Showing papers by "Mark Walker published in 2018"
TL;DR: Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index that confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
252 citations
TL;DR: A systematic review and meta-analysis of observational studies that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted, finding that among the subgroup of women who conceived spontaneously, endometiosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight.
Abstract: STUDY QUESTION How is endometriosis associated with adverse maternal, fetal and neonatal outcomes of pregnancy? SUMMARY ANSWER Women with endometriosis are at elevated risk for serious and important adverse maternal (pre-eclampsia, gestational diabetes, placenta praevia and Cesarean section) and fetal or neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth and neonatal death). WHAT IS KNOWN ALREADY A number of studies have shown an association between endometriosis and certain adverse maternal and fetal outcomes, but the results have been conflicting with potential for confounding by the use of assisted reproductive technology. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis of observational studies (1 January 1990-31 December 2017) that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies; included women greater than 20 weeks gestational age with endometriosis; included a control group of gravid women without endometriosis; and, reported at least one of the outcomes of interest. Each study was reviewed for inclusion, data were extracted and risk of bias was assessed by two independent reviewers. MAIN RESULTS AND THE ROLE OF CHANCE The search strategy identified 33 studies (sample size, n = 3 280 488) for inclusion. Compared with women without endometriosis, women with endometriosis had higher odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01-1.39]), gestational hypertension and/or pre-eclampsia (OR = 1.21 [1.05-1.39]), gestational diabetes (OR = 1.26 [1.03-1.55]), gestational cholestasis (OR = 4.87 [1.85-12.83]), placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38-2.07]), antepartum hospital admissions (OR = 3.18 [2.60-3.87]), malpresentation (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04-2.01]) and cesarean section (OR = 1.86 [1.51-2.29]). Fetuses and neonates of women with endometriosis were also more likely to have preterm premature rupture of membranes (OR = 2.33 [1.39-3.90]), preterm birth (OR = 1.70 [1.40-2.06]), small for gestational age <10th% (OR = 1.28 [1.11-1.49]), NICU admission (OR = 1.39 [1.08-1.78]), stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46-2.16]). Among the subgroup of women who conceived spontaneously, endometriosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight. Among the subgroup of women who conceived with the use of assisted reproductive technology, endometriosis was found to be associated with placenta praevia and preterm birth. LIMITATIONS, REASONS FOR CAUTION As with any systematic review, the review is limited by the quality of the included studies. The diagnosis for endometriosis and the selection of comparison groups were not uniform across studies. However, the effect of potential misclassification would be bias towards the null hypothesis. WIDER IMPLICATIONS OF THE FINDINGS The association between endometriosis with the important and serious pregnancy outcomes observed in our meta-analysis, in particular stillbirth and neonatal death, is concerning and warrants further studies to elucidate the mechanisms for the observed findings. STUDY FUNDING/COMPETING INTEREST(S) Dr Shifana Lalani is supported by a Physicians' Services Incorporated Foundation Research Grant, and Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services. Dr Singh declares conflicts of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors have no conflicts of interests to declare. REGISTRATION NUMBER PROSPERO CRD42015013911.
112 citations
TL;DR: The substrate-tolerant lanthipeptide synthetase ProcM enables the construction of a plasmid-encoded library of bicyclic lanthipesptides, from which an inhibitor of the p6–UEV protein–protein interaction is identified by a reverse two-hybrid screen.
Abstract: In this article we describe the production and screening of a genetically encoded library of 106 lanthipeptides in Escherichia coli using the substrate-tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, which is a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle-budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing substantial structural diversity. Such libraries may be combined with any cell-based assay to identify lanthipeptides with new biological activities.
104 citations
TL;DR: Yeast surface and phage display of lanthipeptides, macrocyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) represents the first examples of bacterial RiPP production in Saccharomyces cerevisiae for identification of variants with new biological activities.
Abstract: Peptide display has enabled identification and optimization of ligands to many targets. These ligands are usually linear or disulfide-containing peptides that are vulnerable to proteolysis or reduction. We report yeast surface and phage display of lanthipeptides, macrocyclic ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain multiple thioether cross-links that bestow their biological activities. We developed C-terminal yeast display of the class II lanthipeptides lacticin 481 and haloduracin β, and randomization of the C-ring of the former was used to select tight binders to αvβ3 integrin. This represents the first examples of bacterial RiPP production in Saccharomyces cerevisiae for identification of variants with new biological activities. We also report N-terminal phage display of the class I lanthipeptide nisin and randomization of its A- and B-rings to enrich binders to a small molecule, lipid II. The successful display and randomization of both class I...
90 citations
University of Ottawa1, Health Canada2, Public Health Agency of Canada3, Oregon State University4, Dalhousie University5, University of New Brunswick6, University of Toronto7, McGill University8, Carleton University9, Environment Canada10, Children's Hospital of Eastern Ontario11, Ottawa Hospital Research Institute12
TL;DR: Enhanced impacts were found among children born to mothers with asthma, who smoked during pregnancy or lived in urban areas during pregnancy, males and children born preterm or of low birthweight.
Abstract: Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence; however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma. 761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6 years) were estimated using Cox regression models. 110 981 children with asthma were identified. In models adjusted for postnatal exposures, second-trimester exposures to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 μm (hazard ratio (HR) per interquartile range (IQR) increase 1.07, 95% CI 1.06–1.09) and nitrogen dioxide (HR per IQR increase 1.06, 95% CI 1.03–1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, who smoked during pregnancy or lived in urban areas during pregnancy, males and children born preterm or of low birthweight. Prenatal exposure to air pollution may have a differential impact on the risk of asthma development, according to maternal and infant characteristics.
59 citations
TL;DR: The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes.
51 citations
TL;DR: This systematic review showed an increased risk of adverse maternal and perinatal outcomes, and the large amount of heterogeneity among most outcomes that were investigated suggest results must be interpreted with caution.
Abstract: Objective To summarize information on the maternal and perinatal outcomes among pregnant women with a maternal age greater or equal to 45 years old compared with women with a maternal age of less than 45. Methods A comprehensive systematic search of online databases from January 1946 through June 2015 was completed. The maternal outcomes were: fetal loss, preterm birth, full-term birth, complications of pregnancy, the type of delivery, and periconception hemorrhage. The fetal outcomes were: intrauterine growth restriction/LGA, fetal anomalies, APGAR score, and neonatal death. Results Twenty articles were included in the systematic review and 15 included in the meta-analysis. There was a 2.60 greater likelihood of fetal loss ( I 2 = 99%). Newborns of women of a very advanced maternal age were 2.49 more likely to have a concerning 5-minute APGAR score. Very advanced maternal age women had a 3.32 greater likelihood of pregnancy complications ( I 2 = 91%). There was a 1.96 greater likelihood of preterm birth at very advanced maternal age ( I 2 = 91%) and a 4 times greater likelihood of having to deliver through Caesarean section ( I 2 = 97%). Conclusion This systematic review showed an increased risk of adverse maternal and perinatal outcomes. The large amount of heterogeneity among most outcomes that were investigated suggest results must be interpreted with caution.
49 citations
TL;DR: A broad review of rare genetic forms of diabetes that have differing diagnostic and/or treatment implications from type 1 and type 2 diabetes is presented, focusing on forms of monogenic diabetes, mitochondrial diabetes, and syndromic diabetes.
Abstract: Diabetes mellitus is a heterogeneous group of conditions defined by resultant chronic hyperglycemia. Given the increasing prevalence of diabetes mellitus and the increasing understanding of genetic etiologies, we present a broad review of rare genetic forms of diabetes that have differing diagnostic and/or treatment implications from type 1 and type 2 diabetes. Advances in understanding the genotype-phenotype associations in these rare forms of diabetes offer clinically available examples of evolving precision medicine where defining the correct genetic etiology can radically alter treatment approaches. In this review, we focus on forms of monogenic diabetes, mitochondrial diabetes, and syndromic diabetes.
23 citations
TL;DR: Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS and suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK.
Abstract: Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation (EPS), a method which induces contraction of muscle cells in vitro The aim of the present study was to assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or compound 991. AMPK activation was assessed by Western blot and glucose uptake measured. Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared with controls. Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS.
20 citations
TL;DR: An electronic audit and feedback programme implemented in maternal-newborn hospitals was associated with clinically relevant practice improvements at the provincial level in the majority of targeted indicators.
Abstract: Objectives To assess the effect of the Maternal Newborn Dashboard on six key clinical performance indicators in the province of Ontario, Canada. Design Interrupted time series using population-based data from the provincial birth registry covering a 3-year period before implementation of the Dashboard and 2.5 years after implementation (November 2009 through March 2015). Setting All hospitals in the province of Ontario providing maternal-newborn care (n=94). Intervention A hospital-based online audit and feedback programme. Main outcome measures Rates of the six performance indicators included in the Dashboard. Results 2.5 years after implementation, the audit and feedback programme was associated with statistically significant absolute decreases in the rates of episiotomy (decrease of 1.5 per 100 women, 95% CI 0.64 to 2.39), induction for postdates in women who were less than 41 weeks at delivery (decrease of 11.7 per 100 women, 95% CI 7.4 to 16.0), repeat caesarean delivery in low-risk women performed before 39 weeks (decrease of 10.4 per 100 women, 95% CI 9.3 to 11.5) and an absolute increase in the rate of appropriately timed group B streptococcus screening (increase of 2.8 per 100, 95% CI 2.2 to 3.5). The audit and feedback programme did not significantly affect the rates of unsatisfactory newborn screening blood samples or formula supplementation at discharge. No statistically significant effects were observed for the two internal control outcomes or the four external control indicators—in fact, two external control indicators (episiotomy and postdates induction) worsened relative to before implementation. Conclusion An electronic audit and feedback programme implemented in maternal-newborn hospitals was associated with clinically relevant practice improvements at the provincial level in the majority of targeted indicators.
20 citations
01 Oct 2018
TL;DR: There was a significant increase in cffDNA screening and a significant decrease in prenatal diagnostic testing among women with a positive multiple-marker screening result, showing the significant impact of public policy and funding decisions on women's choices regarding prenatal testing.
Abstract: BACKGROUND In 2014, Ontario augmented its publicly funded multiple-marker screening program for prenatal aneuploidy by incorporating cell-free fetal DNA (cffDNA) analysis for high-risk pregnancies. We assessed trends in the use of multiple-marker screening, cffDNA screening and prenatal diagnostic testing before and after implementation of public funding. METHODS We conducted a descriptive study based on data from the Better Outcomes Registry & Network (BORN) Ontario. The study population included all pregnant women in Ontario with a singleton pregnancy and an expected date of delivery between July 1, 2012, and Mar. 31, 2016, with pregnancy data captured in BORN. Pregnancy losses and terminations before 20 weeks' gestation not captured in BORN were excluded. We generated descriptive statistics to show trends and regional variations in use. RESULTS The study sample included 534 210 singleton pregnancies. After cffDNA screening was funded for specific indications, uptake of multiple-marker screening increased slightly, from 66.5% to 68.1% (p < 0.001). Uptake of cffDNA screening among women with a positive multiple-marker screening result increased substantially, from 3.2% to 48.8% (p < 0.001). In contrast, the rate of prenatal diagnostic testing in this group decreased from 54.8% to 30.8% (p < 0.001). Although women aged 40 years or older are eligible for primary cffDNA screening, only a small decrease in the use of multiple-marker screening was observed in this group. The greatest use of cffDNA screening and greatest decline in prenatal diagnostic testing were seen in women with a level of risk for trisomy 21 of 1:101-1:200 based on multiple-marker screening. INTERPRETATION After public funding of cffDNA screening was implemented in Ontario, there was a significant increase in cffDNA screening and a significant decrease in prenatal diagnostic testing among women with a positive multiple-marker screening result. These changing patterns show the significant impact of public policy and funding decisions on women's choices regarding prenatal testing.
TL;DR: In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled and this error has now been corrected in the HTML and PDF versions of the article.
Abstract: In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.
TL;DR: In the first year of operation, care was consistent with national guidelines, and morbidity and mortality rates and intervention rates were low for women with low‐risk pregnancies seeking a low‐intervention approach for labor and birth.
TL;DR: The results call into question the association between anti‐&bgr;2GP1 antibodies and placenta‐mediated pregnancy complications, with further research needed.
Abstract: Background While anti-β2 glycoprotein 1 (anti-β2GP1) antibody positivity is included in the diagnostic criteria for antiphospholipid syndrome (APS), the association between anti-β2GP1 and the obstetrical complications of APS has been inconsistently reported and remains unclear. Objective We completed a case–control study nested within the Canadian Ottawa and Kingston (OaK) Birth Cohort to evaluate the association between anti-β2GP1 antibody positivity and placenta-mediated pregnancy complications. Study Design Five hundred cases were randomly selected among pregnant women who experienced any of the following independently adjudicated placenta-mediated pregnancy complications: preeclampsia, placental abruption, late pregnancy loss (≥ 12 weeks' gestation), and birth of a small-for-gestational age (SGA) infant Results Anti-β2GP1 immunoglobulin G (IgG) and/or immunoglobulin M (IgM) antibodies in titers ≥ 20 G/M units (> 99th percentile) were present in 24 of 497 (4.8%) of controls and 33 of 503 (6.6%) of cases. There was no significant difference between cases and controls for the composite outcome of any placenta-mediated pregnancy complications (odds ratio, 1.38, 95% confidence interval [CI], 0.8–2.37, p = 0.25). Conclusion Our results call into question the association between anti-β2GP1 antibodies and placenta-mediated pregnancy complications, with further research needed.
01 Jan 2018
TL;DR: Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Abstract: Genome-wide association studies (GWAS) have identified > 250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Anne E. Justice, Tugce Karaderi1, Heather M. Highland2, Kristin L. Young2 +275 more•Institutions (87)
TL;DR: By examining variants often poorly tagged or entirely missed by genome-wide association studies, novel genes in fat distribution are implicate, stressing the importance of interrogating low-frequency and protein-coding variants.
Abstract: Body fat distribution is a heritable risk factor for a range of adverse health consequences, including hyperlipidemia and type 2 diabetes. To identify protein-coding variants associated with body fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, we analyzed 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries for discovery and 132,177 independent European-ancestry individuals for validation. We identified 15 common (minor allele frequency, MAF ≥ 5%) and 9 low frequency or rare (MAF
23 Jan 2018
TL;DR: This corrects the article DOI: 10.1038/sdata.2017.179 to S Data 2017, which indicates that S Data was first published in 2017, not S Data 2016, which was originally published in 2016.
Abstract: This corrects the article DOI: 10.1038/sdata.2017.179.
University of Oxford1, University of Dundee2, Lund University3, University of Geneva4, Newcastle University5, University of Copenhagen6, University of Exeter7, University of Amsterdam8, University of Eastern Finland9, University of Cambridge10, Technical University of Denmark11, University of Westminster12, National Research Council13, university of lille14, Imperial College London15, Royal Institute of Technology16, Eli Lilly and Company17
TL;DR: Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the IMI DIRECT consortium.
Abstract: Background and aims: Understanding the aetiology, clinical presentation and prognosis of type 2 diabetes (T2D) and optimizing its treatment might be facilitated by biomarkers that help predict a person9s susceptibility to the risk factors that cause diabetes or its complications, or response to treatment. The IMI DIRECT (Diabetes Research on Patient Stratification) Study is a European Union (EU) Innovative Medicines Initiative (IMI) project that seeks to test these hypotheses in two recently established epidemiological cohorts. Here, we describe the characteristics of these cohorts at baseline and at the first main follow-up examination (18-months).
Materials and methods: From a sampling-frame of 24,682 European-ancestry adults in whom detailed health information was available, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm and enrolled into a prospective cohort study (n=2127) undertaken at four study centres across Europe (Cohort 1: prediabetes). We also recruited people from clinical registries with recently diagnosed T2D (n=789) into a second cohort study (Cohort 2: diabetes). The two cohorts were studied in parallel with matched protocols. Endogenous insulin secretion and insulin sensitivity were modelled from frequently sampled 75g oral glucose tolerance (OGTT) in Cohort 1 and with mixed-meal tolerance tests (MMTT) in Cohort 2. Additional metabolic biochemistry was determined using blood samples taken when fasted and during the tolerance tests. Body composition was assessed using MRI and lifestyle measures through self-report and objective methods.
Results: Using ADA-2011 glycaemic categories, 33% (n=693) of Cohort 1 (prediabetes) had normal glucose regulation (NGR), and 67% (n=1419) had impaired glucose regulation (IGR). 76% of the cohort was male, age=62(6.2) years; BMI=28.4(4.0) kg/m2; fasting glucose=5.7(0.6)mmol/l; 2-hr glucose=5.9(1.6) mmol/l [mean(SD)]. At follow-up, 18.5(1.4) months after baseline, fasting glucose=5.8(0.6)mmol/l; 2-hr OGTT glucose=6.1(1.7) mmol/l [mean(SD)]. In Cohort 2 (diabetes): 65% (n=508) were lifestyle treated (LS) and 35% (n=271) were lifestyle + metformin treated (LS+MET). 58% of the cohort was male, age=62(8.1) years; BMI=31(5.0)kg/m2; fasting glucose=7.2(1.4)mmol/l; 2-hr glucose=8.6(2.8)mmol/l [mean(SD)]. At follow-up, 18.2(0.6) months after baseline, fasting glucose=7.8(1.8)mmol/l; 2-hr MMTT glucose=9.5(3.3) mmol/l [mean(SD)].
Conclusion: The epidemiological IMI DIRECT cohorts are the most intensely characterised prospective studies of glycaemic deterioration to date. Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the DIRECT consortium.
TL;DR: Children exposed to cigarette smoke in utero exhibit greater adiposity, and this exposure may have as contributing factors higher screen time, ad libitum energy intake, and a trend for reduced REE.
TL;DR: This study proposed alternate IVF adjustment factors that will produce more accurate screening results within the population of Ontario.
Abstract: Objective The objectives of this study were as follows: (1) to investigate the accuracy of IVF identification on the prenatal screening record from prenatal screening laboratories; (2) to compare the screening markers in IVF and non-IVF pregnancies in the population of Ontario; and (3) to propose more appropriate IVF adjustment factors for the Ontario population. Methods Two years of IVF treatment, data from all fertility clinics in Ontario were merged with the corresponding prenatal screening data from all five prenatal screening labs. New adjustment factors for IVF were developed for each maternal serum screening marker and nuchal translucency measurement. Means and SDs and linear regression models were reported for all prenatal screening records, as well as for records that had IVF identified through the prenatal screening requisition and records that were identified through the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database. Results Significant differences between IVF and non-IVF groups on the basis of the prenatal screening requisition information and CARTR Plus information were found among the ethnicity-adjusted mean multiple of the medians for alpha fetoprotein, first trimester pregnancy-associated plasma protein A, second trimester unconjugated estradiol, first trimester human chorionic gonadotropin, total human chorionic gonadotropin, and dimeric inhibin A. Conclusion This study proposed alternate IVF adjustment factors that will produce more accurate screening results within the population of Ontario.
TL;DR: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Human Reproduction Open, pp. 1–14, 2019 doi:10.1093/hropen/hoz010