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.

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.

Comparison between trans-vaginal and trans-abdominal ultrasound examination of the cervix in the second trimester of pregnancy: a prospective study.

OBJECTIVES: To compare transvaginal (TV) and trans-abdominal (TA) ultrasound assessment of cervical length (CL) at the time of the second-trimester scan for fetal anomalies. METHODS: This was a prospective study including consecutive pregnant women attending the low-risk ultrasound clinic of two fetal medicine centres in Italy. The inclusion criteria were women between 19 + 0 and 22 + 0 weeks of gestation, attending the prenatal ultrasound clinic for the routine second trimester screening for fetal anomalies. The primary outcome was to compare the CL measurement obtained at TV compared to TA ultrasound; the secondary outcome was to report the inter and intra-observer variability of CL measured with the two different approaches. All women underwent TV and TA assessment of the cervix performed by two experienced certified operators, blinded to each other. Intra-class correlation coefficients (ICC) and Bland-Altman analyses were used to analyse the data. RESULTS: Two hundred and fifty women were included in the analysis. All women had anteverted uterus. The mean gestational age at ultrasound was 20.7 ± 0.7 weeks; 1.2 % (3/250) scans were performed at 19 weeks, 49.2 % (123/250) at 20 weeks, 44.8 % (112/250) at 21 weeks and 4.8 % (12/250) at 22 weeks of gestations. Identification of the major landmarks of CL at TA ultrasound was achieved in all the included cases. There was good reliability between CL measured at TA (ICC 0.95, 95 % CI 0.93-0.97 for observer 1 and 0.92 %, 95 % CI 0.89-0.94 for observer 2) and TV ultrasound 0.97, 95 % CI 0.96-0.98 for observer 1 and 0.96, 95 % CI 0.95-0.97 for observer 2). There was also good reliability between the two observers for both the TA and TV assessment of the CL. Mean TA CL was 41.4 ± 5.5 for observer 1 and 40.5 ± 4.8 for observer 2 with no significant differences between the two measurements (mean difference 0.92 mm, 95 % CI -9.7 to 11.2). Likewise, there was no difference between the CL measured at TV ultrasound between the two observers (mean difference -0.83 mm, 95 % CI -5.97 to 4.30). Finally, there was no difference in the mean CL measured at TA compared to TV, either considering the overall population of women (mean difference: -0.43, 955 CI -8.65 to 7.79), or when stratifying the analysis according to the parity status and the operator. CONCLUSIONS: Among experienced operators, there was no difference between TV and TA ultrasound assessment of the CL at the time of the routine anomaly scan for fetal anomaly.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Cervical length as a screening tool for preterm birth in twin pregnancies: a systematic review and critical evaluation of quality clinical practice guidelines.

OBJECTIVES: Twin pregnancies are at increased risk of preterm birth (PTB) compared to singletons. Evaluation of cervical length (CL) represents the optimal tool to screen PTB in singleton. Conversely, there is less evidence on the use of CL in twins. Our aim was to evaluate the methodological quality and clinical heterogeneity of clinical practice guidelines (CPGs) on the CL application in twins using AGREE II methodology. METHODS: MEDLINE, Scopus, and websites of the main scientific societies were examined. The following aspects were evaluated: diagnostic accuracy of CL, optimal gestational age at assessment and interventions in twin pregnancies with reduced CL. The quality of the published CPGs was carried out using "The Appraisal of Guidelines for REsearch and Evaluation (AGREE II)" tool. The quality of guideline was rated using a scoring system. Each considered item was evaluated by the reviewers on a seven-point scale that ranges from 1 (strongly disagree) to 7 (strongly agree). A cut-off >60 % identifies a CPGs as recommended. RESULTS: The AGREE II standardized domain scores for the first overall assessment had a mean of 74 %. The score was more than 60 % in the 66.6 % of CPGs analyzed indicating an agreement between the reviewers on recommending the use of these CPGs. A significant heterogeneity was found; there was no specific recommendation on CL assessment in about half of the published CPGs. There was also significant heterogeneity on the CL cut-off to prompt intervention. CONCLUSIONS: Despite the fact that the AGREE II analysis showed that the majority of the included guidelines are of good quality, there was a significant heterogeneity among CPGs as regard as the indication, timing, and cut-off of CL in twins as well as in the indication of interventions.

Effects of gender on fetal cortical development: a secondary analysis of a prospective cross-sectional study.

OBJECTIVES: The primary objective was to evaluate the effects of fetal sex on fetal cortical development in low-risk pregnancies. Secondary objective was the evaluate the impact of gestational age. METHODS: This was a secondary analysis of a prospective cross-sectional study on low-risk fetuses undergoing fetal neurosonography between 19 and 34 weeks of gestation. The depth of Sylvian Fissure (SF), Parieto Occipital Fissure (POF) and Calcarine Fissure (CF) were evaluated and related to fetal sex. Neurosonographic variables were normalized for fetal head circumference and expressed as multiple of the median (MoM). RESULTS: A total of 344 fetuses were considered (173 male, 171 female). The baseline characteristic of the two groups were similar except a higher birthweight present in male fetuses (p=0.044). The depth SF (p=0.023) CF (p=0.014) and POF (p=0.046) showed significantly higher values in male fetuses when all the gestational age range was considered. However, when data were controlled for gestational age, these differences resulted significant only after 28 weeks. CONCLUSIONS: Differences in cortical development related to gender occur after 28 weeks of gestation with an increase depth of SF, POF and CF in male fetuses.

Ultrasound prediction of fetal macrosomia in pregnancies complicated by diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of ultrasound in identifying fetuses with macrosomia in pregnancies complicated by gestational or pregestational diabetes. METHODS: Medline, Embase and Cochrane databases were searched. Inclusion criteria were singleton pregnancies complicated by diabetes undergoing third-trimester ultrasound evaluation. The index test was represented by ultrasound estimation of fetal macrosomia (estimated fetal weight EFW or abdominal circumference AC >90th or 95th percentile). Subgroup analyses were also performed. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating characteristics model. RESULTS: Twenty studies were included in the systematic review including 8,530 pregnancies complicated by diabetes. Ultrasound showed an overall moderate accuracy in identifying fetuses with macrosomia with a sensitivity of 71.2 % (95 % CI 63.1-78.2), a specificity of 88.6 % (95 % CI 83.9-92.0). The interval between ultrasound and birth of two weeks showed the highest sensitivity and specificity (71.6 %, 95 % CI 47.9-87.3 and 91.7, 95 % CI 86.2-95.5). EFW sensitivity and specificity were 76.6 % (95 % CI 70.1-82.3) and 82.9 % (95 % CI 80.9-84.8), while AC 84.8 % (95 % CI 78.2-90.0) and 73.7 % (95 % CI 71.0-76.4). CONCLUSIONS: Ultrasound demonstrates an overall good diagnostic accuracy in detecting fetal macrosomia in pregnancies with diabetes.

Outcome of fetal congenital pulmonary malformations: a systematic review and meta-analysis.

OBJECTIVES: To report the outcome of fetuses with a prenatal diagnosis of congenital lung malformation (CLM) diagnosed on ultrasound by performing a comprehensive assessment of these outcomes through a systematic review and meta-analysis. CONTENT: CLMs are a heterogeneous group of anomalies that involve the lung parenchyma and its bronchovascular structures. Their presentation and evolution are variable, from entirely asymptomatic lesions with sonographic regression in utero to hydropic fetuses requiring fetal therapy, intrauterine death or neonatal morbidity. A systematic review was conducted in Medline, Embase and Cochrane databases including studies on fetuses with CLM diagnosed prenatally in order to report the in-utero natural history of these lesions. Thirty-nine studies (2,638 fetuses) were included in the final review. SUMMARY: Regression/reduction in size of the lung lesion during pregnancy was reported in 31 % of cases, while its increase in 8.5 % of cases. Intra-uterine death complicated 1.5 % of pregnancies with fetal CLM, while neonatal and perinatal death were 2.2 and 3 %, respectively. Neonatal morbidity occurred in 20.6 % of newborns with CLM; 46 % had surgery, mainly elective. In fetuses with CLM and hydrops, fetal/perinatal loss occurred in 42 %. Assessment of the role of fetal therapy in improving the outcomes of pregnancies complicated by CLM was hampered by the small number of included cases and heterogeneity of type of interventions. OUTLOOK: Fetuses with CLM prenatally diagnosed have a generally favorable outcome. Conversely, there is a low quality of evidence on the actual role of fetal therapy in improving the outcome of fetuses presenting with these anomalies.

Fetal brain development in pregnancies complicated by gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) carries an increased risk of neurocognitive impairment in offsprings. However, the contribution of maternal hyperglycemia in affecting fetal brain development is not fully elucidated yet. The aim of this study was to evaluate fetal brain and sulci development in pregnancies complicated by GDM. METHODS: Prospective observational study including 100 singleton pregnancies complicated by GDM and 100 matched controls. All fetuses underwent neurosonography at 29-34 weeks of gestation, including the assessment of the length of the corpus callosum (CC), cerebellar vermis (CV), Sylvian (SF), parieto-occipital (POF) and calcarine fissures (CF). Sub-group analysis according to the specific treatment regimen adopted (n 67 diet vs. 33 insulin therapy) was also performed. RESULTS: Fetuses from mothers with GDM under insulin therapy had a smaller CC (35.54 mm) compared to both controls (40 mm; p<0.001) and women with GDM under diet (39.26 mm; p=0.022) while there was no difference in the HC between the groups. Likewise, when corrected for HC, CV depth was smaller in fetuses with GDM both under insulin therapy (7.03 mm) and diet (7.05 mm,) compared to controls (7.36 mm; p=0.013). Finally, when assessing the sulci development of the brain SF (p≤0.0001), POF (p≤0.0001) and CF (p≤0.0001) were significantly smaller in fetuses with maternal GDM. Post-hoc analysis showed that fetuses of GDM mothers requiring insulin therapy had significantly lower values of SF (p=0.032), POF (p=0.016) and CF (p=0.001). CONCLUSIONS: Pregnancies complicated by GDM showed a peculiar pattern of fetal brain growth and cortical development and these changes, which are more evident in those requiring insulin supplementation.

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.

Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.

BACKGROUND: The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies. METHODS AND FINDINGS: Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low. CONCLUSIONS: Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.

Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study.

OBJECTIVES: To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection. METHODS: In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection. RESULTS: One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as ≥100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12. CONCLUSIONS: Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load.

Modeling fetal cortical development by quantile regression for gestational age and head circumference: a prospective cross sectional study.

OBJECTIVES: To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). RESULTS: The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable. CONCLUSIONS: We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment.

A systematic review and critical evaluation of quality of clinical practice guidelines on fetal growth restriction.

INTRODUCTION: To systematically identify and critically assess the quality of clinical practice guidelines (CPGs) on management fetal growth restriction (FGR). CONTENT: Medline, Embase, Google Scholar, Scopus and ISI Web of Science databases were searched to identify all relevant CPGs on FGR. SUMMARY: Diagnostic criteria of FGR, recommended growth charts, recommendation for detailed anatomical assessment and invasive testing, frequency of fetal growth scans, fetal monitoring, hospital admission, drugs administrations, timing at delivery, induction of labor, postnatal assessment and placental histopathological were assessed. Quality assessment was evaluated by AGREE II tool. Twelve CPGs were included. Twenty-five percent (3/12) of CPS adopted the recently published Delphi consensus, 58.3% (7/12) an estimated fetal weight (EFW)/abdominal circumference (AC) EFW/AC <10th percentile, 8.3% (1/12) an EFW/AC <5th percentile while one CPG defined FGR as an arrest of growth or a shift in its rate measured longitudinally. Fifty percent (6/12) of CPGs recommended the use of customized growth charts to assess fetal growth. Regarding the frequency of Doppler assessment, in case of absent or reversed end-diastolic flow in the umbilical artery 8.3% (1/12) CPGs recommended assessment every 24-48, 16.7% (2/12) every 48-72 h, 1 CPG generically recommended assessment 1-2 times per week, while 25 (3/12) did not specifically report the frequency of assessment. Only 3 CPGs reported recommendation on the type of Induction of Labor to adopt. The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 50%. OUTLOOK: There is significant heterogeneity in the management of pregnancies complicated by FGR in published CPGs.

Evaluation of an artificial intelligent algorithm (Heartassist™) to automatically assess the quality of second trimester cardiac views: a prospective study.

OBJECTIVES: The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination. METHODS: In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19-23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen's κ coefficient was used to evaluate the agreement rates between both techniques. RESULTS: The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen's κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662-0.992), 0.814 (95 % CI 0.638-0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683-0.992) and three vessel trachea view 0.866 (95 % CI 0.717-0.999), indicating a good agreement between the two techniques. CONCLUSIONS: Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies.

Placenta accreta spectrum disorders clinical practice guidelines: A systematic review.

OBJECTIVES: To objectively assess the quality of the published clinical practice guidelines (CPGs) on the management of pregnancies complicated by placenta accreta spectrum (PAS)disorders. METHODS: MEDLINE, Embase, Scopus, and ISI Web of Science databases were searched. The following aspects related to the management of pregnancies with suspected PAS disorders were evaluated: risk factors for PAS, prenatal diagnosis, role of interventional radiology and ureteral stenting, and optimal surgical management. The assessment of risk of bias and quality assessment of the CPGs were performed using the (AGREE II) tool (Brouwers et al., 2010). To define a CPG as of good quality we adopted a cut-off score >60%. RESULTS: Nine CPGs were included. Specific risk factors for referral were assessed by 44.4% (4/9) of CPGs, mainly consisting in the presence of placenta previa and a prior cesarean delivery or uterine surgery. About 55.6% of CPGs (5/9) suggested ultrasound assessment of women with risk factors for PAS in the second and third trimester of pregnancy and 33.3% (3/9) recommended magnetic resonance imaging (MRI); 88.9% (8/9) of CPGs recommended cesarean delivery at 34-37 weeks of gestation. There was not generally consensus on the use of interventional radiology and ureteral stenting before surgery for PAS. Finally, hysterectomy was the recommend surgical approach by 77.8% (7/9) of the included CPGs. CONCLUSION: Most of the published CPGs on PAS are generally of good quality. There was general agreement among the different CPGs on PAS as a regard as risk stratification, timing at diagnosis and delivery but not on the indication for MRI, use of interventional radiology and ureteral stenting.

Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study.

INTRODUCTION: The aim of the study was to report the prognostic value of cytomegalovirus (CMV) viral load in the amniotic fluid (AF) in predicting the outcome of infected pregnancies. METHODS: Multicenter retrospective study involving 11 Italian referral centers from 2012 to 2021 was conducted. Inclusion criteria were fetuses with confirmed congenital CMV infection. The primary outcome was the prognostic value accuracy of CMV quantitative polymerase chain reaction (qPCR) in AF in predicting the risk of additional anomalies detected either at follow-up ultrasound or fetal magnetic resonance imaging (MRI). The secondary outcome was prediction of postnatal clinical symptoms related to CMV infection. Multivariate logistic regression and area under the curve (AUC) analyses were used to analyze the data. RESULTS: 104 fetuses were included. Associated anomalies detected at follow-up ultrasound or fetal MRI were detected in 14.4% of cases (15/104). Mean AF CMV viral load was significantly higher in fetuses with additional anomalies compared to those without additional anomalies at follow-up ultrasound or fetal MRI (3,346,634.27 ± 402,582.95 vs. 761,934 ± 222513,2 p < 0.001). At multivariate logistic regression analysis, CMV AF viral load was independently associated with the presence of additional anomalies at follow-up ultrasound or MRI, with an OR of 1.07 (p = 0.010), while maternal age (p = 0.24), trimester at maternal infection (p = 0.97), and type of infection (primary vs. non-primary) (p = 0.12) were not. CMV AF viral load had AUC of 0.755 for the occurrence of anomalies due to CMV infection, with an optimal cut-off point of >1,310,520 copies/mL, a sensitivity of 66.7%, a specificity of 84.3%, and a positive likelihood ratio of 4.24. Once excluding fetuses with anomalies at ultrasound or MRI, the diagnostic performance of qPCR in identifying fetuses with symptomatic infection after birth was low, with an AUC of 0.586. CONCLUSION: CMV viral load at second trimester amniocentesis has a moderate accuracy for the occurrence of CMV-related anomalies in fetuses with congenital infection and normal ultrasound at the initial diagnosis. Conversely, prediction of symptomatic infection is low.

Fetal cardiac function evaluation: A review.

The aim of this review is to provide an up to date on the current use of fetal echocardiography in assessing the fetal cardiac function and its potential research and clinical applications. Despite classically is been used for prenatal diagnosis of fetal heart defects, assessment of fetal cardiac function has been recently proposed as a fundamental tool to assess pregnancies complicated by several disorders with long-term impact on post-natal cardiovascular health, such as placental insufficiency and fetal growth restriction. In this review we present anatomical and functional fetal cardiac development mechanisms and an overview of the currently available techniques for evaluating fetal heart function.

Abnormal placenta implantation. Integration between first- and third-trimester imaging in predicting the severity of Placenta Accreta Spectrum (PAS) disorders.

Placenta accreta spectrum (PAS) disorders are pathological conditions correlated to a high risk of adverse maternal surgical outcomes, especially if not diagnosed. In the last 10 years, the literature interest for prenatal diagnosis of PAS disorders has been noticeably greater. More recently, significant progression in prenatal imaging techniques permitted an increase of early identified cases and a more accurate diagnosis of these anomalies, especially in women with multiple risk factors. The aim of this chapter is to give an overhaul on prenatal diagnosis of PAS disorders throughout gestation and to report whether integration between first- and third-trimester ultrasound can predict the development and severity of these anomalies.

The role of ultrasound in the diagnosis and management of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of death or severe morbidity for the mother after delivery. As a consequence healthcare staff working in the delivery room should be trained to perform a prompt diagnosis and adequate management of PPH. Uneventful outcome is induced correct identification of the underlying cause of hemorrhage. Ultrasound is a promising technique for the prompt diagnosis of PPH etiology. Indeed, it is easily available, with relatively low cost, not using ionizing radiation, and can be used in different settings including the labor room, the operating theater and at the bedside of an affected women. In order to be effective Obstetricians should have an adequate knowledge of postpartum ultrasonography. In this article, we will review the sonographic findings occurring in PPH, in the differential diagnosis of the underlying cause of hemorrhage, that include retained placenta, morbidly adherent placenta, rupture of the uterus uterine, vascular anomalies of the uterine arteries and uterine inversion. We will also provide an algorithm to manage PPH according to the ultrasonographic findings.