Publications by authors named "Ken Lim"

25 Publications

  • Page 1 of 1

Outcomes for the first wave of hospitalised patients with COVID-19 in the South Australian context: a retrospective audit.

Intern Med J 2021 02;51(2):189-198

General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Background: The first case of corona virus disease (COVID-19) was detected in South Australia on 1 February 2020. The Royal Adelaide Hospital (RAH) is the state's designated quarantine hospital.

Aim: To determine the characteristics, outcomes and predictors of outcomes for hospitalised patients with coronavirus disease (COVID-19) within the RAH.

Methods: We performed a retrospective audit of 103 patients diagnosed with COVID-19 who were discharged from the RAH between 14 February and 21 May 2020. We collected demographic, clinical and laboratory data through an audit of electronic medical records. The main outcome measures were: (i) the need for oxygen supplementation; (ii) need for intensive care unit (ICU) care; and (iii) death in hospital.

Results: The median age of patients was 60 years (range 19-85). A total of 55 (53%) patients was male. All patients were independent at baseline; 37 (36%) patients suffered from hypertension. Cardiovascular disease, respiratory disease and diabetes were present in fewer than 19 (18%) patients. Obesity was present in 24 (23%) patients; 39 (38%) patients required supplemental oxygen, 18 (17%) required ICU care and 4 (4%) patients died. Older patients were significantly more at risk of oxygen requirement (median 68 vs 57.5 years, P < 0.01), ICU admission (median 66.5 vs 60 years, P = 0.04) and death (median 74.5 vs 60 years, P = 0.02). We did not find a statistically significant association between gender, body mass index and poor outcomes. Lactate dehydrogenase (LDH) was the only parameter at admission associated with oxygen requirement, ICU care and death. Peak LDH, aspartate aminotransferase, alanine aminotransferase, C-reactive protein and neutrophil lymphocyte ratio were significantly associated with oxygen requirement, ICU admission and death (P < 0.05 for all of the above laboratory markers).

Conclusions: Although our sample size was small, we found that certain comorbidities and laboratory values were associated with poor outcomes. This occurred in a setting where care was not influenced by limited hospital and intensive care beds.
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http://dx.doi.org/10.1111/imj.15106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014127PMC
February 2021

N 374 - Évaluation systématique de la longueur cervicale.

J Obstet Gynaecol Can 2019 Mar;41(3):375-387.e1

Toronto (Ont.).

Objectif: Passer en revue les données probantes et fournir une opinion indiquant si l'évaluation systématique de la longueur cervicale pour la prévention de l'accouchement prématuré devrait être adoptée au Canada. RéSULTATS: Les issues évaluées comprennent la prévention de l'accouchement prématuré. DONNéES PROBANTES: Nous avons interrogé les bases de données Knowledge Finder, Medline et Cochrane pour en tirer les articles publiés jusqu'en avril 2018 sur la mesure de la longueur cervicale pour la prévention de l'accouchement prématuré. CRITèRES: Les données obtenues ont été examinées et évaluées par le Comité d'imagerie diagnostique de la SOGC sous la direction des auteurs principaux, et les recommandations ont été formulées selon les lignes directrices rédigées par le Groupe d'étude canadien sur les soins de santé préventifs. AVANTAGES, DéSAVANTAGES, ET COûTS: La prévention de l'accouchement prématuré sans coûts excessifs est très importante pour la santé des mères et des familles. La présente opinion de comité résume les données probantes actuelles sur l'évaluation systématique de la longueur cervicale pour prévenir l'accouchement prématuré au Canada, détermine si elle satisfait les critères de Jungner et Wilson pour un test de dépistage et formule des recommandations pour son utilisation au Canada.

Validation: La présente opinion a été révisée et approuvée par le comité d'imagerie diagnostique de la SOGC et la Société des obstétriciens et gynécologues du Canada (SOGC).

Commanditaire: La Société des obstétriciens et gynécologues du Canada (SOGC).
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http://dx.doi.org/10.1016/j.jogc.2019.01.003DOI Listing
March 2019

No. 374-Universal Cervical Length Screening.

J Obstet Gynaecol Can 2019 Mar;41(3):363-374.e1

Toronto, ON.

Objective: To review the evidence and provide an opinion as to whether universal cervical length screening to prevent preterm birth should be adopted across Canada.

Outcomes: Outcomes evaluated include prevention of preterm birth.

Evidence: Literature searches using Knowledge Finder, Medline and Cochrane databases were searched for articles published up to April 2018 on cervical length screening for prevention of preterm birth.

Values: The evidence obtained was reviewed and evaluated by the Diagnostic Imaging Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care.

Benefits, Harms, And Costs: The prevention of preterm birth in a cost-effective manner is of significant importance to the health of mothers and their families. This committee opinion will summarize the current evidence for universal cervical length screening to prevent preterm birth in Canada, determine whether it meets the Junger and Wilson criteria for screening tests, and make recommendations as to its use in Canada.

Validation: These guidelines have been reviewed and approved by the Diagnostic Imaging Committee of the SOGC and The Society of Obstetricians and Gynaecologists of Canada (SOGC).

Sponsors: The Society of Obstetricians and Gynaecologists of Canada (SOGC).
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http://dx.doi.org/10.1016/j.jogc.2018.09.019DOI Listing
March 2019

The STRIDER trials: ongoing research.

Lancet Child Adolesc Health 2018 03 13;2(3):e3. Epub 2018 Feb 13.

Department of Obstetrics, University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.1016/S2352-4642(18)30036-1DOI Listing
March 2018

Variations from morning to afternoon of middle cerebral and umbilical artery blood flow, and fetal heart rate variability, and fetal characteristics in the normally developing fetus.

J Clin Ultrasound 2018 May 13;46(4):235-240. Epub 2017 Dec 13.

Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia.

Objective: To determine if there are changes in maternal uterine blood flow, fetal brain blood flow, fetal heart rate variability, and umbilical blood flow between morning (AM) and afternoon (PM) in healthy, uncomplicated pregnancies.

Study Design: In this prospective study, 68 uncomplicated singleton pregnancies (mean 35 + 0.7 weeks gestation) underwent a standard observational protocol at both 08:00 (AM) and 13:30 (PM) of the same day. This protocol included Doppler measurements of uterine, umbilical, and fetal middle cerebral artery (MCA) volume flow parameters (flow, HR, peak systolic velocity [PSV], PI, and RI) followed by computerized cardiotocography. Standard descriptive statistics, χ and t tests were used where appropriate. P < .05 was considered significant.

Results: A significant increase in MCA flow and MCA PSV was observed in the PM compared to the AM. This was accompanied by a fall in MCA resistance. Higher umbilical artery resistance indices were also observed in the PM compared to AM. In contrast, fetal heart rate characteristics, maternal uterine artery Doppler flow and resistance indices did not vary significantly between the AM and PM.

Conclusion: In normal pregnancies, variations in fetal cerebral and umbilical blood flow parameters were observed between AM and PM independent of other fetal movements or baseline fetal heart rate. In contrast, uterine flow parameters remained stable across the day. These findings may have implications for the use of serial Doppler parameters used to guide clinical management in high-risk pregnancies.
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http://dx.doi.org/10.1002/jcu.22569DOI Listing
May 2018

No. 352-Technical Update: The Role of Early Comprehensive Fetal Anatomy Ultrasound Examination.

J Obstet Gynaecol Can 2017 Dec;39(12):1203-1211

Vancouver, BC.

Objective: This guideline presents an evidence-based technical update and recommendations for the performance of early comprehensive fetal anatomic scanning (ECFAS) at 11 to 16 weeks' gestation.

Options: Patients at high risk for fetal anomalies and in whom traditional mid-second trimester transabdominal imaging may be challenging or who may benefit from earlier identification of fetal anomalies may be suitable for early fetal anatomy scanning.

Outcomes: This practice may result in earlier identification of fetal anomalies and provide earlier intervention options in high-risk populations and/or in populations where mid-second trimester transabdominal scanning is challenging.

Target Population: This population consists of obstetrical patients in whom mid-second trimester ultrasound scanning will be technically challenging and patients who are at higher risk for major fetal anomalies.

Evidence: Published literature was retrieved through searches of PubMed and Medline in 2016 using key words. Results were restricted to controlled clinical trials, reviews, and observational studies published in English. There were no date restrictions, and searches were updated in the guideline to 2016. Grey (unpublished) literature was identified through searching the websites of health technology assessment and clinical practice guidelines and national and international medical specialty societies. No relevant studies were found.

Validation Methods: The content and recommendations were drafted and agreed on by the principal authors. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework.

Benefits, Harms, And/or Costs: It is anticipated that there will be an increase in earlier detection of major fetal anomalies in the target population with the benefits of earlier interventions for those individuals. In areas where the service is not available the patient may need to travel to a nearby centre. Early fetal anatomy scanning is considered to be safe and is not expected to cause a risk to the pregnancy.

Guideline Update: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published before the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.

Sponsors: This technical update was developed with resources funded by the SOGC.

Summary Statements: RECOMMENDATIONS.
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http://dx.doi.org/10.1016/j.jogc.2017.06.031DOI Listing
December 2017

Détermination de l'âge gestationnel par échographie.

J Obstet Gynaecol Can 2016 Dec 4;38(12S):S391-S403. Epub 2017 Jan 4.

Vancouver (C.-B.).

Objectif: Aider les cliniciens à attribuer un âge gestationnel en fonction des résultats de la biométrie échographique.

Issues: Déterminer si la datation par échographie offre une évaluation plus précise de l'âge gestationnel que la datation en fonction des dernières règles avec ou sans recours à l'échographie. Offrir, aux praticiens et aux chercheurs du domaine des soins de maternité, des lignes directrices factuelles en matière d'attribution de l'âge gestationnel. Identifier les paramètres biométriques échographiques qui sont de fiabilité supérieure lorsque l'âge gestationnel est incertain. Déterminer la rentabilité de l'évaluation de l'âge gestationnel par échographie. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed ou MEDLINE et The Cochrane Library en 2013 au moyen d'un vocabulaire contrôlé et de mots clés appropriés (p. ex. « gestational age », « ultrasound biometry » et « ultrasound dating »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles rédigés en anglais. Aucune restriction n'a été appliquée en matière de dates. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'au 31 juillet 2013. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales.

Valeurs: La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). AVANTAGES, DéSAVANTAGES ET COûTS: L'attribution précise d'un âge gestationnel pourrait réduire l'incidence du déclenchement mené en raison d'une grossesse prolongée et améliorer les soins obstétricaux en nous permettant de planifier la chronologie des interventions nécessaires de façon optimale et d'éviter les interventions inutiles. Une datation plus précise permet l'optimisation de la tenue de tests prénataux de dépistage de l'aneuploïdie. Un algorithme national d'attribution de l'âge gestationnel pourrait atténuer les variations pancanadiennes en matière de pratique pour les cliniciens et les chercheurs. Parmi les désavantages potentiels, on trouve la réattribution possible des dates lorsqu'une pathologie fœtale importante (comme le retard de croissance intra-utérin ou la macrosomie) donne lieu à une divergence entre les résultats de la biométrie échographique et l'âge gestationnel clinique. Une telle réattribution pourrait mener à l'omission d'interventions fœtales justifiées ou à la tenue d'interventions fœtales injustifiées. DéCLARATIONS SOMMAIRES: RECOMMANDATIONS.
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http://dx.doi.org/10.1016/j.jogc.2016.09.048DOI Listing
December 2016

Gadolinium magnetic resonance imaging during pregnancy associated with adverse neonatal and post-neonatal outcomes.

J Pediatr 2017 01;180:291-294

University of British Columbia Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.jpeds.2016.10.061DOI Listing
January 2017

Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes.

Circulation 2016 Aug;134(9):647-55

From Maternal, Child and Youth Health, Surveillance and Epidemiology Division, Centre for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, ON, Canada (S. Liu, W.L., J.A.L.); Department of Obstetrics and Gynaecology, University of British Columbia and the Children's and Women's Hospital of British Columbia, Vancouver, BC, Canada (K.S.J., S. Lisonkova, K.L.); School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada (K.S.J.); Department of Obstetrics and Gynaecology, Dalhousie University, NS, Canada (M.V.d.H.); Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada (J.E.); School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada (J.L.); Departments of Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada (R.S.); and Departments of Pediatrics and Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada (M.S.K.).

Background: Previous studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs).

Methods: We carried out a population-based cohort study (N=5 901 701) of all live births and stillbirths (including late-pregnancy terminations) delivered at ≥20 weeks' gestation in Canada (except Québec and Manitoba) from 1990 to 2011. CHD cases were diagnosed at birth and in infancy (n=72 591). We compared prevalence rates and temporal trends in CHD subtypes before and after 1998 (the year that fortification was mandated). An ecological study based on 22 calendar years, 14 geographic areas, and Poisson regression analysis was used to quantify the effect of folic acid food fortification on nonchromosomal CHD subtypes (n=66 980) after controlling for changes in maternal age, prepregnancy diabetes mellitus, preterm preeclampsia, multiple birth, and termination of pregnancy.

Results: The overall birth prevalence rate of CHDs was 12.3 per 1000 total births. Rates of most CHD subtypes decreased between 1990 and 2011 except for atrial septal defects, which increased significantly. Folic acid food fortification was associated with lower rates of conotruncal defects (adjusted rate ratio [aRR], 0.73, 95% confidence interval [CI], 0.62-0.85), coarctation of the aorta (aRR, 0.77; 95% CI, 0.61-0.96), ventricular septal defects (aRR, 0.85; 95% CI, 0.75-0.96), and atrial septal defects (aRR, 0.82; 95% CI, 0.69-0.95) but not severe nonconotruncal heart defects (aRR, 0.81; 95% CI, 0.65-1.03) and other heart or circulatory system abnormalities (aRR, 0.98; 95% CI, 0.89-1.11).

Conclusions: The association between food fortification with folic acid and a reduction in the birth prevalence of specific CHDs provides modest evidence for additional benefit from this intervention.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998126PMC
August 2016

Determination of Gestational Age by Ultrasound: In Response.

J Obstet Gynaecol Can 2016 05;38(5):432

Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC.

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http://dx.doi.org/10.1016/j.jogc.2016.04.003DOI Listing
May 2016

Multiple Successful Angioembolizations for Refractory Cardiac Failure in a Preterm with Rapidly Involuting Congenital Hemangioma.

AJP Rep 2016 Mar 4;6(1):e99-e103. Epub 2016 Jan 4.

Children's and Women's Health Centre of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.

Rapidly involuting congenital hemangiomas (RICH) are the commonest variety of congenital hemangioma, often diagnosed antenatally as high-flow arteriovenous shunts causing hemodynamic compromise to the fetus. The postnatal management of such patients is often challenging. We present the case of an infant boy who was delivered prematurely at 29 weeks of gestation due to fetal compromise by a RICH, with features of high-output cardiac failure and major systemic hemodynamic steal from peripheral organs. Two early angioembolizations were required to manage his high-output cardiac failure. To our knowledge, this infant is the smallest and earliest newborn case of successful angioembolization for a complex, life-threatening vascular anomaly. We discuss the interventional dilemmas regarding the optimal timing of delivery and early embolization.
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http://dx.doi.org/10.1055/s-0035-1570342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737636PMC
March 2016

Evaluation of the International Association of the Diabetes In Pregnancy Study Group new criteria: gestational diabetes project.

Can J Diabetes 2015 Apr 15;39(2):128-32. Epub 2014 Dec 15.

University of British Columbia, Division of Endocrinology, Vancouver, British Columbia, Canada.

Objective: To examine the diagnostic rates of gestational diabetes (GDM) and maternal/fetal outcomes before and after replacement of the Carpenter and Coustan (C&C) criteria with the International Association Diabetes Pregnancy Study Group (IADPSG) criteria.

Methods: A retrospective analysis of all pregnancies in 2 separate 6-month cohorts in the province of British Columbia. The first C&C cohort was defined as a 6-month period prior to the introduction of the IADPSG 75 g glucose tolerance test on October 1, 2010. The IADPSG cohort was studied during a 6-month period after the change.

Results: There was a significant increase in rates of GDM when using the IADPSG 75 g criteria, from 7.9% (1838 of 23 211) to 9.4% (2104 of 22 397). There were no significant changes in maternal outcomes when using the IADPSG criteria (caesarean section, induction of labour, perineal laceration, pregnancy-induced hypertension, antepartum hemorrhage >20 weeks or postpartum hospital length of stay). The caesarean section rate was not increased according to multivariate analysis (30.9% vs. 29.7%; p=0.073). There were no significant changes in most fetal outcomes when using the IADPSG criteria (mean gestational age at birth, premature birth, meconium, birth trauma, mean birth weight, large for gestational age, small for gestational age, intrauterine growth restriction), but neonatal hypoglycemia was significantly higher (1.6 % vs. 1.3 %; p=0.007).

Conclusions: The rates of GDM were higher when using the new IADPSG criteria. Overall, all of the maternal and most of the fetal outcomes were similar.
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http://dx.doi.org/10.1016/j.jcjd.2014.09.007DOI Listing
April 2015

The impact of maternal positive and negative affect on fetal physiology and diurnal patterns.

Isr J Psychiatry Relat Sci 2014 ;51(2):109-17

Department of Pediatrics University of British Columbia, Vancouver BC, Canada Child and Family Research Institute, University of British Columbia, Vancouver BC, Canada.

Background: While research has shown that maternal mood (depression and/or anxiety) can have effects on the fetus, little is known about whether maternal positive and negative affect influences the fetus.

Method: We examined fetal vascular and heart rate changes at 36 weeks gestation in 53 euthymic mothers according to their Positive and Negative Affect Scale (PANAS) scores.

Results: Mothers who reported high levels of negative affect showed reduced uterine artery flow, decreased fetal heart rate (fHR) variability, an altered diurnal pattern, and decreased uterine artery cross-sectional area compared to mothers who reported low levels of negative affect. Mothers with low positive affect had a steeper diurnal pattern in fHR accelerations and decreased uterine artery mean velocity flow than mothers with high positive affect.

Limitations: Our observational study suffers from a small sample size.

Conclusion: Even in the absence of an Axis I Major Depressive Disorder (MDD), variations in maternal affect appear to be associated with variations in fetal and uterine physiology.
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January 2016

Determination of gestational age by ultrasound.

J Obstet Gynaecol Can 2014 Feb;36(2):171-181

Vancouver BC.

Objective: To assist clinicians in assigning gestational age based on ultrasound biometry.

Outcomes: To determine whether ultrasound dating provides more accurate gestational age assessment than menstrual dating with or without the use of ultrasound. To provide maternity health care providers and researchers with evidence-based guidelines for the assignment of gestational age. To determine which ultrasound biometric parameters are superior when gestational age is uncertain. To determine whether ultrasound gestational age assessment is cost effective.

Evidence: Published literature was retrieved through searches of PubMed or MEDLINE and The Cochrane Library in 2013 using appropriate controlled vocabulary and key words (gestational age, ultrasound biometry, ultrasound dating). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to July 31, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Values: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Benefits, Harms, And Costs: Accurate assignment of gestational age may reduce post-dates labour induction and may improve obstetric care through allowing the optimal timing of necessary interventions and the avoidance of unnecessary ones. More accurate dating allows for optimal performance of prenatal screening tests for aneuploidy. A national algorithm for the assignment of gestational age may reduce practice variations across Canada for clinicians and researchers. Potential harms include the possible reassignment of dates when significant fetal pathology (such as fetal growth restriction or macrosomia) result in a discrepancy between ultrasound biometric and clinical gestational age. Such reassignment may lead to the omission of appropriate-or the performance of inappropriate-fetal interventions. Summary Statements 1. When performed with quality and precision, ultrasound alone is more accurate than a "certain" menstrual date for determining gestational age in the first and second trimesters (≤ 23 weeks) in spontaneous conceptions, and it is the best method for estimating the delivery date. (II) 2. In the absence of better assessment of gestational age, routine ultrasound in the first or second trimester reduces inductions for post-term pregnancies. (I) 3. Ideally, every pregnant woman should be offered a first-trimester dating ultrasound; however, if the availability of obstetrical ultrasound is limited, it is reasonable to use a second-trimester scan to assess gestational age. (I) 4. Notwithstanding Summary Statements 1, 2, and 3, women vary greatly in their awareness of their internal functions, including ovulation, and this self-knowledge can sometimes be very accurate. (III) Recommendations 1. First-trimester crown-rump length is the best parameter for determining gestational age and should be used whenever appropriate. (I-A) 2. If there is more than one first-trimester scan with a mean sac diameter or crown-rump length measurement, the earliest ultrasound with a crown-rump length equivalent to at least 7 weeks (or 10 mm) should be used to determine the gestational age. (III-B) 3. Between the 12th and 14th weeks, crown-rump length and biparietal diameter are similar in accuracy. It is recommended that crown-rump length be used up to 84 mm, and the biparietal diameter be used for measurements > 84 mm. (II-1A) 4. Although transvaginal ultrasound may better visualize early embryonic structures than a transabdominal approach, it is not more accurate in determining gestational age. Crown-rump length measurement from either transabdominal or transvaginal ultrasound may be used to determine gestational age. (II-1C) 5. If a second- or third-trimester scan is used to determine gestational age, a combination of multiple biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) should be used to determine gestational age, rather than a single parameter. (II-1A) 6. When the assignment of gestational age is based on a third-trimester ultrasound, it is difficult to confirm an accurate due date. Follow-up of interval growth is suggested 2 to 3 weeks following the ultrasound. (III-C).
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http://dx.doi.org/10.1016/S1701-2163(15)30664-2DOI Listing
February 2014

Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes.

Diabetologia 2014 Apr 17;57(4):681-9. Epub 2014 Jan 17.

Department of Medicine, Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, BC, Canada.

Aims/hypothesis: The aim of this study was to compare glycaemic control and maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI).

Methods: In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006-2010 were assessed.

Results: Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p < 0.01 for each). Among 113 pregnancies >20 weeks' gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA1c in the first trimester (mean HbA1c 6.90 ± 0.71% (52 ± 7.8 mmol/mol) vs 7.60 ± 1.38% (60 ± 15.1 mmol/mol), p < 0.001), which persisted until the third trimester (mean HbA1c 6.49 ± 0.52% (47 ± 5.7 mmol/mol) vs 6.81 ± 0.85% (51 ± 9.3 mmol/mol), p = 0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p = 0.72). Despite lower HbA1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p = 0.90) or more weight gain (16.3 ± 8.7 vs 15.2 ± 6.2 kg, p = 0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p = 0.007) may have resulted from confounding by parity.

Conclusions/interpretation: In this large multicentre study, women using insulin pumps in pregnancy had lower HbA1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.
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http://dx.doi.org/10.1007/s00125-014-3163-6DOI Listing
April 2014

Prediction of pediatric outcome after prenatal diagnosis and expectant antenatal management of congenital cystic adenomatoid malformation.

Fetal Diagn Ther 2012 3;31(2):94-102. Epub 2012 Feb 3.

Department of Obstetrics and Gynecology, University of British Columbia and the Child and Family Research Institute, Vancouver, B.C., Canada.

Objective: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and antenatal expectant management in a provincial tertiary referral center that does not offer fetal surgery.

Methods: Retrospective cohort of 71 consecutive cases of prenatally diagnosed CCAM meeting study criteria (1996-2004). CVR was calculated on the initial ultrasound at the referral center, and associated with hydrops (Fisher's exact test) and a composite adverse postnatal outcome consisting of death, intubation for respiratory distress, extracorporeal membrane oxygenation, non-elective surgery for symptomatology, or respiratory infection requiring hospital admission (Mann-Whitney test).

Results: A CVR > 1.6 was significantly associated with hydrops (p = 0.003). In addition, the CVR was significantly associated with the composite adverse postnatal outcome (p = 0.004) at a mean age of follow-up of 41 months (range < 1-117 months). For CVR and postnatal outcome, the area-under-the-curve receiver operating characteristic was 0.81 (95% CI 0.69-0.93, p = 0.006), and choosing a CVR cut-off of < 0.56, the negative predictive value was 100% (95% CI 0.85-1.00).

Conclusion: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR < 0.56 predictive of good prognosis after birth.
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http://dx.doi.org/10.1159/000331936DOI Listing
July 2012

Third trimester fetal pulmonary artery Doppler blood flow velocity characteristics following prenatal selective serotonin reuptake inhibitor (SSRI) exposure.

Early Hum Dev 2012 Aug 10;88(8):609-15. Epub 2012 Feb 10.

Department of Obstetrics & Gynecology, University of British Columbia, 50 West 28th Avenue, Vancouver, BC, Canada.

Background: There have been contradictory reports on the risks of persistent pulmonary hypertension (PPHN) in infants exposed to SSRIs in utero. However, there has been no assessment of fetal pulmonary arterial dynamics in such pregnancies. AIMS AND SUBJECTS: To measure fetal right pulmonary artery (RPA) variables using Doppler ultrasound at 36 weeks gestation in fetuses of mothers taking SSRI antidepressants (n=23) and in a control, normal pregnancy group (n=35).

Outcome Measures: At 36 weeks gestation, Doppler ultrasound estimates of Pulsatility Index (PI), Resistance Index (RI), vessel diameter, peak systolic velocity, mean velocity and volume flow were obtained from the fetal right pulmonary artery in a morning session (~0830), before the SSRI mothers took their daily drug dose and in an afternoon session (~1300). Venous blood was drawn at 5 time points across the day (~08:30AM, ~10:30AM, ~13:00PM, ~13:45PM, and ~15:00PM) from the SSRI treated mothers for measurement of plasma SSRI concentration using high performance liquid chromatography tandem mass spectrometry.

Results: There were no differences in the RPA Doppler measures between the control and SSRI-exposed fetuses. However 8 of the 23 latter fetuses experience transient respiratory difficulties at birth and, in these RPA flow was significantly higher than in the SSR-exposed fetuses without respiratory problems. There were, however, no differences in RPA PI and RI between the 2 groups.

Conclusions: In SSRI-exposed infants with transient postnatal respiratory difficulties, fetal RPA flow in increased, likely due to partial constriction of the ductus arteriosus. However, this was not associated with PPHN.
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http://dx.doi.org/10.1016/j.earlhumdev.2012.01.004DOI Listing
August 2012

Outcome of systemic sclerosis associated interstitial lung disease treated with intravenous cyclophosphamide.

Clin Rheumatol 2011 Aug 12;30(8):1099-104. Epub 2011 Apr 12.

Academic Rheumatology, University of Nottingham, Nottingham, UK.

Our objective was to audit the respiratory outcome, toxicity and long-term survival of systemic sclerosis associated interstitial lung disease (SSc-ILD) treated with intravenous (i.v.) cyclophosphamide. We ascertained whether i.v. cyclophosphamide associates with a better outcome in SSc-ILD diagnosed due to a decline in screening lung function than in those diagnosed due to respiratory symptoms. A retrospective case-note audit was carried out for SSc-ILD patients treated with i.v. cyclophosphamide between January 1999 and March 2009 at the Royal Derby, Kings Mill and Nottingham University Hospitals. Forced vital capacity (FVC) and transfer factor at 6, 12 months after starting i.v. cyclophosphamide were the primary end points. Kaplan-Meier curves were plotted to estimate survival. Thirty-seven i.v. cyclophosphamide treatment cycles were administered to 36 patients (27 women). Fourteen cycles associated with side effects and eight were terminated prematurely. SSc-ILD was diagnosed due to respiratory symptoms in 13 and in response to deteriorating screening pulmonary function test (PFT) in 24 instances. Overall, i.v. cyclophosphamide led to stabilisation in lung function. However, the FVC declined by 7% in SSc-ILD presenting with respiratory symptoms over 12 months. These patients had significantly lower FVC at 6 and 12 month than those with SSc-ILD diagnosed due to decline in screening lung function. The 5-year survival was 76.1% (overall), 62.9% (diagnosed due to respiratory symptoms) and 91.5% (diagnosed due to decline in screening lung function, p = 0.05). I.V. cyclophosphamide stabilises lung function in individuals with SSc-ILD and may associate with better respiratory outcome in patients diagnosed on screening PFTs.
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http://dx.doi.org/10.1007/s10067-011-1734-1DOI Listing
August 2011

Third trimester fetal heart rate and Doppler middle cerebral artery blood flow velocity characteristics during prenatal selective serotonin reuptake inhibitor exposure.

Pediatr Res 2011 Jul;70(1):96-101

Department of Obstetrics & Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Prenatal selective serotonin reuptake inhibitor (SSRI) exposure increases the risk for adverse neonatal behavioral outcomes; although it is unknown whether altered brain function is present before birth. We investigated fetal vascular and heart rate changes at 36-wk gestation in SSRI-treated women with mood disorders (n = 29) [exposed (EXP)] and controls (n = 45) [non-EXP (NEXP)]. Fetal middle cerebral artery (MCA) flow parameters and heart rate characteristics were obtained during pre-SSRI dose morning and postdose afternoon sessions. Maternal mood and cord Hb and hematocrit were measured. Basal fetal heart rate (fHR) did not differ between groups or across the day. The fHR short- and long-term variations, accelerations, and duration of high variability episodes remained lower and did not change across the day in EXP, whereas all increased significantly in NEXP. In both groups, MCA flow velocity and volume flow increased significantly across the day. EXP MCA pulsatility index was significantly lower, as was MCA cross-sectional area. EXP cord Hb and hematocrit were significantly increased. Prenatal SSRI exposure reduced fetal MCA flow resistance and fHR variability, before and after an SSRI dose, controlling for maternal mood. These changes and the SSRI-related increased red cell indices suggest possible fetal hypoxia.
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http://dx.doi.org/10.1203/PDR.0b013e31821ba11aDOI Listing
July 2011

Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine.

Am J Hematol 2009 Dec;84(12):790-4

Divisions of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Cytoreductive therapy in systemic mastocytosis (SM) includes several drugs whose individual merit has not been well characterized. We retrospectively studied 108 Mayo Clinic patients who met the 2008 WHO diagnostic criteria for SM and received at least one cytoreductive drug. The numbers of patients who were evaluable for response to treatment with interferon-alpha with or without prednisone (IFN-alpha), hydroxyurea (HU), imatinib mesylate (IM) or 2-chlorodeoxyadenosine (2-CdA) were 40, 26, 22, and 22, respectively. The corresponding overall (major) response rates, according to recently published consensus criteria, were 53% (18%), 19% (0%), 18% (9%), and 55% (37%). The respective overall response rates in indolent SM, aggressive SM and SM associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD) were 60%, 60%, 45% for IFN-alpha, 0, 0, 21% for HU, 14%, 50%, 9% for IM and 56%, 50%, 55% for 2-CdA. The absence of mast cell mediator release symptoms in IFN-alpha-treated patients and presence of circulating immature myeloid cells in 2-CdA-treated patients predicted inferior response. TET2 mutational status did not influence treatment response. Although the major response rates with these four cytoreductive agents were still suboptimal and HU was mainly used in patients with SM-AHNMD, the current study favors 2-CdA or IFN-alpha as first-line current therapy in SM and identifies patients who are likely to respond to such therapy.
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http://dx.doi.org/10.1002/ajh.21561DOI Listing
December 2009

Origin and outcome of pregnancies affected by androgenetic/biparental chimerism.

Hum Reprod 2007 Apr 21;22(4):1114-22. Epub 2006 Dec 21.

Department of Medical Genetics, University of British Columbia, British Columbia, Canada.

Background: Androgenetic diploid cells confined to the placenta have recently been reported in several cases of normally developed fetuses in association with placental mesenchymal dysplasia (PMD).

Methods And Results: We investigated two singleton, mildly growth-restricted, female pregnancies ascertained on the basis of PMD. One case had liver hemangiomas and both infants had multiple skin hemangiomas. Post-natal development was normal. Molecular marker analysis confirmed the diagnosis of androgenetic and normal mixed cell populations in the placenta. Both cases derived from a single maternal genome (M1) and two distinct paternal genomes (P1 and P2). In one case, the androgenetic cell population contained both paternal genomes (P1P2), with one shared in common with the biparental (M1P1) population. In the second case, the androgenetic lineage showed complete homozygosity (P2P2) for a paternal genome not common to the biparental cell population.

Conclusion: These new PMD cases help to define the range of possible clinical presentations of androgenetic/biparental mosaicism or chimerism. Placentas with androgenetic/biparental chimeric cell populations may derive from a single tri-pronuclear (3PN) zygote in which one or more parental genomes are not equally apportioned to the daughter cells in the first cell division.
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http://dx.doi.org/10.1093/humrep/del462DOI Listing
April 2007

Association of HLA class I with severe acute respiratory syndrome coronavirus infection.

BMC Med Genet 2003 Sep 12;4. Epub 2003 Sep 12.

Transfusion Medicine Laboratory, Mackay Memorial Hospital, Taipei, Taiwan.

Background: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection.

Methods: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis.

Results: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279).

Conclusions: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.
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http://dx.doi.org/10.1186/1471-2350-4-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC212558PMC
September 2003

A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination.

Am J Obstet Gynecol 2002 Oct;187(4):853-7

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, British Women's Hospital, University of British Columbia, Vancouver, BC, Canada.

Objective: Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy.

Study Design: Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant.

Results: One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications.

Conclusions: Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.
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http://dx.doi.org/10.1067/mob.2002.127461DOI Listing
October 2002

Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies.

Clin Chem 2002 Oct;48(10):1681-8

Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.

Objective: We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs).

Methods: Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained.

Results: Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R(2) =0.40-0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48).

Conclusions: Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.
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October 2002