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Papers by Gareth Seaward

Research paper thumbnail of Intravenous Immunoglobulin in the Management of Severe Early Onset Red Blood Cell Alloimmunization

Blood, Nov 5, 2021

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) fo... more OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed < 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on 'Statistical Package for Social Science Version 16.0' (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple "top-up" transfusion, and six (35%) phototherapy. CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Research paper thumbnail of Mild ventriculomegaly in the fetus, natural history, associated findings and outcome of isolated mild ventriculomegaly: a literature review

Prenatal Diagnosis, 2001

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Research paper thumbnail of General anesthesia for endoscopic laser for severe TTTS is associated with increased risk of adverse maternal outcome

American Journal of Obstetrics and Gynecology, Dec 1, 2005

To evaluate 3 anaesthesia techniques-general (GA), epidural (ED) and conscious sedation (CS)-empl... more To evaluate 3 anaesthesia techniques-general (GA), epidural (ED) and conscious sedation (CS)-employed for the first 80 cases of laser for severe TTTS. STUDY DESIGN: Data were abstracted from clinical records: major and minor maternal complications and fetal outcomes were compared for all techniques. Univariate comparisons were made using one-way ANOVA and Fisher's exact tests. Multivariate logistic regression was used to identify independent associations with major maternal adverse outcomes. RESULTS: 18 cases were done under GA, 4 under ED and 58 under CS. There was no difference in maternal demographic data between groups. The GA group recorded lower systolic pressures, increased requirements for pressure therapy (p!0.01) and increased intra-operative intravenous fluids (all p!0.02). Major maternal complications (n=13) were more common with GA as compared to the other groups (p!0.01). GA remained independently associated with major maternal complications in multivariate analysis (adjusted OR 36; p=0.03) after controlling for covariates. Pulmonary edema within 24 hrs of the procedure occurred in 8 women, total IV fluid volume was the only factor independently associated with the development of pulmonary edema (adjusted OR 4.5 for each 1000 mL increase in IV fluid). CONCLUSION: GA was associated with increased risk of major maternal complications, particularly pulmonary edema, when compared to ED and CS.

Research paper thumbnail of Outcomes of haemoglobin Bart’s hydrops fetalis following intrauterine transfusion in Ontario, Canada

Archives of Disease in Childhood-fetal and Neonatal Edition, Jul 2, 2020

ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin B... more ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart’s hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive.DesignTo evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent β-thalassaemia (TDT-β).ResultsOf the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-β patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with ‘silent’ ischaemic infarcts.ConclusionsIn patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-β counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Research paper thumbnail of 482: Outcome of pregnancies complicated by fetal parvovirous-B19 infection

American Journal of Obstetrics and Gynecology, 2014

intrapartum conditions are assumed to be part of the risk of elective induction. Association of e... more intrapartum conditions are assumed to be part of the risk of elective induction. Association of elective IOL at 39 weeks and cesarean delivery and NICU admission. In scenario 1, women with documented fetal distress, amniotic infection, hemorrhage, or premature separation of the placenta were excluded from the elective IOL group but retained in the expectant management group. In scenario 2, we assumed that these conditions occurred after the onset of labor, and women with these conditions were retained in both the elective IOL and expectant management groups. NICU, neonatal intensive care unit; OR, odds ratio; CI, 95% confidence interval.

Research paper thumbnail of Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

Prenatal Diagnosis, Feb 25, 2009

Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and ... more Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

Research paper thumbnail of Treatment Options in Fetomaternal Hemorrhage: Four Case Studies

Journal of obstetrics and gynaecology Canada, Oct 1, 2004

Significant fetomaternal hemorrhage (FMH) is an uncommon event that places the fetus at risk of s... more Significant fetomaternal hemorrhage (FMH) is an uncommon event that places the fetus at risk of severe morbidity and mortality. Symptoms and signs at presentation are subtle and, if promptly recognized, appropriate management may permit the fetus to escape serious injury. Four cases of significant FMH were diagnosed in the high-risk obstetrical unit at Mount Sinai Hospital, Toronto, during 2003. Three of the women complained of reduced fetal movements and were investigated initially with a non-stress test, a Kleihauer-Betke test, and ultrasound, including Doppler of the middle cerebral artery. These women all required emergency Caesarean section for non-reassuring fetal status. One fetus was treated by intravascular transfusion. Another identified case was transfused postnatally. One asymptomatic case was identified after spontaneous vaginal birth and also treated by neonatal transfusion. Neurological outcomes were good in all four cases. Reduced fetal movements may be the only complaint of FMH. Increased awareness is required to ensure a diagnosis is made. When a non-stress test for reduced fetal movement is non-reactive, a Kleihauer-Betke test should be ordered, as well as detailed ultrasonography, including fetal Doppler studies. The perinatal prognosis for FMH may improve by facilitating the appropriate use of fetal blood transfusion or delivery by Caesarean section.

Research paper thumbnail of Maternal Red Blood Cell Alloimmunization Managed with Intrauterine Blood Transfusion: Predictors of Poor Outcome

Blood, Nov 5, 2020

Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different... more Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different antigens capable of causing maternal red blood cell (RBC) alloimmunization and severe fetal hemolytic disease. Anti-K and anti-D are responsible for a significant proportion of fetal anemia requiring intrauterine transfusion (IUT). Whilst IUT of packed RBCs improves neonatal survival and morbidity, clinical prognostic indicators are lacking. Our primary objective was to identify predictors of adverse outcome. Methods: We conducted a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada. All pregnant patients alloimmunized with anti-K and anti-D as a single antibody, between 1991 and 2018 were included. Data were obtained from patient medical records, ultrasound reports and information from the transfusion medicine laboratory. Data included maternal demographics, antibody titers, pregnancy history, number of IUTs, hemoglobin (HB) concentration at the beginning and end of all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age at delivery, birth weight, HB at birth and need for neonatal transfusion, phototherapy or intravenous immunoglobulins (IVIG). Our primary outcome was the composite outcome of stillbirth or neonatal death (SB/NND). We also constructed a secondary outcome consisting of top-up neonatal transfusion, exchange transfusion, phototherapy, or use of IVIG. Medians and interquartile ranges (IQR) or mean±SD were used as summary statistics and compared by Mann-Whitney or t-test; p<0.05 was statistically significant. Outcome predictors were identified using multivariable logistic or linear regression analysis; accounting for patient level clustering by marginal Generalized Estimating Equation did not significantly affect variables. Data were analyzed using SPSS. Results: 116 women with 128 pregnancies and 425 IUTs with anti-K or anti-D as a single antibody were identified. Median maternal age was 31 years (27.0-35.0) for anti-K and 32 years (23.6-40.6) for anti-D. The gestational age at 1st IUT differed significantly between anti-K and anti-D (24.3 vs 28.7 weeks respectively, p=0.004). Women with anti-K antibodies required more IUTs than women with anti-D (3.84 vs 3.12 IUTs, p=0.036) and HB at 1st IUT was significantly lower in the anti-K group (5.10 vs 7.05 g/dL, p=0.001) (Table 1). Following initiation of IUT, the time from 1st IUT to delivery was 69.6 days in the anti-K group and 54.6 in the anti-D group (p=0.06). The daily decrease of HB between 1st and 2nd IUT (as a marker of disease severity), development of fetal hydrops and severe preterm birth did not differ significantly between the two groups. Mean gestation age at delivery was 35.0 weeks in the anti-K and 36.0 weeks in the anti-D group (p=0.28), with 87.1% and 93.9% survival (p=0.37), respectively. The proportion of neonates requiring phototherapy, IVIG and exchange/top-up transfusion was comparable across the two antibody groups (Table 1). Regression analysis showed that delivery occurred sooner if HB dropped more rapidly between the first two IUTs (p=0.01). Each additional transfusion gained on average 22.5 days in utero (Table 2). In multivariable analysis, gestational age at 1st IUT was the only predictor of a SB/NND outcome (adjusted OR 0.79 [95%CI 0.67-0.93]; p=0.006). With 1st IUT at 23 weeks, the risk of SB/NND was 8%, but only 2.5% at 28 weeks and <0.01% at 36 weeks (Table 3). Gestational age at delivery (adjusted OR 1.11 [95%CI 1.00 to 1.23]; p=0.046) and HB at 1st IUT (adjusted OR 0.84 [95%CI 0.72 to 0.99]; p=0.038) were the only predictors of a composite adverse blood product requirement/intervention outcome (Table 4). The odds of blood product requirement/intervention postnatally at 1st IUT (median HB at 1st IUT of 6.6g/dL) at 28 weeks were 43% and increased by a further 38% for delivery at 34 weeks. Conclusion: The earlier in gestation that IUTs are implemented, the higher the odds of a SB/NND; however the later the gestation at delivery, the greater the odds of the neonate requiring blood products post-partum. The greater the HB drop between the 1st and 2nd IUT, the shorter the 'time between the first IUT and delivery', which increases the odds of a SB/NND outcome. Disclosures Garbowski: Vifor Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Consultancy. Shehata:Ferring: Honoraria.

Research paper thumbnail of Is There a Role for Titre Monitoring in Kell Alloimmunized Pregnancies?

Blood, Nov 13, 2019

Background: Kell and Rhesus (Rh) maternal red blood cell (RBC) alloimmunization are the most comm... more 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<0.0001). No pregnancy required an intervention with an anti-K titer < 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.

Research paper thumbnail of OP23.09: Perinatal outcome in fetuses with dislodged pleuroamniotic shunts (PAS)

Ultrasound in Obstetrics & Gynecology, Sep 1, 2017

Short oral presentation abstracts Objectives: An interstitial laser ablation becomes a good candi... more Short oral presentation abstracts Objectives: An interstitial laser ablation becomes a good candidate for the prenatal treatment of chorioangioma, sacrococcygeal teratoma, selective fetal growth restriction and twin reversed arterial perfusion sequence in early gestation. The aim of this study was to describe the in vitro results of interstitial laser coagulation in different types of laser generator, power and time. Methods: Total 144 placentae were interstitially ablated with PlexoLong 19 gauge needle, 400 micron laser fiber and Nd:YAG or Diode at 12 power-time combinations (5, 10, 15 seconds versus 15, 20, 25, 30 watts). We evaluated the diameter of coagulated zone using ultrasound and histopathology. Results: Mean coagulated placental diameter (ultrasound) was shown in figure 1. Ablated size measurement by ultrasound was slightly larger than microscopy (p<0.001). The average length (histopathology) after 5, 10 and 15 seconds of coagulation were 5.12, 7.00 and 7.85 mm (±0.16), and after using power 15, 20, 25 and 30 watt were 5.20, 6.36, 7.08 and 7.99 mm (±0.21), respectively. In addition, using the Diode was significantly wider than using Nd:YAG in coagulated diameter (p<0.001). Histology of the placental tissue showed gradual change in degree of thermal damage and period of time. Conclusions: Interstitial laser ablation particular Diode, seems to be an effective prenatal treatment when the feeding vessels are smaller than 8 mm in diameter.

Research paper thumbnail of Natural History of Ventriculomegaly in Fetal Agenesis of the Corpus Callosum

Journal of Ultrasound in Medicine, Sep 9, 2019

Objectives-To assess the natural evolution of the size of the fetal lateral ventricles throughout... more Objectives-To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. Methods-Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. Results-In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P < .001). In 79 cases that had longitudinal follow-up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean AE SD, 0.6 AE 1.5 versus 0.6 AE 1.1 mm; P = .45). Conclusions-Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long-term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining longterm follow-up of these cases.

Research paper thumbnail of Ultrasound-guided laser treatment of hydropic fetal lung lesions with a systemic arterial supply

American Journal of Obstetrics and Gynecology, Dec 1, 2003

To report innovative minimally invasive fetal therapy for massive lung lesions associated with hy... more To report innovative minimally invasive fetal therapy for massive lung lesions associated with hydrops. STUDY DESIGN: 2 cases, followed prospectively. RESULTS: 2 hydropic fetuses, at 19 and 23 wks, respectively, had massive bronchopulmonary sequestrations occupying most of the chest and everting the diaphragm well into the abdomen. A large aortic feeding vessel was identified in each case. Using IV sedation and continuous ultrasound guidance, an 18g needle was placed intra-amniotically, through which a longer 22g needle was advanced into the fetal IHV to sample, paralyze, and anesthetize the fetus. This was then redirected into one of the larger cysts, and microbubble contrast agent (Levovist) was injected to document cyst communication. A 600-micron ND: YAG laser fiber was passed through the 18g needle, and the tip was placed adjacent to the feeding vessel, which was successfully ablated in each case. In the first case at 19 wks, finally a fetal Rocket pleuroamniotic shunt was placed, traversing several cysts. The left-sided mass resolved dramatically in size over the next 3 wks, and hydrops resolved completely. A healthy 3.7-kg male, requiring no assisted ventilation, was born at 39 wks. The involved lobe was resected the next day; pediatric follow-up is entirely normal. At 23 wks, GA was used for the 2nd right-sided mass and no shunt was placed: 2 wks later, there has been some mass shrinkage; so far, hydrops persists. The pregnancy is ongoing. CONCLUSION: The prognosis for large fetal cystic chest masses associated with hydrops is dismal-all die. This has prompted attempts at treatment by open fetal surgery, with mixed results and a high risk of premature labor. We have demonstrated an excellent outcome by US-guided laser ablation of the systemic arterial supply. This is a preferable, much less invasive approach to such lesions-with far less risk of premature labor. A fetal pleuroamniotic shunt may have a beneficial adjunctive effect.

Research paper thumbnail of Placental characteristics of severely discordant monochorionic (MC) diamniotic (DA) twins

American Journal of Obstetrics and Gynecology, Dec 1, 2004

Research paper thumbnail of 665 Clinical value of non-invasive tests to predict fetal anemia

American Journal of Obstetrics and Gynecology, Dec 1, 2001

Research paper thumbnail of <i>De novo WNT5A</i>-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype

Clinical Genetics, May 24, 2014

Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic feature... more Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway.

Research paper thumbnail of Thoraco-amniotische Shunts in fetalen makrozystischen Lungentumoren

Zeitschrift Fur Geburtshilfe Und Neonatologie, Nov 1, 2011

Research paper thumbnail of OC08.05: Are serial MRIs of any value in the assessment of cerebral ischemic injury following co-twin demise?

Ultrasound in Obstetrics & Gynecology, Sep 1, 2015

Objectives: Hypotensive ischemic injury may result in transient changes on intrauterine magnetic ... more Objectives: Hypotensive ischemic injury may result in transient changes on intrauterine magnetic resonance imaging (MRI) in monochorionic (MC) pregnancies. Our aim was to evaluate the use of serial MRIs in the evaluation of ischemic injury following co-twin demise. Methods: We reviewed all MC pregnancies who had more than one MRI (diffusion-weighted and T2) with co-twin demise at our tertiary care centre. Pregnancy demographics, ultrasound and MRI findings and obstetric outcomes were collected between 2005 and 2015. Results: A total of 15 MC pregnancies had co-twin demise and serial MRIs, including 13 MC/diamniotic (DA) twins, 1 monoamniotic (MA) and 1 triplet with an MC/DA pair were reviewed. Six cases were complicated by Twin-twin transfusion syndrome (TTTS), 5 of which demised before treatment and 1 post-laser ablation of placental anastomoses, 6 had selective intrauterine growth restriction (sIUGR), 1 was MA and 2 had an unexplained intrauterine fetal death (IUFD). The vast majority of MRIs (14/15) were done within 7 days following IUFD. Of these, 3 had normal MRIs which remained normal on subsequent MRI and one was initially normal (done one day after IUFD), but subsequently showed extensive white matter injury. Eleven cases had abnormal MRI findings, of which four lesions significantly evolved (left occipital infarct resolved, multifocal small infarcts revolved, thick germinal matrix normalised and cerebellar bleed decreased in size) and the remainder seven cases had similar lesions on subsequent MRI. Conclusions: An initial MRI, especially if done within 7 days after co-twin demise in MC pregnancies, should warrant a subsequent MRI to evaluate the evolution of ischemic changes and help in the counselling of couples. OC08.06 Is neurosonography predictive of MRI findings after co-twin demise in monochorionic pregnancies?

Research paper thumbnail of 437: Fetal pleuroamniotic shunting for macrocystic lung lesions

American Journal of Obstetrics and Gynecology, 2011

Monochorionic twins have increased perinatal morbidity and mortality due to a variety of factors,... more Monochorionic twins have increased perinatal morbidity and mortality due to a variety of factors, including twin-twin transfusion syndrome (TTTS) and increased risk of congenital anomalies. The objective of this study was to describe the non-cardiac anomalies in monochorionic twins afflicted with TTTS. STUDY DESIGN: This was a retrospective study of 221 consecutive cases of TTTS treated with laser surgery between March 2006 and May 2010. Major versus minor non-cardiac congenital anomalies were classified according to the Western Australian Birth Defects Registry system (BMJ 1997;315:1260-1265). Because of the secondary cardiac derangements that arise in association with TTTS, cases with cardiac anomalies were excluded from the analysis. Anomalies were diagnosed by antepartum ultrasound and/or review of neonatal medical records. Statistical analyses were performed using Fisher's exact and chi square tests. A p-value Ͻ 0.05 was considered significant. RESULTS: Non-cardiac congenital anomalies were identified in a total of 24 individual twins (5.4%). There was a significantly increased rate of non-cardiac anomalies in the donor twin (8.1%, 18/221) versus the recipient twin (2.7%, 6/221, pϭ0.019). Comparing cases with and without non-cardiac anomalies, there were no differences in frequency of Quintero Stage III/IV cases (68% vs. 67%, pϭ1.0), gestational week of laser surgery (20.2 Ϯ 1.9 vs. 20.7 Ϯ 2.4, pϭ0.39), gestational week at delivery (32.0 Ϯ 4.6 vs. 32.4 Ϯ 4.3, pϭ0.75), 30-day survival of the donor (68% vs. 74%, pϭ0.84), and 30-day survival of the recipient (73% vs. 83%, pϭ0.36), respectively. Of the 18 donor fetuses with anomalies, 10 (55.6%) were considered major. Of the 6 recipient fetuses with anomalies, 3 (50%) were major. CONCLUSIONS: An increased incidence of non-cardiac structural anomalies was found in donor twins versus recipient twins in cases of TTTS. The etiology of this difference is unknown, but it may in part be related to early blood flow disturbances seen in twin-twin transfusion syndrome.

Research paper thumbnail of OP33.10: In fetal gastroschisis, perinatal outcome is better following induction of labour at 37 weeks than with expectant management

Ultrasound in Obstetrics & Gynecology, Sep 1, 2012

The aim of the present study was to explore the possible use of 3D Power Doppler Angiography (3D ... more The aim of the present study was to explore the possible use of 3D Power Doppler Angiography (3D PDA) using VOCALTM software (GE Healthcare, USA) assessing different fetal cerebral regions in normal and growth restricted fetuses (IUGR). Methods: 77 AGA and 55 IUGR (24-36 ws gestation). IUGR were divided in 3 groups: group 1 (n = 28): Late onset IUGR (> 34 ws) with normal bidimensional Doppler flow analysis, group 2 (n = 11): early onset IUGR (< 34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), normal middle cerebral artery (MCA) PI and normal ductus venosus (DV) PI, group 3 (n = 16): early onset IUGR (< 34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), abnormal MCA PI and pathological DV PI. Two regions of interest (ROI) were defined within the fetal brain. The first ROI (zone 1) is anterior respect the cavum septi pellucidi (CSP). The second ROI (zone 2) is obtained tracing a contour between the temporal bones as wide as the CSP. 3D-PDA vascular indexes (VI = vascularization, FI = flow, VFI = vascularization and flow) were determined in both areas for both AGA and IUGR fetuses by one operator. Results: VFI values demonstrated increased blood flow in frontal zone compared to control group (AGA) in ''early onset IUGR'' (in both groups 2-3 with and without abnormal 2D MCA findings). VI and VFI values demonstrated increased blood flow in frontal zone and decreased blood flow in temporal zone compared to control group (AGA) in ''late onset IUGR'' with preferential increment in bloody supply to the frontal region to protect general cognitive functions. Conclusions: 3DPDA analysis could be considered a valid method to identify earlier vascular redistribution in IUGR fetuses comparing to 2D velocimetry. 3DPDA could become an additional parameter to adjust the monitoring intervals in the evaluation of high risk fetuses.

Research paper thumbnail of The role of amniotic fluid interphase fish analysis in patient management

International journal of gynaecology and obstetrics, 2000

Research paper thumbnail of Intravenous Immunoglobulin in the Management of Severe Early Onset Red Blood Cell Alloimmunization

Blood, Nov 5, 2021

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) fo... more OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks&#39; gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed &amp;lt; 20 weeks&#39; gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks&#39; gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb&#39;s between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on &#39;Statistical Package for Social Science Version 16.0&#39; (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses &amp;lt;20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple &quot;top-up&quot; transfusion, and six (35%) phototherapy. CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Research paper thumbnail of Mild ventriculomegaly in the fetus, natural history, associated findings and outcome of isolated mild ventriculomegaly: a literature review

Prenatal Diagnosis, 2001

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Research paper thumbnail of General anesthesia for endoscopic laser for severe TTTS is associated with increased risk of adverse maternal outcome

American Journal of Obstetrics and Gynecology, Dec 1, 2005

To evaluate 3 anaesthesia techniques-general (GA), epidural (ED) and conscious sedation (CS)-empl... more To evaluate 3 anaesthesia techniques-general (GA), epidural (ED) and conscious sedation (CS)-employed for the first 80 cases of laser for severe TTTS. STUDY DESIGN: Data were abstracted from clinical records: major and minor maternal complications and fetal outcomes were compared for all techniques. Univariate comparisons were made using one-way ANOVA and Fisher's exact tests. Multivariate logistic regression was used to identify independent associations with major maternal adverse outcomes. RESULTS: 18 cases were done under GA, 4 under ED and 58 under CS. There was no difference in maternal demographic data between groups. The GA group recorded lower systolic pressures, increased requirements for pressure therapy (p!0.01) and increased intra-operative intravenous fluids (all p!0.02). Major maternal complications (n=13) were more common with GA as compared to the other groups (p!0.01). GA remained independently associated with major maternal complications in multivariate analysis (adjusted OR 36; p=0.03) after controlling for covariates. Pulmonary edema within 24 hrs of the procedure occurred in 8 women, total IV fluid volume was the only factor independently associated with the development of pulmonary edema (adjusted OR 4.5 for each 1000 mL increase in IV fluid). CONCLUSION: GA was associated with increased risk of major maternal complications, particularly pulmonary edema, when compared to ED and CS.

Research paper thumbnail of Outcomes of haemoglobin Bart’s hydrops fetalis following intrauterine transfusion in Ontario, Canada

Archives of Disease in Childhood-fetal and Neonatal Edition, Jul 2, 2020

ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin B... more ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart’s hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive.DesignTo evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent β-thalassaemia (TDT-β).ResultsOf the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-β patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with ‘silent’ ischaemic infarcts.ConclusionsIn patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-β counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Research paper thumbnail of 482: Outcome of pregnancies complicated by fetal parvovirous-B19 infection

American Journal of Obstetrics and Gynecology, 2014

intrapartum conditions are assumed to be part of the risk of elective induction. Association of e... more intrapartum conditions are assumed to be part of the risk of elective induction. Association of elective IOL at 39 weeks and cesarean delivery and NICU admission. In scenario 1, women with documented fetal distress, amniotic infection, hemorrhage, or premature separation of the placenta were excluded from the elective IOL group but retained in the expectant management group. In scenario 2, we assumed that these conditions occurred after the onset of labor, and women with these conditions were retained in both the elective IOL and expectant management groups. NICU, neonatal intensive care unit; OR, odds ratio; CI, 95% confidence interval.

Research paper thumbnail of Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

Prenatal Diagnosis, Feb 25, 2009

Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and ... more Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

Research paper thumbnail of Treatment Options in Fetomaternal Hemorrhage: Four Case Studies

Journal of obstetrics and gynaecology Canada, Oct 1, 2004

Significant fetomaternal hemorrhage (FMH) is an uncommon event that places the fetus at risk of s... more Significant fetomaternal hemorrhage (FMH) is an uncommon event that places the fetus at risk of severe morbidity and mortality. Symptoms and signs at presentation are subtle and, if promptly recognized, appropriate management may permit the fetus to escape serious injury. Four cases of significant FMH were diagnosed in the high-risk obstetrical unit at Mount Sinai Hospital, Toronto, during 2003. Three of the women complained of reduced fetal movements and were investigated initially with a non-stress test, a Kleihauer-Betke test, and ultrasound, including Doppler of the middle cerebral artery. These women all required emergency Caesarean section for non-reassuring fetal status. One fetus was treated by intravascular transfusion. Another identified case was transfused postnatally. One asymptomatic case was identified after spontaneous vaginal birth and also treated by neonatal transfusion. Neurological outcomes were good in all four cases. Reduced fetal movements may be the only complaint of FMH. Increased awareness is required to ensure a diagnosis is made. When a non-stress test for reduced fetal movement is non-reactive, a Kleihauer-Betke test should be ordered, as well as detailed ultrasonography, including fetal Doppler studies. The perinatal prognosis for FMH may improve by facilitating the appropriate use of fetal blood transfusion or delivery by Caesarean section.

Research paper thumbnail of Maternal Red Blood Cell Alloimmunization Managed with Intrauterine Blood Transfusion: Predictors of Poor Outcome

Blood, Nov 5, 2020

Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different... more Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different antigens capable of causing maternal red blood cell (RBC) alloimmunization and severe fetal hemolytic disease. Anti-K and anti-D are responsible for a significant proportion of fetal anemia requiring intrauterine transfusion (IUT). Whilst IUT of packed RBCs improves neonatal survival and morbidity, clinical prognostic indicators are lacking. Our primary objective was to identify predictors of adverse outcome. Methods: We conducted a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada. All pregnant patients alloimmunized with anti-K and anti-D as a single antibody, between 1991 and 2018 were included. Data were obtained from patient medical records, ultrasound reports and information from the transfusion medicine laboratory. Data included maternal demographics, antibody titers, pregnancy history, number of IUTs, hemoglobin (HB) concentration at the beginning and end of all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age at delivery, birth weight, HB at birth and need for neonatal transfusion, phototherapy or intravenous immunoglobulins (IVIG). Our primary outcome was the composite outcome of stillbirth or neonatal death (SB/NND). We also constructed a secondary outcome consisting of top-up neonatal transfusion, exchange transfusion, phototherapy, or use of IVIG. Medians and interquartile ranges (IQR) or mean±SD were used as summary statistics and compared by Mann-Whitney or t-test; p&amp;lt;0.05 was statistically significant. Outcome predictors were identified using multivariable logistic or linear regression analysis; accounting for patient level clustering by marginal Generalized Estimating Equation did not significantly affect variables. Data were analyzed using SPSS. Results: 116 women with 128 pregnancies and 425 IUTs with anti-K or anti-D as a single antibody were identified. Median maternal age was 31 years (27.0-35.0) for anti-K and 32 years (23.6-40.6) for anti-D. The gestational age at 1st IUT differed significantly between anti-K and anti-D (24.3 vs 28.7 weeks respectively, p=0.004). Women with anti-K antibodies required more IUTs than women with anti-D (3.84 vs 3.12 IUTs, p=0.036) and HB at 1st IUT was significantly lower in the anti-K group (5.10 vs 7.05 g/dL, p=0.001) (Table 1). Following initiation of IUT, the time from 1st IUT to delivery was 69.6 days in the anti-K group and 54.6 in the anti-D group (p=0.06). The daily decrease of HB between 1st and 2nd IUT (as a marker of disease severity), development of fetal hydrops and severe preterm birth did not differ significantly between the two groups. Mean gestation age at delivery was 35.0 weeks in the anti-K and 36.0 weeks in the anti-D group (p=0.28), with 87.1% and 93.9% survival (p=0.37), respectively. The proportion of neonates requiring phototherapy, IVIG and exchange/top-up transfusion was comparable across the two antibody groups (Table 1). Regression analysis showed that delivery occurred sooner if HB dropped more rapidly between the first two IUTs (p=0.01). Each additional transfusion gained on average 22.5 days in utero (Table 2). In multivariable analysis, gestational age at 1st IUT was the only predictor of a SB/NND outcome (adjusted OR 0.79 [95%CI 0.67-0.93]; p=0.006). With 1st IUT at 23 weeks, the risk of SB/NND was 8%, but only 2.5% at 28 weeks and &amp;lt;0.01% at 36 weeks (Table 3). Gestational age at delivery (adjusted OR 1.11 [95%CI 1.00 to 1.23]; p=0.046) and HB at 1st IUT (adjusted OR 0.84 [95%CI 0.72 to 0.99]; p=0.038) were the only predictors of a composite adverse blood product requirement/intervention outcome (Table 4). The odds of blood product requirement/intervention postnatally at 1st IUT (median HB at 1st IUT of 6.6g/dL) at 28 weeks were 43% and increased by a further 38% for delivery at 34 weeks. Conclusion: The earlier in gestation that IUTs are implemented, the higher the odds of a SB/NND; however the later the gestation at delivery, the greater the odds of the neonate requiring blood products post-partum. The greater the HB drop between the 1st and 2nd IUT, the shorter the &#39;time between the first IUT and delivery&#39;, which increases the odds of a SB/NND outcome. Disclosures Garbowski: Vifor Pharma: Consultancy, Membership on an entity&#39;s Board of Directors or advisory committees; Imara: Consultancy. Shehata:Ferring: Honoraria.

Research paper thumbnail of Is There a Role for Titre Monitoring in Kell Alloimmunized Pregnancies?

Blood, Nov 13, 2019

Background: Kell and Rhesus (Rh) maternal red blood cell (RBC) alloimmunization are the most comm... more 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.

Research paper thumbnail of OP23.09: Perinatal outcome in fetuses with dislodged pleuroamniotic shunts (PAS)

Ultrasound in Obstetrics & Gynecology, Sep 1, 2017

Short oral presentation abstracts Objectives: An interstitial laser ablation becomes a good candi... more Short oral presentation abstracts Objectives: An interstitial laser ablation becomes a good candidate for the prenatal treatment of chorioangioma, sacrococcygeal teratoma, selective fetal growth restriction and twin reversed arterial perfusion sequence in early gestation. The aim of this study was to describe the in vitro results of interstitial laser coagulation in different types of laser generator, power and time. Methods: Total 144 placentae were interstitially ablated with PlexoLong 19 gauge needle, 400 micron laser fiber and Nd:YAG or Diode at 12 power-time combinations (5, 10, 15 seconds versus 15, 20, 25, 30 watts). We evaluated the diameter of coagulated zone using ultrasound and histopathology. Results: Mean coagulated placental diameter (ultrasound) was shown in figure 1. Ablated size measurement by ultrasound was slightly larger than microscopy (p<0.001). The average length (histopathology) after 5, 10 and 15 seconds of coagulation were 5.12, 7.00 and 7.85 mm (±0.16), and after using power 15, 20, 25 and 30 watt were 5.20, 6.36, 7.08 and 7.99 mm (±0.21), respectively. In addition, using the Diode was significantly wider than using Nd:YAG in coagulated diameter (p<0.001). Histology of the placental tissue showed gradual change in degree of thermal damage and period of time. Conclusions: Interstitial laser ablation particular Diode, seems to be an effective prenatal treatment when the feeding vessels are smaller than 8 mm in diameter.

Research paper thumbnail of Natural History of Ventriculomegaly in Fetal Agenesis of the Corpus Callosum

Journal of Ultrasound in Medicine, Sep 9, 2019

Objectives-To assess the natural evolution of the size of the fetal lateral ventricles throughout... more Objectives-To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. Methods-Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. Results-In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P < .001). In 79 cases that had longitudinal follow-up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean AE SD, 0.6 AE 1.5 versus 0.6 AE 1.1 mm; P = .45). Conclusions-Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long-term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining longterm follow-up of these cases.

Research paper thumbnail of Ultrasound-guided laser treatment of hydropic fetal lung lesions with a systemic arterial supply

American Journal of Obstetrics and Gynecology, Dec 1, 2003

To report innovative minimally invasive fetal therapy for massive lung lesions associated with hy... more To report innovative minimally invasive fetal therapy for massive lung lesions associated with hydrops. STUDY DESIGN: 2 cases, followed prospectively. RESULTS: 2 hydropic fetuses, at 19 and 23 wks, respectively, had massive bronchopulmonary sequestrations occupying most of the chest and everting the diaphragm well into the abdomen. A large aortic feeding vessel was identified in each case. Using IV sedation and continuous ultrasound guidance, an 18g needle was placed intra-amniotically, through which a longer 22g needle was advanced into the fetal IHV to sample, paralyze, and anesthetize the fetus. This was then redirected into one of the larger cysts, and microbubble contrast agent (Levovist) was injected to document cyst communication. A 600-micron ND: YAG laser fiber was passed through the 18g needle, and the tip was placed adjacent to the feeding vessel, which was successfully ablated in each case. In the first case at 19 wks, finally a fetal Rocket pleuroamniotic shunt was placed, traversing several cysts. The left-sided mass resolved dramatically in size over the next 3 wks, and hydrops resolved completely. A healthy 3.7-kg male, requiring no assisted ventilation, was born at 39 wks. The involved lobe was resected the next day; pediatric follow-up is entirely normal. At 23 wks, GA was used for the 2nd right-sided mass and no shunt was placed: 2 wks later, there has been some mass shrinkage; so far, hydrops persists. The pregnancy is ongoing. CONCLUSION: The prognosis for large fetal cystic chest masses associated with hydrops is dismal-all die. This has prompted attempts at treatment by open fetal surgery, with mixed results and a high risk of premature labor. We have demonstrated an excellent outcome by US-guided laser ablation of the systemic arterial supply. This is a preferable, much less invasive approach to such lesions-with far less risk of premature labor. A fetal pleuroamniotic shunt may have a beneficial adjunctive effect.

Research paper thumbnail of Placental characteristics of severely discordant monochorionic (MC) diamniotic (DA) twins

American Journal of Obstetrics and Gynecology, Dec 1, 2004

Research paper thumbnail of 665 Clinical value of non-invasive tests to predict fetal anemia

American Journal of Obstetrics and Gynecology, Dec 1, 2001

Research paper thumbnail of <i>De novo WNT5A</i>-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype

Clinical Genetics, May 24, 2014

Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic feature... more Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway.

Research paper thumbnail of Thoraco-amniotische Shunts in fetalen makrozystischen Lungentumoren

Zeitschrift Fur Geburtshilfe Und Neonatologie, Nov 1, 2011

Research paper thumbnail of OC08.05: Are serial MRIs of any value in the assessment of cerebral ischemic injury following co-twin demise?

Ultrasound in Obstetrics & Gynecology, Sep 1, 2015

Objectives: Hypotensive ischemic injury may result in transient changes on intrauterine magnetic ... more Objectives: Hypotensive ischemic injury may result in transient changes on intrauterine magnetic resonance imaging (MRI) in monochorionic (MC) pregnancies. Our aim was to evaluate the use of serial MRIs in the evaluation of ischemic injury following co-twin demise. Methods: We reviewed all MC pregnancies who had more than one MRI (diffusion-weighted and T2) with co-twin demise at our tertiary care centre. Pregnancy demographics, ultrasound and MRI findings and obstetric outcomes were collected between 2005 and 2015. Results: A total of 15 MC pregnancies had co-twin demise and serial MRIs, including 13 MC/diamniotic (DA) twins, 1 monoamniotic (MA) and 1 triplet with an MC/DA pair were reviewed. Six cases were complicated by Twin-twin transfusion syndrome (TTTS), 5 of which demised before treatment and 1 post-laser ablation of placental anastomoses, 6 had selective intrauterine growth restriction (sIUGR), 1 was MA and 2 had an unexplained intrauterine fetal death (IUFD). The vast majority of MRIs (14/15) were done within 7 days following IUFD. Of these, 3 had normal MRIs which remained normal on subsequent MRI and one was initially normal (done one day after IUFD), but subsequently showed extensive white matter injury. Eleven cases had abnormal MRI findings, of which four lesions significantly evolved (left occipital infarct resolved, multifocal small infarcts revolved, thick germinal matrix normalised and cerebellar bleed decreased in size) and the remainder seven cases had similar lesions on subsequent MRI. Conclusions: An initial MRI, especially if done within 7 days after co-twin demise in MC pregnancies, should warrant a subsequent MRI to evaluate the evolution of ischemic changes and help in the counselling of couples. OC08.06 Is neurosonography predictive of MRI findings after co-twin demise in monochorionic pregnancies?

Research paper thumbnail of 437: Fetal pleuroamniotic shunting for macrocystic lung lesions

American Journal of Obstetrics and Gynecology, 2011

Monochorionic twins have increased perinatal morbidity and mortality due to a variety of factors,... more Monochorionic twins have increased perinatal morbidity and mortality due to a variety of factors, including twin-twin transfusion syndrome (TTTS) and increased risk of congenital anomalies. The objective of this study was to describe the non-cardiac anomalies in monochorionic twins afflicted with TTTS. STUDY DESIGN: This was a retrospective study of 221 consecutive cases of TTTS treated with laser surgery between March 2006 and May 2010. Major versus minor non-cardiac congenital anomalies were classified according to the Western Australian Birth Defects Registry system (BMJ 1997;315:1260-1265). Because of the secondary cardiac derangements that arise in association with TTTS, cases with cardiac anomalies were excluded from the analysis. Anomalies were diagnosed by antepartum ultrasound and/or review of neonatal medical records. Statistical analyses were performed using Fisher's exact and chi square tests. A p-value Ͻ 0.05 was considered significant. RESULTS: Non-cardiac congenital anomalies were identified in a total of 24 individual twins (5.4%). There was a significantly increased rate of non-cardiac anomalies in the donor twin (8.1%, 18/221) versus the recipient twin (2.7%, 6/221, pϭ0.019). Comparing cases with and without non-cardiac anomalies, there were no differences in frequency of Quintero Stage III/IV cases (68% vs. 67%, pϭ1.0), gestational week of laser surgery (20.2 Ϯ 1.9 vs. 20.7 Ϯ 2.4, pϭ0.39), gestational week at delivery (32.0 Ϯ 4.6 vs. 32.4 Ϯ 4.3, pϭ0.75), 30-day survival of the donor (68% vs. 74%, pϭ0.84), and 30-day survival of the recipient (73% vs. 83%, pϭ0.36), respectively. Of the 18 donor fetuses with anomalies, 10 (55.6%) were considered major. Of the 6 recipient fetuses with anomalies, 3 (50%) were major. CONCLUSIONS: An increased incidence of non-cardiac structural anomalies was found in donor twins versus recipient twins in cases of TTTS. The etiology of this difference is unknown, but it may in part be related to early blood flow disturbances seen in twin-twin transfusion syndrome.

Research paper thumbnail of OP33.10: In fetal gastroschisis, perinatal outcome is better following induction of labour at 37 weeks than with expectant management

Ultrasound in Obstetrics & Gynecology, Sep 1, 2012

The aim of the present study was to explore the possible use of 3D Power Doppler Angiography (3D ... more The aim of the present study was to explore the possible use of 3D Power Doppler Angiography (3D PDA) using VOCALTM software (GE Healthcare, USA) assessing different fetal cerebral regions in normal and growth restricted fetuses (IUGR). Methods: 77 AGA and 55 IUGR (24-36 ws gestation). IUGR were divided in 3 groups: group 1 (n = 28): Late onset IUGR (> 34 ws) with normal bidimensional Doppler flow analysis, group 2 (n = 11): early onset IUGR (< 34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), normal middle cerebral artery (MCA) PI and normal ductus venosus (DV) PI, group 3 (n = 16): early onset IUGR (< 34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), abnormal MCA PI and pathological DV PI. Two regions of interest (ROI) were defined within the fetal brain. The first ROI (zone 1) is anterior respect the cavum septi pellucidi (CSP). The second ROI (zone 2) is obtained tracing a contour between the temporal bones as wide as the CSP. 3D-PDA vascular indexes (VI = vascularization, FI = flow, VFI = vascularization and flow) were determined in both areas for both AGA and IUGR fetuses by one operator. Results: VFI values demonstrated increased blood flow in frontal zone compared to control group (AGA) in ''early onset IUGR'' (in both groups 2-3 with and without abnormal 2D MCA findings). VI and VFI values demonstrated increased blood flow in frontal zone and decreased blood flow in temporal zone compared to control group (AGA) in ''late onset IUGR'' with preferential increment in bloody supply to the frontal region to protect general cognitive functions. Conclusions: 3DPDA analysis could be considered a valid method to identify earlier vascular redistribution in IUGR fetuses comparing to 2D velocimetry. 3DPDA could become an additional parameter to adjust the monitoring intervals in the evaluation of high risk fetuses.

Research paper thumbnail of The role of amniotic fluid interphase fish analysis in patient management

International journal of gynaecology and obstetrics, 2000