John Kingdom

University of Toronto, Toronto, Ontario, Canada

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Publications (298)1318.42 Total impact

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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
  • Prenatal Diagnosis 07/2015; 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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    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: 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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    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-P27 · 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
  • 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; DOI:10.3109/14767058.2014.963047 · 1.37 Impact Factor
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    ABSTRACT: Background Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. Methods In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Findings Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4–24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8–26·3%]; risk difference −1·8% [95% CI −10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI −6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3–18·4; p=0·01). Interpretation Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.
    The Lancet 11/2014; 384(9955). DOI:10.1016/S0140-6736(14)60793-5 · 45.22 Impact Factor
  • Lise Huynh · John Kingdom · Sabrina Akhtar
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    ABSTRACT: Objective: To review the recent evidence behind the association of low levels (ie, below the fifth percentile) of pregnancy-associated plasma protein A (PAPP-A) with adverse perinatal outcomes and to integrate new findings with the recommendations made by the Society of Obstetricians and Gynaecologists of Canada in 2008. Quality of evidence: A review of recently published articles revealed that current evidence is sparse and mixed for the association of low PAPP-A level with small size for gestational age, preterm delivery, hypertensive disorders of pregnancy, and stillbirth. There is limited evidence that suggests an association between low PAPP-A levels and spontaneous pregnancy loss. Recent studies suggest that low PAPP-A levels are associated with abnormal placentation, which might be the root cause of the adverse perinatal outcomes of interest. Main message: The evidence behind the association of low PAPP-A levels with adverse perinatal outcomes is both lacking and mixed. However, recent data do suggest an association between low PAPP-A levels and abnormal placentation. This emerging topic currently lacks strong evidence-based guidelines, yet has potential important implications for perinatal outcomes. Collaboration with obstetric specialists regarding pregnant women who have low PAPP-A levels in the context of normal first-trimester aneuploidy screening results might aid clinical decision making about pregnancy and placental surveillance. Conclusion: While the clinical meaning of a low PAPP-A level detected in the context of normal fetal aneuploidy screening remains under debate, pregnant patients with such results should be counseled that at present no strong evidence exists to justify an ongoing ultrasound surveillance program.
    Canadian family physician Medecin de famille canadien 10/2014; 60(10):899-903. · 1.34 Impact Factor
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    ABSTRACT: Objective: To assess whether singleton pregnancies conceived by assisted reproductive technology (ART) are associated with an increased use of intrapartum interventions when compared with spontaneous singleton pregnancies. Methods: In total, 1327 ART pregnancies and 5222 spontaneous pregnancies during the period 2004 to 2008 were extracted from BORN (Better Outcomes Registry and Network) Ontario's information system. The incidences of common intrapartum interventions were compared, and different classification systems for Caesarean section were used to compare the indications for these between singleton pregnancies following ART with or without intracytoplasmic sperm injection and singleton spontaneously conceived pregnancies. Results: Compared with spontaneous singleton pregnancies, the ART group had increased incidences of internal electronic fetal monitoring (OR 1.60; 95% CI 1.37 to 1.87), artificial rupture of membranes (OR 1.39; 95% CI 1.17 to 1.66), oxytocin augmentation of labour (OR 1.51; 95% CI 1.28 to 1.77), induction of labour (OR 1.31; 95% CI 1.14 to 1.50), and Caesarean section (OR 1.40; 95% CI 1.24 to 1.60). Conclusion: Singleton pregnancies resulting from ART were associated with more frequent use of several intrapartum interventions, including Caesarean section.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 09/2014; 36(9):795-802.
  • Placenta 09/2014; 35(9):A76. DOI:10.1016/j.placenta.2014.06.245 · 2.71 Impact Factor
  • Anjali Kulkarni · Emily Wright · John Kingdom
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    ABSTRACT: Objective: To measure the effect of a web-based educational tool on baseline knowledge of the risks and benefits of delivery by Caesarean section in healthy nulliparous women. Methods: We constructed a web-based educational tool to provide evidence-based information on the potential benefits and risks of CS for healthy nulliparous women in the second trimester. We included women with an uncomplicated singleton pregnancy who were receiving antenatal care at Mount Sinai Hospital. Eligible women logged into the website to undertake a pre-test survey. After completing this survey, they received access to the educational tool, followed by a link to a second survey. The surveys collected baseline demographics and assessed participants' knowledge of the perceived safety and risks of vaginal delivery and CS, their sources of information, and the influence of these sources on their views. Results: Seventy-three participants completed both surveys. Participants had a high baseline preference (84%) for vaginal delivery. The mean score for knowledge about vaginal delivery and CS increased significantly between the surveys, from 47% to 76% (P < 0. 001). There was no significant change in preference for mode of delivery between the two surveys. In both surveys, more participants responded that they were a "little fearful" or "not fearful at all" of vaginal deliveries. In the second survey, significantly more responded that they were "very fearful" or "fearful" of CS (P < 0.05). Increased knowledge about specific risks of vaginal delivery did not deter participants from preferring a vaginal delivery. However, knowledge of risks associated with CS made them more likely to have "very favourable" or "somewhat favourable" views of vaginal delivery. Ethnicity and country of birth were not found to have a significant effect on preferred mode of delivery. Conclusions: We demonstrated that a web-based educational tool significantly increased knowledge of the risks and benefits of vaginal delivery and CS. However, the educational intervention did not significantly change preferences.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 09/2014; 36(9):768-775.
  • Ultrasound in Obstetrics and Gynecology 09/2014; 44(S1):131-132. DOI:10.1002/uog.13849 · 3.85 Impact Factor
  • Ultrasound in Obstetrics and Gynecology 09/2014; 44(S1):116-116. DOI:10.1002/uog.13850 · 3.85 Impact Factor

Publication Stats

8k Citations
1,318.42 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
    • University of London
      Londinium, England, United Kingdom
  • 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
  • 1995–1997
    • University College London
      • • Department of Cell and Developmental Biology
      • • Division of Medicine
      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