Intravenous immunoglobulin for the treatment of severe maternal alloimmunization: individual patient data meta-analysis.

OBJECTIVE: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies. DATA SOURCES: Medline, Embase, and Cochrane Library were systematically searched until June 2023. STUDY ELIGIBILITY CRITERIA: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn. METHODS: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework. RESULTS: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. CONCLUSION: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease.

Characteristics and Outcomes of Fetal Cardiac Rhabdomyoma With or Without mTOR Inhibitors, a Systematic Review and Meta-Analysis.

OBJECTIVES: To investigate the characteristics and outcomes of fetal cardiac rhabdomyoma with or without prenatal use of mammalian target of rapamycin inhibitor (mTORi). SEARCH STRATEGY: We systematically searched PubMed, Scopus, and Web of Science until June 2023. SELECTION CRITERIA: Studies reporting on pregnancies with fetal cardiac rhabdomyoma were included. DATA COLLECTION AND ANALYSIS: A meta-analysis of proportions was conducted only on studies that included three or more cases. RESULTS: A systematic review included 61 studies reporting on 400 fetuses with cardiac rhabdomyoma, of which 52 studies (389 fetuses) had expectant management and 9 studies (11 fetuses) were managed with mTORi. The meta-analysis included 26 studies reporting on 354 fetuses. Prenatally, 14% (95% CI 4-36) had pericardial effusion, 13% (95% CI 6-27) had arrhythmia, 16% (95% CI 7-31) had outflow tract obstruction, and 10% (95% CI 4-21) had hydrops. Fetal demise occurred in 12% (95% CI 5-30). Before delivery, tumor size reduction was noted in 13%, and after birth in 58%. Following birth, 8% (95% CI 3-14) had neonatal death and 9% (95% 4-17) required cardiac surgery. 60% (95% CI 41-79) of cases were diagnosed with tuberous sclerosis. Seizures were reported only in cases with a tuberous sclerosis diagnosis (41/71 infants). For the 9 studies reporting all together on 11 fetuses with tuberous sclerosis receiving prenatal mTORi, they showed improvement in the size of cardiac rhabdomyoma as well as outflow obstruction and none had fetal demise or neonatal death, and none required postnatal cardiac surgery. CONCLUSIONS: We report on the natural history of prenatal cardiac rhabdomyoma, including characteristics, progression, and survival. We report 11 fetuses with tuberous sclerosis and cardiac rhabdomyoma receiving prenatal mTORi, showing promising results.

Right ventricular outflow tract obstruction in twin-to-twin transfusion syndrome undergoing laser surgery: A systematic review and meta-analysis.

INTRODUCTION: We aimed to investigate the incidence, prenatal factors and outcomes of twin-to-twin transfusion (TTTS) with right ventricular outflow tract obstruction (RVOTO). MATERIAL AND METHODS: A systematic search was conducted to identify relevant studies published until February 2023 in English using the databases PubMed, Scopus and Web of Science. Studies reporting on pregnancies with TTTS and RVOTO were included. The random-effect model pooled the mean differences or odds ratios (OR) and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 17 studies encompassing 4332 TTTS pregnancies, of which 225 cases had RVOTO, were included. Incidence of RVOTO at time of TTTS diagnosis was 6%. In all, 134/197 (68%) had functional pulmonary stenosis and 62/197 (32%) had functional pulmonary atresia. Of these, 27% resolved following laser and 55% persisted after birth. Of those persisting, 27% required cardiac valve procedures. Prenatal associations were TTTS stage III (53% vs 39% in no-RVOTO), stage IV TTTS (28% in RVOTO vs 12% in no-RVOTO) and ductus venosus reversed a-wave (60% in RVOTO vs 19% in no-RVOTO). Gestational age at laser and gestational age at delivery were comparable between groups. Survival outcomes were also comparable between groups, including fetal demise of 26%, neonatal death of 12% and 6-month survival of 82% in RVOTO group. Findings were similar when subgroup analysis was done for studies including head-to-head analysis. CONCLUSIONS: RVOT occurs in about 6% of the recipient twins with TTTS, especially in stages III and IV and those with reversed ductus venosus a-wave. The findings from this systematic review support the need for a thorough cardiac assessment of pregnancies complicated by TTTS, both before and after laser, to maximize perinatal outcome, and the importance of early diagnosis of TTTS and timely management.

Role of Cerebroplacental Ratio in Predicting the Outcome of Pregnancies Complicated by Diabetes.

INTRODUCTION: Our objective was to evaluate the strength of association and diagnostic performance of cerebroplacental ratio (CPR) in predicting the outcome of pregnancies complicated by pre- and gestational diabetes mellitus. METHODS: PubMed, Embase, Cochrane, and Google Scholar databases were searched. Inclusion criteria were pregnancies complicated by gestational or pregestational diabetes undergoing ultrasound assessment of CPR. The primary outcome was a composite score of perinatal mortality and morbidity as defined by the original publication. The secondary outcomes included preterm birth gestational age (GA) at birth, mode of delivery, fetal growth restriction (FGR) or small for GA (SGA) newborn, neonatal birthweight, perinatal death (PND), Apgar score <7 at 5 min, abnormal acid-base status, neonatal hypoglycemia, admission to neonatal intensive care unit (NICU). Furthermore, we aimed to perform a number of sub-group analyses according to the type of diabetes (gestational and pregestational), management adopted (diet insulin or oral hypoglycemic agents), metabolic control (controlled vs. non-controlled diabetes), and fetal weight (FGR, normally grown, and large for GA fetuses). Head-to-head meta-analyses were used to directly compare the risk of each of the explored outcomes. For those outcomes found to be significant, computation of diagnostic performance of CPR was assessed using bivariate model. RESULTS: Six studies (2,743 pregnancies) were included. The association between low CPR and adverse composite perinatal outcome was not statistically significant (p = 0.096). This result did not change when stratifying the analysis using CPR cut-off below 10th (p = 0.079) and 5th (p = 0.545) centiles. In pregnancies complicated by GDM, fetuses with a low CPR had a significantly higher risk of birthweight <10th percentile (OR: 5.83, 95% confidence interval [CI] 1.98-17.12) and this association remains significant when using a CPR <10th centile (p < 0.001). Fetuses with low CPR had also a significantly higher risk of PND (OR: 6.15, 95% CI 1.01-37.23, p < 0.001) and admission to NICU (OR 3.32, 95% CI 2.21-4.49, p < 0.001), but not of respiratory distress syndrome (p = 0.752), Apgar score <7 at 5 min (p = 0.920), abnormal acid-base status (p = 0.522), or neonatal hypoglycemia (p = 0.005). These results were confirmed when stratifying the analysis including only studies with CPR <10th centile as a cut-off to define abnormal CPR. However, CPR showed a low diagnostic accuracy for detecting perinatal outcomes. CONCLUSION: CPR is associated but not predictive of adverse perinatal outcome in pregnancies complicated by gestational diabetes. The findings from this systematic review do not support the use of CPR as a universal screening for pregnancy complication in women with diabetes.

Diagnostic accuracy of Doppler ultrasound in predicting perinatal outcome in pregnancies at term: A prospective longitudinal study.

INTRODUCTION: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term. MATERIAL AND METHODS: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36+0 and 37+6  weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data. RESULTS: In all, 600 consecutive singleton pregnancies from 36 weeks of gestation were included in the study. Mean MCA PI (1.1 ± 0.2 vs 1.5 ± 0.4, P < 0.001) and cerebroplacental ratio (1.4 ± 0.4 vs 1.9 ± 0.6, P < 0.001) were lower, whereas uterine arteries PI (0.8 ±0.2 vs 0.7 ±0.3, P = 0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P = 0.399) or estimated fetal weight centile (P = 0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P = 0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P = 0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P = 0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P = 0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P = 0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor. CONCLUSIONS: MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.

Diagnostic accuracy of magnetic resonance imaging in detecting the severity of abnormal invasive placenta: a systematic review and meta-analysis.

INTRODUCTION: Accurate prenatal diagnosis of abnormally invasive placenta (AIP) is fundamental because it significantly reduces maternal morbidities. MATERIAL AND METHODS: Medline, Embase, CINAHL and the Cochrane databases were searched. The primary aim of the present review was to elucidate the diagnostic accuracy of prenatal magnetic resonance imaging (MRI) in recognizing the severity of AIP, defined as the depth and topography of invasion. The secondary aim was to ascertain the strength of association between each MRI sign and the depth of placental invasion and to test their individual predictive accuracy in detecting such invasion. Inclusion criteria were studies on women who had prenatal MRI for ultrasound suspicion or the presence of clinical risk factors for AIP. Estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were calculated using the hierarchical summary receiver characteristics curve model, and individual data random-effect logistic regression was used to calculate OR. RESULTS: Twenty studies (1080 pregnancies undergoing MRI mainly for the ultrasound suspicion of AIP) were included. MRI showed a sensitivity of 94.4% [95% confidence interval (CI) 15.8-99.9], 100% (95% CI 75.3-100) and 86.5% (95% CI 74.2-94.4) for detection of placenta accreta, increta and percreta, respectively; the corresponding values for specificity were 98.8% (95% CI 70.7-100), 97.3% (95% CI 93.3-99.3), 96.8% (95% CI 93.5-98.7). MRI identified 100% of cases with S1 and 100% of those with S2 invasion confirmed at surgery. Among the different MRI signs, intra-placental dark bands showed the best sensitivity for the detection of placenta accreta, increta and percreta; as well as abnormal intra-placental vascularity, uterine bulging was associated with a higher risk of increta and percreta, exophitic mass and bladder tenting with placenta percreta. CONCLUSION: Prenatal MRI has an excellent diagnostic accuracy in identifying the depth and the topography of placental invasion. However, these findings come mainly from studies in which MRI was performed as a secondary imaging tool in women already screened for AIP on ultrasound and might not reflect its actual diagnostic performance in detecting the severity of these disorders.

Diagnostic accuracy of ultrasound in detecting the depth of invasion in women at risk of abnormally invasive placenta: A prospective longitudinal study.

INTRODUCTION: The aim of this study was to assess the diagnostic accuracy of ultrasound in detecting the depth of abnormally invasive placenta in women at risk. MATERIAL AND METHODS: Prospective longitudinal study including women with placenta previa and at least one prior cesarean delivery or uterine surgery. Depth of abnormally invasive placenta was defined as the degree of trophoblastic invasion through the myometrium and was assessed with histopathological analysis. The ultrasound signs explored were: loss of clear zone, placental lacunae, bladder wall interruption, uterovesical hypervascularity, and increased vascularity in the parametrial region. RESULTS: In all, 210 women were included in the analysis. When using at least one sign, ultrasound had an overall sensitivity of 100% (95% CI 96.5-100) and overall specificity of 61.9 (95% CI 51.9-71.2) for all types of abnormally invasive placenta. Using two ultrasound signs increased the diagnostic accuracy in terms of specificity (100%, 95% CI 96.5-100) but did not affect sensitivity. When stratifying the analysis according to the depth of placental invasion, using at least one sign had a sensitivity of 100% (95% CI 93.7-100) and 100% (95% CI 92.6-100) for placenta accreta/increta and percreta, respectively. Using three ultrasound signs improved the detection rate for placenta percreta with a sensitivity of 100% (95% CI 92.6-100) and a specificity of 77.2% (95% CI 69.9-83.4). CONCLUSION: Ultrasound has a high diagnostic accuracy in detecting the depth of placental invasion when applied to a population with specific risk factors for anomalies such as placenta previa and prior cesarean delivery or uterine surgery.

Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: a systematic review and meta-analysis.

INTRODUCTION: Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP). MATERIAL AND METHODS: Medline, Embase, CINAHL and The Cochrane databases were searched. The ultrasound signs explored were: loss of hypoechoic (clear) zone in the placental-uterine interface, placental lacunae, bladder wall interruption, myometrial thinning, focal exophitic mass, placental lacunar flow, subplacental vascularity, and uterovesical hypervascularity. RESULTS: Twenty studies (3209 pregnancies) were included. Ultrasound had an overall good diagnostic accuracy in identifying the depth of placental invasion with sensitivities of 90.6%, 93.0%, 89.5%, and 81.2% for placenta accreta, increta, accreta/increta, and percreta, respectively; the corresponding specificities were 97.1%, 98.4%, 94.7%, and 98.9%. Placental lacunae had sensitivities of 74.8%, 88.6%, and 76.3% for the detection of placenta accreta, increta, and percreta, respectively. Sensitivity and specificity of loss of the clear zone in identifying placenta accreta were 74.9% and 92.0%, whereas the corresponding figures for placenta increta and percreta were 91.6% and 76.9%, and 88.1% and 71.1%. Lacunar flow had sensitivities of 81.2%, 84.3%, and 45.2% for the detection of placenta accreta, increta, and percreta respectively; the corresponding figures for specificity were 84.0%, 79.7%, and 75.3%. Sensitivity of uterovesical hypervascularity was low for the detection of placenta accreta (12.3%) but high for placenta increta (94.4%) and percreta (86.2%); the corresponding figures for specificity were 90.8%, 88.0% and 88.2%, respectively. CONCLUSIONS: Ultrasound has an overall good diagnostic accuracy in recognizing the depth and the topography of placental invasion.

Cervical Pessary for Preventing Preterm Birth in Singleton Pregnancies With Short Cervical Length: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in singleton gestations with a second trimester short cervix. METHODS: Electronic databases were searched from their inception until February 2016. We included randomized clinical trials (RCTs) comparing the use of the cervical pessary with expectant management in singletons pregnancies with transvaginal ultrasound cervical length (TVU CL) ≤25 mm. The primary outcome was incidence of SPTB <34 weeks. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Three RCTs (n = 1,420) were included. The mean gestational age (GA) at randomization was approximately 22 weeks. The Arabin pessary was used as intervention in all three trials, and was removed by vaginal examination at approximately 37 weeks. Cervical pessary was not associated with prevention of SPTB <37 (20.2% vs 50.2%; RR 0.50, 95% CI 0.23 to 1.09), <34, <32, and <28 weeks, compared to no pessary. No differences were found in the mean of GA at, interval from randomization to delivery, incidence of preterm premature rupture of membranes and of cesarean delivery, and in neonatal outcomes. The Arabin pessary was associated with a significantly higher risk of vaginal discharge. CONCLUSIONS: In singleton pregnancies with a TVU CL ≤25mm at 200 -246 weeks, the Arabin pessary does not reduce the rate of spontaneous preterm delivery or improve perinatal outcome. Individual patient data meta-analysis may clarify whether cervical pessary may be beneficial in subgroups, such as only singleton gestations without prior SPTB or by different CL cutoffs.

Pregnancy outcome and long-term follow-up of fetuses with isolated increased NT: a retrospective cohort study.

OBJECTIVE: To assess the prevalence of associated findings, diagnosed either prior to or after birth, among fetuses with increased nuchal translucency (NT) and normal karyotype and to investigate the prevalence of children under therapy at school age, among cases confirmed to be isolated both prior to and after birth. METHODS: Retrospective cohort study of all singleton pregnancies were referred for the 1st trimester screening for Down syndrome between January 2004 and December 2006. Cases with NT >95th percentiles who undertook fetal karyotype were analyzed. We evaluated the prevalence of the following: (i) abnormal fetal karyotype, (ii) associated structural abnormalities, (iii) genetic syndromes, and (iv) children needing treatment (i.e. medications or psychopedagogical intervention) at school age. RESULTS: There were 19 106 women screened for Down syndrome. Among them, 846 (4.4%) had a NT >95th centile, of whom 541 (64.0%) undertook fetal karyotyping, 422 (78.0%) had normal karyotype, two (0.5%) opted for termination of pregnancy, and four (1.0%) ended in miscarriages. Among the 384 cases thought to be "normal" prior to birth, 14 (3.6%) were lost at follow-up and 10 (2.7%) had an associated abnormality diagnosed postnatally. Among the cases confirmed to be isolated, 10/270 (3.7%) were under treatment at the time of telephonic interview with parents. CONCLUSIONS: Parents should be informed that fetuses with increased NT and normal karyotype need detailed ultrasound scans during pregnancy and detailed pediatric evaluation at birth; if these are normal, the risk from adverse outcome at school age is the same as for general population.

π-Conjugated zwitterions as paradigm of donor-acceptor building blocks in organic-based materials.

The very peculiar characteristics of zwitterions, as well as a clearand unambiguous definition, have been overlooked in past literature. However, these compounds are particularly important in view of the impact they have had in the recent past and will likely continue to have in the future as components of performing functional organic and hybrid materials. In this Account, we primarily aim to define critically important organic concepts of zwitterions regarding both their design and nomenclature. We will particularly focus on a specific kind of zwitterions we define as π-conjugated zwitterions. These types of zwitterions are systems pertaining to the class ofdonor-acceptor (push-pull) molecules. In the ground state, they are preferentially represented in terms of an electron donor moiety bearing a negative net charge, and electron acceptor one bearing a positive net charge connected by a conjugated bridge. As such, they are possibly the most effective example of push-pull structure, possessing relevant features for applications like nonlinear optics, photovoltaics, imaging, and high capacitance dielectrics. In addition, the interaction between these dipolar compounds and the environment is highly specific and can be exploited in the construction of well-organized nanostructures, both in solution and in the solid state. According to the Gold Book of IUPAC for nomenclature, the distinction between zwitterions and the charged molecule called a betaine is subtle. The betaine is a particular class of zwitterion possessing an onium atom not bearing a hydrogen. The two terms are often considered equivalent, thus generating confusion while retrieving literature. In this Account, we define and describe π-conjugated zwitterions systems that are dipolar in the ground state, admitting resonance limiting structures that are neutral and chargeless. For the purpose of this Account and to the benefit of researchers striving to retrieve materials-related zwitterion literature data, we suggest to use the term π-zwitterions instead of the commonly used plain term "zwitterions". We show that this definition enables the clear identification of a class of compounds having unique properties distinct from "dipolar conjugated compounds." We describe the most common donor and acceptor groups in π-zwitterions. In particular, we focus our attention on the special case of the nitrile functionality, which tends to be contiguous to a negative charge. We also address special emphasis to benzenoid components that are substituted by heteroaromatic units in π-zwitterions, because the HOMO-LUMO energetic consequences are specifically involved in these cases. We make reference to the paradigmatic case of π-zwitterions second order nonlinear optical properties. Here, the value of the first hyperpolarizability ß versus the alternation in bond length turns out to be a measure of the balance of the chargeless and the dipolar contribution to the description of the zwitterion ground state. We also report literature data, collected both from our group and others, concerning π-zwitterions containing heteroaromatic and/or nitrile groups, those based on the most performing acceptors so far described, and merocyanines. With particular reference to merocyanines, we show how π-zwitterions can play a fundamental role in the fast growing field of organic photovoltaics. Finally, we present π-zwitterions made up of heteroaromatic groups that open new scenarios in heteroaromatic chemistry.

Number of episodes of reduced fetal movement at term: association with adverse perinatal outcome.

OBJECTIVE: The aims of this study were evaluation of the association of reduced fetal movements (RFM) and small-for-gestational-age (SGA) birth at term and to explore if fetal and maternal outcomes are different with single vs repeated episodes of RFM and normal fetal assessment test results. STUDY DESIGN: This was a retrospective cohort study of all singleton pregnancies referred for RFMs at a tertiary fetal medicine unit from January 2008 through September 2014. Ultrasound and Doppler indices were obtained from a computerized ultrasound database and pregnancy outcome was collected from hospital records. RESULTS: Of the 21,944 women with a singleton pregnancy booked for maternity care during the study period, 1234 women (5.62%) reported RFMs >36+0 weeks. Of these, 1029 women (83.4%) reported a single episode of RFM and 205 (16.6%) had ≥2 presentations for RFM. Women with repeated RFMs had a significantly higher mean uterine artery pulsatility index in the second trimester. The prevalence of SGA baby at birth in women presenting with a single episode as compared to repeated episodes of RFM was 9.8% and 44.2%, respectively (odds ratio, 7.3; 95% confidence interval, 5.1-10.4; P < .05). CONCLUSION: Repeated episodes of RFMs at term are more likely to occur in women with high second-trimester uterine artery Doppler resistance indices and are strongly associated with the birth of SGA infants. Women presenting with repeated episodes of RFM should be treated as being at high risk of placental dysfunction irrespective of the results of prenatal ultrasound and Doppler assessment.

The natural history of monoamniotic twin pregnancies: a case series and systematic review of the literature.

OBJECTIVE: To describe the natural history of monoamniotic twin pregnancies in contemporary practice. METHOD: Cohort study of monochorionic monoamniotic twin pregnancies with two live fetuses diagnosed at less than 16 weeks and prospectively followed up between 2004 and 2013. A systematic review of the literature using Medline, Embase and Scopus to determine the perinatal mortality rate after 24 weeks of gestation in monoamniotic twins was also performed. RESULTS: Twenty pregnancies were analyzed. Four were terminated (in three cases as a result of fetal abnormalities). Another six miscarried spontaneously. Among ten pregnancies reaching viability, there was double intrauterine death in one, and both fetuses were alive at delivery in the other nine. There were no neonatal deaths. Overall survival for fetuses alive at the initial scan was 18/40 (45%; 95% CI 29 to 62%). At meta-analysis of 13 studies (including the current series), the perinatal mortality rate after 24 weeks was 4.5% (95% CI 3.3 to 5.8%). CONCLUSIONS: Despite early diagnosis and intensive monitoring, of those fetuses alive before 16 weeks less than half survive until the neonatal period. Most losses are attributable to fetal abnormalities and spontaneous miscarriage and are therefore unlikely to be reduced by further improvements in fetal assessment and monitoring. © 2014 John Wiley & Sons, Ltd.

The role of second trimester uterine artery Doppler in pregnancies with systemic lupus erythematosus.

OBJECTIVE: The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE). METHODS: Cohort study of consecutive pregnancies complicated with SLE during a period of 12 years is used. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight <10th percentile. Adverse pregnancy outcome (APO) was defined as one of the following: pre-eclampsia (PE), SGA, placental abruption, stillbirth, or neonatal death. Differential diagnosis between PE and renal flare was made according to SLE-disease activity index. RESULTS: There are 70 pregnancies in 64 women. PE was observed in four cases (6%), SGA in five cases (7%), and APO in seven cases (10%). mUtA PI showed a sensitivity and a specificity of 1.0 (95% CI 0.5-1.0) and 1.0 (95% CI 0.95-1.0) for PE, 0.40 (95% CI 0.12-0.77) and 0.97 (95% CI 0.89-0.99) for SGA, and 0.57 (95% CI 0.25-0.84) and 1.0 (95% CI 0.94-1.0) for APO, respectively. CONCLUSION: Our findings suggest that uterine artery Doppler is confirmed to be a high sensitivity and a high specificity test for predicting PE even in SLE patients.

The prognostic role of various indices and ratios of Doppler velocimetry in patients with pre-eclampsia.

Doppler velocimetry is a non-invasive method to monitor pregnancies complicated by pre-eclampsia. We aimed to assess the predictive value of adverse perinatal or maternal outcome of three ratios, i.e. middle cerebral to umbilical arteries pulsatility indices (PI), middle cerebral to uterine arteries PI and uterine to umbilical arteries PI, compared with that of uterine and umbilical arteries PI in pre-eclamptic patients. This is a cohort study on 168 singleton pregnancies between January 2010 and June 2013. Doppler velocimetry was performed at the diagnosis of pre-eclampsia. Logistic regression analysis was performed and receiver-operating characteristics (ROC) curves were calculated to determine the predictive ability of each Doppler index. Multivariate analysis was run to adjust results for confounding parameters. Seventy-eight cases were complicated by adverse perinatal outcome, 79 by maternal one, 49 by both. Considering perinatal outcome, area under ROC curve was 0.730 for uterine arteries PI, 0.691 for umbilical artery PI and 0.834 for middle cerebral to uterine arteries PI ratio, while for maternal one 0.720 for uterine arteries PI, 0.686 for umbilical artery PI and 0.817 for middle cerebral to uterine arteries PI ratio. At multivariate analysis, only middle cerebral to uterine arteries PI ratio remain statistically significant for both outcomes (p = 0.001). The cited ratio appeared more accurate than all other considered indices in predicting perinatal and maternal outcomes in patients affected by pre-eclampsia.

Brief report: successful pregnancies but a higher risk of preterm births in patients with systemic sclerosis: an Italian multicenter study.

OBJECTIVE: To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). METHODS: Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months). RESULTS: SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years. CONCLUSION: Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies.

Effects of antenatal recognition and follow-up on perinatal outcomes in small-for-gestational age infants delivered after 36 weeks.

OBJECTIVE: To compare perinatal outcomes of late small-for-gestational age (SGA, birthweight <10th percentile) infants, according to antenatal recognition. DESIGN: Retrospective study. SETTING: Tertiary referral center. POPULATION: All singleton pregnancies with SGA (birthweight <10th percentile) infants born ≥36 weeks' gestation from January 2007 to April 2009. METHODS: Chart review of 771 pregnancies. SGA infants identified prior to delivery (group A) were compared with those not identified (group B). MAIN OUTCOME MEASURES: Mode of delivery, perinatal complications, admission to neonatal intensive care unit (NICU). In group A, receiver operating characteristic (ROC) analysis and area under the curve (AUC) of antenatal tests to predict NICU admission were calculated. RESULTS: In 17% of infants, SGA was recognized before birth (group A), whereas in 83% it was recognized only at birth (group B). Infants with the most severe degree of SGA (birthweight <3rd percentile) were more frequently diagnosed antenatally (30%). Admission to NICU (14 vs. 3%, p < 0.001) and cesarean delivery (42 vs. 26%; p < 0.001) were more likely in group A. Adverse outcomes related to hypoxia were all observed in group B, but the difference was not significant. In antenatally detected fetuses a combination of fetal abdominal circumference, umbilical artery pulsatility index and middle cerebral artery pulsatility index z-scores was useful for prediction of NICU admission (AUC = 0.94). CONCLUSION: Antenatal recognition of late SGA may improve perinatal outcomes. However, admission to neonatal intensive care and cesarean delivery were more frequent among SGA infants recognized antenatally.

Cervical cerclage in twin pregnancies.

PURPOSE: To evaluate the outcomes of cervical cerclage (CC) in twin pregnancies. METHODS: Retrospective analysis of twin pregnancies undergoing CC between January 2001 and December 2009 at our Institution. CC was offered in case of a cervical length measurement ≤ 20 mm (ultrasound-indicated CC) or in case of cervical dilatation with membranes at or beyond the external cervical os (physical examination-indicated CC). Cervicovaginal and rectal swabs were obtained preoperatively. Perioperative antibiotics and tocolysis were administered. RESULTS: There were 28 cases of ultrasound-indicated and 14 of physical examination-indicated CC. Positive swab cultures were observed in 21 % of cases. The incidence of preterm delivery <34 weeks was 32 % [95 % confidence interval (CI) 16-52 %] and 50 % (95 % CI 23-77 %) in the ultrasound-indicated and physical examination-indicated CC group, respectively. The incidence of premature rupture of membranes <34 weeks was 21 % (95 % CI 8-41 %) and 29 % (95 % CI 8-58 %) in the ultrasound-indicated and physical examination-indicated CC group, respectively. Perinatal survival was 96 % (95 % CI 88-100 %) in the ultrasound-indicated CC group, and 86 % (95 % CI 67-96 %) in the physical examination-indicated CC group. CONCLUSIONS: We showed a high-risk of preterm delivery in both groups, but with a high overall perinatal survival. Our data stress the importance of re-evaluating the efficacy of CC in twin pregnancies by properly designed clinical trials, particularly if it is physical examination indicated.

Monkeypox infection in pregnancy: a systematic review and metaanalysis.

OBJECTIVE: The World Health Organization has recently declared a monkeypox outbreak as a public health emergency of global concern. The main aim of this systematic review was to ascertain the maternal and perinatal outcomes of pregnancies complicated by monkeypox infection. DATA SOURCES: The Medline, Embase, and Cochrane databases were searched on June 25, 2022 utilizing combinations of the relevant medical subject heading terms, key words, and word variants for "monkeypox" and "pregnancy." STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The outcomes observed were miscarriage; intrauterine, neonatal, and perinatal death; preterm birth, vertical transmission, and maternal symptoms. A metaanalysis of proportions was used to analyze the data. RESULTS: Four studies were included. All the cases in the present systematic review presented with symptoms and signs of monkeypox infection. There was no case of maternal death. Miscarriage occurred in 39% of cases (95% confidence interval, 0-89.0), whereas intrauterine fetal death occurred in 23.0% (95% confidence interval, 0-74.0) of cases. The overall incidence of late fetal and perinatal loss was 77.0% (95% confidence interval, 26.0-100), whereas only 23% (95% confidence interval, 0-74.0) of the included fetuses survived to birth. The incidence of preterm birth before 37 weeks of gestation was 8.0% (95% confidence interval, 0-62.0). Vertical transmission occurred in 62.0% (95% confidence interval, 3.0-100) of cases. When stratifying the analysis according to gestational age at infection, fetal loss was found to occur in 67.0% (95% confidence interval, 9.0-99.0) of cases with first-trimester infection and in 82.0% (95% confidence interval, 17.0-100) of those with second-trimester infection. CONCLUSION: Monkeypox infection in pregnancy is associated with a high risk of perinatal loss and vertical transmission. The preliminary results from this systematic review affected by a very small number of included cases highlight the need for thorough maternal and fetal surveillance in pregnancies complicated by monkeypox infection.

Diagnostic yield with exome sequencing in prenatal severe bilateral ventriculomegaly: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to determine the incremental diagnostic yield of prenatal exome sequencing after negative chromosomal microarray analysis results in prenatally diagnosed bilateral severe ventriculomegaly or hydrocephalus; another objective was to categorize the associated genes and variants. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022 using 4 databases (Cochrane Library, Web of Science, Scopus, and MEDLINE). STUDY ELIGIBILITY CRITERIA: Studies in English reporting on the diagnostic yield of exome sequencing following negative chromosomal microarray analysis results in cases of prenatally diagnosed bilateral severe ventriculomegaly were included. METHODS: Authors of cohort studies were contacted for individual participant data, and 2 studies provided their extended cohort data. The incremental diagnostic yield of exome sequencing was assessed for pathogenic/likely pathogenic findings in cases of: (1) all severe ventriculomegaly; (2) isolated severe ventriculomegaly (as the only cranial anomaly); (3) severe ventriculomegaly with other cranial anomalies; and (4) nonisolated severe ventriculomegaly (with extracranial anomalies). To be able to identify all reported genetic associations, the systematic review portion was not limited to any minimal severe ventriculomegaly case numbers; however, for the synthetic meta-analysis, we included studies with ≥3 severe ventriculomegaly cases. Meta-analysis of proportions was done using a random-effects model. Quality assessment of the included studies was performed using the modified STARD (Standards for Reporting of Diagnostic Accuracy Studies) criteria. RESULTS: A total of 28 studies had 1988 prenatal exome sequencing analyses performed following negative chromosomal microarray analysis results for various prenatal phenotypes; this included 138 cases with prenatal bilateral severe ventriculomegaly. We categorized 59 genetic variants in 47 genes associated with prenatal severe ventriculomegaly along with their full phenotypic description. There were 13 studies reporting on ≥3 severe ventriculomegaly cases, encompassing 117 severe ventriculomegaly cases that were included in the synthetic analysis. Of all the included cases, 45% (95% confidence interval, 30-60) had positive pathogenic/likely pathogenic exome sequencing results. The highest yield was for nonisolated cases (presence of extracranial anomalies; 54%; 95% confidence interval, 38-69), followed by severe ventriculomegaly with other cranial anomalies (38%; 95% confidence interval, 22-57) and isolated severe ventriculomegaly (35%; 95% confidence interval, 18-58). CONCLUSION: There is an apparent incremental diagnostic yield of prenatal exome sequencing following negative chromosomal microarray analysis results in bilateral severe ventriculomegaly. Although the greatest yield was found in cases of nonisolated severe ventriculomegaly, consideration should also be given to performing exome sequencing in cases of isolated severe ventriculomegaly as the only brain anomaly identified on prenatal imaging.