Prenatal identification of invasive placentation using ultrasound in women with placenta previa and prior cesarean delivery.

OBJECTIVE: To evaluate the performance of ultrasound for antenatal identification of invasive placentation in women with placenta previa in the setting of prior cesarean delivery. STUDY DESIGN: This was a multicenter, retrospective, cohort study. Singleton pregnancies at risk of placenta accreta because of persistent placenta previa in the setting of prior cesarean delivery who delivered at four centers, from January 2010 to May 2020, were included in the study. For this study, pregnancies with diagnosis of accreta, increta, or percreta were considered under the umbrella term of placenta accreta. All women with placenta previa identified in the second trimester had a follow-up ultrasound at 32-34 weeks. Only those with prior cesarean delivery were considered at risk of placenta accreta. Women were considered with suspected accreta in case of suspected prenatal ultrasound. Women with suspected placenta accreta had delivery planned via cesarean hysterectomy at 34+0 - 35+6 weeks, without any attempt to remove the placenta. The primary endpoint of the study was the performance of ultrasound for antenatal identification of invasive placentation. The following ultrasound signs were evaluated: placenta lacunae; loss of clear space; increased vascularity between myometrium and placenta; intracervical lake; rail sign; uterovesical hypervascularity; increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region; and disruption of bladder-myometrial interface. RESULTS: 180 singleton pregnancies with placenta previa in the setting of prior cesarean delivery were identified. Of them, 155 (86.1%) had antenatal suspected placenta accreta based on ultrasound, having at least one sign of invasive placentation. Of the 155 suspected cases, 99 had confirmed placenta accreta at the time of delivery. Among the 99 cases of confirmed placenta accreta, all of them had at least one sign of invasive placentation at ultrasound. Among the 81 cases with placenta previa, prior cesarean delivery, without placenta accreta, 25/81 (30.9%) had ultrasound scan negative for sign of invasive placentation, and 56/81 (69.1%) had at least one sign of invasive placentation). In particular, 12/81 (14.8%) had placenta lacunae, 16/81 (19.8%) had loss of clear space, 20/81 (24.7%) had increased vascularity between myometrium and placenta, 9/81 (11.1%) had intracervical lake, 14/81 (17.3%) had rail sign, 14 (17.3%) had uterovesical hypervascularity, 5/81 (6.2%) had increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region, 8/81 (9.9%) had disruption of bladder-myometrial interface. In the group of women with confirmed placenta accreta, the most common sign recorded was the disruption of bladder-myometrial interface, being recorded in 88/99 women. Disruption of bladder-myometrial interface had the highest sensitivity in detection placenta accreta. Women with disruption of bladder-myometrial interface at ultrasound had 73-fold increase in the risk of placenta accreta compared to those who did not. CONCLUSION: Prenatal ultrasound has an excellent diagnostic accuracy in identifying invasive placentation in women with placenta previa and prior cesarean delivery.

Sonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Controlled ovarian stimulation leads to cardiovascular changes in patients undergoing in vitro fertilization.

OBJECTIVE: To study hemodynamic changes along controlled ovarian stimulation in women undergoing in vitro fertilization. STUDY DESIGN: Prospective observational cohort study conducted at Mother and Child Department of University Hospital Federico II, in Naples, Italy, between April 2021 and July 2022. Sixty-eight infertile patients undergoing controlled ovarian stimulation with gonadotropin, antagonist protocol and a fresh embryo transfer were included. Haemodynamic assessment was carried out using UltraSonic Cardiac Output Monitor at baseline (T1), estradiol peak (T2), fresh embryo-transfer day (T3). To evaluate relationships between quantitative variables and groups a Student T test for independent data was assessed. One-way analysis of variance (ANOVA) was used to determine the differences between the means of three time points (T1, T2 and T3) for quantitative variables. A mixed-model analysis of variance (ANOVA) was used to determine the differences between groups, among time points (T1, T2 and T3). RESULTS: Sixty-eight patients were included. Significant differences over the three time points have been observed for CO (f = 3.78 l/min; p = 0.025), SVI (f = 3.56 ml/m2;p = 0.013), and RSVI (f = 4.84 dscm-5 m2; p = 0.009). No significant differences in trends have been found between beta hCG positive and beta hCG negative groups. There were no significant differences in maternal hemodynamic parameters at time-point T3 between patients treated with hCG 10,000 UI and with Triptorelin. Patients considered at increased risk of hyperstimulation reported a significant increase in SVI at baseline (26.9 ± 9.0 mL/m2 vs 21.9 ± 7.0 mL/m2; p = 0.010). CONCLUSION: According to the results of our study, during controlled ovarian stimulation with antagonist protocol, patients undergo significant changes in maternal cardiovascular parameters over a very short period.

Ultrasound prediction of fetal macrosomia in pregnancies complicated by diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of ultrasound in identifying fetuses with macrosomia in pregnancies complicated by gestational or pregestational diabetes. METHODS: Medline, Embase and Cochrane databases were searched. Inclusion criteria were singleton pregnancies complicated by diabetes undergoing third-trimester ultrasound evaluation. The index test was represented by ultrasound estimation of fetal macrosomia (estimated fetal weight EFW or abdominal circumference AC >90th or 95th percentile). Subgroup analyses were also performed. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating characteristics model. RESULTS: Twenty studies were included in the systematic review including 8,530 pregnancies complicated by diabetes. Ultrasound showed an overall moderate accuracy in identifying fetuses with macrosomia with a sensitivity of 71.2 % (95 % CI 63.1-78.2), a specificity of 88.6 % (95 % CI 83.9-92.0). The interval between ultrasound and birth of two weeks showed the highest sensitivity and specificity (71.6 %, 95 % CI 47.9-87.3 and 91.7, 95 % CI 86.2-95.5). EFW sensitivity and specificity were 76.6 % (95 % CI 70.1-82.3) and 82.9 % (95 % CI 80.9-84.8), while AC 84.8 % (95 % CI 78.2-90.0) and 73.7 % (95 % CI 71.0-76.4). CONCLUSIONS: Ultrasound demonstrates an overall good diagnostic accuracy in detecting fetal macrosomia in pregnancies with diabetes.

Maternal Reassurance, Satisfaction, and Anxiety after First-Trimester Screening for Aneuploidies: Comparison between Contingent Screening and Universal Cell-Free DNA Testing.

BACKGROUND: This study aims to evaluate maternal reassurance, satisfaction, and anxiety after two different strategies for the first-trimester screening for aneuploidies. METHODS: Patients between 11 + 3 and 13 + 6 weeks of gestation attending the first-trimester screening at Department of Mother and Child, University Hospital Federico II, Naples, Italy have been recruited and randomly allocated to contingent screening or universal cell-free fetal DNA testing (cffDNA). Questionnaires to measure reassurance, satisfaction, and anxiety have been filled twice: (Q1) after randomization and (Q2) after receiving results. Anxiety was measured by an Italian-version short form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI); child-related anxiety was measured by the 11-item Pregnancy-Related Anxiety Questionnaire-Revised Regardless of Parity (PRAQ-R2 scale); fear of bearing a physically or mentally handicapped child was measured considering only four items (item 4, 9, 10, and 11) of the PRAQ-R2 scale. RESULTS: 431 patients were recruited: 205 (49%) were randomized in the contingent screening arm, 226 (51%) in the cfDNA arm. Maternal reassurance, satisfaction, and anxiety were not different in the two groups. CONCLUSION: A contingent screening for aneuploidies in the first trimester seems able to ensure the same maternal reassurance and satisfaction as a cfDNA analysis in the low-risk population and to not affect maternal anxiety.

Unveiling therapeutic potentials and exploring maternal-fetal health benefits of metformin in pregnancy: A scoping review.

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre-eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence-based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management.

Exploring the Relationship between Neuroticism and Perinatal Depressive Symptoms: Findings from a 2-Year, Multicenter Study in Italy.

Neuroticism is a personality trait associated with the risk of affective disorders and perinatal depression. We investigated the relationship between different levels of neuroticism, psychological characteristics, and depressive symptoms in a sample of pregnant women (N = 2631) who accessed the gynecology departments in the Puglia Region (Italy) from July 2020 to November 2022. Women were assessed for depressive symptoms and associated risk factors in their third trimester of pregnancy (T0) and after childbirth (T1), and followed-up at 6 months and 1 year after delivery if presenting signs of depression (T2-T3). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen depressive symptoms, and neuroticism was assessed through the subscales of the NEO Five Factor Inventory. Standardized measures of resilience, coping strategies, partner attachment, and quality of life were also employed. Higher levels of neuroticism were significantly associated with: (a) higher scores on the EPDS; (b) higher anxiety in the experience of close relationships; (c) lower psychological wellbeing; (d) lower levels of resilience; (e) lower levels of active coping; and (f) higher levels of self-blame. Our findings may suggest that neuroticism is a specific associated factor of perinatal depression and should be routinely assessed in the clinical screening of pregnant women in order to promote an early referral to psychological or psychiatric support services.

A national survey on current practice of ultrasound in labor ward.

OBJECTIVES: Use of ultrasonography has been suggested as an accurate adjunct to clinical evaluation of fetal position and station during labor. There are no available reports concerning its actual use in delivery wards. The aim of this survey was to evaluate the current practice regarding the use of ultrasonography during labor. METHODS: A questionnaire was sent to members of the Italian Society of Ultrasound in Obstetrics and Gynecology employed in delivery wards. The qFeuestionnaire was made up of 22 questions evaluating participant characteristics and the current use of ultrasound in labor in their hospital of employment. The answers were grouped according to participant characteristics. RESULTS: A total of 200 participants replied. Ultrasound was considered useful before an operative vaginal delivery by 59.6 % of respondents, while 51.8 and 52.5 % considered it useful in the management of prolonged first and second stages of labor, respectively. The major indication for ultrasound use during labor was the assessment of fetal occiput position. The major difficulties in its application were the perceived lack of training and the complexity of the ultrasound equipment use. Participants that reported fewer difficulties were those employed in hospitals with a higher number of deliveries or having delivery units with more years of experience using ultrasound in labor, or those who had attended specific training courses. CONCLUSIONS: The results indicate that, despite the reported evidence of a higher accuracy of ultrasound compared to clinical evaluation in assessing fetal position and station, its use is still limited, even amongst maternal-fetal medicine practitioners specialized in ultrasonography.

Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. OBJECTIVE: To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. STUDY DESIGN: This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. RESULTS: A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. CONCLUSION: The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1S expression.

Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1S). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S. These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

The impact of body mass index on the pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study.

BACKGROUND: Body Mass Index (BMI) is an informative factor on body fatness which has been associated to higher levels of Perinatal Depression (PD) and complications during pregnancy. We aimed to explore the impact of pre-pregnancy and postnatal BMI on the risk of Perinatal Depression and pregnancy outcomes among women recruited at their third trimester of pregnancy. METHODS: We report on findings from a large multi-centre study conducted in the South of Italy and involving 1611 women accessing three urban gynaecological departments from July to November 2020. Pregnant women were assessed at their third trimester of pregnancy (T0) and after the childbirth (T1) ;The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time (T0 and T1) as well as other standardized measures for neuroticism, resilience, and quality of life at baseline. BMI (T0 and T1) and other socio-demographic and clinical characteristics have been collected. RESULTS: Over-weight and obesity (higher levels of BMI) were associated with higher risk of PD (higher scores of EPDS), higher neuroticism and poorer subjective psychological well-being among enrolled women. Also, obesity and over-weight were associated with lower education, higher number of physical comorbidities, medical treatments and complications during pregnancy. CONCLUSIONS: Over-weight and obesity may impact on mental health and pregnancy outcome of women enrolled. Psycho-educational interventions aimed to improve the management of physical and emotional issues may reduce the risk of PD and complications during pregnancy.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.

BACKGROUND: Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. METHODS: Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. RESULTS: We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). CONCLUSIONS: In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

Coping as a Mediator between Attachment and Depressive Symptomatology Either in Pregnancy or in the Early Postpartum Period: A Structural Equation Modelling Approach.

Peripartum depression (PPD) is a major complication of pregnancy, and numerous risk factors have been associated with its onset, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women's attachment style and depressive symptomatology in pregnancy and one week after giving birth in a large sample of women (N = 1664). Our hypothesis was that the relationship between anxious and avoidant attachment and depressive symptomatology would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), and Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment also has an indirect significant effect on postpartum depressive symptomatology through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depressive symptoms. Our findings revealed that not only is it important to consider attachment in understanding peripartum depressive symptomatology, but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. STUDY DESIGN: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. CONCLUSION: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

The Role of Plasma Cells as a Marker of Chronic Endometritis: A Systematic Review and Meta-Analysis.

Chronic endometritis (CE) is the persistent inflammation of the endometrial lining associated with infertility and various forms of reproductive failures. The diagnosis of CE is based on the histological evidence of stromal plasma cells; however, standardized methods to assess plasma cells are still lacking. In the present paper, we aimed to determine the most appropriate plasma cell threshold to diagnose CE based on pregnancy outcomes. Three electronic databases were searched from their inception to February 2022 for all studies comparing pregnancy outcomes between patients with CE and patients without CE. The relative risk (RR) of pregnancy, miscarriage, and/or live birth rates were calculated and pooled based on the plasma cell threshold adopted. A p-value < 0.05 was considered significant. Nine studies adopting different thresholds (1 to 50 plasma cells/10 HPF) were included. In the meta-analysis, we only found a significant association between miscarriage rate and a plasma cell count ≥ 5/10 HPF (RR = 2.4; p = 0.007). Among studies not suitable for meta-analysis, CE showed an association with worsened pregnancy only when high thresholds (10 and 50/10 HPF) were adopted. In conclusion, our study suggests that the presence of plasma cells at low levels (<5/10 HPF) may not predict worsened pregnancy outcomes. Based on these findings, a threshold of ≥5 plasma cells/10 HPF may be more appropriate to diagnose CE.

The impact of COVID-19 pandemic on obstetrics and gynecology hospitalization rate and on reasons for seeking emergency care: a systematic review and meta-analysis.

BACKGROUND: During the lockdown due to COVID-19 pandemic, utilization of emergency care units has been reported to be reduced for obstetrical and gynaecological reasons. The aim of this systematic review is to assess if this phenomenon reduced the rate of hospitalizations for any reason and to evaluate the main reasons for seeking care in this subset of the population. METHODS: The search was conducted using the main electronic databases from January 2020 to May 2021. The studies were identified with the use of a combination of: "emergency department" OR "A&E" OR "emergency service" OR "emergency unit" OR "maternity service" AND "COVID-19" OR "COVID-19 pandemic" OR "SARS-COV-2" and "admission" OR "hospitalization". All the studies that evaluated women going to obstetrics & gynecology emergency department (ED) during the COVID-19 pandemic for any reason were included. RESULTS: The pooled proportion (PP) of hospitalizations increased from 22.7 to 30.6% during the lockdown periods, in particular from 48.0 to 53.9% for delivery. The PP of pregnant women suffering from hypertensive disorders increased (2.6 vs 1.2%), as well as women having contractions (52 vs 43%) and rupture of membranes (12.0 vs 9.1%). Oppositely, the PP of women having pelvic pain (12.4 vs 14.4%), suspected ectopic pregnancy (1.8 vs 2.0), reduced fetal movements (3.0 vs 3.3%), vaginal bleeding both for obstetrical (11.7 vs 12.8%) and gynecological issues (7.4 vs 9.2%) slightly reduced. CONCLUSION: During the lockdown, an increase in the proportion of hospitalizations for obstetrical and gynecological reasons has been registered, especially for labor symptoms and hypertensive disorders.

Do Anti-SARS-CoV-2 Monoclonal Antibodies Have an Impact on Pregnancy Outcome? A Systematic Review and Meta-Analysis.

Monoclonal antibodies (mAbs) have been used as a rescue strategy for pregnant women affected by COVID-19. To explore its impact on maternal-fetal health, we included all observational studies reporting maternal, fetal, delivery and neonatal outcomes in women who underwent mAbs infusion for COVID-19. Primary outcome was the percentage of preterm delivery. We used meta-analyses of proportions to combine data for maternal, fetal, delivery and neonatal outcome of women treated with mAbs for COVID-19 and reported pooled proportions and their 95% confidence intervals (CIs) for categorical variables or mean difference (MD) with their 95% confidence intervals for continuous variables. Preterm birth was observed in 22.8% of cases (95% CI 12.9-34.3). Fetal distress was reported in 4.2% (95% CI 1.6-8.2). Gestational hypertension and pre-eclampsia were observed in 3.0% (95% CI 0.8-6.8) and 3.4% (95% CI 0.8-7.5) of cases, respectively. Fetal growth restriction was observed in 3.2% of fetuses (95% CI 0.8-7.0). Secondary prophylaxis with mAbs is currently considered the best treatment option for people with mild to moderate COVID-19 disease. More attention should be paid to infants born from mothers who were treated with mAbs, for the risk of immunosuppression.

The role of ultrasound in the diagnosis and management of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of death or severe morbidity for the mother after delivery. As a consequence healthcare staff working in the delivery room should be trained to perform a prompt diagnosis and adequate management of PPH. Uneventful outcome is induced correct identification of the underlying cause of hemorrhage. Ultrasound is a promising technique for the prompt diagnosis of PPH etiology. Indeed, it is easily available, with relatively low cost, not using ionizing radiation, and can be used in different settings including the labor room, the operating theater and at the bedside of an affected women. In order to be effective Obstetricians should have an adequate knowledge of postpartum ultrasonography. In this article, we will review the sonographic findings occurring in PPH, in the differential diagnosis of the underlying cause of hemorrhage, that include retained placenta, morbidly adherent placenta, rupture of the uterus uterine, vascular anomalies of the uterine arteries and uterine inversion. We will also provide an algorithm to manage PPH according to the ultrasonographic findings.