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Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111–0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082–5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690–6.900). Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

PURPOSE: To evaluate the maternal and neonatal safety of vaginal delivery in women with HIV following the implementation of a national protocol in Italy. METHODS: Vaginal delivery was offered to all eligible women who presented antenatally at twelve participating clinical sites. Data collection and definition of outcomes followed the procedures of the National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Pregnancy outcomes were compared according to the mode of delivery, classified as vaginal, elective cesarean (ECS) and non-elective cesarean section (NECS). RESULTS: Among 580 women who delivered between January 2012 and September 2017, 142 (24.5%) had a vaginal delivery, 323 (55.7%) had an ECS and 115 (19.8%) had an NECS. The proportion of vaginal deliveries increased significantly over time, from 18.9% in 2012 to 35.3% in 2017 (p

Objectives To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Design Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. Setting University and hospital clinics. Population Pregnant women with HIV. Methods Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Main outcome measures Rate of invasive testing, intrauterine death, HIV transmission. Results Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. Conclusions The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. Tweetable abstract No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study.Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC.The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030).In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

SUMMARYYoung pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001–2016, 9·0% were in women P< 0·001). Younger women had a lower rate of planned pregnancy (23·2%vs.37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36–0·69), were more frequently diagnosed with HIV in pregnancy (46·5%vs.20·9%, OR 3·29, 95% CI 2·54–4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (vs.99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

AIM: To evaluate pregnancy outcome in women with fetal membranes at or beyond external os who underwent exam-indicated cerclage or conservative management. MATERIAL AND METHODS: Retrospective cohort study including 52 patients with fetal membranes at or beyond external os between 17 and 27 weeks of gestation, treated in two third-level hospitals, between January 2001 and April 2009. The outcomes of interest of the study, prolongation of pregnancy and neonatal survival rate, were stratified according to type of management, parity, clinical conditions and blood tests at admission and calculated using the Kaplan-Meier algorithm. RESULTS: Of 52 women, 37 received exam-indicated cerclage and 15 were managed conservatively. The rate of patients still pregnant beyond 180 days within the cerclage group differed significantly from those of the conservative management group (80% vs 0%, respectively) (P-value

Aim: Pre-eclampsia is a syndrome characterized by endothelium dysfunction, systemic inflammation, and kidney injury that could be associated with increased levels of neutrophil gelatinase-associated lipocalin (NGAL). We investigated whether serum and urinary NGAL may have a clinical value in defining the severity of pre-eclampsia. Patients and Methods: This cross-sectional case–control study enrolled 18 women with pre-eclampsia matched for gestational age with 22 uncomplicated pregnancies. We evaluated the correlation between NGAL levels and blood pressure and 24-hour proteinuria values by linear regression. Results: Linear regression disclosed a positive and significant correlation between urinary NGAL and 24-hour proteinuria. Serum NGAL appeared to be higher, but not significantly different, in severe pre-eclampsia. Conclusion: These preliminary data indicate that NGAL may correlate with an inflammatory renal involvement in severe preeclampsia. Further studies would be useful to better estimate the clinical value of an NGAL increase for evaluating the possibility of delivery induction.

OBJECTIVES: Monoamniotic twin pregnancies are at increased risk of perinatal complications, primarily owing to the risk of cord entanglement. There is no recommendation on whether such pregnancies should be managed in hospital or can be safely managed in an outpatient setting, and the timing of planned delivery is also a subject of debate. The aim of this study was to compare the perinatal outcomes of inpatient vs outpatient fetal surveillance approaches employed among 22 participating study centers, and to calculate the fetal and neonatal death rates according to gestational age, in non-anomalous monoamniotic twins from 26 weeks' gestation. METHODS: The MONOMONO study was a multinational cohort study of consecutive women with monochorionic monoamniotic twin pregnancies, who were referred to 22 university hospitals in Italy, the USA, the UK and Spain, from January 2010 to January 2017. Only non-anomalous uncomplicated monoamniotic twin pregnancies with two live fetuses at 26 + 0 weeks' gestation were included in the study. In 10 of the centers, monoamniotic twins were managed routinely as inpatients, whereas in the other 12 centers they were managed routinely as outpatients. The primary outcome was intrauterine fetal death. We also planned to assess fetal and neonatal death rates according to gestational age per 1-week interval. Outcomes are presented as odds ratio (OR) with 95% CIs. The main outcome was analyzed using both standard logistic regression analysis, in which each fetus was treated as an independent unit, and a generalized mixed-model approach, with each twin pair treated as a cluster unit, considering that the outcome for a twin is not independent of that of its cotwin. RESULTS: 195 consecutive pregnant women with a non-anomalous uncomplicated monoamniotic twin gestation (390 fetuses) were included. Of these, 75 (38.5%) were managed as inpatients and 120 (61.5%) as outpatients. The overall perinatal loss rate was 10.8% (42/390) with a peak fetal death rate of 4.3% (15/348) occurring at 29 weeks' gestation. There was no significant difference in mean gestational age at delivery (31 weeks), birth weight (∼1.6 kg), or emergency delivery rate between the inpatient and outpatient surveillance groups. Based on generalized mixed-model analysis, there was no statistically significant difference in fetal death rates between inpatient management commencing from around 26 weeks compared with outpatient surveillance protocols from 30 weeks (3.3% vs 10.8%; adjusted OR 0.21 (95% CI, 0.04-1.17)). Maternal length of stay in the hospital was 42.1 days in the inpatient group, and 7.4 days in the outpatient group (mean difference 34.70 days (95% CI, 31.36-38.04 days). From 32 + 0 to 36 + 6 weeks, no fetal or neonatal death in either group was recorded. 46 fetuses were delivered after 34 + 0 weeks, and none of them died in utero or within the first 28 days postpartum. CONCLUSION: In uncomplicated monoamniotic twins, inpatient surveillance is associated with similar fetal mortality as outpatient management. After 31 + 6 weeks, and up to 36 + 6 weeks, there were no intrauterine fetal deaths or neonatal deaths. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-β2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti-β2 glycoprotein-I, and/or lupus anticoagulant), and were treated with low-dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti-β2 glycoprotein-I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51-0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22-1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19-2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17-2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22-2.94). In women with only 1 positive test result, women with anti-β2 glycoprotein-I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P1 antibody positivity, triple-positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22-0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15-2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti-β2 glycoprotein-I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when

Objective: This study aimed to conduct a systematic review of the clinical outcomes reported for pregnant patients with coronavirus disease 2019. Data Sources: The PubMed, CINAHL, and Scopus databases were searched using a combination of key words such as “Coronavirus and/or pregnancy,” “COVID and/or pregnancy,” “COVID disease and/or pregnancy,” and “COVID pneumonia and/or pregnancy.” There was no restriction of language to allow collection of as many cases as possible. Study Eligibility Criteria: All studies of pregnant women who received a coronavirus disease 2019 diagnosis using acid nucleic test, with reported data about pregnancy, and, in case of delivery, reported outcomes, were included. Study Appraisal and Synthesis Methods: All the studies included have been evaluated according to the tool for evaluating the methodological quality of case reports and case series described by Murad et al. Results: Six studies that involved 51 pregnant women were eligible for the systematic review. At the time of the report, 3 pregnancies were ongoing; of the remaining 48 pregnant women, 46 gave birth by cesarean delivery, and 2 gave birth vaginally; in this study, 1 stillbirth and 1 neonatal death were reported. Conclusion: Although vertical transmission of severe acute respiratory syndrome coronavirus 2 infection has been excluded thus far and the outcome for mothers and neonates has been generally good, the high rate of preterm delivery by cesarean delivery is a reason for concern. Cesarean delivery was typically an elective surgical intervention, and it is reasonable to question whether cesarean delivery for pregnant patients with coronavirus disease 2019 was warranted. Coronavirus disease 2019 associated with respiratory insufficiency in late pregnancies certainly creates a complex clinical scenario.

BACKGROUND Insufficient and imprecise information during pregnancy can lead to an overestimation of maternal and fetal risk associated to various exposures during gestation. OBJECTIVE This study aimed to assess whether expert obstetrical counseling in cases of maternal infections at risk of vertical transmission could impact maternal perception of risk and the tendency to terminate pregnancy. STUDY DESIGN This is a monocentric prospective observational study of 185 consecutive pregnant women with confirmed diagnosis of infectious diseases at risk of vertical transmission during the first or second trimester of pregnancy. Patients were divided into 2 different groups, according to the type infectious disease: infections at high risk of fetal damages and infections at low risk. Every woman included in the study underwent medical counseling with a physician with experience of vertically transmitted infections. Moreover, each woman involved in the study was offered a detailed second trimester ultrasound scan. Maternal concern for their pregnancy and the disposition to interrupt the pregnancy were investigated by 2 questionnaires submitted to patients before and after medical expert counseling; a third questionnaire was completed only by those women who decided to undergo second trimester ultrasound scan at our hospital. RESULTS Of the 185 consecutive patients meeting the inclusion criteria, 171 (92.4%) filled out the visual analog scale for concern about the baby's health both before and after medical consultation. After medical consultation, there was a significant decrease in mean visual analog scale for concern: from 67.1±26.0 to 41.3±28.8 (change score, –25.8; 95% confidence interval, –29.9 to –21.7). Higher baseline levels of concern had more room for reduction, and infections at high fetal risk of damage were associated with lower decrease in concern. However, risk perception decreased in both low-risk and high-risk pregnancies. Notably, 82 patients (53.2%) underwent ultrasonography and filled out the visual analog scale after examination. The mean score after examination was 28.3±24.4 and significantly lower than the mean score registered after consultation (change score, –16.6; 95% confidence interval, –22.9 to –10.3). A total of 162 women (87.6%) declared their tendency to interrupt pregnancy both before and after the consultation. There was a significant decrease in mean tendency from 42.1±32.6 to 22.7±27.1 (change score, –19.4; 95% confidence interval, –23.6 to –15.2). Regression analysis revealed that both low- and high-risk patients significantly reduced their tendency. A total of 73 patients (45.1%) underwent ultrasonography and filled out the visual analog scale after examination. The mean score after examination was 9.9±20.6 and significantly lower than the mean score registered after consultation (change score, –13.4; 95% confidence interval, –19.1 to –7.7). CONCLUSION Our results confirm the importance of a comprehensive and sufficient expert medical counseling that, on one hand, can reduce maternal risk perception, improving quality of life for mothers, and, on the other hand, can lead to feasible results, reducing a woman's disposition to termination of pregnancy.

Shortly after the acceptance of our review [1] an additional study on the use of valacyclovir in pregnant women with primary cytomegalovirus (CMV) infection to prevent vertical transmission has been published by De Santis et al [2]. The authors reported a case series of 12 pregnant women treated with off-label valacyclovir 8g per day following primary CMV infection in the first half of pregnancy and stopped in case of negative amniocentesis. The observed rate of positivity at amniocentesis was 17% (2 positive amniocentesis of 12 performed) compatible with a ≈50% reduction of vertical transmission when compared to the 30-35% rate reported in literature [3]. These results are consistent to those reported by Shahar-Nissan K et al in the preliminary report on their clinical placebo-controlled trial [4] and confirm that valacyclovir may reduce the rate of vertical transmission by the time of amniocentesis. However, among the 10 pregnant women with a negative amniocentesis described by De Santis, three delivered a congenitally infected newborn of which one developed moderate unilateral sensory neural loss at 18 months of age. Amongst these three women with negative amniocentesis who delivered a congenitally infected newborn, two presented a new CMV DNAemia after valacyclovir discontinuation. The authors interpret their finding as the result of an efficient control of viral replication and prevention of during the antiviral treatment, with subsequent resurgence of viral and vertical transmission. They suggested the need of controlled trial to evaluate valacyclovir treatment prolonged until the delivery regardless of amniocentesis results. However the possibility of false negative amniocentesis cannot be completely excluded. In particular the authors used 0.4mL of amniotic fluids to extract the CMV-DNA which is lower compared to those used in other reference laboratory (1mL) [5] and this could have affected the sensitivity of the test. In another recent paper (not captured by our review of literature since indexed with the keyword “citomegalovirus” unlike “cytomegalovirus”), De Santis et al described a case series on the use of high dose valacyclovir (8g/day) until delivery in confirmed fetal asymptomatic CMV infections [6]. Of the eleven in utero treated newborns, only one was symptomatic at birth and he developed profound bilateral hearing loss at six month requiring bilateral cochlear implant. Another developed a sensorineural hearing loss at 8 months of age. Surprisingly, three newborns had negative serology and virological tests at birth inducing authors to speculate that treatment can even allow viral clearance in case of low amniotic fluids viral load. To sum up, these two studies confirmed data from previous literature, namely the excellent maternal tolerance and the benefit of valacyclovir in reducing fetal CMV infections at time of amniocentesis [4] and the possible role of the drug in the in utero treatment of confirmed fetal infection [7]. We look forward to see the results of the still partially published randomized, double-blind, placebo-controlled study [4], which will probably add further important information.

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

Objectives:The primary objective was to quantify the risk of perinatal mortality in non‐anomalous monochorionic monoamniotic (MCMA) twin pregnancies complicated by birth‐weight (BW) discordance. The secondary objectives were to investigate the effect of inpatientvsoutpatient fetal monitoring on the risk of mortality in weight‐discordant MCMA twin pregnancies, and to explore the predictive accuracy of BW discordance for perinatal mortality. Methods:This analysis included data on 242 MCMA twin pregnancies (484 fetuses) from three major research collaboratives on twin pregnancy (MONOMONO, STORK and NorSTAMP). The primary outcomes were the risks of intrauterine (IUD), neonatal (NND) and perinatal (PND) death, according to weight discordance at birth from ≥ 10% to ≥ 30%. The secondary outcomes were the association of inpatientvsoutpatient fetal monitoring with the risk of mortality in weight‐discordant pregnancies, and the accuracy of BW discordance in predicting mortality. Logistic regression and receiver‐operating‐characteristics‐curve analyses were used to analyze the data. Results:The risk of IUD was significantly increased in MCMA twin pregnancies with BW discordance ≥ 10% (odds ratio (OR), 2.2; 95% CI, 1.1–4.4;P= 0.022) and increased up to an OR of 4.4 (95% CI, 1.3–14.4;P= 0.001) in those with BW discordance ≥ 30%. This association remained significant on multivariate logistic regression analysis for BW‐discordance cut‐offs ≥ 20%. However, weight discordance had low predictive accuracy for mortality, with areas under the receiver‐operating‐characteristics curve of 0.60 (95% CI, 0.46–0.73), 0.52 (95% CI, 0.33–0.72) and 0.57 (95% CI, 0.45–0.68) for IUD, NND and PND, respectively. There was no difference in the risk of overall IUD, single IUD, double IUD, NND or PND between pregnancies managed as an inpatient compared with those managed as an outpatient, for any BW‐discordance cut‐off. Conclusions:MCMA twin pregnancies with BW discordance are at increased risk of fetal death, signaling a need for increased levels of monitoring. Despite this, the predictive accuracy for mortality is low; thus, detection of BW discordance alone should not trigger intervention, such as iatrogenic delivery. The current data do not demonstrate an advantage of inpatient over outpatient management in these cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVES To compare the efficiency of electronic spatiotemporal image correlation (eSTIC) with that of conventional STIC to acquire four-dimensional (4D) fetal cardiac volumes of diagnostic quality. METHODS This was a randomized controlled trial of 100 patients in mid-gestation with normal sonograms. In half of the cases, STIC volumes of the fetal heart were obtained with a conventional mechanical 4D probe and in the remaining cases eSTIC volumes were obtained with an electronic 4D probe. Examinations were kept within the timeframe allotted for a standard examination of fetal anatomy, and a maximum of two attempts were made at obtaining a 4D cardiac volume. Datasets were stored on a computer and subsequently analyzed and categorized as being of optimal, satisfactory or inadequate quality, depending on whether or not it was possible to perform an extended basic cardiac examination, including obtaining a three vessels and trachea view, as well as a clear reconstruction of both the aortic and ductal arches in the sagittal plane. RESULTS The eSTIC volume datasets were more frequently of optimal or satisfactory diagnostic quality compared with conventional STIC (94% vs 76%, P < 0.0001). Failure to obtain an eSTIC volume of adequate quality was in all cases the consequence of an unfavorable position of the fetus. CONCLUSIONS Compared with a standard mechanical probe, the electronic 4D probe facilitates acquisition of sonographic cardiac volumes in mid-trimester fetuses. In our hands, eSTIC volumes of optimal or satisfactory diagnostic quality, allowing a detailed offline evaluation of the fetal heart, were obtained in more than 90% of cases within the time frame of a standard examination of fetal anatomy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To evaluate perinatal outcomes in case of non-primary maternal cytomegalovirus (CMV) infection. Methods: We performed a retrospective cohort study of pregnant women with active CMV infection referred to our unit over a 15-year period (January 2000 to December 2014). Non-primary infection was diagnosed on the basis of the results of confirmatory serological and virological tests (avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate and the percentage of symptomatic congenital infection were determined in this group of patients. Results: A total of 205 pregnant women were enrolled. Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out of 3 symptomatic newborns presented a pathologic second-trimester ultrasound scan. Conclusion: Maternal immunity offers substantial protection against intrauterine transmission of CMV infection, but not against disease once the fetus is infected.

Objective: To evaluate the impact of Hepatitis B virus (HBV) coinfection on response to antiretroviral treatment in pregnant women with HIV.Methods: Retrospective analysis of a large case series of pregnant women with HIV in Italy; outcome measures were CD4 changes, HIV viral load, and main pregnancy outcomes (preterm delivery, low birthweight, intrauterine growth restriction, mode of delivery, and major birth defects). Results: Rate of HBV coinfection among 1462 pregnancies was 12.0%. Compared to the HBV-uninfected, HBV-coinfected women had a significantly lower median CD4 cell gain between first and third trimester (26.5 vs. 60 cells/mm(3), p=0.034), with similar rate of undetectable (< 50 copies/ml) HIV-RNA at third trimester (70.5% vs. 65.2%, p=0.229), and no differences in all the main maternal and infant outcomes. A multivariable linear regression analysis identified four variables significantly and independently associated with a lower CD4 response in pregnancy: HBV coinfection (-35 cells/mm(3)), being on antiretroviral treatment at conception (-59.7 cells/mm(3)), AIDS status (-59.8 cells/mm(3)) and higher first CD4 levels in pregnancy (-0.24 cells per unitary CD4 increase). Conclusions: HBV coinfection had no adverse influence on the main pregnancy outcomes or on HIV viral load suppression in late pregnancy but was associated with a significantly reduced CD4 response in pregnancy. This effect might have clinical relevance, particularly in women with advanced immune deterioration.

Background: The Congenital Human Cytomegalovirus Infection Prevention (CHIP) study, a randomized, blinded, placebo-controlled trial, demonstrated that the efficacy of hyperimmune globulin (HIG) was not different from that of placebo regarding transmission of cytomegalovirus (CMV) from mothers to newborns. Our aim was to analyze histologically HIG effects on placentas collected for the CHIP study. Materials and Methods: Virological and histological analyses were performed on 40 placentas from transmitter and nontransmitter HIG-treated and untreated mothers by assessing the number of CMV-positive cells, tissue viral load, tissue damage, and compensatory mechanisms. Results: The HIG and placebo groups showed no significant differences in the number of CMV-positive cells (median number in 10 fields at 10 high-power fields: 2.5 vs. 2, p = 0.969) and viral load (median load: 5 copies/5 ng vs. 10.5 copies/5 ng, p = 0.874). Regarding histological examination, the scores of parameters related to tissue damage and hypoxic parenchymal compensation were higher in transmitters except for chorangiosis, with statistically significant differences observed for chronic villitis (p = 0.007), calcification (p = 0.011), and the total score of tissue damage (p < 0.001). The HIG and placebo groups showed no significant differences for all tissue damage and compensation parameters and overall scores. Discussion: HIGs are not able to reduce placental viral load and histological damage, which was significantly associated only with infection.

Background Human Cytomegalovirus (HCMV) is the most common cause of childhood hearing loss and can lead to neurodevelopmental delay. To date, few studies have examined the correlation between maternal viremia and congenital HCMV infection. The aim of our study was to ascertain if HCMV DNA in the peripheral blood of pregnant women with primary HCMV infection at the time of amniocentesis may have a prognostic value in terms of congenital infection and neonatal symptomatic disease. Methods We performed a prospective observational study of pregnant women referred to our maternal-fetal medicine division with suspected HCMV infection. Primary infection was diagnosed based on seroconversion for HCMV and/or HCMV immunoglobulin M-positive and low or moderate HCMV immunoglobulin G avidity. At the time of amniocentesis, maternal blood samples were collected and analyzed by means of real-time polymerase chain reaction to determine the presence of viral DNAemia. Fetuses and newborns were evaluated for the presence of congenital infection and symptomatic disease. Results A total of 239 pregnant women were enrolled; 32 blood samples (13.4%) were positive, and 207 (86.6%) were negative for HCMV DNA. The overall rate of transmission was 23.4%. Fifteen infected patients (26.8%) were symptomatic. Vertical transmission occurred in 14 women (43.8%) with positive and 42 (20.3%) with negative results for HCMV DNAemia (P = .006; odds ratio, 3.06; 95% confidence interval, 1.41-6.64). Symptomatic infection occurred in 6 (42.9%) infected fetuses or newborns from women with and in 9 (21.4%) from women without viral DNAemia (P = .16). Conclusion Maternal viremia at amniocentesis is associated with a 3-fold greater chance of congenital infection, but it is not correlated with symptomatic disease.

The objective was to review the evidence supporting various perioperative technical and management strategies for transvaginal cervical cerclage. We performed MEDLINE, PubMed, EMBASE, and COCHRANE searches with the terms, cerclage, cervical cerclage, cervical insufficiency, and randomized trials, plus each technical aspect (eg, suture, amniocentesis, etc) considered. The search spanned 1966 through September 2012 and was not restricted by language. Each retrieved manuscript was carefully evaluated, and any pertinent references from the reports were also obtained and reviewed. All randomized trials covering surgical and selected perioperative, nonsurgical aspects of cerclage were included in the review. The evidence was assessed separately for history-, ultrasound-, and physical examination-indicated cerclage. Evidence levels according to the new method outlined by the US Preventive Services Task Force were assigned based on the evidence. There are no grade A high-certainty recommendations regarding technical aspects of transvaginal cervical cerclage. Grade B moderate-certainty recommendations include performing a fetal ultrasound before cerclage to ensure fetal viability, confirm gestational age, and assess fetal anatomy to rule out clinically significant structural abnormalities; administering spinal, and not general, anesthesia; performing a McDonald cerclage, with 1 stitch, placed as high as possible; and outpatient setting. Unfortunately, no other recommendations can be made regarding the other technical aspects of cerclage.

Objective To evaluate the outcome of pregnancies complicated by placental insufficiency and abnormal umbilical artery Doppler prior to viability. Design A retrospective cohort study. Setting Italy. Population Singleton pregnancies with fetal growth restriction and absence of end-diastolic velocities (AEDVs) in the umbilical arteries prior to 24 weeks. Methods A retrospective cohort study of singleton pregnancies with fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks. Main outcome measures Fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks. Results Of 16 fetuses first seen at 20–23 weeks, only 12 survived and one of these developed cerebral palsy. Severe hypertensive disorders occurred in three mothers. In four women, the Doppler waveforms progressively improved and developed a normal pulsatility. These fetuses had a better outcome than those that had persistent alterations: they were delivered later (34 versus 28 weeks), had a larger birthweight (1598 versus 630 g) and developed fewer complications. Conclusions Placental insufficiency with AEDV in the umbilical arteries prior to fetal viability is associated with a high probability of perinatal death and neonatal complications. However, progressive amelioration of Doppler indices occurs in a subset of women, and these fetuses have a much better outcome.

Introduction There are several published clinical trials of the use of tranexamic acid (TXA) in an obstetric setting, but no consensus on its use or guidelines for management. Material and methods The aim of this meta-analysis was to evaluate the effectiveness of TXA in reducing blood loss when given prior to cesarean delivery. We performed a systematic search in electronic databases. We included all randomized controlled trials comparing the use of TXA prior to cesarean delivery with controls (either placebo or no treatment). Results Nine trials with 2365 women were included in the analysis. Women who received TXA had significantly less postpartum blood loss, a lower drop in hemoglobin and a lower incidence of postpartum hemorrhage and severe postpartum hemorrhage compared with controls. Moreover, the number of women who needed additional uterotonic agents was significantly lower in the TXA group than in controls. The percentage of women who required blood transfusions at, or immediately after, cesareans was significantly lower in the intervention group than in the controls. There was no difference in the incidence of thromboembolic events in the two groups. Conclusions Prophylactic TXA given before cesarean skin incision in women undergoing cesarean delivery, under spinal or epidural anesthesia, significantly decreases blood loss, including postpartum hemorrhage and severe postpartum hemorrhage, in addition to the standard prophylactic oxytocin given after delivery of the neonate. The effect of TXA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p<0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p<0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease.

Objective The aim of this study was to evaluate the incidence of cervical lacerations with cerclage removal planned before labor compared to after the onset of labor by a systematic review of published studies. Study design Searches were performed in electronic databases from inception of each database to November 2014. We identified all studies reporting the rate of cervical lacerations and the timing of cerclage removal (either before or after the onset of labor). The primary outcome was the incidence of spontaneous and clinically significant intrapartum cervical lacerations (i.e. lacerations requiring suturing). Results Six studies, which met the inclusion criteria, were included in the analysis. The overall incidence of cervical lacerations was 8.9% (32/359). There were 23/280 (6.4%) cervical lacerations in the planned removal group, and 9/79 (11.4%) in the removal after labor group (odds ratio 0.70, 95% confidence interval 0.31–1.57). Conclusions In summary, planned removal of cerclage before labor was not shown to be associated with statistically significant reduction in the incidence of cervical lacerations. However, since that our data probably did not reach statistical significance because of a type II error, further studies are needed.

Objective To assess the feasibility of the prenatal diagnosis using fetal neurosonography of brain injuries in the surviving fetus after the demise of a monochorionic cotwin. Methods This was a retrospective observational study in the period 1990–2004 of monochorionic twin pregnancies with a single fetal demise. A detailed sonographic evaluation of the intracranial anatomy of the surviving twin had been performed whenever possible using a multiplanar approach and from 1999, fetal magnetic resonance imaging was offered as well. Postnatal follow-up was obtained in all cases. Results In six of nine cases, abnormal neurosonographic findings were identified including intracranial hemorrhage, brain atrophy, porencephaly and periventricular echogenicities evolving into polymicrogyria. Prenatal diagnosis of brain lesions was confirmed postnatally and all affected infants who survived had severe neurological sequelae. Two fetuses had normal cerebral structures both on the prenatal neurosonogram and on postnatal imaging and were following normal developmental milestones, one at 1 and the other at 5 years of age. In one case the neurosonographic examination was suboptimal and the infant was found at birth to have a porencephalic cyst. Fetal magnetic resonance imaging was performed in two cases and confirmed the ultrasound diagnosis. Conclusions Prenatal neurosonography is a valuable tool for the prediction of neurological outcome in fetuses surviving after the intrauterine death of a monochorionic cotwin. Although our experience is limited, we suggest that magnetic resonance imaging should also be offered. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE: To derive a birth weight predictive equation and to compare its diagnostic value with that of ultrasound. METHODS: A longitudinal observational cohort study, including singleton pregnancies at term, was performed at St. Orsola-Malpighi Hospital, University of Bologna (Italy). A birth weight prediction formula, including symphysis-fundal height (SFH), BMI, maternal abdominal circumference (mAC) and parity was derived from a general linear model (GLM) (retrospective study). Moreover, on a new series of patients, the fetal weight was estimated by using both GLM and ultrasound using Hadlock formula (prospective study). The residual analysis and the intraclass correlation coefficient (ICC) were used to test the accuracy of methods in predicting birth weight. RESULTS: Between January and November 2012, 1034 patients were included in the retrospective study and 44 in the prospective one. The following GLM was derived: estimated birth weight (g) = 1485.61 + (SFH (cm) × 23.37) + (11.62 (cm) × mAC) + [BMI × (-6.81)] + (parity (0 = nulliparous, 1 = multiparous) × 72.25). When prospectively applied, the GLM and ultrasound provided a percentage of prediction within ±10% of the actual weight of 73% and 84%, respectively. Ultrasound estimation, as opposite of GLM one, was significantly associated with neonatal weight (R(2 )= 0.388, F = 26.607, p value

The measurement of transepidermal water loss (TEWL) is important for evaluating the integrity of the barrier function of the stratum corneum. Normal TEWL values in healthy adults and in children ages 2 and older are well known, but few studies have been performed in infants and neonates. TEWL in healthy neonates younger than 24 hours old was assessed and compared with that of an adult study population. We also studied possible correlations between this parameter, gestational age, and mode of delivery. A prospective study was conducted in healthy newborns. The areas tested were the volar forearm and the popliteal fossa. Ninety-nine healthy newborns were enrolled and 33 healthy adults were analyzed as controls. Statistically significant differences were noted between newborns and adults in TEWL (p < 0.01). Newborns had a much higher mean TEWL than adults. Differences in the morphology and physiology between newborn and mature skin can explain the higher TEWL in newborns. Higher TEWL could also be due to the sudden functional adaptation of the skin immediately after delivery, when the newborn transits from a liquid to the dry, gaseous extrauterine environment. Functional evaluation of the neonatal skin barrier is important mainly because maintaining skin integrity facilitates cutaneous adaptation.

Objective: To present our experience of symptomatic cerebral cavernous malformations (CCMs) in pregnancy and to review the literature on the topic. Methods: We retrospectively collected a case series of symptomatic CCMs during pregnancy or the puerperium. A literature search was performed to identify all similar reports. Results: We collected 16 cases of symptomatic CCMs. Haemorrhage occurred in 10 patients. Two patients opted for termination of pregnancy. Delivery occurred preterm in four cases, in only one case due to neurological symptoms at 30 weeks' gestation. Caesarean section was performed in 9 cases; concern over CCM was the indication for delivery in eight of these cases. Four out of 16 patients underwent neurosurgery, three during pregnancy. Conclusion: Symptomatic CCMs seldom require neurosurgery either during or after pregnancy and are not associated with preterm delivery.

Aim: The aim of this paper was to evaluate the lower uterine segment (LUS) thickness through transvaginal sonography in late preterm and full term pregnancies with a single previous Cesarean section, to correlate the obtained LUS measurements with intraoperative observations, and to identify a predictive cut-off value in order to select the best candidates for a vaginal birth after Cesarean delivery (VBAC). Methods: Two hundred and fourteen women with a single previous Cesarean section who had an ultrasound measurement of the LUS thickness (stratified in S1, S2 and S3) in pregnancy were enrolled. The outcome of interest was the visual finding of a thin uterine scar at the time of the iterative Cesarean section. Linear regression was used to correlate the LUS thickness with gestational age (GA). A ROC curve has been used to determine the detection rate (DR) and the risk of each actual value of LUS thickness versus a thin uterine scar (outcome of interest). Results: The LUS thickness was correlated with the gestational age (R2=0.034, P-value =0.005). The DR as estimated by ROC curves to detect a translucent lower uterine segment (S3) was 94.1% at a false positive rate (FPR) of 20%. The correspondent cut-off value was 1.8 mm. Finally a likelihood ratio (LR) of observing S3 was estimated. At the quoted cut-off of 1.8 mm the LR was 3. As demonstrated, for a segment of 1 mm the LR was instead about 13. Conclusion: The obtained values lead us to the conclusion that a thickness less than 1.8 mm can be reasonably considered a valid cut-off value to identify patients with a higher risk of thin uterine scar.

Objectives: To evaluate whether transvaginal ultrasound cervical length (TVU CL) can predict antepartum bleeding (APB) in women with low-lying placenta. Study design: A retrospective study was performed including pregnancies with low-lying placenta for which third trimester TVU CL was available. Multiple pregnancies were excluded. Short cervix was defined as TVU CL ≤25mm. Outcomes of interest were compared with respect to the TVU CL. Results: Forty three cases of singleton pregnancies complicated by low-lying placenta in third trimester were identified. Short cervix was reported in 8 cases (19%). APB (75% vs. 31 %, p = 0.02), blood transfusions (25% vs. 3%, p = 0.02), lower birth weight (2246 vs. 2985g, p = 0.02), and neonatal intensive care unit (NICU) admissions (50% vs. 17%, p = 0.04) were more frequent in the women with short cervix. Rate of unplanned cesarean delivery for APB was similar between both the groups (25% vs. 28%, p = 0.83). Conclusions: In women with low-lying placenta persisting into third trimester, short cervical length can be used as a predictor for APB

Objective: The aim was to determine the outcome of pregnancies complicated by maternal Parvovirus B19 (B19) infection. Method: Among 175 pregnant women referred to our clinic because of suspicion of a B19 infection, 63 with confirmed laboratory diagnosis of acute/recent B19 infection were followed up by ultrasound and Doppler measurement of the middle cerebral artery peak systolic velocity. Results: The vertical transmission rate was 31.7% (20/63). Of the 20 infected, 8 had hydrops, 1 had signs suggestive of meconium peritonitis and 1 had an isolated hydrothorax. Three fetuses presenting with hydrops were treated with intrauterine blood transfusion. Two of them died while the last showed resolution of anemia. Among the five untreated hydropic fetuses, one presented with mild signs that resolved spontaneously, two died at 16 and 17 weeks of gestation and two had also cardiomegaly and the parents opted for elective termination of pregnancy. All the anemic fetuses had middle cerebral artery peak systolic velocity values more than 1.8 multiples of the median. No stillbirth occurred. Conclusions: The outcome of uncomplicated cases with B19 infection is good. In the presence of hydrops prognosis was very poor. It seems therefore logical to attempt to pick up this ominous signs early. © 2012 John Wiley & Sons, Ltd.

OBJECTIVE: To compare the fetal loss rate

Although no precise figures are available, many congenital brain lesions arise from intrauterine disruption, frequently due to obstetric complications. The most common entities include intracranial hemorrhage, ischemic lesions, thrombosis of venous vessels and infections. Accurate prenatal diagnosis is possible in many of these cases. However, the findings may be subtle, particularly in the early stage of the disruptive process. Identification of these conditions requires therefore specific expertise, the combination of fetal neurosonography and magnetic resonance, and frequently there is a need for serial examinations. Targeted diagnostic imaging should be offered to obstetric patients with conditions predisposing to prenatal cerebral insults.

Objective We evaluated whether a discriminant model of prediction based on quantitative distribution of a panel of biomolecules in maternal serum can discriminate normal pregnancies from those who will develop preeclampsia (PE) prior to onset of clinical symptoms at 11–15 weeks' gestation. Methods Case control study encompassing 56 women destined to develop PE cases matched 1:3 for gestational age with 168 controls. After multiple of median (MoM) conversion of all available markers, comprising total Activin A (t-activin A), P-selectin, and vascular endothelial growth factor receptor (VEGFR) the combined likelihood ratios generated for each marker were used to calculate, for each patient enrolled in the study, the odds of being affected given a positive results (OAPR) of developing PE. For all the analyses performed, the type II error was < 20% with a type I error fixed at 5%. Results Data were expressed in MoM of controls. P-selectin was identified as the marker with the best discriminant ability between controls and PE, followed by (t-activin A). No significant differences in VEGFR were observed between cases and controls. By using a 3% prevalence of PE (or, about 1:33) we found that the median OAPR of developing PE for the 56 cases was 1:9 or 10% (1:1–1:417). The median OAPR of PE for controls was 1:40 or 2.5% (range, 1:6–1:4205). Detection rate of the statistical model, with a 5% false-positive rate was 59%. Conclusion This analysis revealed that maternal serum markers assessed at the first and second trimester of pregnancy in asymptomatic patients can improve the early detection of cases at higher risk of developing PE. Copyright © 2007 John Wiley & Sons, Ltd.

Objective The objective of the study was to assess the effectiveness of ultrasound in the antenatal prediction of symptomatic congenital cytomegalovirus (CMV) infection. Study Design The sonograms of 650 fetuses from mothers with primary CMV infection were correlated to fetal or neonatal outcome. Infection status was disclosed by viral urine isolation at birth or CMV tissue inclusions at autopsy. Classification of symptomatic disease was based on postnatal clinical or laboratory findings or macroscopic evidence of tissue damage at autopsy. Results Ultrasound abnormalities were found in 51 of 600 mothers with primary infection (8.5%) and 23 of 154 congenitally infected fetuses (14.9%). Symptomatic congenital infection resulted in 1 of 23 and 68 of 131 cases with or without abnormal sonographic findings, respectively. Positive predictive values of ultrasound vs symptomatic congenital infection was 35.3% relating to all fetuses or infants from mothers with primary infection and 78.3% relating to fetuses or infants with congenital infection. Conclusion When fetal infection status is unknown, ultrasound abnormalities predict symptomatic congenital infection in only a third of cases.

Objectives To calculate the risk of developing pre-eclampsia (PET) in a consecutive series of low-risk women at 18–24 weeks' gestation, using recently published logistic regression models. Methods This was a prospective study, with complete follow-up, in a consecutive series of unselected low-risk singleton pregnancies. Uterine artery pulsatility index as well as a combination of maternal factors were recorded at 18–24 weeks' gestation. The distribution of the estimated risks for the 16 PET patients was compared with that obtained for 136 women who had a normal pregnancy, as assessed by routine testing. A receiver–operating characteristics (ROC) curve was plotted to evaluate the detection rate at fixed false-positive rates (FPRs) of 5%, 10% and 20% and the corresponding odds cut-offs. Results Just 1/16 (6.2%) women with PET developed the disease before the 34th week of gestation. Using the ‘All PET’ logistic regression model, for 16 PET cases the overall median odds was 1 : 1454, higher compared with that of 1 : 41635 estimated for controls. Using the ‘PET ≥ 34 weeks’ model, the median odds of the 15 women who developed PET late was 1 : 3405, compared with 1 : 40785 for controls. In the case of PET before 34 weeks, the risk was 1 : 426373 vs. 1 : 4159823126 estimated for controls (‘PET < 34 weeks’ model). Detection rates for the All PET model were 18%, 50% and 62% at a FPR of 5%, 10% and 20%, respectively. For the PET ≥ 34 weeks model these detection rates were 6%, 46% and 60%, respectively. Conclusion Even though the individual odds estimation is too low to represent the real risk of PET, the recently published logistic regression models detected more than 60% of PET at a FPR of 20% for both All PET and PET ≥ 34 weeks models. Using these models in clinical practice does not seem to give any significant improvement over Doppler alone in the prediction of PET, but the use of a PET-specific odds instead of an actual Doppler value alone seems to be useful for clinical management. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

The purpose of this study was to determine if diagnostic tests performed in a reference laboratory and the correct interpretation and communication of results by an expert physician to the patient can reduce the rate of unnecessary abortions among women with positive cytomegalovirus (CMV) immunoglobulin M antibody titers.This was a retrospective study of 1857 consecutive pregnant women with positive screening for IgM anti-CMV, in the first or second trimester of pregnancy, referred to our unit for further diagnostic evaluation. Patients with available follow-up were divided into 2 groups according to the results of confirmatory serologic testing: women with a CMV serologic profile suggestive of primary infection and hence at high risk of vertical transmission (group 1) and women with a CMV serologic profile consistent with nonprimary infection or past infection (group 2). The number of expected pregnancy terminations and the prevented fraction of abortions was calculated.Of 445 group 1 patients, 53 (11.9%) elected to terminate the pregnancy after being informed of the results of diagnostic tests; in contrast, only 5 (0.4%) women in group 2 underwent terminations (P.001). At autopsy, 38 fetuses in group 1 proved infected. No information on fetal infection is available for pregnancies terminated in the first trimester (15 in group 1; 5 in group 2). We estimated thator = 196 (11.9%) of all patients in groups 1 and 2 (n = 1650 patients) would have elected abortion on the basis of the positive result of screening for fetal CMV infection. After the results of confirmatory tests, only 58 women (53 in group 1 and 5 in group 2) elected to terminate the pregnancy. Thus, the number of abortions is presumed to have been decreased by 73% (P.001).The correct interpretation and communication of confirmatory test results by expert physicians to pregnant women with positive screening for IgM anti-CMV may significantly reduce the rate of unnecessary abortions.

To assess sonographically brain anatomy in fetuses with severe anemia due to red blood cell alloimmunization undergoing intrauterine intravascular transfusions.Multiplanar neurosonography was performed in seven consecutive hydropic fetuses undergoing intrauterine transfusions (mean gestational age 22 +/- 2.5 weeks; mean hemoglobin concentration at the first transfusion 2.3 +/- 1.0 g/dL).Abnormal cerebral findings were identified in four out of seven fetuses. An intracerebellar hemorrhage developed in two fetuses after the first transfusion and one fetus that had severe brain edema before the first transfusion was later found to have cystic periventricular leukomalacia. In one fetus unilateral ventriculomegaly was noted after the first transfusion. Two fetuses were terminated. The remaining pregnancies had an uneventful course, the infants were delivered between 34 and 36 gestational weeks and were alive and well at the time of writing. Prenatal diagnosis of brain injury was always confirmed except for the case with ventriculomegaly that underwent spontaneous intrauterine resolution.Fetuses with extreme anemia due to red blood cell alloimmunization can be salvaged by intrauterine transfusion. In some of these cases brain injury may occur prenatally, and the risk seems to be particularly high when the hemoglobin concentration at the time of the first transfusion isor= 2 g/dL. We suggest that in these pregnancies detailed fetal neuroimaging by either multiplanar sonography and/or magnetic resonance imaging is indicated.

Objective This study was undertaken to determine the predictive accuracy for preterm birth of transvaginal ultrasound (TVU) of the cervix in women with a prior cone biopsy. Study design Pregnant patients with a history of cervical cone biopsy by cold knife, loop electrosurgical excision procedure (LEEP), or laser were monitored prospectively with TVU of the cervix between 16 and 24 weeks. The predictive value of TVU was evaluated by using less than 25 mm cervical length as criteria for the definition of a short cervix. The primary outcome was spontaneous preterm birth less than 35 weeks. Results Of 109 women with prior cone biopsy identified, 55 had LEEP, 45 cold knife, and 9 laser cone biopsies. Thirty (28%) had a short cervix, with 9 (30%) having spontaneous preterm birth less than 35 weeks. Seventy-nine (72%) did not have a short cervix, with 5 (6%) having spontaneous preterm birth less than 35 weeks. The sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth were 64%, 78%, 30%, and 94%, respectively (relative risk [RR] 4.7, 95% CI 1.6-15.3). Conclusion TVU of the cervix is predictive of preterm birth in women with prior cone biopsy.

Objective To determine (1) if fetal DNA (fDNA) in the maternal circulation in women affected by preeclampsia correlates with the time elapsed from the onset of symptoms to the time of blood collection, and (2) if the inclusion of this variable improves the discrimination between affected and unaffected patients by using fDNA distributions. Methods Plasma were collected from 34 women at 33.7 ± 3.9 weeks' gestation, affected by preeclampsia, and bearing a single male fetus. fDNA was extracted from 1.5-mL plasma samples, and the SRY and β-globin gene were analyzed by real-time quantitative PCR. MoMs (multiple of the control median) were calculated by using a log equation of 102 normal cases. Log MoMs were then plotted against the time elapsed from onset of symptoms to blood collection (expressed in days) by means of a log-linear regression. Adjusted MoMs were then calculated. ROC curves were used to test the discrimination obtained by using adjusted MoMs. Results The median MoMs of controls and preeclamptic patients were 1.00 ± 1.53 and 2.62 ± 2.70 respectively. By plotting log MoM fDNA against the time elapsed from onset of symptoms to blood collection, we found a significant positive correlation, (p-value < 0.001, R2 = 0.55, F = 38.97, from 1 to 50 days). The adjusted median fDNA MoM was 2.66 ± 2.50. Areas under the curves, as estimated by ROC curves, were 76.7 for unadjusted and 85.5 for adjusted MoMs respectively (p-value = 0.02). Conclusions The effect of a further covariate showed that (1) fDNA passage from trophoblasts to maternal circulation for unit of time is proportional to the duration of the damage and that (2) increased discrimination can be obtained in comparison to normal subjects. Copyright © 2004 John Wiley & Sons, Ltd.

A complete mole coexisting with dichorionic twins was diagnosed by the combined use of sonography and chorionic villus sampling at 10 weeks gestation. The pregnancy resulted in the death of one fetus at 31 weeks from presumed feto-maternal haemorrhage, while the other fetus survived in good condition. A summary of the available literature, combined with this report, reveals a total of seven pregnancies with twins and a coexistent complete mole. Only two out of 14 fetuses survived. Maternal complications included one case of pre-eclampsia and one persistent trophoblastic tumour. Accurate diagnosis of complete mole is possible by genetic analysis of chorionic villi obtained with standard transabdominal sampling. Twins with a coexistent complete mole will usually undergo miscarriage. However, fetal survival is possible and the maternal risks seem limited. A concomitance between gestational trophoblastic disease and the occurrence of feto-maternal haemorrhage is observed.

Objective The objective of the study was to identify a cerebral ultrasound finding indicative of fetal cytomegalovirus (CMV) infection at midgestation. Study Design All fetuses of 218 patients with primary CMV infection underwent prospective transvaginal neurosonographic examination at 20-22 weeks' gestation. Results Transvaginal sonography identified a periventricular echogenic halo with well-defined borders in 6 infected fetuses at a mean gestational age of 20.5 weeks. Transabdominal axial views of the fetal head were normal in all cases. All patients opted for termination of pregnancy. Autopsy in 2 fetuses showed changes compatible with subacute white matter injury resembling telencephalic leukomalacia. Conclusion A fetal cerebral periventricular halo disclosed by transvaginal sonography at midgestation in pregnant patients with recent CMV infection is suggestive of fetal infection and may be associated with white matter lesions.

OBJECTIVE: To evaluate outcomes of women with prior ultrasound-indicated cerclage, who in their subsequent pregnancy were either followed by transvaginal ultrasound cervical length screening or received a planned history-indicated cerclage. METHODS: Multicenter cohort study of singleton gestations with a prior ultrasound-indicated cerclage performed from 1994 to 2014. We evaluated three pregnancies in the study participants: first pregnancy with prior spontaneous preterm birth at less than 37 weeks of gestation; second pregnancy with ultrasound-indicated cerclage for cervical length 25 mm or less; and the third index pregnancy managed with either transvaginal ultrasound cervical length screening with ultrasound-indicated cerclage for cervical length 25 mm or less or planned history-indicated cerclage. The primary outcome was incidence of spontaneous preterm birth at less than 37 weeks of gestation. We planned a subgroup analysis for women who delivered at less than 32 weeks of gestation compared with 32 weeks of gestation or greater in their prior ultrasound-indicated cerclage pregnancy. RESULTS: Of 102 singleton gestations included, 38 (37.3%) were followed with transvaginal ultrasound cervical length screening and 64 (62.7%) underwent history-indicated cerclage. Of 38 women in the transvaginal ultrasound group, 18 (47.4%) underwent ultrasound-indicated cerclage for cervical length 25 mm or less. After adjusting for confounders, the rate of spontaneous preterm birth at less than 37 weeks of gestation was similar between transvaginal ultrasound cervical length screening and history-indicated cerclage groups (36.8% compared with 43.8%; adjusted odds ratio 0.77, 95% confidence interval 0.47-1.45). Secondary outcomes were also similar in both groups. All women (n=7) who delivered at less than 32 weeks of gestation in their prior pregnancy and subsequently had transvaginal ultrasound screening received ultrasound-indicated cerclage in the index pregnancy compared with only 35.5% of women who delivered at 32 weeks of gestation or greater in their prior pregnancy. CONCLUSION: Women with prior ultrasound-indicated cerclage have similar outcomes if they receive either transvaginal ultrasound cervical length screening with ultrasound-indicated cerclage for cervical length 25 mm or less or planned history-indicated cerclage in the subsequent pregnancy. Less than 50% of the transvaginal ultrasound cervical length screening group require a repeat ultrasound-indicated cerclage in the subsequent pregnancy.