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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

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.

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.

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.

The perspective proposed by this article will focus on perinatal palliative care as a strategy for improving the quality of life of neonates with life-limiting conditions when extending the patient's life is no longer the goal of care. This manuscript reports the creation of an innovative program of perinatal palliative care called “Percorso Giacomo” (Giacomo's Pathway) at Sant'Orsola Hospital in Bologna, Italy in 2013. Key features include interdisciplinary collaboration between professionals from obstetrics, neonatology and other specialties aiming to reach the most detailed fetal and neonatal diagnosis and prognosis; communication and engagement with the family to discuss goals of care and prepare a birthing plan that follows the family's desires and expectations; and personalized care to achieve comfort for each newborn and support for families according to their social, cultural, and religious backgrounds.

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 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.

The use of stem cells for regenerative applications and immunomodulatory effect is increasing. Amniotic epithelial cells (AECs) possess embryonic-like proliferation ability and multipotent differentiation potential. Despite the simple isolation procedure, inter-individual variability and different isolation steps can cause differences in isolation yield and cell proliferation ability, compromising reproducibility observations among centers and further applications. We investigated the use of a new technology as a diagnostic tool for quality control on stem cell isolation. The instrument label-free separates cells based on their physical characteristics and, thanks to a micro-camera, generates a live fractogram, the fingerprint of the sample. Eight amniotic membranes were processed by trypsin enzymatic treatment and immediately analysed. Two types of profile were generated: a monomodal and a bimodal curve. The first one represented the unsuccessful isolation with all recovered cell not attaching to the plate, while for the second type, the isolation process was successful, but we discovered that only cells in the second peak were alive and resulted adherent. We optimized a Quality Control (QC) method to define the success of AEC isolation using the fractogram generated. This predictive outcome is an interesting tool for laboratories and cell banks that isolate and cryopreserve fetal annex stem cells for research and future clinical applications.

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: There is limited information on pregnancy loss in women with HIV, and it is still debate whether HIV-related markers may play a role. Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. Methods: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (

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.

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.

At 32 weeks of gestation, a peripheral maternal blood sample was collected for measurement of mRNAs for Ki-67, KiSS-1 metastasis-suppressor (KISS1), PLAC1, PlGF, VEGF and Flt-1 genes. Amounts of mRNA samples were expressed in terms of copies per millilitre and were also measured in 32 pregnant women at 31 to 33 gestational weeks with normal placentation (controls). All the cases included in the study were dated by ultrasound in the first trimester. Copies were converted into multiples of the median (MoM) of unaffected pregnancies. Normal distribution was tested by Kolmogorov–Smirnov test. As we had only one case of placenta accreta data were examined and compared only by visual inspection.Our results are consistent with a possible involvement of KISS1, PLAC1 and VEGF genes in placenta accreta development. These results could allow a more in depth follow-up during the pregnancy in centers where molecular genetics laboratories are available

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.

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.

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 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.