A novel ABCC9 variant in a Greek family with Cantu syndrome affecting multiple generations highlights the functional role of the SUR2B NBD1.

Cantu syndrome (CS) (OMIM #239850) is an autosomal dominant multiorgan system condition, associated with a characteristic facial phenotype, hypertrichosis, and multiple cardiovascular complications. CS is caused by gain-of-function (GOF) variants in KCNJ8 or ABCC9 that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (KATP) channels. A novel heterozygous ABCC9 variant, c.2440G>T; p.Gly814Trp, was identified in three individuals from a four generation Greek family. The membrane potential in cells stably expressing hKir6.1 and hSUR2B with p.Gly814Trp was hyperpolarized compared to cells expressing WT channels, and inside-out patch-clamp assays of KATP channels formed with hSUR2B p.Gly814Trp demonstrated a decreased sensitivity to ATP inhibition, confirming a relatively mild GOF effect of this variant. The specific location of the variant reveals an unrecognized functional role of the first glycine in the signature motif of the nucleotide binding domains in ATP-binding cassette (ABC) protein ion channels.

Effect of type III female genital mutilation on obstetric outcomes: A systematic review and meta-analysis.

Background: Controversial evidence suggests a potential association between female genital mutilation (FGM/C) and adverse obstetric outcomes, with type III FGM/C (infibulation) carrying the greatest risk. The aim of this systematic review and meta-analysis was to assess current rate of adverse obstetric outcomes in women with type III female genital mutilation and cutting (FGM/C; infibulation) delivering across different settings worldwide. Methods: We searched PubMed, Scopus, Embase, and ClinicalTrials.gov databases from inception to Jan 1, 2023. Studies were selected if they included the main outcome of postpartum haemorrhage (PPH) or secondary outcomes, which included major conditions affecting maternal-neonatal health during labour and delivery. DerSimonian-Laird random effects meta-analysis including pooled effect estimates with corresponding 95 % confidence intervals was performed. Heterogeneity was assessed using the I2 statistic. Meta regression for relevant covariates was performed when data on relevant confounders were available. The Newcastle-Ottawa scale (NOS) was used to assess quality of observational studies. The level of evidence was assessed with the GRADE method. Results: 14 observational studies including 15,320 type III FGM/C women and 59,347 controls were eligible. The risk for postpartum haemorrhage was significantly increased in type III FGM/C, in the main analysis (OR 1.83, 95 % CI 1.03 to 3.24, I2 = 93 %), in pooling of data adjusted for confounders (aOR 1.76, CI 1.42 to 2.17, I2 = 0 %), and in sensitivity analysis of higher quality studies with NOS≥7 (OR 2.76, CI 1.38 to 5.51, I2 = 95 %). Meta-regression showed that nulliparity was significantly and positively associated with postpartum haemorrhage. Similarly, analysis of data adjusted for confounders showed an increased risk of episiotomy in type III FGM/C (aOR 1.56, CI 1.03 to 2.35, I2 = 52 %). Sensitivity analysis of studies with NOS≥7 revealed a significant increase for episiotomy (OR 7.53, CI 1.19 to 47.54, I2 = 96 %), perineal tears (OR 4.24, CI 1.09 to 16.46, I2 = 66 %), prolonged second stage of labour (OR 5.19, 95 % CI 1.00 to 26.85, I2 = 66 %), and Apgar score less than 7 (OR 4.19, CI 1.64 to 10.70, I2 = 0 %). No difference was found regarding obstetric anal sphincter injuries and mode of delivery in these women. Deinfibulation achieved similar obstetric and neonatal outcomes to women who never had type III FGM. The overall quality of the studies was adequate (median NOS score: 7; IQR: 6-8), the level of evidence, according to the GRADE assessment, was low. Conclusions: These results consistently show an increased risk of adverse obstetric outcomes in women with FGM/C type III. Infibulation substantially increases the risk for PPH, particularly in nulliparae. Systematic Review registration: PROSPERO CRD42023421993.

Breaking Bad News During Prenatal Screening: The Role of Professional Obstetricians and Midwives in Greece.

INTRODUCTION: Breaking bad news is one of the most difficult responsibilities in medical practice. Although medical staff in clinical practice often encounter situations that necessitate the announcement of unpleasant news, there is a lack of training regarding their communication with patients and their families. Effective interaction between medical staff and pregnant women constitutes a crucial component of breaking down unpleasant news. This research aimed to investigate the knowledge and attitude of health professionals, particularly obstetricians, and midwives, regarding the announcement of bad news during prenatal screening. METHODS: The study was conducted between September 2017 and April 2018. One hundred professional obstetricians and midwives involved in fetal and prenatal medicine in Greece were part of the study. The study consisted of two parts: the first covered the emotional state of healthcare professionals during the announcement of unpleasant news, and the second covered the appropriate way to inform unpleasant results during prenatal testing. RESULTS: In this study, only 41% of the participants considered that they felt comfortable discussing issues related to the diagnosis of an unpleasant result during prenatal testing with the pregnant woman/patient, or her relatives, and 85% accepted that they had experienced feelings of sadness, anxiety, or guilt when announcing unpleasant results. Furthermore, 87% of the participants believed that the non-verbal communication component (eye contact, body language) plays an important role in breaking bad news. Finally, 65% considered that prolonged monitoring of the ultrasound screen during prenatal screening does not increase the anxiety of pregnant women when carried out for a better medical opinion. CONCLUSIONS: Delivering bad news during prenatal screening creates stress for the parents. As far as the ethical, cultural, psychological, and legal complicity of healthcare professionals is concerned, communicating unpleasant news has been a subject of discussion by many experts. It is important to understand the concerns of women regarding the risks of counseling.

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.

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.

Sentinel lymph node biopsy for breast cancer during pregnancy: A comprehensive update.

BACKGROUND: Pregnant patients diagnosed with breast cancer (PrBC) may receive substantially different treatments compared to general population, considering that certain treatment options cannot be applied during pregnancy due to their potential harmful effects to the foetus. Regarding the use of sentinel lymph node biopsy (SLNB) in pregnant patients, potential concerns include foetal harm from radiation exposure, possible teratogenic effects of blue dyes and maternal anaphylaxis to isosulfan. OBJECTIVE: The main objective of the present systematic review is to summarize and present current knowledge and up-to-date evidence about the safety and efficacy of SLNB in PABC. METHODS: MEDLINE, Google Scholar and UpToDate databases were searched up to 22 January 2023. Articles studying the safety and effectiveness of SLNB in patients for PrBC were eligible for inclusion in the present review. RESULTS: In total, 63 articles that met the inclusion criteria were included in this study. Forty-seven articles were strongly in favour of performing SLNB in PABC, 4 articles were partially in favour, 10 articles were strongly against and 2 articles were partially against performing SLNB in PABC. Sub-categorization based on type of study showed that the majority of studies in favour were of higher level of evidence than those against. Furthermore, there were overall 12 studies reporting on outcomes. There were overall 382 women with PrBC that underwent SLNB. Full data were reported for 237 cases. Overall live birth rate was 95.8%, while overall neonatal complication rate was 3.4%. No case of maternal side effects or anaphylactic reaction, maternal death, stillbirth and neonatal death was reported (0%). CONCLUSIONS: Sentinel lymph node biopsy seems to be safe and effective technique for breast cancer during pregnancy.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

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.

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.

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 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.

Third-trimester cervical length assessment for the prediction of spontaneous late preterm birth.

BACKGROUND: The usefulness of cervical length (CL) measurement in asymptomatic pregnancies in the third trimester of pregnancy is not certain. Therefore, the objective of this study was to assess the performance of CL measurement at 31-34 gestational weeks for the prediction of spontaneous late preterm birth (PTB). MATERIALS AND METHODS: This was a prospective study of women with a singleton pregnancy, who had their routine third-trimester scan at 31-34 weeks. The CL was measured transvaginally and was tested, together with maternal demographic and obstetric parameters, for the prediction of late PTB (34 to 36 weeks), using logistic regression and ROC curve analysis. RESULTS: Overall, from a population of 1003 women that consented to participate in the study, 42 (4.2%) delivered at 34-36 gestational weeks. A significant association was identified between gestational age at birth and CL (rho = 0.182, p < .001), and there were significant differences in the CL between cases of late preterm and term births (p < .001). Cervical length alone could predict 17% of late PTB for a 10% false positive rate, corresponding to 22 mm. A model combining CL with parity and method of conception can identify 35% of pregnancies resulting in late PTB, at a false positive rate of 10% (AUC: 0.750; 95% CI: 0.675-0.824). CONCLUSIONS: CL assessment at 31-34 gestational weeks may contribute to the prediction of late PTB when combined with maternal characteristics.

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.

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 expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review.

The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.

Pregnancy outcome of confined placental mosaicism: meta-analysis of cohort studies.

OBJECTIVE: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls. DATA SOURCES: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved. STUDY ELIGIBILITY CRITERIA: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture. METHODS: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I2 statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319). RESULTS: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I2=72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I2=0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I2= 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed. CONCLUSION: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance.

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.

Physical Health, Media Use, Stress, and Mental Health in Pregnant Women during the COVID-19 Pandemic.

Background: The COVID-19 pandemic has led to significant changes in the care of pregnant women and their fetuses. Emerging data show elevated depression and anxiety symptoms among pregnant women. Aims: The purpose of this article is to investigate the psychological and behavioral impact of the COVID-19 pandemic on pregnant women in Greece during the first national lockdown. Methods: We used a cross-sectional, anonymous survey to collect data in two fetal medicine clinics in the largest urban centers of Greece during the months of April and May 2020. The questionnaire was largely based on the CoRonavIruS Health Impact Survey (CRISIS), and assessed sociodemographic characteristics, general health and obstetric data and COVID-19-related worries and life changes. Mood symptoms, substance use and lifestyle behaviors were assessed at two time points (3 months prior to the pandemic and the 2 weeks before taking the survey), while perceived stress was measured with the perceived stress scale (PSS-14). Results: A total of 308 pregnant women (Mage = 34.72), with a mean gestation of 21.19 weeks participated in the study. Over one-third of the women found COVID-19 restrictions stressful, and their highest COVID-19-related worry was having to be isolated from their baby. Mean PSS-14 score was 21.94, suggesting moderate stress. The strongest predictors of stress were physical and mental health status before COVID-19 and having experienced a stressful life event during their pregnancy. Compared to 3 months before the pandemic, women reported higher scores on mood symptoms (p < 0.001), TV use (p = 0.01) and social media use (p = 0.031) in the last 2 weeks before taking the survey. Conclusion: Our study provides important preliminary evidence of the negative impact of the COVID-19 pandemic and the lockdown on pregnant women's well-being and functioning.

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.