Use of elexacaftor/tezacaftor/ivacaftor combination in pregnancy.

INTRODUCTION: Management of cystic fibrosis has recently stepped forward with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, although data on potential adverse effects are lacking for many categories of patients, such as pregnant women. METHODS: We report one of the first reports on the outcome of pregnancy in a woman treated with Elexacaftor/Tezacaftor/Ivacaftor during the second and third trimester of pregnancy, showing a significant improvement of respiratory status, compared with the first trimester when the medication was discontinued due to unknown and, therefore, potential teratogenic effects. Also, we performed the review of the existing literature on the topic. RESULTS: The course of pregnancy was uneventful, with reference to major obstetric complications, and the patient delivered a healthy neonate. These results were similar to those coming from other short series of pregnant women affected by cystic fibrosis and treated with CFTR modulators during pregnancy. CONCLUSIONS: Thus, despite the lack of evidence on the topic, the use of Elexacaftor/Tezacaftor/Ivacaftor in pregnancy seems to be apparently not associated with major adverse events, thus opening optimistic scenarios in terms of management of these patients.

Three-tiered fetal heart rate interpretation system and adverse neonatal and maternal outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the rate of adverse neonatal or maternal outcomes in parturients with fetal heart rate tracings categorized as I, II or, III within the last 30 to 120 minutes of delivery. DATA SOURCES: The MEDLINE Ovid, Scopus, Embase, CINAHL, and Clinicaltrials.gov databases were searched electronically up to May 2022, using combinations of the relevant medical subject heading terms, keywords, and word variants that were considered suitable for the topic. STUDY ELIGIBILITY CRITERIA: Only observational studies of term infants reporting outcomes of interest with category I, II, or III fetal heart rate tracings were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The coprimary outcome was the rate of either Apgar score <7 at 5 minutes or umbilical artery pH <7.00. Secondary outcomes were divided into neonatal and maternal adverse outcomes. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Random-effect meta-analyses of proportions were used to estimate the pooled rates of each categorical outcome in fetal heart rate tracing category I, II, and III patterns, and random-effect head-to-head meta-analyses were used to directly compare fetal heart rate tracings category I vs II and fetal heart rate tracing category II vs III, expressing the results as summary odds ratio or as mean differences with relative 95% confidence intervals. RESULTS: Of the 671 articles reviewed, 3 publications met the inclusion criteria. Among them were 47,648 singletons at ≥37 weeks' gestation. Fetal heart rate tracings in the last 30 to 120 minutes before delivery were characterized in the following manner: 27.0% of deliveries had category I tracings, 72.9% had category II tracings, and 0.1% had category III tracings. A single study, which was rated to be of poor quality, contributed 82.1% of the data and it did not provide any data for category III fetal heart rate tracings. When compared with category I fetal heart rate tracings (0.74%), the incidence of an Apgar score <7 at 5 minutes were significantly higher among deliveries with category II fetal heart rate tracings (1.51%) (odds ratio, 1.56; 95% confidence interval, 1.23-1.99) and among those with category III tracings (14.63%) (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). When compared with category II tracings, category III tracings also had a significantly higher likelihood of a low Apgar score at 5 minutes (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). The incidence of an umbilical artery pH <7.00 were similar among those with category I and those with category II tracings (0.08% vs 0.24%; odds ratio, 2.85; 95% confidence interval, 0.41-19.55). When compared with category I tracings, the incidence of an umbilical artery pH <7.00 was significantly more common among those with category III tracings (31.04%; odds ratio, 161.56; 95% confidence interval, 25.18-1036.42); likewise, when compared with those with category II tracings, those with category III tracings had a significantly higher likelihood of having an umbilical artery pH <7.00 (odds ratio, 42.29; 95% confidence interval, 14.29-125.10). Hypoxic-ischemic encephalopathy occurred with similar frequency among those with categories I and those with category II tracings (0 vs 0.81%; odds ratio, 5.86; 95% confidence interval, 0.75-45.89) but was significantly more common among those with category III tracings (0 vs 18.97%; odds ratio, 61.43; 95% confidence interval, 7.49-503.50). Cesarean delivery occurred with similar frequency among those with category I (13.41%) and those with category II tracings (11.92%) (odds ratio, 0.87; 95% confidence interval, 0.72-1.05) but was significantly more common among those with with category III tracings (14.28%) (odds ratio, 3.97; 95% confidence interval, 1.62-9.75). When compared with those with category II tracings, cesarean delivery was more common among those with category III tracings (odds ratio, 4.55; 95% confidence interval, 1.88-11.01). CONCLUSION: Although the incidence of an Apgar score <7 at 5 minutes and umbilical artery pH <7.00 increased significantly with increasing fetal heart rate tracing category, about 98% of newborns with category II tracings do not have these adverse outcomes. The 3-tiered fetal heart rate tracing interpretation system provides an approximate but imprecise measurement of neonatal prognosis.

Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses with and without cardiac malformations: Literature review.

Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus Vaccination in Pregnancy: Implications for Maternal and Infant Immunity.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Identification and Validation of miR-222-3p and miR-409-3p as Plasma Biomarkers in Gestational Diabetes Mellitus Sharing Validated Target Genes Involved in Metabolic Homeostasis.

Gestational diabetes mellitus (GDM) causes both maternal and fetal adverse outcomes. The deregulation of microRNAs (miRNAs) in GDM suggests their involvement in GDM pathogenesis and complications. Exosomes are extracellular vesicles (EVs) of endosomal origin, released via exocytosis into the extracellular compartment. Through EVs, miRNAs are delivered in distant target cells and are able to affect gene expression. In this study, miRNA expression was analyzed to find new miRNAs that could improve GDM classification and molecular characterization. MiRNA were profiled in total plasma and EVs in GDM patients and normal glucose tolerance (NGT) women. Samples were collected at third trimester of gestation from two diabetes centers. MiRNA expression was profiled in a discovery cohort using the multiplexed NanoString nCounter Human v3 miRNA. Validation analysis was performed in a second independent cohort using RT-qPCR. A set of miRNAs resulted to be differentially expressed (DE) in total plasma and EVs in GDM. Among them, total plasma miR-222-3p and miR-409-3p were validated in the independent cohort. MiR-222-3p levels correlated with fasting plasma glucose (FPG) (p < 0.001) and birth weight (p = 0.012), whereas miR-409-3p expression correlated with FPG (p < 0.001) and inversely with gestational age (p = 0.001). The major validated target genes of the deregulated miRNAs were consistently linked to type 2 diabetes and GDM pathophysiology. MiR-222-3p and miR-409-3p are two circulating biomarkers that could improve GDM classification power and act in the context of the molecular events leading to the metabolic alterations observed in GDM.

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.

Pregnancy outcome in systemic lupus erythematosus patients: a monocentric cohort analysis.

OBJECTIVE: SLE is an autoimmune disease, mainly affecting women of childbearing age, with possible impact on pregnancy. In this study, we evaluated pregnancy outcomes in all pregnant patients affected by SLE, followed in the context of a rheumatology/gynaecology multi-disciplinary team. METHODS: Since 2008, we evaluated 70 consecutive pregnancies occurring in 50 SLE patients referring to the Lupus Clinic of Sapienza University of Rome; as controls we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases. RESULTS: By comparing SLE patients and controls, we did not find differences in terms of pregnancy outcomes, except for the occurrence of small for gestational age, which was significantly higher in the SLE group (22.8% vs 11%, P =0.003). Small for gestational age was associated with the positivity for anti-dsDNA, anti-Sm and anti-RNP (P =0.009, P =0.02, P =0.002, respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium periods (44.3%). Flare during pregnancy was associated with anti-SSA (P =0.02), while puerperium relapse with previous MMF treatment (P =0.01) and haematological flare during pregnancy (P =0.03). CONCLUSION: The present study confirms how pre-gestational counselling and a multi-disciplinary approach could result in positive pregnancy outcomes for SLE patients. The high percentage of disease relapse justifies even more the need for multi-disciplinary management.

Breastfeeding in women affected by systemic lupus erythematosus: Rate, duration and associated factors.

OBJECTIVE: Breastfeeding is a crucial moment for both mothers and child, providing a beneficial effect on child survival, nutrition, development and on maternal health. Despite the prevalent involvement of childbearing women in systemic lupus erythematosus (SLE), breastfeeding is still a neglected topic. The objective of this study was to evaluate breastfeeding frequency, duration and associated factors in SLE women. METHODS: We consecutively enrolled SLE pregnant women reporting demographic, clinical, serological, gynaecological and obstetric data. Breastfeeding experience was evaluated by using a specific questionnaire. Disease activity was assessed before and during pregnancy as well as during postpartum. RESULTS: A total of 57 pregnancies in 43 SLE women were included in the present study. In almost all the pregnancies, mothers planned to breastfeed their child (96.5%) and forty-one (71.9%) actually did breastfeed. The median time of breastfeeding was 3 months (IQR 7). Non-breastfeeding women showed a more frequent caesarean section (p = 0.0001), IUGR occurrence (p = 0.004) and disease relapse (p = 0.0001) after pregnancy. When comparing patients according with breastfeeding duration (cut-off 6 months), we found a significant more frequent smoking habitus (p = 0.02), caesarean section (p = 0.009), and joint involvement during postpartum (p = 0.0001) in women breastfeeding for less than or equal to 6 months, together with higher median BMI (p = 0.0001). Moreover, breastfeeding duration was positively associated with disease duration and hydroxychloroquine (HCQ) treatment during disease history, pregnancy and postpartum. CONCLUSIONS: SLE women didn't show lower breastfeeding rate in comparison with general population but they presented higher prevalence of early discontinuation within three months. Early interruption was positively associated with smoking, BMI, joint involvement; meanwhile disease duration and HCQ treatment during postpartum were positively associated with a longer breastfeeding duration.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

INTRODUCTION: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. METHODS: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). RESULTS: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. CONCLUSION: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

Hypoplasia of the Corpus Callosum: A Single Center Experience and a Concise Literature Review.

AimCorpus callosum hypoplasia is described as a fully formed corpus callosum with reduced thickness. Our purpose is to evaluate the current knowledge about this anomaly including it's effect on the neurodevelopmental outcome and to report our single center experience. Methods: PubMed, Medline and reference lists were searched using combinations of these terms: "Hypoplasia of corpus callosum and prenatal diagnosis" and "neurodevelopmental outcome". Results: Eleven studies were included, with a final population of 48 patients (45 cases from literature plus 3 of our own cases). Hypoplasia of the corpus callosum was detected by ultrasound scan alone in 77% of cases: magnetic resonance confirmed the ultrasound suspicion in the remaining 23% of cases. Isolated form was detected in 31% cases. Adverse fetal outcomes occurred in 62% of cases, while 38% of cases were born alive. The neurodevelopmental outcome was found to be normal in 33% of cases. Conclusion: Antenatal detection of corpus callosum hypoplasia remains challenging. Counseling is difficult because neurodevelopmental outcomes are variable.

Delayed versus immediate pushing in the second stage of labor in women with neuraxial analgesia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials was to evaluate the effect of delayed versus immediate pushing in the second stage of labor on mode of delivery and other outcomes in women with neuraxial analgesia. DATA SOURCES: The research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and the Cochrane Library as electronic databases, from the inception of each database to August 2019. No restrictions for language or geographic location were applied. STUDY ELIGIBILITY CRITERIA: Selection criteria included only randomized controlled trials in pregnant women randomized to either delayed or immediate pushing during the second stage of labor. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was mode of delivery. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals using the random effects model of DerSimonian and Laird. An I2 (Higgins I2) value of greater than 0% was used to identify heterogeneity. RESULTS: Twelve randomized controlled trials, including 5445 women with neuraxial analgesia randomized to delayed versus immediate pushing during the second stage of labor, were included in the meta-analysis. Of the 5445 women included in the meta-analysis, 2754 were randomized to the delayed pushing group and 2691 to the immediate pushing group. No significant difference between delayed and immediate pushing was found for spontaneous vaginal delivery (80.9% versus 78.3%; relative risk, 1.05; 95% confidence interval, 1.00-1.10; 12 randomized controlled trials, 5540 women), operative vaginal delivery (12.8% versus 14.6%; relative risk, 0.89; 95% confidence interval, 0.75-1.08; 11 randomized controlled trials, 5395 women), and cesarean delivery (6.9% versus 7.9%; relative risk, 0.89; 95% confidence interval, 0.73-1.07; 11 randomized controlled trials; 5395 women). Women randomized to the delayed pushing group had a significantly shorter length of active pushing (mean difference, -27.54 minutes; 95% confidence interval, -43.04 to -12.04; 7 randomized controlled trials, 4737 women) at the expense of a significantly longer overall duration of the second stage of labor (mean difference, 46.17 minutes; 95% confidence interval, 32.63-59.71; 8 studies; 4890 women). The incidence of chorioamnionitis (9.1% versus 6.6%; relative risk, 1.37, 95% confidence interval, 1.04-1.81; 1 randomized controlled trial, 2404 women) and low umbilical cord pH (2.7% versus 1.3%; relative risk, 2.00; 95% confidence interval, 1.30-3.07; 5 randomized controlled trials, 4549 women) were significantly higher in the delayed pushing group. CONCLUSION: In women with spontaneous or induced labor at term with neuraxial analgesia, delayed pushing in the second stage does not affect the mode of delivery, although it reduces the time of active pushing at the expense of a longer second stage. This prolongation of labor was associated with a higher incidence of chorioamnionitis and low umbilical cord pH. Based on these findings, delayed pushing cannot be routinely advocated for the management of the second stage.

Diagnosis & management of imported malaria in pregnant women in non-endemic countries.

Malaria in pregnancy is an important cause of maternal and foetal morbidity and is a potentially life-threatening infection. With ever-growing global exchanges, imported malaria in pregnancy is becoming an issue of concern in non-endemic countries where women, because of low immunity, have higher risk of severe diseases and death. Malaria in pregnancy is a dangerous condition which can be associated with important consequences for both mother and child such as stillbirth, low birth weight, maternal anaemia. In non-endemic-countries it is more frequent in its severe form which can lead to maternal death if not treated adequately. Specific anti-malarial interventions such as the use of repellents and insecticide treated bed nets in addition to chemoprophylaxis should be used by pregnant women if they are travelling to endemic areas. In cases of confirmed infection, specific treatment regimens vary according to gestational age and the presence of complications. Malaria should be considered a global health problem, increasingly involving western countries. Clinicians all over the world need to be prepared for this emerging disease both in terms of prevention and therapy.

An observational study to assess Italian obstetrics providers' knowledge about preventive practices and diagnosis of congenital cytomegalovirus.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can be easily prevented by hygienic measures. Up to date the majority of the studies in literature highlighted a reduction in cCMV antenatal counseling and its prevention. Our purpose was to evaluate obstetrics providers' knowledge about cCMV infection, management and the behavioral practices to avoid it. METHODS: This is a cross-sectional survey carried out in Umberto I Hospital, "Sapienza" University of Rome between November 2019 and January 2020. We recruited 148 specialists and residents in Obstetrics and Gynecology through online anonymous multiple-choice 13-questions, 10 min-survey comparing responses between the two groups. RESULTS: A total of 94.6% of all participants said they always prescribe cytomegalovirus (CMV) serum screening: 73.6% of them regularly counsel about preventive practices, with specialists recording higher percentages (85.4 vs. 65.1%, p<0.005). We identified a good knowledge about the diagnostic pathway, but only 58.1% of our population knows the correct time of late amniocentesis. 12.2% of providers do not consider magnetic resonance (MRI) as a complementary exam. CONCLUSIONS: Prevention of maternal seroconversion is crucial: even if our data show an acceptable knowledge about antenatal counseling, we encourage clinicians to firmly inform and educate women about behavioral measures.

Treatment with Gonadotropin Releasing Hormone Agonists in Systemic Lupus Erythematosus Patients Receiving Cyclophosphamide: A Long-term Follow-up Study.

BACKGROUND: Cyclophosphamide treatment has been associated with ovarian function impairment. Co-treatment with gonadotropin-releasing hormone-analogue (GnRH-a) seems to be able to prevent this complication. However, even though data are available on neoplastic patients, limited data have been published on systemic lupus erythematosus (SLE) women cohorts. OBJECTIVES: To evaluate GnRH-a efficacy on ovarian function preservation in SLE women receiving cyclophosphamide treatment. METHODS: The authors performed a retrospective study including SLE women requiring cyclophosphamide treatment and compared those treated with and without GnRH-a (case and controls, respectively). All patients were evaluated before cyclophosphamide treatment and every 3 months in the following years. Ovarian function was evaluated using hormonal profiles. RESULTS: The study comprised 33 SLE cyclophosphamide-treated women: 18 co-treated with triptorelin and 15 controls. The mean follow-up was 8.1 ± 5.1 years (range 4-11). Premature ovarian failure (POF) prevalence was significantly lower in SLE women treated by cyclophosphamide plus triptorelin compared to controls (11.1% vs. 33.3%, P = 0.0002). The occurrence of POF was significantly associated with higher age at the time of cyclophosphamide treatment (P = 0.008). Only patients in the GnRH-a treated group had successful pregnancies. CONCLUSIONS: The study provides information about the efficacy of co-treatment with GnRH-a in SLE women receiving cyclophosphamide, as demonstrated by the lower POF incidence compared to untreated subjects, based on long-term follow-up. These results reinforce the use of GnRH-a for fertility preservation in premenopausal SLE patients treated by cyclophosphamide.

Obstetrical outcomes in women with history of breast cancer: a systematic review and meta-analysis.

PURPOSE: Potential risk of adverse obstetrical outcomes has been shown among breast cancer survivors. Therefore, the aim of this systematic review and meta-analysis was to evaluate the relationship between history of breast cancer (BC) and obstetrical outcomes. METHODS: PubMed, EMBASE, and Medline were searched from the inception of each database to April 2019. Selection criteria included prospective and retrospective cohort studies of BC pregnant survivors. The meta-analysis was performed by computing odds ratios (ORs) using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale and the review was registered with PROSPERO number CRD42019127716. RESULTS: Four studies, including 1466 cases of BC survivors and 6,912,485 controls, were included. Compared with controls, a higher incidence of obstetrical complication was found in women with history of BC. The incidence of preterm birth (PTB) in the study group was 11.05% compared with 7.79% in the control group (1.68, 95% confidence interval 1.43-1.99). Breast cancer history was also associated with low birth weight (LBW) (study group: 9.26% vs. control group: 5.54%, 1.88, CI 95% 1.55-2.27), cesarean section (CS) (study group: 19.76% vs. control group 10.81%, 1.78, CI 95% 1.39-2.27), intrauterine fetal death (IUFD) (study group: 0.004% vs. control group 0.36%, of 1.25 CI 95% 0.36-4.35), and fetal anomalies (study group: 5.8% vs. control group: 4.26%, 1.45 CI 95% 1.01-2.09). CONCLUSIONS: History of BC was associated with adverse obstetrical outcomes.

Birthweight discordance and neonatal morbidity in twin pregnancies: A systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review was to quantify the association between birthweight discordance and neonatal morbidity in twin pregnancies. MATERIAL AND METHODS: MEDLINE, Embase and Cinahl databases were searched. Studies reporting the occurrence of morbidity in twins affected compared with those not affected by birthweight discordance were included. The primary outcome was composite neonatal morbidity (including neurological, respiratory, infectious morbidities, abnormal acid-base status and necrotizing enterocolitis). The secondary outcomes were the individual morbidities. Sub-group analysis according to chorionicity, gestational age at birth and fetal weight (smaller vs larger twin) was also performed. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Twenty studies (10 851 twin pregnancies) were included. The risk of composite morbidity was significantly higher in the pregnancies with birthweight discordance ≥15% (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.0-1.9), ≥20% (OR 2.2, 95% CI 1.40-3.45), ≥25% (OR 2.5, 95% CI 1.8-3.6), and ≥30% (OR 3.4, 95% CI 2.2-3.2). In dichorionic twins, birthweight discordance ≥15% (OR 2.4, 95% CI 1.65-3.46), ≥20% (OR 2.2, 95% CI 1.3-3.8), ≥25% (OR 2.7, 95% CI 1.4-5.1) and ≥30% (OR 3.6, 95% CI 2.3-5.7) were all significantly associated with composite neonatal morbidity. Analysis of monochorionic twins was hampered by the very small number of included studies, which precluded adequate statistical power. Monochorionic twins with a birthweight discordance ≥20% were at significantly higher risk of composite neonatal morbidity (OR 2.2, 95% CI 1.1-4.9) compared with those presenting with lesser degree of discordance. When stratifying the analysis according to gestational age at birth and fetal size, twins with birthweight discordance ≥15%, 20%, 25% and 30% delivered at ≥34 weeks were at higher risk of neonatal morbidity compared with controls, but there was no difference in the risk of morbidity between the larger and the smaller twin in the discordant pair. CONCLUSIONS: Birthweight discordance is associated with neonatal morbidity in twin pregnancies. The strength of this association persists for dichorionic twins. It was not possible to extrapolate robust evidence on monochorionic twins due to the low power of the analysis due to the small number of included studies.

Congenital jugular vein phlebectasia or aneurysma: A rare entity in prenatal diagnosis.

Vascular malformations arising from the wall of the external jugular vein are rare and appeared most commonly in pediatric population. Here, we present a case of vascular malformation in the left external jugular vein diagnosed in a fetus during third trimester ultrasound. This is the first described case in prenatal diagnosis.

New-onset ulcerative colitis in pregnancy associated to toxic megacolon and sudden fetal decompensation: Case report and literature review.

Ulcerative colitis (UC) is a chronic inflammatory disease rarely arising during gestation. Because the available information is based on case reports or small retrospective studies, diagnosis may be difficult and treatment is still controversial. A case of toxic megacolon developing in late pregnancy associated to a sudden fetal decompensation is described. Diagnostic and clinical topics of acute UC onset in pregnancy are debated.A primipara, 34 years old, 33/0 weeks of gestation, was admitted with a diagnosis of preterm labor, associated to acute bloody diarrhea (up to 10 daily motions) and cramping abdominal pain. A diagnosis of new-onset early-stage UC was made by sigmoidoscopy. An intensive care regimen including hydrocortisone, antibiotics and parenteral nutrition was immediately started. Magnetic resonance imaging of maternal abdomen, fostered by the worsening patient conditions, evidenced dilatation of the entire colon and a severely hampered of fetal muscular tone.Toxic megacolon complicated by superimposed Clostridium difficile infection was associated to a sudden fetal decompensation diagnosed by chance during maternal abdominal magnetic resonance imaging. An emergency cesarean section was mandatory. According to a senior surgeon's decision, total colectomy was not immediately performed following cesarean section with reference to the absence of colonic perforation. We obtained a good short-term maternal outcome and an uncomplicated neonatal course. Counseling of those patients must be focused on timely and multidisciplinary intervention in order to improve the course of maternal disease and to prevent fetal distress.