John Kingdom

University of Toronto, Toronto, Ontario, Canada

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Publications (250)1110.32 Total impact

  • Journal of the American Heart Association 11/2015; 4(11):e002414. DOI:10.1161/JAHA.115.002414 · 4.31 Impact Factor
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    ABSTRACT: Background: Late-onset intrauterine growth restriction (IUGR) results from failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late gestation fetus. Limitations in current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a non-invasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods. Objectives: To use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset intrauterine growth restriction (IUGR) fetuses. Study design: A prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebro-placental ratio were acquired using ultrasound. A score of ≥2 out of 4 following parameters defined IUGR: 1) birth weight ≤3(rd) centile or ≥20% drop in centile in estimated fetal weight; 2) lowest cerebro-placental ratio after 30 weeks <5(th) centile; 3) ponderal index <2.2; 4) placental histology meets pre-defined criteria for placental under-perfusion. Measurements were compared between the two groups (t-test) and correlations between parameters were analyzed (Pearson's correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver operating characteristic curves. Results: We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks gestation. IUGR fetuses had lower umbilical vein (P=0.004) and pulmonary blood flow (P=0.01) and higher superior vena caval flow (P<0.0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normals (P<0.0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index and cerebro-placental ratio were all significantly lower in IUGR fetuses, while there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow, and inversely with oxygen delivery, oxygen consumption, umbilical vein T2 and cerebro-placental ratio. ROC curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow AUC = 0.94 (95%CI 0.87-1.00) versus cerebro-placental ratio AUC = 0.80 (95%CI 0.64-0.97). Conclusions: MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, while reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain-sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.
    American journal of obstetrics and gynecology 10/2015; DOI:10.1016/j.ajog.2015.10.004 · 4.70 Impact Factor
  • Kelsey McLaughlin · Sascha Drewlo · John D Parker · John C.P. Kingdom ·

    Hypertension 10/2015; DOI:10.1161/HYPERTENSIONAHA.115.05770 · 6.48 Impact Factor
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    Brian Cox · Katherine Leavey · Ursula Nosi · Frances Wong · John Kingdom ·
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    ABSTRACT: The placenta is the essential organ of mammalian pregnancy and errors in its development and function are associated with a wide range of human pathologies of pregnancy. Genome sequencing has led to methods for investigation of the transcriptome (all expressed RNA species) using microarrays and next-generation sequencing, and implementation of these techniques has identified many novel species of RNA including: micro-RNA, long noncoding RNA, and circular RNA. These species can physically interact with both each other and regulatory proteins to modify gene expression and messenger RNA to protein translation. Transcriptome analysis is actively used to investigate placental development and dysfunction in pathologies ranging from preeclampsia and fetal growth restriction to preterm labor. Genome-wide gene expression analysis is also being applied to identify prognostic and diagnostic biomarkers of these disorders. In this comprehensive review we summarize transcriptome biology, methods of isolation and analysis, application to placental development and pathology, and use in diagnostic analysis in maternal blood. Key information for analysis methods is organized into quick reference tables where current analysis techniques and tools are cited and compared. We have created this review as a practical guide and starting reference for those interested in beginning an investigation into the transcriptome of the placenta.
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    ABSTRACT: The association between low birth weight and premature cardiovascular disease has led to the "prenatal origin of adult disease-hypothesis". We postulated that fetal growth restriction is associated with cardiovascular changes detectable at birth and in early infancy. Fifty-two appropriately grown fetuses (AGA) and 60 growth-restricted fetuses (FGR) with (n = 20) or without (n = 40) absent or reversed end-diastolic umbilical artery blood flow were prospectively examined by echocardiography before birth, at 1 week and 6 months of life. The impact of growth restriction on postnatal blood pressure, heart rate, cardiovascular dimensions, and function, as well as on vascular morphology of umbilical cord vessels was studied. FGR fetuses displayed significant blood flow redistribution and were delivered earlier with lower birth weights than AGA fetuses. After adjustment for gender, gestational age, and weight at birth, there were no intergroup differences in blood pressure, heart rate, left ventricular morphology, mass, and performance, and in cord vessel morphology. During the first 6 months of life brachioradial pulse wave velocity increased more in FGR fetuses, while other parameters describing vascular stiffness remained comparable between the groups. Fetal growth restriction had no detectable adverse impact on cardiovascular dimensions and function at birth. Cardiovascular findings also remained comparable during the first 6 months of life between the groups except a higher increase in brachioradial pulse wave velocity in the FGR group. Our observations suggest that abnormalities that link reduced intrauterine growth with premature cardiovascular diseases may commence later in childhood, indicating a potential window for screening and prevention.
    Heart and Vessels 09/2015; DOI:10.1007/s00380-015-0742-5 · 2.07 Impact Factor
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    N. Melamed · R. Greg · R. Windrim · A. Toi · J.C. Kingdom ·

    Ultrasound in Obstetrics and Gynecology 09/2015; 46(S1):48-48. DOI:10.1002/uog.15089 · 3.85 Impact Factor

  • Ultrasound in Obstetrics and Gynecology 09/2015; 46(S1):23-23. DOI:10.1002/uog.15018 · 3.85 Impact Factor
  • F. Ghasemi · E. Wright · M. Yampolsky · P. Shah · S. Keating · R. Windrim · J.C. Kingdom ·

    Ultrasound in Obstetrics and Gynecology 09/2015; 46(S1):55-55. DOI:10.1002/uog.15110 · 3.85 Impact Factor
  • A. Rahman · Y. Zhou · L. Cahill · M. Seed · J. C. Kingdom · C. Macgowan · J. G. Sled ·

    Ultrasound in Obstetrics and Gynecology 09/2015; 46(S1):113-114. DOI:10.1002/uog.15289 · 3.85 Impact Factor
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    ABSTRACT: What's already known about this topic? Rarely, prenatal fetal inguinoscrotal hernia may be diagnosed during intra-uterine life. To date, few cases have been published in the literature. The pathogenetic mechanism underlying fetal inguinal hernia remains unclear. What does this study add? This is the first case of fetal inguinoscrotal hernia associated with bowel dilatation This study presents a possible causative relationship between the multiple fetal findings. Inguinal hernia can be found in up to 0.88-4.4% of neonates and infants. Rarely, inguinal hernia may be already diagnosed during intra-uterine life. To date, only 11 cases have been published in the literature. The mechanism underlying fetal inguinal hernia remains unclear, as does the issue of whether it is secondarily complicated by bowel obstruction during fetal life. Here we describe a case of a pregnancy complicated by prenatal ultrasound findings of fetal bowel dilatation in the presence of fetal inguinoscrotal hernia. The case presentation is followed by a discussion regarding the possible causative relationship between the multiple fetal findings and a review of the literature on fetal inguinal hernia.
    Prenatal Diagnosis 07/2015; 35(11). DOI:10.1002/pd.4657 · 3.27 Impact Factor
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    ABSTRACT: The objective of this study was to compare the in vitro contractile effects of the combination of oxytocin (low dose and high dose) with either ergonovine or carboprost in myometrial strips from women undergoing cesarean delivery (CD), and to study the effect of oxytocin pretreatment on these contractions. We hypothesized that the use of ergonovine or carboprost in combination with oxytocin would improve contractility compared with oxytocin alone. Myometrial samples obtained from women undergoing elective CD were pretreated in organ bath chambers with either oxytocin 10 M (experimental) or physiological salt solution (control) for 2 hours. They were then washed and subjected to dose-response testing with oxytocin, ergonovine, or carboprost (10 to 10 M), either alone or in combination with a fixed low-dose (10 M) (LDOx) or high-dose (10 M) (HDOx) oxytocin. The amplitude, frequency, area under the curve, and motility index (amplitude × frequency) of contractions during the dose-response period were analyzed with linear regression models, and compared among the groups. The primary outcome was the motility index across the study groups. One hundred sixty-nine experiments were done in samples obtained from 56 women. The mean square root of the motility index [standard error] (√g·contractions/10 min) of oxytocin was significantly higher in the control (3.40 [0.24]) versus experimental group (2.02 [0.15]) (P < 0.001). When all control groups were compared, the motility index of oxytocin (3.21 [0.25]) was higher than that of ergonovine (2.13 [0.30], P < 0.001 [multiple comparisons adjusted P value, P < 0.001]), carboprost (1.88 [0.10], P < 0.001 [P < 0.001]), ergonovine + LDOx (2.07 [0.15], P < 0.001 [P < 0.001]), and carboprost + LDOx (1.82 [0.15], P < 0.001 [P < 0.001]) and was not different than that of ergonovine + HDOx (3.39 [0.32], P = 0.68 [P = 0.99]) and carboprost + HDOx (2.68 [0.30], P = 0.20 [P = 0.60]). However, in oxytocin-pretreated groups, carboprost + LDOx (motility index: 2.53 [0.08], P = 0.001 [multiple comparisons adjusted P value, P = 0.002]) and ergonovine + HDOx (2.82 [0.15], P < 0.001 [P < 0.001]) exhibited significantly superior contractility response compared with oxytocin alone, while ergonovine + LDOx (2.47 [0.13], P = 0.01 [P = 0.08]) and carboprost + HDOx (2.51 [0.20], P = 0.05 [P = 0.24]) showed higher mean contractility response compared with oxytocin alone but failed to reach statistical significance in adjusted analyses. The attenuation of oxytocin-induced contractility in oxytocin-pretreated myometrial strips is in keeping with the previously established oxytocin-receptor desensitization phenomenon. Oxytocin is the most effective of the uterotonics tested if the myometrium is not preexposed to oxytocin. However, in the oxytocin-pretreated myometrium, a synergistic response is evident, and the combination of oxytocin with either ergonovine or carboprost produces superior response compared with oxytocin alone. Further in vivo studies in humans are necessary to determine whether these differences identified in vitro are clinically significant.
    Anesthesia and analgesia 03/2015; 120(5). DOI:10.1213/ANE.0000000000000682 · 3.47 Impact Factor
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    ABSTRACT: The objective of the study was to evaluate the efficacy and safety of combined prophylactic intraoperative internal iliac artery balloon occlusion and postoperative uterine artery embolization in the conservative management (uterine preservation) of women with invasive placenta undergoing scheduled caesarean delivery. Ten women (mean age 35 years) with invasive placenta choosing caesarean delivery without hysterectomy had preoperative insertion of internal iliac artery occlusion balloons, intraoperative inflation of the balloons, and immediate postoperative uterine artery embolization with absorbable gelatin sponge. A retrospective review was performed with institutional review board approval. Outcome measures were intraoperative blood loss, transfusion requirement, hysterectomy rate, endovascular complications, surgical complications, and postoperative morbidity. All women had placenta increta or percreta, and concomitant complete placenta previa. Mean gestational age at delivery was 36 weeks. In 6 women the placenta was left undisturbed in the uterus, 2 had partial removal of the placenta, and 2 had piecemeal removal of the whole placenta. Mean estimated blood loss during caesarean delivery was 1.2 L. Only 2 patients (20%) required blood transfusion. There were no intraoperative surgical complications, endovascular complications, maternal deaths, or perinatal deaths. Three women developed postpartum complications necessitating postpartum hysterectomy; the hysterectomy rate was therefore 30% and uterine preservation was successful in 70%. Combined bilateral internal iliac artery balloon occlusion and uterine artery embolization may be an effective strategy to control intraoperative blood loss and preserve the uterus in patients with invasive placenta undergoing caesarean delivery. Copyright © 2015 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.
    Canadian Association of Radiologists Journal 03/2015; 66(2). DOI:10.1016/j.carj.2014.08.002 · 0.52 Impact Factor
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    Emily Bartsch · Alison L Park · John C Kingdom · Joel G Ray ·
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    ABSTRACT: Preeclampsia (PE) increases maternal and perinatal morbidity and mortality. Based on a multitude of data from randomized clinical trials, clinical practice guidelines endorse using ASA to prevent PE in women who are "at risk." However, data are lacking about the level of absolute risk to warrant starting ASA prophylaxis. We present two approaches for objectively determining the minimum absolute risk for PE at which ASA prophylaxis is justified. The first is a new approach-the minimum control event rate (CERmin). The second approach uses a pre-existing concept-the minimum event rate for treatment (MERT). Here we show how the CERmin is derived, and then use the CERmin and the MERT to guide us to a reasonable risk threshold for starting a woman on ASA prophylaxis against PE based on clinical risk assessment. We suggest that eligible women need not be at "high risk" for preeclampsia to warrant ASA, but rather at some modestly elevated absolute risk of 6-10%. Given its very low cost, its widespread availability, ease of administration and its safety profile, ASA is a highly attractive agent for the prevention of maternal and perinatal morbidity worldwide.
    PLoS ONE 03/2015; 10(3):e0116296. DOI:10.1371/journal.pone.0116296 · 3.23 Impact Factor
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    ABSTRACT: -Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging (MRI) technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. -We measured fetal brain size, oxygen saturation and blood flow in the major vessels of the fetal circulation in 30 late gestation fetuses with CHD and 30 normal controls using phase contrast MRI and T2 mapping. Fetal hemodynamic parameters were calculated using a combination of MRI flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (p<0.001), and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (p < 0.001), while cerebral blood flow and cerebral oxygen extraction were no different from controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (p = 0.08) and 32% reduction cerebral VO2 in CHD fetuses (p < 0.001), which were associated with a 13% reduction in fetal brain volume (p < 0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral VO2 (r = 0.37 p = 0.004). -This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.
    Circulation 03/2015; 131(15). DOI:10.1161/CIRCULATIONAHA.114.013051 · 14.43 Impact Factor
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    The Lancet 02/2015; 385(9969). DOI:10.1016/S0140-6736(15)60287-2 · 45.22 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/1532-429X-17-S1-O92 · 4.56 Impact Factor

  • Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/1532-429X-17-S1-P201 · 4.56 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/1532-429X-17-S1-P27 · 4.56 Impact Factor
  • Nir Melamed · John Kingdom ·

    American Journal of Obstetrics and Gynecology 01/2015; 212(1):S263-S264. DOI:10.1016/j.ajog.2014.10.573 · 4.70 Impact Factor
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    ABSTRACT: Abstract Objectives: To determine the most reproducible method for the sonographic measurement of placental length. Methods: A prospective study of women with singleton pregnancies who underwent sonographic measurement of placental dimensions during mid-gestation. Two sonographers independently determined placental length using 3 different approaches (linear, curve-linear and panoramic) and placental thickness. Reproducibility was assessed by the Bland-Altman method and Interclass Correlation Coefficient (ICC). Results: Overall 34 women were included in the study. The curve-linear approach for the measurement of placental length was associated with the highest reproducibility (mean inter-observer difference of -0.10 cm) compared to the linear and panoramic approaches (mean difference -0.15 cm and -0.29 cm, respectively). Similarly, the ICC was highest for the curve-linear length approach (0.974) compared with the linear length and panoramic length approaches (0.956 and 0.926, respectively). Measurements of maximum placental thickness was also associated with a very good ICC (0.954). Conclusions: The curve-linear method for the measurement of placental length in the 2(nd) trimester appears to be the most reproducible approach. This technique may prove useful as an adjunct screening method, along with uterine artery Doppler and maximum placental thickness, to screen for major placental complications of pregnancy in the second trimester.
    Journal of Maternal-Fetal and Neonatal Medicine 11/2014; 28(14):1-22. DOI:10.3109/14767058.2014.963047 · 1.37 Impact Factor

Publication Stats

7k Citations
1,110.32 Total Impact Points


  • 1998-2015
    • University of Toronto
      • • Department of Obstetrics and Gynaecology
      • • Mount Sinai Hospital
      Toronto, Ontario, Canada
    • Mount Sinai Hospital, Toronto
      • • Department of Obstetrics and Gynecology
      • • Department of Anesthesia
      • • Department of Fetal Medicine
      Toronto, Ontario, Canada
  • 1998-2014
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada
  • 2004-2011
    • Mount Sinai Hospital
      New York, New York, United States
  • 2001-2011
    • Sinai Hospital
      Mount Sinai, New York, United States
    • RWTH Aachen University
      Aachen, North Rhine-Westphalia, Germany
  • 2010
    • University of Adelaide
      • Discipline of Obstetrics and Gynaecology
      Tarndarnya, South Australia, Australia
    • SickKids
      • Division of Rheumatology
      Toronto, Ontario, Canada
  • 1990-1999
    • University of Glasgow
      • • Institute of Cardiovascular and Medical Sciences
      • • School of Life Sciences
      Glasgow, Scotland, United Kingdom
  • 1997
    • University College London
      Londinium, England, United Kingdom
  • 1996
    • Justus-Liebig-Universität Gießen
      • Institut für Veterinär-Anatomie, -Histologie und -Embryologie
      Gießen, Hesse, Germany
  • 1994
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 1991
    • The Queen's Medical Center
      Honolulu, Hawaii, United States