Mode of delivery and peripartum outcome in women with heart disease according to the ESC guidelines: an Italian multicenter study.

INTRODUCTION: The European Society of Cardiology (ESC) guidelines (GL) provide indications on the mode of delivery in women with heart disease. However available data suggests that the rate of Cesarean Delivery (CD) is high and widely variable among such patients. In this study, we aimed to investigate the degree of adherence to the ESC recommendations among women delivering in four tertiary maternity services in Italy and how this affects the maternal and neonatal outcomes. MATERIAL AND METHODS: Retrospective multicenter cohort study including pregnant women with heart disease who gave birth between January 2014 and July 2020. Composite adverse maternal outcome (CAM) was defined by the occurrence of one or more of the following: major postpartum hemorrhage, thrombo-embolic or ischemic event, de novo arrhythmia, heart failure, endocarditis, aortic dissection, need for re-surgery, sepsis, maternal death. Composite Adverse Neonatal outcome (CAN) was defined as cord arterial pH <7.00, APGAR <7 at 5 min, admission to the intensive care unit, and neonatal death. We compared the incidence of CAM and CAN between the cases with planned delivery in accordance (group "ESC consistent") or in disagreement (group "ESC not consistent") with the ESC GL. RESULTS: Overall, 175 women and 181 liveborn were included. A higher frequency of CAN was found when delivery was not planned accordingly to the ESC guidelines [("ESC consistent" 9/124 (7.2%) vs "ESC not consistent" 13/57 (22.8%) p = 0.002 OR 3.74 (CI 95% 1.49-9.74) , while the occurrence of CAM was comparable between the two groups. At logistic regression analysis, the gestational age at delivery was the only parameter independently associated with the occurrence of CAN (p = 0.006). CONCLUSION: Among pregnant women with heart disease, deviating from the ESC guidelines scheduling cesarean delivery does not seem to improve maternal outcomes and it is associated with worse perinatal outcomes, mainly due to lower gestational age at birth.

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. OBJECTIVES: The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. SOURCES: Two databases (PubMed and ClinicalTrial.gov) were reviewed. CONTENT: Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. IMPLICATIONS: Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study.

Electronic spatiotemporal image correlation improves four-dimensional fetal echocardiography.

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.

Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study.

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 < 0.001). Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelines showed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribing physicians might prefer either drug in some particular situations where the different impacts of treatment on lipid profile and bilirubin may have clinical relevance.

Sonographic evaluation of the lower uterine segment thickness in women with a single previous Cesarean section.

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.

Outcome of severe placental insufficiency with abnormal umbilical artery Doppler prior to fetal viability.

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.

Parvovirus B19 in pregnancy: possible consequences of vertical transmission.

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.

Prospective evaluation of the risk of pre-eclampsia using logistic regression analysis.

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 34(th) 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 >or= 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 >or= 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 >or= 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.

Accurate neurosonographic prediction of brain injury in the surviving fetus after the death of a monochorionic cotwin.

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.

X-linked heterochromatin distribution in the holocentric chromosomes of the green apple aphid Aphis pomi.

Chromatin organization in the holocentric chromosomes of the green apple aphid Aphis pomi has been investigated at a cytological level after C-banding, NOR, Giemsa, fluorochrome staining and fluorescent in situ hybridization (FISH). C-banding technique showed that heterochromatic bands are exclusively located on X chromosomes. This data represents a peculiar feature that clearly contradicts the equilocal distribution of heterochromatin typical of monocentric chromosomes. Moreover, silver staining and FISH carried out with a 28S rDNA probe localized rDNA genes on one telomere of each X chromosome; CMA3 staining reveals that these silver positive telomeres are the only GC-rich regions among A. pomi heterochromatin, whereas all other C-positive bands are DAPI positive thus containing AT-rich DNA.

Sonographic demonstration of brain injury in fetuses with severe red blood cell alloimmunization undergoing intrauterine transfusions.

OBJECTIVE: To assess sonographically brain anatomy in fetuses with severe anemia due to red blood cell alloimmunization undergoing intrauterine intravascular transfusions. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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 is

Prenatal diagnosis of a complete mole coexisting with a dichorionic twin pregnancy: case report.

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.

Outcome of antenatally diagnosed intracranial hemorrhage: case series and review of the literature.

OBJECTIVES: Prenatal diagnosis of intracranial hemorrhage (ICH) has been widely reported. Hemorrhages may occur either within the cerebral ventricles, subdural space or infratentorial fossa. The aim of this study was to determine the sonographic criteria for the diagnosis of fetal ICH, the role of in utero magnetic resonance imaging (MRI) and the outcome of this condition. METHODS: The archives of our ultrasound laboratory and the literature were searched for all cases of antenatally diagnosed ICH. A grading system was used to classify the intraventricular lesions as suggested in postnatal sonographic studies. RESULTS: Adding our series of 16 fetuses to the 93 cases identified in the literature, a group of 109 fetal ICHs was obtained: 89 were intracerebral (79 intraventricular and 10 infratentorial) and 20 were subdural hemorrhages. Intraventricular lesions were mostly classified as severe (32 each for Grades III and IV). In 27 cases antenatal MRI was performed additionally to ultrasound and confirmed the sonographic findings. Of the entire group, 65 infants (59%) were reported to be alive 1 month after birth (51 intraventricular hemorrhages, three infratentorial hemorrhages, 11 subdural hematomas). At 12 months, of the 48 infants whose follow-up was available, 25 or 52% were judged neurologically normal (17/36 or 47% among the intraventricular hemorrhages, 6/9 or 66% among the hematomas, and 2/3 or 66% among the infratentorial hemorrhages). CONCLUSIONS: Fetal ICH may be accurately identified and categorized by antenatal sonography. The outcome is usually poor, especially for those fetuses affected by higher-grade intraventricular hemorrhages.

Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers.

Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1.5 to 2 g/d, to our knowledge the highest dosage yet reported. Effects were evaluated on conjugated bile acids (BA) in amniotic fluid (15 of 20 patients) and umbilical cord serum obtained at delivery (20 of 22 newborns), as compared with 10 untreated patients (amniotic fluid, 9 of 10 patients; cord serum, 9 of 10 newborns). Liver function tests, serum BA and UDCA were evaluated on enrollment and then weekly until 1 week after delivery. Maternal serum conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acids levels fell (18.5 +/- 1.9 to 10.5 +/- 1.9 micromol/L, and 5.8 +/- 0.8 to 2.97 +/- 0.7 micromol/L, respectively [P <.01]) in treated patients, and remained unaffected (20.0 +/- 3.1 vs. 20.3 +/- 2.3, and 5.6 +/- 0.6 vs. 5.4 +/- 0.5, respectively [P = not significant]) in untreated ones. Serum conjugated UDCA levels rose to 16.5 +/- 1.8 micromol/L (P<.001). Median values of CCA and CCDCA in amniotic fluid around delivery were 4.9 +/- 12.4 and 4.8 +/- 7.7 micromol/L, respectively, in treated patients, as against 17.9 +/- 27.5 and 18.5 +/- 20.9 micromol/L in untreated ones. In treated mothers, CCA and CCDCA concentrations in cord blood were 6.0 +/- 0.9 and 5.2 +/- 0.95 micromol/L, respectively, as against 21.9 +/- 5.6 and 18.9 +/- 2.1 micromol/L in untreated ones. In treated patients, median UDCA values in amniotic fluid and cord blood were 0.8 +/- 2.4 and 0.9 +/- 0.14 micromol/L, respectively. We conclude that increasing the dose of UDCA more effectively controls ICP and improves maternal clinical outcome after delivery.

Survival analysis of transfused fetuses affected by Rh-alloimmunization.

The aim of the present study was to evaluate the survival rate of a group of 86 fetuses affected by Rh-alloimmunization submitted to intrauterine red blood cell transfusion. All the women had antibody titres> or = 1:32 at the time of their enrollment in the study. Crude fetal survival rate was 89.5% (77/86 cases). Data were stratified according to specific cut-off points of (1) pre-transfusion fetal haemoglobin expressed as the rate between the observed and the estimated value for each gestational age at the time of the first transfusion; (2) the difference between the haemoglobin at the beginning of the second-transfusion less that at the end of the first transfusion (delta haemoglobin); and (3) presence of ultrasound detected anomalies. Statistically significant stratification of the survival rate was observed for the level of pre-transfusion fetal haemoglobin (95% and 76.9%, respectively, p= 0.009) using a cut-off value of < 70% and > or = 70% of the expected value. Again, delta haemoglobin showed a different survival rate when a cut-off value of 6 g/dl was used to generate subgroups of fetuses: 94.6% and 80%, respectively (p= 0.0145). Among the ultrasound anomalies, the presence of hydrops showed a correlation with the survival rates. The quoted values were 97.83% (absence) and 80.0% (presence) respectively (p= 0.0058). Cox regression showed a significant association of the studied variables with the outcome (survival). The presence of hydrops was the best predictor (Odds ratio= 8.7, p= 0.0073) followed by Delta haemoglobin (Odds ratio= 2.0, p= 0.0422). The rate of pre-treatment fetal haemoglobin < 70% of the expected value did not add any significant valu and was thus removed from the final model. Weight at delivery expressed in grams showed a direct correlation with the survival rate (Odds ratio= 0.9, p= 0.1529) and was added into the model as an adjustment quantitative variable.