Cerebral Artery Peak Systolic Velocity Research Articles

Performance of Antenatal Diagnostic Criteria of Twin-Anemia-Polycythemia Sequence.

This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak systolic velocity (PSV) measurements without non-TAPS-related demise or major anomalies were included. Course of disease, antenatal intervention, additional ultrasound features, and perinatal outcomes were compared between each criteria and onset. Forty-nine cases of TAPS and 203 non-TAPS controls were identified. The incidence of TAPS was 19.2%, 15.7%, 7.8%, and 6.3% for ΔPSV MoM > 0.373, ΔPSV MoM > 0.5, traditional, and Delphi consensus criteria, respectively (p < 0.001). The incidence of antenatal intervention was 55.1, 62.5, 75.0, and 87.5%, respectively. Furthermore, cases detected according to the Delphi consensus criteria had a higher rate of progression or intervention compared to cases detected with ΔPSV MoM > 0.373 (87.0 vs. 59.0%, p = 0.037). TAPS had a significantly higher birth weight discordance than uncomplicated MCDA twins (25.3 vs. 7.3%, p < 0.001). Application of four different diagnostic criteria for TAPS leads to significant differences in the incidence, severity, and antenatal intervention. The Delphi criteria identified more severe cases likely to require intervention, and the delta PSV > 0.373 criteria identified milder cases, without a significant impact on neonatal outcomes.

Ultrasound Features of Fetal Anemia Lessons From Hemoglobin Bart Disease.

Insights gained from this review are as follows: (1) Ultrasound is highly effective in early detection of fetal hemoglobin (Hb) Bart disease. (2) The most sensitive parameters in predicting Hb Bart anemia appear to be the cardiac diameter-to-thoracic diameter ratio, middle cerebral artery peak systolic velocity, and placental thickness. (3) Several other ultrasound markers are helpful in increasing specificity, such as hepatosplenomegaly. (4) Hydrops fetalis is not a consequence of heart failure but rather of hypervolemia and high vascular permeability of fetuses, whereas heart failure is a very late consequence of a long-standing overworked heart. (5) Management guidelines for fetuses at risk of Hb Bart disease are proposed.

Middle Cerebral Artery Doppler Velocimetry for the Diagnosis of Twin Anemia Polycythemia Sequence: A Systematic Review.

Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies.

Intrauterine transfusions for maternofetal red‐blood‐cell incompatibility in monochorionic diamniotic twin pregnancy

Maternal alloimmunization to fetal red-blood-cell (RBC) antigens may cause hemolytic disease in the fetus with severe anemia. Intrauterine transfusions (IUTs) in twin pregnancy represent 1.5% of all fetal transfusions for RBC alloimmunization1, 2. Here, we present a case of a monochorionic diamniotic twin pregnancy complicated by severe anti-D maternofetal incompatibility, monitored by fetal middle cerebral artery (MCA) peak systolic velocity (PSV) and treated successfully by repeat IUTs of a single cotwin. The patient was referred to our center at 24 weeks' gestation for suspected fetal anemia. Fetal middle cerebral artery (MCA) peak systolic velocity (PSV) reached 1.64 multiples of the median (MoM) in Twin A and 2.02 MoM in Twin B. Both fetuses presented with ascites. Twin A was transfused with 30 mL of packed RBC. Pretransfusion hemoglobin (Hb) was 3.0 g/dL, with a Kleihauer–Betke test (KBT) result of 100% in fetal blood3, 4. Post-transfusion Hb increased to 8.8 g/dL and KBT decreased to 18%. MCA-PSV decreased from 1.64 to 1.19 MoM in Twin A and from 2.02 to 1.64 MoM in Twin B. Thirty minutes later, as MCA-PSV remained above 1.5 MoM in Twin B, an IUT of 15 mL was administered to Twin B, which enabled Hb level in Twin B to increase from 8.1 to 11.4 g/dL, and KBT in fetal blood decreased from 17% to 10%. The direct antiglobulin test showed a result of 3+ (high intensity) and cord bilirubin was over 70 µmol/L. These findings were suggestive of ongoing hemolytic disease. For subsequent IUTs at 25 + 4, 27 + 3 and 30 + 3 weeks' gestation, only Twin A was transfused. This strategy allowed for the normalization of MCA-PSV in both fetuses (Figure 1, Table 1). Cesarean section was performed at 31 weeks' gestation for non-reassuring fetal-heart tracing. The first delivered male neonate had birth weight of 1330 g, arterial cord blood pH of 7.37, Hb of 11.3 g/dL and bilirubin of 90 µmol/L. The second neonate had birth weight of 1310 g, arterial cord blood pH of 7.43, Hb of 11.5 g/dL and bilirubin of 88 µmol/L. Placental colored dye injection showed several arterioarterial anastomoses. The twins had respiratory distress syndrome which was treated by non-invasive ventilatory support. Severe jaundice worsened despite intensive phototherapy and albumin infusion, requiring exchange transfusion in both neonates. Two transfusions at 15 and 45 days were also needed. The neonates were discharged at 66 days postpartum. In this case, during the first IUT, transplacental intertwin anastomoses were demonstrated by (1) MCA-PSV values in Twin B decreasing after IUT of Twin A, (2) KBT in fetal blood already being reduced in Twin B after IUT of Twin A but before IUT of Twin B, and (3) Hb in Twin B being similar to that observed in Twin A after IUT of Twin A but before IUT of Twin B. To our knowledge, this is the first reported case demonstrating the contribution of MCA-PSV to monitoring monochorionic twin pregnancy complicated by RBC alloimmunization, treated by repeat IUTs of a single cotwin. One case of a monochorionic twin pregnancy in which IUTs performed in turn in each cotwin has been reported, without using MCA-PSV monitoring2. In cases of fetal anemia caused by Rh alloimmunization in monochorionic twin gestations, it appears sufficient to transfuse only one of the fetuses at 2–3 week intervals.

The Limitations of Middle Cerebral Artery Peak Systolic Velocity and the Need for Certification [38A

INTRODUCTION: In fetuses at risk for anemia, middle cerebral artery-peak systolic velocity (MCA-PSV) may have a 12% false-positive rate. Guidelines suggest MCA-PSV is superior to amniocentesis for detection of anemia, provided the correct technique is used. We aim to describe the limitations of MCA-PSV in the diagnosis of fetal anemia and the need for MCA-PSV certification for tertiary care fetal centers. METHODS: This is a university based single-center retrospective study of 47 sensitized pregnancies suspected to have fetal anemia that underwent amniocentesis. Fetal anemia was suspected on elevated MCA-PSV &gt;1.5 MoM. Amniotic fluid ΔOD450 was measured in all pregnancies. Fetuses with amniotic fluid ΔOD450 in zone 3 on Liley's chart, underwent cordocentesis for the assessment of fetal anemia. Intrauterine fetal transfusion (IUT) was performed in fetuses confirmed with anemia. Fetal anemia indicating IUT was defined as ≥5 SD below the mean for GA and Hematocrit ≤30%. RESULTS: Among sensitized pregnancies with elevated fetal MCA-PSV, 19 (40.4%) had elevated ΔOD450 measurements. Of these 19 fetuses, 15 (78.9%) required IUT. In 28/47 (59.6%) with normal ΔOD450, elevated MCA-PSV incorrectly predicted fetal anemia, increasing the amniocentesis related risks. This is much higher than the published false positive results of 12%. CONCLUSION: The decreased specificity of MCA-PSV for fetal anemia diagnoses may be associated with user variability. While MCA-PSV has clinical benefit for the initial workup, the additional amniocentesis confirmation reduced the need for cordocentesis. Amniocentesis also has risks and to further reduce the need for invasive diagnostic testing, we recommend a Certification for MCA-PSV Doppler sonography.

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age.

ObjectiveTo investigate whether perioperative fetal hemodynamic changes in twin‐to‐twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years.MethodsDoppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008‐2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley‐III cognitive/motor developmental test‐score > 2SD below the mean.ResultsLong‐term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA‐PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17‐21.05, P = .03), a change from normal umbilical artery pulsatility index (UA‐PI) presurgery to UA‐PI >p95 postsurgery (OR 4.19; 95% CI: 1.04‐16.87, P = .04), a change from normal to MCA‐PSV >1.5MoM (OR 4.75; 95% CI: 1.43‐15.77, P = .01).ConclusionPerioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.

Selective intrauterine growth restriction (SIUGR) type II: proposed subclassification to guide surgical management

Background Optimal surgical management of monochorionic diamniotic twins complicated by selective intrauterine growth restriction (SIUGR) type II is unknown. Surgical management may involve selective laser photocoagulation of communicating vessels (SLPCV), which offers the possibility of dual twin survivors versus umbilical cord occlusion (UCO) of the SIUGR twin. Objective To identify patient characteristics associated with SIUGR twin survival for those undergoing SLPCV. Study design All patients studied were those who underwent fetal treatment for SIUGR type II at our center from 2006–2018. SIUGR type II was defined as an estimated fetal weight <10th percentile with persistent absent and/or reversed end diastolic flow in the umbilical artery of the SIUGR twin, in the absence of twin-twin transfusion syndrome. Patients were offered SLPCV versus UCO, and those undergoing SLPCV, patient characteristics associated with 30-day survival of the SIUGR twin were examined using bivariate analysis and multiple logistic regression models. Results Fifty-four consecutive SIUGR type II patients were treated, 45 via SLPCV and nine via UCO. Of the 45 SLPCV cases, there were 16 (35.6%) with SIUGR twin (and dual) survival. SIUGR twin survival appeared associated with middle cerebral artery (MCA) peak systolic velocity (psv) <1.5 multiples of the median, and forward atrial systolic flow in the ductus venosus (DV). In a post hoc analysis, we subsequently categorized patients as: SIUGR type IIa (N = 32 (71.1%)): normal MCA psv, and normal DV waveform, versus SIUGR type IIb (N = 13 (28.9%)): MCA psv ≥1.5 multiples of the median, and/or DV with absent or reversed atrial systolic flow. Thirty-day survival of the SIUGR twin was 50% for type IIa and 0% for type IIb. Conclusion Over one-third of SIUGR type II patients experienced dual survival after treatment with laser surgery. Normal MCA psv and normal DV waveforms were associated with SIUGR type II survival of the SIUGR twin. Post hoc exploration and subclassification of SIUGR type II patients by preoperative Doppler indices created two groups, one (type IIa) with 50% survival and one (type IIb) with 0% survival of the SIUGR twin after laser surgery. Upon further confirmation, these findings may provide guidance for counseling patients and conducting fetal therapy.

Defining critical antibody titre in column agglutination method to guide fetal surveillance

IntroductionA critical anti D antibody titre, defined for the conventional tube method of Indirect Coomb’s test (ICT), when employed in the more sensitive column method could result in unnecessary referrals and frequent obstetric doppler scans. This study aimed to compare anti D titres by tube and column method in antenatal mothers, to assess their correlation with fetal anemia and to determine a critical titre for the column method. MethodsForty six antenatal mothers with anti D antibody were included in the study. Antibody titration was performed by serial twofold dilution of serum by both column and tube method and were correlated with middle cerebral artery peak systolic velocity (MCA PSV) measurement by Doppler ultrasonography. Receiver operating curve (ROC) was used to determine the cut-offs for critical titre by tube and column method in predicting fetal anemia. ResultsColumn method had a median titre 3 fold higher than tube method. There was a significant association between fetal anemia by USG with median critical titres determined for both column (p = 0.031) and tube method (p = 0.016). ROC analysis showed the cut off for critical titres in column method as 64 with 90 % sensitivity, 72.7 % specificity and 75.38 % accuracy. ConclusionsThe use of critical titre for anti D antibody, defined for the tube method, when applied to the column agglutination method would lead to increased referrals to specialized fetal medicine centres. Rather, an Anti D titre of 64 by column method can predict the likelihood of fetal anemia and should be considered as the critical titre to guide patient referrals.

Maternal Utero-Placental Perfusion Discordance in Monochorionic-Diamniotic Twin Pregnancies with Selective Growth Restriction Assessed by Three-Dimensional Power Doppler Ultrasound.

BackgroundThe aim of this study was to assess the correlation between selective growth restriction (sGR) and co-twin utero-placental perfusion discordance by using three-dimensional power Doppler (3DPD).Material/MethodsWe prospectively recruited 60 sGR and 64 normal monochorionic-diamniotic (MCDA) twin pregnancies. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were assessed by 3DPD, while umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), pulsatility index (MCA-PI), and cerebroplacental ratio (CPR) were assessed by conventional Doppler imaging.ResultsIn sGR co-twins, the VI, FI, VFI, MCA-PI, and CPR were significantly lower, while the UA-PI and MCA-PSV were significantly greater, in the smaller fetuses compared with the larger fetuses; significant differences were also observed in the VI, FI, VFI, CPR, and UA-PI in normal co-twins. Compared with the appropriately grown twins, the discordances of the VI, FI, VFI, UA-PI, MCA-PI, and CPR were increased in the sGR cohort. The discordances of the VI, FI, VFI, UA-PI, MCA-PI, and CPR were associated with birthweight discordance, and the FI discordance and CPR discordance were independently associated with sGR. The combination of the FI and CPR discordance showed a higher predictive accuracy for sGR, with an area under the ROC curve of 0.813, and a sensitivity and specificity of 68.33% and 85.94%, respectively.ConclusionsMCDA twin pregnancies with birthweight discordance presented utero-placental perfusion deterioration assessed by 3DPD prior to sGR diagnosis. Co-twin utero-placental perfusion discordance was significantly correlated with growth discordance, and this correlation was more predictive of sGR when 3DPD was combined with conventional Doppler imaging.

Doppler middle cerebral artery peak systolic velocity measurement as diagnostic tool for fetal anemia after in-utero transfusions in red blood cell alloimmunisation

Background/Aim. Doppler sonography of fetal middle cerebral artery peak systolic velocity (MCA-PSV) can be used to predict fetal anemia and the need for in utero intravascular transfusion (IUIT) in red blood cell (RBC) alloimmunisation pregnancies. The aim of this study was to evaluate whether measurement of MCA-PSV in fetuses that had undergone one to three transfusions is a good diagnostic tool for fetal anemia. Methods. Study included 36 pregnancies treated due to RBC alloimmunisation in our tertiary referral center during the 5-year period (2012?2017). We measured MCA-PSV and hematocrit (Hct) in all patients. In seven pregnancies there was a need to perform sequential IUITs for correction of fetal anemia. In these patients we compared MCA-PSV and Hct values before and after every transfusion. Results. Hct and MCA-PSV correlated negatively before transfusion therapy (p = 0.035) and after the second transfusion (p = 0.046). Contrary, after the first (p = 0.954), before the second (p = 0.738), as well as before (p = 0.092) and after (p = 0,741) the third transfusions there were no significant correlations between Hct and MCAPSV values. Hct values before and after transfusions were positively associated (p = 0.001), but MCA-PSV were not (p = 0.296). According to performed receiver operating characteristic (ROC) analysis the cut-off point of MCA-PSV for investigated patients was 1.22 multiples of its median (MoM). Conclusion. There is a reduction in MCA-PSV accuracy for assessing fetal anemia in previously transfused fetuses. Larger studies are needed to explain the reasons for these findings and potentially set new referral values of MCA-PSV for better diagnostics of fetal anemia.

A patient with a giant placental chorioangioma in whom measurement of the middle cerebral artery peak systolic velocity was useful for determining the timing of delivery

A patient with a giant placental chorioangioma in whom measurement of the middle cerebral artery peak systolic velocity was useful for determining the timing of delivery

Longitudinal Doppler references for monochorionic twins and comparison with singletons.

ObjectivesTo construct monochorionic (MC) twin-specific longitudinal Doppler references for umbilical artery pulsatility index (UA-PI), middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and ductus venosus (DV) PI derived from a strictly selected cohort of uncomplicated MC twins. The secondary aim of the study was to compare our findings with singleton reference charts.MethodsA retrospective evaluation was made of all consecutive uncomplicated MC twin pregnancies referred to our Unit from 2010 to 2018. Fortnightly serial examinations were performed of UA-PI, MCA-PI, MCA-PSV and DV-PI, according with the clinical protocol, from 20 to 37 weeks of gestation. We included cases with at least four ultrasound examinations, delivery at our hospital and complete neonatal follow up. A two-step method was used to trace the estimated centile curves: estimation of the median was performed with appropriate fractional polynomials by a multilevel model and estimation of the external centiles through the residuals (quantile regression). The comparison with singletons was made by plotting the references derived from the present study on the referred charts commonly used for singletons.ResultsThe study group comprised 150 uncomplicated MC twin pairs. Estimated centiles (3rd, 5th, 10th, 50th, 90th, 95th, 97th) of UA-PI, MCA-PI, MCA-PSV and DV-PI in function of the gestational age are presented. The comparison with singletons showed substantial differences, with higher UA-PI and lower MCA-PI and PSV median values in MC twins. Median DV PI values were similar to the values for singletons, while the upper centiles were higher in MC twins.ConclusionsThis study sets out MC twin-specific longitudinal references for UA-PI, MCA-PI, MCA-PSV and DV-PI derived from the largest series of uncomplicated MC twin pregnancies presently available. The comparison with singleton reference values underscores the deviation from physiology that is intrinsic to these unique pregnancies and supports the need for MC twin-specific charts.

Performance of fetal middle cerebral artery peak systolic velocity for prediction of anemia in untransfused and transfused fetuses: systematic review and meta-analysis.

To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses. A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed. Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased. MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic Performance of Doppler Ultrasonography for the Detection of Fetal Anemia: A Meta-analysis.

This study evaluates the diagnostic performance of Doppler ultrasound in diagnosing fetal anemia. Data were taken from relevant study reports published in peer-reviewed journals identified after a literature search in electronic databases. Random effects meta-analyses were performed by pooling the effect sizes of diagnostic indices (sensitivity, specificity, positive/negative predictive values, and false-positive rate) or correlation coefficients reported by individual studies. As a result, 31 studies (1848 pregnancies; gestation age, 28.25 weeks [95% confidence interval {CI}, 26.87-29.63]) were included in the meta-analysis. Anemia was found in 63.7% (95% CI, 49.7-77.7) fetuses, and severe anemia was found in 36.7% (95% CI, 26.9-46.4) fetuses. Sensitivity and specificity of Doppler ultrasound for detecting fetal anemia in alloimmunized fetuses at middle cerebral artery peak systolic velocity cutoff of 1.5 multiple of median for gestation age were 83.42% (95% CI, 71.75-95.09) and 80.30% (95% CI, 73.58-87.02), respectively. Positive predictive value, negative predictive value, and false-positive rate were 76.35% (95% CI, 65.98-86.72), 80.0% (95% CI, 76.63-83.37), and 10.4% (95% CI, 5.9-14.9), respectively. Correlation coefficient between hematological anemia and Doppler ultrasound-measured blood flow velocity was -0.706 (95% CI, -0.765 to -0.635; P < 0.00001). In conclusion, Doppler ultrasound-measured middle cerebral artery peak systolic velocity at 1.5 multiple of median provides good diagnostic strength for the detection of alloimmunized fetal anemia. A strong correlation between Doppler velocimetric measures and hematological anemia is also observed.

Is There a Role for Titre Monitoring in Kell Alloimmunized Pregnancies?

Background: Kell and Rhesus (Rh) maternal red blood cell (RBC) alloimmunization are the most common causes of severe fetal haemolytic disease. Widespread use of anti-D immune globulin has dramatically reduced the incidence of Rh(D) alloimmunization, leaving K alloimmunization responsible for a significant proportion of cases of fetal anemia requiring intrauterine transfusion ( ). K antigens are expressed on fetal erythrocytes at 10-11 weeks and k antigens at 6-7 weeks gestation (Tovey et al, 1986). In alloimmunized women, erythroid specific antibodies traverse the placenta, causing immune destruction of fetal erythroid cells leading to progressive haemolytic anaemia. The mechanism of fetal anaemia in K alloimmunization differs somewhat from that in Rh-D, in that anti-K antibodies cause suppression of fetal erythropoiesis (Gariod et al, 2004; Weiner et al, 1996). Whilst IUT of RBCs has improved fetal and neonatal survival, important information such as the critical anti-K titres to guide appropriate timing and frequency of IUT, is somewhat conflicting. Currently anti-K alloimmunized pregnancies do not have a standardized protocol for titer monitoring throughout pregnancy and, once alloimmunized, patients are usually referred to a regional fetal center for close ultrasound (US) surveillance. Our primary objective is to determine from a retrospective analysis of our population whether there is a critical anti-K titer that should trigger intensive US monitoring or intervention and to investigate the rate of progression of fetal anemia following IUTs. Methods: This is a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada, of all pregnant patients with anti-K as the primary alloimmunizing antibody, between 1991 and 2018. MSH is the largest fetal medicine center in Canada and the largest referral center for IUTs. Ethical approval was granted by the Research Ethics Board (REB # 12-0113-C). Data were obtained from a database of patient medical records, US reports and the transfusion medicine laboratory, including maternal demographics, pregnancy history, presence of other alloantibodies and hemoglobin concentration before and after all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age (GA) at delivery, birth weight and need for neonatal exchange transfusion, phototherapy or IVIG. Data were analyzed using GraphPad Prism 6 and linear correlations are expressed as a p-value. Results: Thirty-eight women underwent 163 IUTs in 44 pregnancies where K was the predominant antibody. Two patients in whom anti-K was a secondary antibody were excluded. In 5 of these pregnancies, 2 had a total of three alloantibodies and 5 had 2 alloantibodies each. The median maternal age was 31 (29 - 35) years. Four women had a history of intrauterine fetal death (IUFD) and 9 of neonatal haemolytic disease. The median GA at 1st IUT was 24.2 weeks (14.9-34.7), and there was a median of 4 IUTs per patient. There were seven cases of hydrops fetalis. The number of IUTs a patient received throughout pregnancy was correlated directly with the anti-K titer (Figure 1). Every 4-fold dilution resulted in a further increase in the IUT number by 2.2 above the mean of 2.5 at a titer of 1:32 (p=0.0137). Figure 2 illustrates the correlation between the GA at 1st IUT and antibody titer. IUTs were required at earlier GAs if the titers were higher. Following a 1:32 titer, every 2-fold titer increase reduced the mean gestational age at 1st IUT by 2 weeks (p&lt;0.0001). No pregnancy required an intervention with an anti-K titer &lt; 1:32. The median fetal Hb at the first IUT was 48 (8-91) g/L with an average daily decrease of hemoglobin of 4.7 g/L/day between the first and second IUT (Figure 3), which is similar to the 4.1 g/L/day previously reported in Rh(D) alloimmunization. The median GA was 37.1 (24-39.7) weeks at delivery with median birth weight centile of 59.5%; 8.9% of neonates required a blood transfusion and 24.4% required phototherapy. There were four IUFDs and one neonatal . Conclusion: Our data support a critical anti-K titer of 1:32 and support a role for anti-K titer monitoring as a predictor of disease severity, counselling women appropriately and establishing a balance between paternal K antigen typing, US middle cerebral artery peak systolic velocity monitoring of the fetus and IUTs. Disclosures Garbowski: Vifor Pharma: Consultancy; Imara: Consultancy.

Intraperitoneal transfusion for severe, early-onset rhesus disease requiring treatment before 20 weeks of gestation: A consecutive case series

ObjectiveTo describe the management and perinatal outcomes of pregnancies affected by severe, early onset Rhesus isoimmunization treated with fetal intraperitoneal transfusions (IPTs). Study designA ten-year consecutive case series of fetuses undergoing IPTs before 20 weeks gestation at Wessex Fetal Medicine Unit, Southampton, UK.Women with fetuses at risk of early onset fetal anaemia (before 20 weeks gestation) were identified from their obstetric history and maternal antibody levels at the time of booking. They were referred to our tertiary referral center. The decision to initiate transfusion was aided by middle cerebral artery peak systolic velocity as an indicator of fetal anaemia. No fetus was hydropic at the first transfusion.IPTs were commenced from as early as 15 weeks gestation in fetuses with difficult vascular access and performed regularly using this method until the cord could be successfully entered for intravascular transfusions.The main outcome measures were procedure and non procedure-related perinatal losses. Results11 fetuses underwent 45 IPTs. 10/11 (91%) were delivered after 33 weeks gestation. There was one perinatal loss 1/11 (9%: 95% C.I 1.6–38%) from a cord accident during intravascular transfusion at 26 weeks gestation. There were no procedure related fetal losses or complications at the time of early IPTs. ConclusionsPrevious studies report a perinatal loss rate with early intrauterine transfusion of 24% in gestations below 20 weeks using the intravascular route. This series suggests that intraperitoneal transfusion can be a safe and effective treatment for severe fetal anaemia at early gestations where vascular access is difficult.

Management and outcome of pregnancies in women with red cell isoimmunization: a 15-year observational study from a tertiary care university hospital

BackgroundThe aims of this study were to determine the prevalence of the different anti-erythrocytic alloantibodies, to describe pregnancy outcomes according to a low-risk and high-risk classification for fetal anemia and to determine the factors that influence adverse perinatal outcomes.MethodsThis retrospective observational study included women referred to our center following the identification of maternal anti-erythrocytic alloantibodies between 2002 and 2017. Pregnancies were classified as high risk for fetal anemia in cases with clinically significant antibodies, no fetal-maternal compatibility and titers ≥1:16 or any titration in cases of Kell system incompatibility. In high-risk pregnancies, maternal antibody titration and the fetal middle cerebral artery peak systolic velocity (MCA-PSV) were monitored. Low-risk pregnancies underwent routine pregnancy follow-up.ResultsMaternal antibodies were found in 337 pregnancies, and 259 (76.9%) of these antibodies were clinically significant. The most frequent antibodies were anti-D (53%) and anti-K (19%). One hundred forty-three pregnancies were classified as low risk for fetal anemia, 65 (25%) cases were classified as no fetal-maternal incompatibility, 78 had clinically nonsignificant antibodies, 4 (2.8%) resulted in first-trimester pregnancy loss, and 139 (97.2%) resulted in livebirths. Of the 194 high-risk pregnancies, 38 had titers < 1:16 (resulting in 38 livebirths), and 156 had titers ≥1:16 or anti-K antibodies. In the last group, 6 cases miscarried before 18 weeks, 93 had a MCA-PSV < 1.5 multiples of the median (MoM), resulting in 3 perinatal deaths that were unrelated to fetal anemia, one termination and 89 livebirths; and 57 had a MCA-PSV > 1.5 MoM, resulting in 3 intrauterine deaths, 6 terminations and 48 livebirths. Ninety-two intrauterine transfusions were performed in 45 fetuses (87% anti-D). Adverse outcomes were related to a MCA-PSV > 1.5 MoM (p < 0.001), hydrops (p < 0.001) and early gestational age at first transfusion (p = 0.029)ConclusionAnti-D remains the most common antibody in fetuses requiring intrauterine transfusion. A low or high-risk classification for fetal anemia based on the type of antibody, paternal phenotype and fetal antigen allows follow-up of the pregnancy accordingly, with good perinatal outcomes in the low-risk group. In the high-risk group, adverse perinatal outcomes are related to high MCA-PSV, hydrops and early gestational age at first transfusion.

Effect of maternal corticosteroid provision on middle cerebral artery peak systolic velocity readings in the potentially anaemic fetus prior to planned intrauterine transfusion.

Middle Cerebral Artery Peak Systolic Velocity (MCA-PSV) is the main tool for determining need for and timing of intrauterine transfusions (IUT) for severe fetal anaemia. It has been suggested that steroids temporarily decrease MCA-PSV, potentially increasing false-negative MCA-PSV findings in anaemic fetuses. We therefore aimed to assess whether maternal corticosteroid administration prior to IUT is associated with clinically significant temporary decreases in MCA-PSV. Retrospective review 2005-2016 of steroid provision prior to IUT, with correlation of MCA-PSV pre- and post-steroid administration and haemoglobin at IUT. In 23 identified cases, there was no significant difference between average MoM pre- and post-steroid (1.71±0.41 vs. 1.66±0.38, -2.9% mean, P=0.4). There was also no significant difference between pre- and post-steroid MoM taken within 3days of each other (n=19, P=0.21). However, post-steroid MCA-PSV decreased by >15% in 6/23 cases (A-B zone in two cases, B-C zone in one case). This study found no sizeable, generalised effect of corticosteroid administration on MCA-PSV readings in the potentially anaemic fetus. A minority showed substantial shifts where reliance on post-steroid MCA-PSV could have unfavourably altered clinical management. Ultimately, further large-scale research is required before we can discount the potential impact of steroids on MCA-PSV values.

Anemia fetal, diagnóstico y manejo actual

La anemia fetal es una condición poco frecuente en nuestro medio, pero potencialmente letal para el feto, si no se diagnostica y maneja oportunamente. Las causas son diversas, desde autoinmunes (isoinmunización Rh) a infecciosas (parvovirus B19), hemogobinopatías, hemorragia feto materna y complicaciones del embarazo monocoriónico. El diagnóstico puede ser por métodos invasivos (cordocentesis) o no invasivos (pico de velocidad sistólica de la arteria cerebral media – PVS-ACM), aunque se prefiere los últimos. El tratamiento consiste en la transfusión intrauterina, la cual permite sobrevida hasta en 90% de casos, sin secuelas neurológicas. El presente artículo revisa aspectos acerca de la definición, clasificación, causas, diagnóstico y manejo actualizado de la anemia fetal.

Hemodynamic Surveillance of Unilateral Carotid Artery Stenting in Patients With or Without Contralateral Carotid Occlusion by TCD/TCCD in the Early Stage Following Procedure.

Objective: To evaluate the cerebral hemodynamic variations in patients with unilateral carotid artery stenosis and contralateral carotid occlusion (CCO) in hours following carotid artery stenting (CAS) by transcranial Doppler (TCD) or transcranial color-code Doppler (TCCD).Methods: Sixty-five consecutive patients who underwent unilateral CAS were enrolled. Among them, 14 patients had ipsilateral severe stenosis and CCO (CCO group) while the other 51 patients had only unilateral severe carotid stenosis without CCO (UCS group). All patients underwent TCD or TCCD monitoring before, at 1 and 3 h after CAS. We monitored bilateral middle cerebral artery (MCA) peak systolic velocity (PSV), pulsatility index (PI), and blood pressure (BP), and compared that data between two groups.Results: In UCS group, ipsilateral MCA PSV increased relative to baseline at 1 h (96 ± 30 vs. 85 ± 26 cm/s, 15%, P < 0.001) and 3 h (97 ± 29 vs. 85 ± 26 cm/s, 17%, P < 0.001) following CAS. Significant PI increases were observed at 1 and 3 h following CAS on the ipsilateral side. In CCO group, ipsilateral MCA PSV increased relative to baseline at 1 h (111 ± 30 vs. 83 ± 26 cm/s, 35%, P < 0.001) and 3 h (107 ± 28 vs. 83 ± 26 cm/s, 32%, P <0.001) following CAS. The magnitude of ipsilateral MCA PSV increase was significantly higher in CCO group compared with UCS group at 1 h (P = 0.002) and 3 h (P = 0.024) following CAS, while BP similarly decreased between the two groups. On the contralateral side, significant MCA PSV increases were observed following CAS in CCO group but not in UCS group. Bilateral MCA PSV increases were higher in patients with a stenosis degree of ≥90% than in patients with stenosis degree of 70–89% only in CCO group.Conclusion: The ipsilateral MCA PSV and PI increase moderately in the initial hours after unilateral CAS in patients without CCO. In patients with CCO, the ipsilateral, and contralateral MCA PSV increase significantly in the early stage following CAS. CCO is a factor of the increased blood flow velocity in ipsilateral MCA after unilateral CAS.