Sarah Keating

University of Toronto, Toronto, Ontario, Canada

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Publications (88)246.5 Total impact

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    ABSTRACT: Fetal infection with human parvovirus B19 (hParvo-B19) has been mainly associated with fetal anemia, while data regarding other fetal hematological effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia following fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies complicated by fetal hParvo-B19 infection which underwent fetal blood sampling (FBS). The characteristics and outcome of fetuses with severe thrombocytopenia (< 50 x10(9)/L) were compared with those of fetuses with a platelet concentration ≥ 50 x10(9)/L. (controls). Fetuses in whom 3 FBS's were performed (N=4) were analyzed to assess the natural history of platelet levels following fetal hParvo-B19 infection. A total of 37 pregnancies affected by fetal hParvo-B19 infection were identified. Of the 29 cases which underwent FBS and had information regarding fetal platelets, 11 (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6±0.9 vs. 5.5±3.6 g/dL, p=0.01), lower reticulocyte count (9.1±2.8% vs. 17.3±10.6%, p=0.02), and lower gestational age (GA) at the time of diagnosis (21.4±3.1 vs. 23.6±2.2 wks, p=0.03). Both the fetal death rate within 48 hrs of FBS (27.3% vs. 0%, p=0.02), and the risk of prematurity (100.0% vs. 13.3%, p<0.001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the 2(nd) trimester, but in some cases persisted into the 3(rd). Intrauterine transfusion (IUT) of RBCs resulted in a further mean decrease of 40.1±31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common following fetal hParvo-B19 infection, can be further worsened by IUT and may be associated with an increased risk of procedure related fetal loss following either FBS or IUT. Copyright © 2015 Elsevier Inc. All rights reserved.
    American Journal of Obstetrics and Gynecology 01/2015; DOI:10.1016/j.ajog.2015.01.048 · 3.97 Impact Factor
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    ABSTRACT: Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy. Copyright © 2014. Published by Elsevier B.V.
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    ABSTRACT: Decidual leukocytes are critical to the development of the fetomaternal interface, regulating tolerance to the semi-allogeneic fetus and vascular transformation of the uterine spiral arteries. Despite the continuation of these processes beyond the first trimester of pregnancy, the second trimester has largely been unstudied, with investigation focusing on early gestation and term tissues. We sought to characterize changes in decidual leukocyte populations from first to second trimester. Multicolor flow cytometry was performed on isolated decidual leukocytes from elective terminations of pregnancy between 6 and 20 weeks of gestation for study of first (6-12 weeks) and second trimesters (13-20 weeks). Specific subpopulations were identified by comparison to isotype and fluorescent-minus-one (FMO) controls. Decidual natural killer cells (CD56(+)CD16(-)CD3(-)) did not change in number, although a population of dNK with decreased CD56 brightness was observed in second trimester decidua. CD14(+)HLA-DR(+) macrophage numbers declined from first to second trimester (p = 0.031), yet a CD163(+)CD206(+) subset designating alternatively activated M2-like macrophages increased during the same period (p = 0.015). Intermediate CD205(+) dendritic cells demonstrated significant decline (p = 0.022), but immature CD209(+) and mature CD83(+) dendritic cells did not differ between trimesters. Total CD3(+) and CD3(+)CD4(+) T lymphocytes increased (p = 0.0079, p = 0.0028); CD3(+)CD8(+) T cells trended towards increase but did not differ significantly. Several changes in leukocyte subsets are observed in the second trimester that promote a tolerogenic and angiogenic decidual microenvironment through mid-gestation. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Placenta 11/2014; 35:1027-1034. DOI:10.1016/j.placenta.2014.09.018 · 3.29 Impact Factor
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    ABSTRACT: To determine the incidence of temporal lobe dysplasia (TLD) detected on prenatal ultrasound in thanatophoric dysplasia (TD) over an 11-year period in a tertiary referral centre. An 11-year retrospective review of perinatal autopsies was performed from 2002 to 2013 to identify cases of TD. The ultrasound images and corresponding reports of all TD cases were reviewed for TLD. The same set of images subsequently underwent a retrospective review by a perinatal radiologist with knowledge of the TLD feature to determine whether they could be identified. There were 31 TD cases that underwent perinatal autopsy. Prenatal ultrasound imaging was available to review in 24/31 (77%) cases. Mean gestational age (GA) of TD diagnosis was 21.3 weeks (range: 18-36 weeks). TLD was identified and reported in 6/24 (25%) cases; all six cases occurred after 2007. Retrospective interpretation of the ultrasound images identified features of TLD in 10 additional cases. In total, 16/24 (67%) cases displayed sonographic evidence of TLD. Temporal trends show that TLD features were present in 50% (5/10) of all TD cases from 2002-2006 and in 79% (11/14) of the cases from 2007-2013. Currently, the detection rate of TLD by ultrasound is low but may be increased by modified brain images that enhance visualization of the temporal lobes. Prenatal identification of TLD may help in the prenatal diagnosis of TD and thus provide more accurate prenatal counseling and guide molecular investigations to confirm the specific diagnosis of TD.
    Ultrasound in Obstetrics and Gynecology 11/2014; 44(5). DOI:10.1002/uog.13337 · 3.56 Impact Factor
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    ABSTRACT: We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyelia in Chiari malformations, infarct like histology, or old hemorrhage in 8 cases of syringomyelia. Vernicomyelia did not occur in the absence of syrinx formation. The syringes extended from the sites of dysraphism, in ascending or descending patterns. The syringes were usually in a major proportion anatomically distinct from a dilated or denuded central canal and tended to be dorsal and paramedian or median. We suggest that fetal syringomyelia in Chiari II malformation and other dysraphic states is often established prior to midgestation, has contributions from the primary malformation as well as from secondary in utero injury and is anatomically and pathophysiologically distinct from post natal syringomyelia secondary to hindbrain crowding.
    08/2014; 2(1):91. DOI:10.1186/PREACCEPT-1099742865133283
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Introduction: Heparin is often prescribed during pregnancy with the intention of improving perinatal outcomes on the basis that it exerts an anticoagulant action in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates that heparin's beneficial effects in pregnancy may result from 'non-anticoagulant' effects including the promotion of angiogenesis. Methods: To study the effect of heparin within the placenta, we performed secondary analyses on a pilot trial where 32 women with negative thrombophilia screens and second-trimester evidence of placental insufficiency were randomized to standard care or antenatal self-administration of unfractionated heparin (UFH) 7500IU twice-daily. Serial placental ultrasound images were reviewed and compared with histo-pathologic findings following delivery. Results: There were no differences between the two arms in either the evolution of abnormal placental lesions on ultrasound (p = 0.75) or evidence of maternal vascular under-perfusion on histopathology (p = 0.89). In pregnancies considered at increased risk for adverse pregnancy outcomes based on previous history or abnormal serum marker screen, early (second-trimester) placental ultrasound, reflecting developmental pathology had better test characteristics (sensitivity 77.8%; positive predictive value 80.8%) for predicting adverse pregnancy outcomes than third-trimester ultrasound that is reflective of placental thrombotic injury. Conclusions: Administration of UFH did not prevent the development or evolution of abnormal placental lesions on placental ultrasound or evidence of maternal vascular underperfusion on placental histopathology. Second-trimester placental ultrasound may be of value in predicting those at greatest risk of adverse outcomes. Crown Copyright
    Placenta 07/2014; 35(10). DOI:10.1016/j.placenta.2014.07.010 · 3.29 Impact Factor
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    ABSTRACT: Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders, affecting approximately 2.4-4.5/10,000 births. We performed a retrospective review of the perinatal autopsies conducted between the years 2002-2011at our centre. The study population consisted of fetuses diagnosed with skeletal dysplasia with subsequent termination, stillbirth and live-born who died shortly after birth. Of the 2,002 autopsies performed, 112 (5.6%) were diagnosed with skeletal dysplasia. These 112 cases encompassed 17 of the 40 groups of Nosology 2010. The two most common nosology groups were osteogenesis imperfecta [27/112 (24%)] and the FGFR3 chondrodysplasias [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia (TD) type 1 [20(17.9%)], and osteogenesis imperfecta (OI) type 2 [20 (17.9%)]. The combined radiology, pathology, and genetic investigations and grouping the cases using Nosology 2010 resulted in a specific diagnosis in 96/112 of the cases.
    Clinical Genetics 05/2014; DOI:10.1111/cge.12434 · 3.65 Impact Factor
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    ABSTRACT: Introduction Decidual leukocytes are critical to the development of the fetomaternal interface, regulating tolerance to the semi-allogeneic fetus and vascular transformation of the uterine spiral arteries. Despite the continuation of these processes beyond the first trimester of pregnancy, the second trimester has largely been unstudied, with investigation focusing on early gestation and term tissues. We sought to characterize changes in decidual leukocyte populations from first to second trimester. Methods Multicolour flow cytometry was performed on isolated decidual leukocytes from elective terminations of pregnancy between 6 and 20 weeks of gestation for study of first (6-12 weeks) and second trimesters (13-20 weeks). Specific subpopulations were identified by comparison to isotype and fluorescent-minus-one (FMO) controls. Results Decidual natural killer cells (CD56+CD16-CD3-) did not change in number, although a population of dNK with decreased CD56 brightness was observed in second trimester decidua. CD14+HLA-DR+ macrophage numbers declined from first to second trimester (p = 0.031), yet a CD163+CD206+ subset designating alternatively activated M2-like macrophages increased during the same period (p = 0.015). Intermediate CD205+ dendritic cells demonstrated significant decline (p = 0.022), but immature CD209+ and mature CD83+ dendritic cells did not differ between trimesters. Total CD3+ and CD3+CD4+ T lymphocytes increased (p = 0.0079, p = 0.0028); CD3+CD8+ T cells trended towards increase but did not differ significantly. Conclusion Several changes in leukocyte subsets are observed in the second trimester that promote a tolerogenic and angiogenic decidual microenvironment through mid-gestation.
    Placenta 01/2014; · 3.29 Impact Factor
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    ABSTRACT: To describe the prenatal sonographic features and the results of DNA analysis on three fetuses with Dyssegmental Dysplasia, Silverman-Handmaker Type (DD-SH). A retrospective review of three fetuses with confirmed DD-SH was conducted. The fetal ultrasound findings, radiological characteristics and results of the mutation analysis of the HSPG2 gene were reviewed. There were 3 cases in two families with DD-SH diagnosed prenatally. The main prenatal ultrasound and radiological features of DD-SH were severe limb shortening and vertebral segmentation and fusion defects (anisospondyly). DNA analysis of the HSPG2 gene showed that the two affected fetuses in a non-consanguineous family had a compound heterozygote for the c.646G > T transversion in exon 7 and a c.5788C > T transition in exon 46. The fetus born to the consanguineous couple had a homozygous mutation c.1356-27_1507 + 59del. DD-SH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Fetal X-rays and DNA analysis of the HSPG2 gene are important for confirmation of the diagnosis and for pre-implantation and prenatal diagnosis in pregnancies at risk. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 11/2013; 33(11). DOI:10.1002/pd.4193 · 2.68 Impact Factor
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    ABSTRACT: Objective To report three different antenatal therapeutic approaches for fetal lung masses associated with hydrops. Methods Three prospectively followed cases are described, and all 30 previously published minimally invasive cases of fetal therapy for hydropic lung masses are reviewed. ResultsThree hydropic fetuses with large intrathoracic lung masses presented at 17, 25 and 21 weeks of gestation, respectively. An aortic feeding vessel was identified in each case and thus a bronchopulmonary sequestration (BPS) was suspected. Under ultrasound guidance, the feeding vessel was successfully occluded with interstitial laser (Case 1), radiofrequency ablation (RFA) (Case 2) and thrombogenic coil embolization (Case 3). Complete (Cases 1 and 2) or partial (Case 3) resolution of the lung mass and hydrops was observed. A healthy infant was born at term after laser therapy (Case 1), and the involved lung lobe was resected on day 2 of postnatal life. In Case 2, hydrops resolved completely following RFA, but an iatrogenic congenital diaphragmatic hernia and abdominal wall defect became apparent 4 weeks later. The neonate died from sepsis following spontaneous preterm labor at 33 weeks. In Case 3, despite technical success in complete vascular occlusion with coils, a stillbirth ensued 2 days after embolization. Conclusions The prognosis of large microcystic or echogenic fetal chest masses associated with hydrops is dismal. This has prompted attempts at treatment by open fetal surgery, with mixed results, high risk of premature labor and consequences for future pregnancies. We have demonstrated the possibility of improved outcome following ultrasound-guided laser ablation of the systemic arterial supply. Despite technical success, RFA and coil embolization led to procedure-related complications and need further evaluation. Copyright (c) 2013 ISUOG. Published by John Wiley & Sons Ltd.
    Ultrasound in Obstetrics and Gynecology 09/2013; 42(4). DOI:10.1002/uog.12515 · 3.56 Impact Factor
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    ABSTRACT: Objectives: To determine the pathologic basis and clinical associations of excessively thick placentas observed at second-trimester ultrasound examinations. Methods: Maximum sonographic placental thickness was correlated with clinical outcomes, maximum placental thickness after delivery and placental pathologic findings in a retrospective cohort of 19 singleton high-risk pregnancies noted to have a placental length to thickness ratio ≤ 2.0, in the second trimester. Findings were compared with an intermediate group of 21 high risk pregnancies, and a control group of 18 low-risk pregnancies. Increased maximum placental thickness (>28 mm) and abnormal placental deflation following delivery (pathology-sonography maximum thickness below -2mm) were defined by the upper and lower quartile values respectively in the control group. Results: The study group exhibited significantly more adverse outcomes and gross pathological placental features as compared to both the intermediate and control groups. Despite increased sonographic placental thickness (median 55mm [range 41 to 75] vs. 27 [21.7 to 41], p<0.0001 vs. 26 [23 to 36], p<0.0001) study and control placentas had similar maximal thickness following delivery (median 24mm [range 10 to 50] vs. 27 [15 to 40], p=0.82 vs. 28.5 [18 to 44], p=0.42). Placental pathology-sonography difference (<-2mm) in the study group (median -30 [-41 to 0]) was significantly greater than either the intermediate (-2 [-11 to 9], p<0.0001) or control (1.5 [-10 to 18], p<0.0001) groups and was significantly associated with abnormal development of the gas-exchanging placental villi (distal villous hypoplasia) (p=0.0001). Conclusions: Increased second trimester sonographic placental thickness represents a pathologic finding associated with severe adverse perinatal outcomes. This observation is due to over-inflation of the inter-villous space by maternal blood rather than by adaptive formation of functional placental tissue. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
    Ultrasound in Obstetrics and Gynecology 09/2013; 42(3). DOI:10.1002/uog.12386 · 3.56 Impact Factor
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    ABSTRACT: Severely-growth discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of monochorionic twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate expression and regulation of genes known to be involved in angiogenesis.We studied 10 severely growth-discordant monochorionic twin placentas (birth weight difference≥20%) without twin-twin-transfusion syndrome (TTTS) and 5 growth-concordant monochorionic twin placentas. Growth discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis related genes were measured by PCR array. Enzyme-linked immuno-sorbent assay (ELISA) and immuno-histochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression.The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included Leptin (24.6 fold, p=0.017), Flt1 (fms-like tyrosine kinase 1, 2.4 fold, p=0.016) and Eng (Endoglin, 1.86 fold, p= 0.078). None of the other 84 angiogenesis related genes showed significant differences. ELISA confirmed significantly increased Leptin protein expression (49.22 vs. 11.03 pg/mL, p=0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the Leptin promotor region suggesting the inhibition of binding of a transcriptional activator / inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any bias in placental sampling by random sampling from two different sites and by avoiding sampling from areas with grossly visible abnormalities using a standardized sampling protocol.In conclusion, the smaller twin's placenta is characterized by differentially-increased gene expressions for Flt1 and Eng mRNA that may be causally-associated with the villous pathology driven by abnormal feto-placental angiogenesis. The substantial up-regulation of Leptin mRNA may be epigenetically conferred and relevant to the post-natal risk of metabolic syndrome in IUGR offspring with placental pathology. Growth discordant MC twins offer unique insights into the epigenetic basis of perinatal programming.
    Molecular Human Reproduction 07/2013; DOI:10.1093/molehr/gat048 · 3.48 Impact Factor
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    ABSTRACT: Nephronophthisis associated ciliopathies (NPHP-AC) are a group of phenotypically related conditions that include Joubert syndrome, Meckel syndrome, nephronophthisis (NPHP), and Senior-Loken syndrome. We report on a male fetus with prenatal ultrasound findings at 24 weeks of gestation of anhydramnios, large and echogenic kidneys and situs inversus totalis. Histopathology revealed nephronophthisis and tracheal mucosa electron microscopy revealed ciliary dysgenesis. DNA analysis of the NPHP genes showed a previously unreported homozygous mutation, p.Arg603* (c.1078+1G>A), in the INVS/NPHP2 gene. This mutation is thought to abolish the splice donor site for exon 8, which likely disrupts the normal splicing of the INVS/NPHP2 gene. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 07/2013; 161(7). DOI:10.1002/ajmg.a.36036 · 2.30 Impact Factor
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    ABSTRACT: OBJECTIVES: To review the association between associated ultrasound findings, placental pathology and prognosis in pregnancies complicated by massive subchorionic thrombo-hematoma(MTH)/Breus' mole. METHOD: We identified 14 cases of MTH from January 2004 to December 2012. MTH was defined by: > 1 cm thickness hematoma, and extensive (≥ 50%) involvement of the fetal surface of the placenta. Patient information, details of initial presentation and perinatal outcome were obtained from the manual and electronic chart records. Ultrasound findings were related to pregnancy outcomes and associated placental pathology. Participants were stratified based on birth outcome into survivors (live births, n = 7) and non-survivors (NND or IUFD/TOP, n = 7). RESULTS: All 14 cases of MTH were suspected on ultrasound and confirmed by pathology assessment. All cases in the non-survivors group had abnormal umbilical artery Doppler waveforms compared to none in the survivors (p = 0.02). All cases in the non-survivor group had extreme preterm deliveries (p = 0.02). Birth weight was significantly reduced in the non-survivor group (p = 0.001), and 5/7 cases were diagnosed with severe intrauterine growth restriction, compared to none in the survivor group (p = 0.02). CONCLUSION: MTH/Breus' mole may be diagnosed in the second trimester by ultrasound assessment of the placenta. Normal fetal growth and umbilical artery Doppler waveforms are associated with perinatal survival. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 06/2013; DOI:10.1002/pd.4176 · 2.68 Impact Factor
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    ABSTRACT: Objective: To assess the effectiveness of a multidisciplinary team approach to reduce severe maternal morbidity in women with invasive placenta previa. Methods: We conducted a prospective study of 33 women with placenta previa and increta-percreta (diagnosed by ultrasound and/or magnetic resonance imaging) delivering at Mount Sinai Hospital, Toronto, following the introduction in January 2008 of a team-based approach to women with this condition. We included women who delivered by June 2012. We reviewed antenatal outpatient and inpatient records for use of six pre-defined team components by the attending staff obstetrician: (1) antenatal maternal-fetal medicine consultation, (2) surgical gynaecology consultation, (3) antenatal MRI, (4) interventional radiology consultation and preoperative placement of balloon catheters in the anterior divisions of the internal iliac arteries, (5) pre-planned surgical date, and (6) surgery performed by members of the invasive placenta surgical team. Antenatal course, delivery, and postpartum details were recorded to derive a five-point composite severe maternal morbidity score based on the presence or absence of: (1) ICU admission following delivery, (2) transfusion > 2 units of blood, (3) general anaesthesia start or conversion, (4) operating time in highest quartile (> 125 minutes), and (5) significant postoperative complications (readmission, prolonged postpartum stay, and/or pulmonary embolism). Results: All 33 women survived during this time period. Two thirds (22/33) had either five or six of the six components of multidisciplinary care. Increasing use of multidisciplinary team components was associated with a significant reduction in composite morbidity (R2 = 0.228, P = 0.005). Conclusion: Team-based assessment and management of women with invasive placenta previa is likely to improve maternal outcomes and should be encouraged on a regional basis.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 05/2013; 35(5):417-25.
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    ABSTRACT: We report on a child with prenatal onset of overgrowth associated with thick, excessive wrinkled skin and other abnormalities including cleft palate, Chiari malformation and polymicrogyria. His clinical features do not resemble any of the known reported overgrowth syndromes. Genetic evaluations, including karyotype, oligoarray, methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) for 11p11.2 region, CDKN1C sequencing, GPC3 sequencing and dosage analysis, and HRAS sequencing, have been un-revealing. Immunohistochemistry done on the patient's cultured skin fibroblasts showed normally assembled elastic fibers and normal pattern of chondroitin sulfate deposition with defective deposition of Collagen I fibers. In addition, there were high levels of immuno-detectable metalloproteinase 3 (MMP3) and undetectable tissue inhibitor of metalloproteinase 1 (TIMP1). The defective collagen deposition in the fibroblast culture could be reversed by the broad spectrum MMP inhibitor, doxycycline. We also present evidence that the fibroblasts of this patient have an increased rate of cellular proliferation. We propose that this is a previously unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts. © 2012 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 09/2012; 158A(10):2373-81. DOI:10.1002/ajmg.a.35570 · 2.30 Impact Factor
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    ABSTRACT: To determine the utility of measuring maximum placental length in the second trimester to predict a small for gestational age placenta by weight at delivery in clinically high-risk women. Placental dimensions determined by 2-dimensional (2-D) real-time ultrasound at 19-23 weeks' gestation were compared to post-natal placental weights and pathology in 95 high-risk patients with singleton pregnancies. Maximum placental length <10.0 cm performed poorly (false positive rate 25.5%) for the detection of a small placenta by weight at delivery. Placental pathology examination revealed eccentric cord insertion to be an important explanation for poor screening test result, since this finding was significantly more common in the false negative group (length ≥10.0 cm, weight <10th percentile) compared with the true negative group (length ≥10.0 cm, weight ≥10th percentile) (15/28 vs. 9/38, Fisher's exact test, p = 0.005). Prediction of reduced placental weight by 2-D ultrasound determination of maximum placental length in clinically high-risk pregnancies confounded by the phenomenon of asymmetric chorion regression. Refinement of 2-D ultrasound methods to include orthogonal plane measurements, or replacement by 3-D techniques is predicted to significantly improve the effectiveness of diagnosing small placentas in-utero.
    Placenta 07/2012; 33(10):845-9. DOI:10.1016/j.placenta.2012.07.010 · 3.29 Impact Factor
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    ABSTRACT: Distal villous hypoplasia is a form of placental villous maldevelopment that has the potential to cause significant intrauterine growth restriction with adverse consequences for fetal viability, neurodevelopmental outcome and adult cardiovascular health. It is characterized by a sparse, poorly developed distal villous tree with abnormally shaped, elongated, slender villi and widening of the intervillous space. Generally, villi show widespread trophoblast abnormalities with thinning of the villous trophoblast layer, reduction in cytotrophoblast numbers, evidence of a widespread increase in syncytiotrophoblast nuclear senescence and wave-like syncytial knots. Investigation of pregnancies with false positive serum screening tests for fetal aneuploidy/structural defects can help identify pregnancies at risk of placental insufficiency, particularly when combined with ultrasound assessment of placental morphology at 19–22 weeks. Identification of pregnancies with multiple abnormal tests of placental function permits high-risk specialist referral to optimize maternal-fetal outcome.
    Diagnostic Histopathology 05/2012; 18(5):195–200. DOI:10.1016/j.mpdhp.2012.02.005
  • Journal of Reproductive Immunology 05/2012; 94(1):38. DOI:10.1016/j.jri.2012.03.306 · 2.37 Impact Factor
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    ABSTRACT: Since pregnancies with a male fetus have higher perinatal complications attributed to placental dysfunction, including severe pre-eclampsia and intrauterine growth restriction, the objective of our study was to formally evaluate placental pathology for a placental origin of these sex-specific differences. Retrospective study at Mount Sinai Hospital in Toronto, Canada. Identification of 262 singleton pregnancies affected by severe pre-eclampsia and/or intrauterine growth restriction who delivered between 22 and 32 weeks' gestation from 2000 to 2010. Detailed placental pathology was reviewed, and data from 140 pregnancies with male fetuses were compared with 122 pregnancies with female fetuses. A comparison group of 40 unaffected pregnancies who delivered in the same gestational range was used to determine baseline rates of placental pathology. Detailed placental pathology, including placental development/differentiation, velamentous umbilical cord insertion, maternal-fetal interface pathology, villous infarction, hemorrhagic lesions, villous development, and fetal vascular under-perfusion. Impaired placental development and differentiation was equally common amongst males (73/140, 52.1%) and females (69/122, 56.6%). Male placentas exhibited significantly higher rates of chronic deciduitis (17.9% vs. 9.0%; relative risk [RR] 1.98, 95% confidence interval [CI] 1.02-3.86) and velamentous umbilical cord insertion (9.5% vs. 1.7%; RR 5.66, 95% CI 1.30-24.6), and a significantly lower frequency of villous infarction (55.4% vs. 73.7%; RR 0.75, 95% CI 0.62-0.90) than female placentas. No significant differences were noted for other lesions. Fetal sex exerts a differential effect on the placental pathology that mediates severe pre-eclampsia and/or IUGR. Placental pathology at birth may provide insight into the mechanisms linking adverse in utero events with long-term adult disease since, for example, a male tendency to an inflammatory pathology at the maternal-fetal interface may be linked to the excess risk of coronary artery disease.
    Placenta 04/2012; 33(7):568-71. DOI:10.1016/j.placenta.2012.03.011 · 3.29 Impact Factor

Publication Stats

836 Citations
246.50 Total Impact Points

Institutions

  • 2005–2015
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 2005–2014
    • Mount Sinai Hospital, Toronto
      • • Department of Obstetrics and Gynecology
      • • Department of Pathology and Laboratory Medicine
      • • Department of Medical Imaging
      Toronto, Ontario, Canada
  • 2011
    • Sinai Hospital
      Mount Sinai, New York, United States
  • 2008
    • SickKids
      Toronto, Ontario, Canada
  • 2003–2006
    • Mount Sinai Hospital
      New York City, New York, United States