising tool against peritoneal carcinomatosis by altering the tumor microenvironment.

STORK: Collaborative Online Monitoring of Pregnancies Complicated with Gestational Diabetes Mellitus.

Background: A novel digital platform, named STORK, was developed in the COVID-19 pandemic when clinic visits were restricted. A study of its clinical use during the pandemic was conducted. The study aims to advance the state of the art in monitoring and care of pregnancies complicated with gestational diabetes mellitus (GDM) via online collaboration between patients and care providers. Methods: This study involved 31 pregnant women diagnosed with GDM and 5 physicians. Statistical comparisons were made in clinic-visit frequency and adverse outcomes between the STORK group and a historical control group of 32 women, compatible in size, demographics, anthropometrics and medical history. Results: The average number of submitted patient measurements per day was 3.6±0.4. The average number of clinic visits was 2.9±0.7 for the STORK group vs. 4.1±1.1 for the control group (p<0.05). The number of neonatal macrosomia cases was 2 for the STORK group vs. 3 for the control group (p>0.05); no other adverse incidents. Conclusions: The patient compliance with the pilot use of STORK was high and the average number of prenatal visits was reduced. The results suggest the general feasibility to reduce the average number of clinic visits and cost, with enhanced monitoring, case-specific adaptation, assessment and care management via timely online collaboration.

Different pregnancy outcomes according to the polycystic ovary syndrome diagnostic criteria: a systematic review and meta-analysis of 79 studies.

OBJECTIVE: To correlate the distinct diagnostic criteria of polycystic ovary syndrome (PCOS) with the development of maternal and neonatal complications. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Pregnant women with PCOS. INTERVENTION(S): Maternal and neonatal complications were compared among women with PCOS diagnosed with different criteria. MAIN OUTCOME MEASURE(S): The primary outcomes of gestational diabetes mellitus and preeclampsia (PE) were assessed for every diagnostic criterion. RESULT(S): Seventy-nine studies were included. Regarding gestational diabetes, the overall pooled prevalence was 14% (95% confidence interval [CI], 11%-18%; I2, 97%), reaching the highest level when polycystic ovarian morphology on ultrasound and 1 of the remaining 2 Rotterdam criteria (1/2 Rotterdam criteria) were used (18%; 95% CI, 13%-24%; I2, 20%) and the lowest when polycystic morphology on ultrasound and hyperandrogenism were used (3%; 95% CI, 0%-19%; I2, not applicable). Regarding PE, the overall pooled prevalence was 5% (95% CI, 4%-7%; I2, 82%). The highest PE prevalence was reported when the National Institutes of Health criteria were used (14%; 95% CI, 5%-33%; I2, 90%) and the lowest when menstrual irregularities and 1 of the 2 Rotterdam criteria were used (2%; 95% CI, 1%-3%; I2, not applicable). CONCLUSION(S): The prevalence of gestational diabetes mellitus in pregnant women with PCOS does not differ according to the criteria used; however, women diagnosed with PCOS per the National Institutes of Health criteria are at higher risk of PE.

The Effect of Physical Exercise on Oxidation Capacity and Utero-Placental Circulation in Pregnancies with Gestational Diabetes Mellitus and Uncomplicated Pregnancies, a Pilot Study.

Background: Gestational diabetes mellitus (GDM) is associated with aggravated oxidation capacity and utero-placental circulation, while aerobic exercise could improve both. The study aims to assess oxidation capacity and utero-placental circulation before and after a bout of aerobic exercise in GDM and uncomplicated pregnancies.; Methods: In this cross-sectional study, women with GDM (GDMs) and women with uncomplicated pregnancies(controls), underwent 30 min of moderate intensity cycling. Total antioxidant capacity (TAC), catalase activity (CAT), reduced glutathione (GSH), Uterine Arteries (UtA PI) and Umbilical Artery (UmA PI) pulsatility indexes were estimated prior-to, immediately after and one hour after exercise; Results: In each group, 25 pregnant women were included. In both groups, between prior-to and immediately after exercise, TAC and CAT increased, while GSH decreased, (p < 0.001). In GDMs, CAT was lower than controls at any time point (p < 0.05), while in GDMs delta(Δ) CAT (prior-to and immediately after exercise) was lower than controls (p = 0.003). In GDMs, UtA PI centiles decreased between prior-to and either immediately or one hour after exercise, while they did not change in controls. In GDMs, pre-conceptional BMI and weight gain predicted negatively ΔTAC (prior-to to one hour after exercise); Conclusions: Moderate intensity exercise bout improves oxidation capacity in GDM and uncomplicated pregnancies, although at a lesser extent in the former. Exercise leads to decreased UtA arteries resistance in women with GDM.

World Federation for Ultrasound in Medicine Review Paper: Incidental Findings during Obstetrical Ultrasound.

Although the prevalence of incidental findings revealed during an obstetric ultrasound examination is low, the findings may include adnexal and cervical masses, uterine or urinary congenital malformations, free fluid in the pouch of Douglas or tortuous vessels (varices). Adnexal masses are the most common finding and vary in imaging characteristics. They are mainly unilateral, cystic masses with a low risk of malignancy that are treated conservatively. The International Ovarian Tumor Analysis scoring models may be helpful in differentiating benign from malignant masses. For those masses >5 cm, follow-up is recommended, and resection could be considered to avoid risk of torsion, rupture and hemorrhage, which may compromise pregnancy outcome. Uterine masses such as fibroids are commonly diagnosed early in the first trimester and should be followed up during pregnancy to evaluate any changes. Transabdominal and transvaginal ultrasound is the first-line test for the diagnosis of such incidentalomas; however, magnetic resonance ultrasound may have a useful role in excluding malignancy potential. As a result of their low frequency and the lack of good evidence, there are no specific guidelines on the management of incidentalomas detected at obstetric scans. Their management should follow the related general guidelines for ovarian, cervical and uterine masses, with individualized management depending on the pregnancy status.