287 results on '"Jane Halliday"'
Search Results
2. A decade of non‐invasive prenatal screening in Australia: National impact on prenatal screening and diagnostic testing
- Author
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Lisa Hui and Jane Halliday
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Obstetrics and Gynecology ,General Medicine - Abstract
Prenatal screening for aneuploidy has undergone immense changes over the past two decades. In 2013 cell-free DNA-based non-invasive prenatal testing (NIPT) became a new self-funded option primarily for Down syndrome screening, but also other aneuploidies and genetic conditions. The numbers of Medicare item claims for prenatal diagnostic procedures have halved since the introduction of NIPT, while billings for serum screening fell by 40% over the same period, on a background of steady births. Australia is now observing historically low rates of prenatal diagnostic testing. These data provide an informative snapshot of historic changes in prenatal screening and diagnosis, as our sector prepares for the impending impacts of other advances in genomics on maternity care. They also highlight the need to address equity and quality issues that arise when consumers must bear the full costs of improved genomic tests in the absence of Medicare funding.
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- 2022
3. Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review
- Author
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Alison Luk Young, Aalya Imran, Michael J. Spoelma, Rachel Williams, Katherine M. Tucker, Jane Halliday, Laura E. Forrest, Claire E. Wakefield, and Phyllis N. Butow
- Subjects
Genetics ,Genetics (clinical) - Abstract
Interventions to assist family communication about inherited cancer risk have the potential to improve family cancer outcomes. This review aimed to evaluate the efficacy of proband-mediated interventions employed within genetics clinics to increase disclosure of genetic risk to at-risk relatives. MEDLINE, Embase, CINAHL, PubMed and PsycINFO were searched for publications between 1990–2020. The quality of studies was assessed. From 5605 records reviewed, 9 studies (4 randomised control trials and 5 cohort studies) were included involving families with BRCA1, BRCA2 and Lynch syndrome. Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4–60.0% contacted a genetics clinic and 22.8–76.2% had genetic testing after they were counselled at a genetics clinic. Significant differences between intervention and control group were reported on all three outcomes by one study, and with relatives contacting a genetics clinic by another study. The studies suggest but do not conclusively show, that tailored genetic counselling with additional follow-up can increase both the proportion of informed relatives and relatives who contact the genetics clinic. With the increase in germline testing, interventions are required to consider the family communication process and address post-disclosure variables (e.g., relative’s perceptions, emotional reactions) through engagement with probands and relatives to maximise the public health benefit of identifying inherited cancer risk in families.
- Published
- 2022
4. Correspondence on 'Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG)' by Gregg et al
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Sarah Righetti, Lisa Dive, Alison D. Archibald, Lucinda Freeman, Belinda McClaren, Anaita Kanga-Parabia, Martin B. Delatycki, Nigel G. Laing, Edwin P. Kirk, Ainsley J. Newson, Kristine Barlow-Stewart, Stephanie Best, Kirsten Boggs, Camron Ebzery, Samantha Edwards, Zoe Fehlberg, Lara Fitzgerald, Jane Halliday, Katrina Harrison, Jillian Kennedy, Janet Long, John Massie, Erin Tutty, Richard Allcock, Jade Caruana, Rachael Casella, Mark Davis, Tristan Hardy, Sarah Jelenich, Sebastian Lunke, Julie McGaughran, and Gina Ravenscroft
- Subjects
Heredity ,Pregnancy ,Genetics, Medical ,Humans ,Mass Screening ,Female ,Genetic Testing ,Genomics ,United States ,Genetics (clinical) - Published
- 2022
5. Reproductive function in men conceived with in vitro fertilization and intracytoplasmic sperm injection
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Sarah R. Catford, Jane Halliday, Sharon Lewis, Moira K. O’Bryan, David J. Handelsman, Roger J. Hart, John McBain, Luk Rombauts, David J. Amor, Richard Saffery, and Robert I. McLachlan
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Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2022
6. Evidence for assisted reproductive technology associated epigenetic variation in humans
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Boris Novakovic, Jasmine Dennison, Stephanie Cheng, Mark Green, Sharon Lewis, Jane Halliday, and Richard Saffery
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- 2023
7. Contributors
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Montserrat C. Anguera, Ina Anreiter, Maria Becker, Nicolò Caporale, Stephanie Cheng, Cristina Cheroni, Stephanie Cheung, Aaron Ciechanover, Coralina Collar-Fernández, Jasmine Dennison, Sonja Entringer, Dov Feldberg, Katie A. Fennell, Anne Gabory, Donato Gemmati, Marek Glezerman, Mila Gorchkova, Denis Gorobets, Mark Green, Jane Halliday, Anthony J. Hannan, Lucas B. Hoffmann, Claudine Junien, Olena M. Kocur, Jari M. Lahti, Marianne J. Legato, Sharon Lewis, Boris Novakovic, Asher Ornoy, Susan Ozanne, Gianpiero D. Palermo, Terence Y. Pang, Zeenal H. Patel, Jacob Peedicayil, Luciana Pellegrini Pisani, Zev Rosenwaks, Richard Saffery, Daniel Sapozhnikov, Keshav K. Singh, Marla B. Sokolowski, Hermona Soreq, Sarah Stucchi, Moshe Szyf, Giuseppe Testa, Veronica Tisato, Felix Vaura, Gal Warhaftig, Liza Weinstein-Fudim, Philip Xie, and Gal Yadid
- Published
- 2023
8. Does being conceived by assisted reproductive technology influence adult quality of life?
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Karin Hammarberg, Jane Halliday, Joanne Kennedy, David P. Burgner, David J. Amor, Lex W. Doyle, Markus Juonala, Sarath Ranganathan, Liam Welsh, Michael Cheung, Robert McLachlan, John McBain, and Sharon Lewis
- Subjects
Reproductive Medicine ,Obstetrics and Gynecology ,General Medicine - Abstract
Numerous studies have investigated the physical health and development of children and adolescents conceived with assisted reproductive technology (ART). Less is known about the quality of life of ART-conceived adults. This study explores the contributions of being conceived with ART and psychosocial cofactors present in young adulthood to the quality of life of adults aged 22-35 years. Young adults conceived through ART or natural conception (NC) completed questionnaires which included a standardized measure of quality of life (World Health Organization Quality of Life - Brief assessment (WHOQoL-BREF)) when aged 18-28 years (T1) and again when aged 22-35 years (T2). The WHOQoL-BREF has four domains: (i) Physical, (ii) Psychological, (iii) Social relationships and (iv) Environment. A total of 193 ART-conceived and 86 NC individuals completed both questionnaires. When accounting for other cofactors in multivariable analyses, being ART-conceived was strongly associated with higher scores (better quality of life) on the Social relationships, and Environment WHOQoL-BREF domains at T2. In addition, less psychological distress, a better relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more of the WHOQoL-BREF domains at T2. In conclusion, being ART-conceived can confer advantages in quality of life in adulthood, independent of psychosocial cofactors.
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- 2022
9. Development and use of the Australian reproductive genetic carrier screening decision aid
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Martin B. Delatycki, Ainsley J Newson, Alison D Archibald, Jane Halliday, Kristine Barlow-Stewart, Emily A King, and Belinda J McClaren
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Decision Making ,Ethnic group ,Delphi method ,Genetic Carrier Screening ,Pilot Projects ,Article ,Decision Support Techniques ,law.invention ,Pregnancy ,law ,Genetics ,Content validity ,Humans ,Mass Screening ,Relevance (law) ,Genetics (clinical) ,computer.programming_language ,Medical education ,Australia ,Cognition ,CLARITY ,Female ,Psychology ,computer ,Delphi - Abstract
Reproductive genetic carrier screening (RGCS) may be offered to all individuals and couples, regardless of family history or ethnicity. “Mackenzie’s Mission” (MM) is an Australian RGCS pilot study, evaluating the offer of couple-based screening for ~1300 genes associated with around 750 autosomal and X-linked recessive childhood-onset conditions. Each member of the couple makes an individual decision about RGCS and provides consent. We developed a decision aid (RGCS-DA) to support informed decision-making in MM, suitable for couples who were either non-pregnant or in early pregnancy. A Delphi approach invited experts to review values statements related to various concepts of RGCS. Three review rounds were completed, seeking consensus for relevance and clarity of statements, incorporating recommended modifications in subsequent iterations. The final RGCS-DA contains 14 statements that achieved Delphi consensus plus the attitude scale of the measure of informed choice. This was then evaluated in cognitive talk aloud interviews with potential users to assess face and content validity. Minimal wording changes were required at this stage. After this process, the RGCS-DA was piloted with 15 couples participating in MM who were then interviewed about their decision-making. The RGCS-DA prompted discussion within couples and facilitated in depth consideration of screening. There was reassurance when values aligned and a sense of shared decision-making within the couple. This RGCS-DA may become a very useful tool in supporting couples’ decision making and contribute to RGCS being feasible for scaled-up implementation.
- Published
- 2021
10. Pre‐natal and post‐natal diagnosis of congenital upper limb differences: The first 3 years of the Australian Hand Difference Register
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Jane Halliday, Christopher J. Coombs, Joanne Kennedy, Lisa Hui, Daniel J. Wilks, David O'Keefe, and David McCombe
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Poland anomaly ,Population ,Australia ,Infant, Newborn ,Computer-assisted web interviewing ,Hand ,medicine.disease ,VACTERL association ,Upper Extremity ,Thumb ,Family medicine ,Pediatrics, Perinatology and Child Health ,Epidemiology ,Health care ,medicine ,Humans ,Upper Extremity Deformities, Congenital ,Medical diagnosis ,Child ,business ,education ,Psychosocial - Abstract
Aims Children with a congenital upper limb difference (CoULD) are a diverse group who often require multidisciplinary care and long-term support for functional and social impacts. The Australian Hand Difference Register (AHDR) provides a national database of children born with a CoULD and aims to facilitate research and improve health care for affected children. Using data from the first 3 years of its operation, we analysed the demographic and clinical features of participating families, including type of CoULDs and the frequency of pre-natal and syndromic diagnoses. Methods Families were recruited from tertiary plastic surgery, orthopaedic and genetics clinics, as well as by self-referral. Hand differences were classified by the consulting physician according to the Oberg-Manske-Tonkin classification system. Primary carers were invited to complete an online questionnaire covering demographic information, pregnancy and newborn outcomes and diagnostic details. Results Between August 2017 and September 2020, 822 families consented and 320 questionnaires were reviewed. CoULDs were detected pre-natally in 66 (20.6%) and post-natally in 248 children (77.5%); data for 6 (1.9%) children were missing. The most common CoULDs were radial polydactyly, symbrachydactyly with ectodermal elements and radial longitudinal deficiency, hypoplastic thumb. Twenty-seven children (8.4%) had an associated syndrome, 7 diagnosed pre-natally and 19 post-natally; the most common were VACTERL association, Poland anomaly, Holt-Oram and ectrodactyly-ectodermal dysplasia-clefting syndromes. Conclusions The AHDR is a valuable resource for understanding the relative frequencies of CoULDs. Participation will assist future research into the diagnostic journeys of children with CoULDs, including risk factors, diagnosis and psychosocial impacts.
- Published
- 2021
11. Peer Review Report For: Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service [version 2; peer review: 2 approved]
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Jane Halliday
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- 2022
12. Child health after preimplantation genetic testing
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Leeanda Wilton, Anne Glynn, David J. Amor, Sharon Lewis, and Jane Halliday
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Male ,0301 basic medicine ,medicine.medical_specialty ,Biopsy ,medicine.medical_treatment ,Child health ,Social Skills ,03 medical and health sciences ,Child Development ,0302 clinical medicine ,medicine ,Humans ,Caesarean section ,Child ,Preimplantation Diagnosis ,Retrospective Studies ,Genetic testing ,Pregnancy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Child Health ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,Mental health ,030104 developmental biology ,Reproductive Medicine ,Child, Preschool ,Family medicine ,Cohort ,Well-being ,Female ,Family Relations ,business ,Developmental Biology - Abstract
Research question Despite the increasing use of preimplantation genetic testing (PGT) for aneuploidy and monogenic diseases, for children conceived using PGT there is limited follow-up beyond 2 years of age. This study examined the health, well-being and development of school-aged children (5–8 years old) conceived following PGT. Design Retrospective cohort study of children conceived after IVF with PGT (exposed cohort) and children conceived after IVF without PGT (unexposed cohort) at two IVF clinics in Melbourne, born between 2000 and 2008, recruited with a 1:2 ratio. Mothers of the children completed a questionnaire asking child-specific questions regarding health and well-being, mental health, development, educational achievement and family-specific questions regarding family functioning and parent–child attachment. Results A total of 155 participants were recruited to the PGT cohort and 303 participants to the IVF-only cohort. There were no differences between the two cohorts with regards to maternal characteristics, birth defect frequency and pregnancy characteristics, apart from delivery by Caesarean section, which was more frequent in PGT singletons (55%) compared with IVF-only singletons (36%). While no significant differences between the PGT and IVF-only cohorts were found for the majority of general health and psychological scales, there were differences when compared with population data. Children in the exposed cohort appeared to have more positive outcomes in many of the measures. Conclusion The data from this study suggest that PGT does not cause adverse outcomes in children. However, the nature (self-report) and small sample size of the study must be taken into consideration when interpreting the data.
- Published
- 2021
13. YourChoice A Decision Aid App for Genomic Prenatal Testing
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Cate Nagle, Lisa Hui, Taryn Charles, Helen Wright, and Jane Halliday
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Maternity and Midwifery ,Obstetrics and Gynecology - Published
- 2022
14. It takes a village: Influencing policy and practice to prevent alcohol use in pregnancy and promote better outcomes for individuals living with Fetal Alcohol Spectrum Disorder
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Amy Finlay-Jones, Elizabeth Elliott, Astrid Chapman, Jane Halliday, Heather Jones, Natalie Kippin, Narelle Mullan, Hayley Passmore, Tracy Reibel, Neil Reynolds, Martyn Symons, Tracey Tsang, Rochelle Watkins, and Carol Bower
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Information Systems and Management ,Policy ,Alcohol Drinking ,Ethanol ,Fetal Alcohol Spectrum Disorders ,Pregnancy ,Australia ,Humans ,Health Informatics ,Female ,reproductive and urinary physiology ,Information Systems ,Demography - Abstract
Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by exposure to alcohol in utero. It has pervasive, lifelong impacts and is recognised as a major public health concern in many countries where alcohol is used. The FASD Research Australia Centre of Research Excellence (CRE) was funded by the National Health and Medical Research Council to generate and translate evidence to address prevention, diagnosis, and management of FASD in Australia. The current paper describes the approach to policy and practice impact taken by our CRE, including our stakeholder engagement processes and the key principles that underlie our approach. We provide examples of policy and practice influence in FASD prevention, diagnosis and management that have been achieved over the past five years and discuss challenges that are routinely faced in the translation of our work.
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- 2022
15. Peer Review Report For: Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service [version 1; peer review: 1 approved with reservations]
- Author
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Jane Halliday
- Published
- 2022
16. Post-Operative Copeptin Analysis Predicts Which Patients Do Not Develop Diabetes Insipidus After Pituitary Surgery
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Hussam Rostom, Sean Noronha, Bahram Jafar-Mohammadi, Christine May, Anouk Borg, Jane Halliday, Simon Cudlip, Tim James, Nishan Guha, Brian Shine, and Aparna Pal
- Abstract
Background: Diabetes insipidus (DI) is a recognised complication of pituitary surgery, with diagnosis requiring clinical observation aided by plasma and urine electrolytes and osmolalities. Copeptin is a stable surrogate marker of AVP release and has potential to facilitate prompt diagnosis of post-operative DI. This assay has been shown to accurately predict which patients are likely to develop DI following pituitary surgery. Objective: To determine whether copeptin analysis can be used to predict which patients are at risk of developing DI following transsphenoidal adenomectomy (TSA).Methods: 78 patients undergoing TSA had samples taken for copeptin pre-operatively and at day 1 post-TSA. The majority of patients also had samples from day 2, day 8, and week 6 post-TSA. Results from patients who developed post-operative DI (based on clinical assessment, urine and plasma biochemistry and the need for treatment with DDAVP) were compared to those who did not. Patients with any evidence of pre-operative DI were excluded.Results: Of 78 patients assessed, eleven were clinically determined to have developed DI. Differences were observed between patients with DI and those without in post-operative samples. Of note, there was a significant difference in plasma copeptin at day 1 post-operation (p=0.010 on Kruskal-Wallis test), with copeptin levels greater than 3.4 pmol/L helping to rule out DI (91% sensitivity, 55% specificity at this cut off).Conclusion: In the post-TSA setting, copeptin is a useful rule-out test in patients with values above a defined threshold, which may facilitate earlier decision making and shorter hospital stays.
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- 2022
17. Post-pituitary surgery copeptin analysis as a 'rule-out' test for post-operative diabetes insipidus
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Hussam Rostom, Sean Noronha, Bahram Jafar-Mohammadi, Christine May, Anouk Borg, Jane Halliday, Simon Cudlip, Tim James, Nishan Guha, Brian Shine, and Aparna Pal
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism - Abstract
Background Diabetes insipidus (DI) is a recognised complication of pituitary surgery, with diagnosis requiring clinical observation aided by plasma and urine electrolytes and osmolalities. Copeptin is a stable surrogate marker of AVP release and has potential to facilitate prompt diagnosis of post-operative DI. This assay has been shown to accurately predict which patients are likely to develop DI following pituitary surgery. Objective To determine whether copeptin analysis can be used to predict which patients are at risk of developing DI following trans-sphenoidal surgery (TSS). Methods Seventy-eight patients undergoing TSS had samples taken for copeptin pre-operatively and at day 1 post-TSS. The majority of patients also had samples from day 2, day 8, and week 6 post-TSS. Results from patients who developed post-operative DI (based on clinical assessment, urine and plasma biochemistry and the need for treatment with DDAVP) were compared to those who did not. Patients with any evidence of pre-operative DI were excluded. Results Of 78 patients assessed, 11 were clinically determined to have developed DI. Differences were observed between patients with DI and those without in post-operative samples. Of note, there was a significant difference in plasma copeptin at day 1 post-operation (p = 0.010 on Kruskal–Wallis test), with copeptin levels greater than 3.4 pmol/l helping to rule out DI (91% sensitivity, 55% specificity at this cut off). Conclusion In the post-TSS setting, copeptin is a useful rule-out test in patients with values above a defined threshold, which may facilitate earlier decision making and shorter hospital stays.
- Published
- 2022
18. Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review
- Author
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Alison Luk, Young, Aalya, Imran, Michael J, Spoelma, Rachel, Williams, Katherine M, Tucker, Jane, Halliday, Laura E, Forrest, Claire E, Wakefield, and Phyllis N, Butow
- Abstract
Interventions to assist family communication about inherited cancer risk have the potential to improve family cancer outcomes. This review aimed to evaluate the efficacy of proband-mediated interventions employed within genetics clinics to increase disclosure of genetic risk to at-risk relatives. MEDLINE, Embase, CINAHL, PubMed and PsycINFO were searched for publications between 1990-2020. The quality of studies was assessed. From 5605 records reviewed, 9 studies (4 randomised control trials and 5 cohort studies) were included involving families with BRCA1, BRCA2 and Lynch syndrome. Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4-60.0% contacted a genetics clinic and 22.8-76.2% had genetic testing after they were counselled at a genetics clinic. Significant differences between intervention and control group were reported on all three outcomes by one study, and with relatives contacting a genetics clinic by another study. The studies suggest but do not conclusively show, that tailored genetic counselling with additional follow-up can increase both the proportion of informed relatives and relatives who contact the genetics clinic. With the increase in germline testing, interventions are required to consider the family communication process and address post-disclosure variables (e.g., relative's perceptions, emotional reactions) through engagement with probands and relatives to maximise the public health benefit of identifying inherited cancer risk in families.
- Published
- 2022
19. Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence
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Mitchell Bestry, Martyn Symons, Alexander Larcombe, Evelyne Muggli, Jeffrey M. Craig, Delyse Hutchinson, Jane Halliday, and David Martino
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Mammals ,DNA methylation ,Alcohol Drinking ,Review ,Fetal alcohol spectrum disorder ,Pregnancy ,Prenatal Exposure Delayed Effects ,Prenatal alcohol exposure ,Genetics ,Animals ,Female ,Epigenetics ,Molecular Biology ,Genetics (clinical) ,Developmental Biology - Abstract
Background Prenatal alcohol exposure (PAE) is associated with a range of adverse offspring neurodevelopmental outcomes. Several studies suggest that PAE modifies DNA methylation in offspring cells and tissues, providing evidence for a potential mechanistic link to Fetal Alcohol Spectrum Disorder (FASD). We systematically reviewed existing evidence on the extent to which maternal alcohol use during pregnancy is associated with offspring DNA methylation. Methods A systematic literature search was conducted across five online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, EMBASE, Google Scholar and CINAHL Databases were searched for articles relating to PAE in placental mammals. Data were extracted from each study and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) was used to assess the potential for bias in human studies. Results Forty-three articles were identified for inclusion. Twenty-six animal studies and 16 human studies measured offspring DNA methylation in various tissues using candidate gene analysis, methylome-wide association studies (MWAS), or total nuclear DNA methylation content. PAE dose and timing varied between studies. Risk of bias was deemed high in nearly all human studies. There was insufficient evidence in human and animal studies to support global disruption of DNA methylation from PAE. Inconclusive evidence was found for hypomethylation at IGF2/H19 regions within somatic tissues. MWAS assessing PAE effects on offspring DNA methylation showed inconsistent evidence. There was some consistency in the relatively small number of MWAS conducted in populations with FASD. Meta-analyses could not be conducted due to significant heterogeneity between studies. Conclusion Considering heterogeneity in study design and potential for bias, evidence for an association between PAE and offspring DNA methylation was inconclusive. Some reproducible associations were observed in populations with FASD although the limited number of these studies warrants further research. Trail Registration: This review is registered with PROSPERO (registration number: CRD42020167686).
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- 2022
20. Association of assisted reproductive technology with long-term offspring cardiometabolic health: a multi-cohort study
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Ahmed Elhakeem, Amy E Taylor, Hazel M Inskip, Jonathan Huang, Toby Mansell, Carina Rodrigues, Federica Asta, Sophie M Blaauwendraad, Siri E Håberg, Jane Halliday, Margreet W Harskamp-van Ginkel, Jian-Rong He, Vincent WV Jaddoe, Sharon Lewis, Gillian M Maher, Yannis Manios, Fergus P McCarthy, Irwin KM Reiss, Franca Rusconi, Theodosia Salika, Muriel Tafflet, Xiu Qiu, Bjørn O Åsvold, David Burgner, Jerry KY Chan, Luigi Gagliardi, Romy Gaillard, Barbara Heude, Maria C Magnus, George Moschonis, Deirdre Murray, Scott M Nelson, Daniela Porta, Richard Saffery, Henrique Barros, Johan G Eriksson, Tanja GM Vrijkotte, and Deborah A Lawlor
- Abstract
ObjectivesTo examine association of conception by assisted reproductive technology (ART) with offspring cardio-metabolic health outcomes, and whether these differ by offspring age.DesignMulti-cohort study.SettingFourteen population-based cohort studies with offspring from the UK, Ireland, France, the Netherlands, Portugal, Greece, Italy, Norway, Singapore, and Australia for meta-analysis of various ages. Four cohorts (three European and one Singaporean) with repeated measures for pooled age-change (from 3 to 26 years) trajectory analysis.ParticipantsYoung people sampled from the general population with complete data on mode of conception, confounders, and ≥1 cardio-metabolic outcome measured after birth.ExposuresConception by ART versus natural conception (NC).Main outcome measuresSystolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), glucose, insulin, and glycated haemoglobin (HbA1c).ResultsBetween 35,780 (605 ART) and 4,502 (67 ART) offspring were included in meta-analysis of various ages for each outcome. Mean age at outcome assessment ranged from 13 months to 27.4 years, with most cohorts ((11/14) having mean age mmHg; 95%CI: -1.91 to 0.14), DBP (−0.50mmHg; -1.65 to 0.66), and HR (0.02beats/min; -1.00 to 1.03). Cholesterol measures were higher in ART-conceived than NC offspring, for TC (mean % difference: 2.54%; 0.46 to 4.61), HDLc (4.17%; 1.79 to 6.56), and LDLc (4.95%; 0.99 to 8.92), whereas triglycerides were similar (−1.53%; -6.19 to 3.13). No clear differences were seen for glucose (0.25%; -1.38 to 1.88), insulin (−5.04%; -13.20 to 3.12), or HbA1c (−0.07%; -0.14 to 0.00). Trajectory models in up to 17,244 (244 ART) offspring showed that early life trajectory differences were consistent with the above pooled results and showed higher SBP emerging from mid-adolescence to adulthood with ART (e.g., predicted mean difference in SBP at age 26 years for ART versus NC was 5.06mmHg; 1.76 to 8.35).ConclusionsChildren conceived through ART had higher cholesterol and similar blood pressure and hyperglycaemic/insulin resistance measures compared with NC children. Whilst overall this is reassuring, our trajectory analysis in a sub-group of cohorts suggested that those conceived by ART may go on to develop higher blood pressure in early adulthood. Our study shows the importance of follow-up into adulthood and requires validation by independent studies with different study designs including within-sibship and mechanistic studies.
- Published
- 2022
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21. A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women
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Evelyne Muggli, Stephen Hearps, Jane Halliday, Elizabeth J. Elliott, Anthony Penington, Deanne K. Thompson, Alicia Spittle, Della A. Forster, Sharon Lewis, and Peter J. Anderson
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Multidisciplinary ,Alcohol Drinking ,Ethanol ,Pregnancy ,Prenatal Exposure Delayed Effects ,Australia ,Humans ,Female ,Longitudinal Studies ,Pregnant Women ,Uncategorized - Abstract
Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health messages about possible adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy.
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- 2022
- Full Text
- View/download PDF
22. What you need to know about brain abscesses
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Marta de Andres Crespo, Jane Halliday, and Chris McKinnon
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medicine.medical_specialty ,Neurology ,business.industry ,Nausea ,Brain Abscess ,General Medicine ,medicine.disease ,Neurosurgical Procedures ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Vomiting ,Humans ,030212 general & internal medicine ,Neurosurgery ,Radiology ,medicine.symptom ,business ,Abscess ,Brain abscess ,Meningitis ,030217 neurology & neurosurgery - Abstract
A brain abscess is a focal accumulation of pus in the brain parenchyma arising from direct inoculation, contiguous spread from local anatomical structures or haematogenous seeding from a remote source of infection. It can result in significant morbidity and mortality, making early diagnosis and treatment vital. Only one fifth of patients present with the classic triad of headache, fever and focal neurological symptoms. More commonly patients show signs and symptoms of raised intracranial pressure alone, such as confusion or reduced conscious level, headache, nausea and vomiting, which can be a presentation of many intracranial pathologies. Distinguishing an abscess from other pathologies such as meningitis and tumours is crucial, as clinically these can present in similar ways, but their management and outcomes are very different. Diffusion-weighted magnetic resonance imaging brain scans can help localise the lesion and differentiate ring-enhancing lesions caused by a brain abscess from malignant tumours. Cerebral abscesses are considered a neurosurgical emergency; early stabilisation, diagnosis and management in a neurosurgical centre is important in reducing morbidity and mortality.
- Published
- 2020
23. State‐wide utilization and performance of traditional and cell‐free DNA‐based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study
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B. Hutchinson, J Harraway, E Kluckow, Mark D. Pertile, Ricardo Palma-Dias, A Poulton, Debbie Nisbet, Anthea Lindquist, Melody Menezes, R. McCoy, Jane Halliday, Zeffie Poulakis, L. Bonacquisto, A Howden, Nicole Martin, L. Gugasyan, A Kulkarni, Lisa Hui, F. da Silva Costa, and Michael T. Bethune
- Subjects
Adult ,medicine.medical_specialty ,Victoria ,Population ,Aneuploidy ,Chromosome Disorders ,Prenatal diagnosis ,Sensitivity and Specificity ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Pregnancy ,Prenatal Diagnosis ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Genetic Testing ,030212 general & internal medicine ,education ,False Negative Reactions ,Retrospective Studies ,Chromosome Aberrations ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,Retrospective cohort study ,General Medicine ,medicine.disease ,Pregnancy Trimester, First ,Reproductive Medicine ,Cell-free fetal DNA ,Products of conception ,Cytogenetic Analysis ,Chromosome abnormality ,Female ,Medical Record Linkage ,business ,Cell-Free Nucleic Acids ,Record linkage - Abstract
OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and
- Published
- 2020
24. Exome sequencing in newborns with congenital deafness as a model for genomic newborn screening: the Baby Beyond Hearing project
- Author
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Elly Lynch, Jane Halliday, Sharon Lewis, Anna Jarmolowicz, Clara Gaff, Melissa Martyn, Lilian Downie, David J. Amor, and Sebastian Lunke
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Population ,Decisional conflict ,Deafness ,030105 genetics & heredity ,03 medical and health sciences ,Neonatal Screening ,Hearing ,medicine ,Humans ,Exome ,Genetic Testing ,Child ,education ,Genetics (clinical) ,Exome sequencing ,Genetic testing ,education.field_of_study ,Newborn screening ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Infant ,Genomics ,030104 developmental biology ,Family medicine ,Cohort ,Medical genetics ,business - Abstract
Genomic newborn screening raises practical and ethical issues. Evidence is required to build a framework to introduce this technology safely and effectively. We investigated the choices made by a diverse group of parents with newborns when offered tiered genomic information from exome sequencing. This population-derived cohort comprised infants with congenital deafness. Parents were offered exome sequencing and choice regarding the scope of analysis. Options were choice A, diagnostic analysis only; choice B, diagnostic analysis plus childhood-onset diseases with medical actionability; or choice C, diagnostic analysis plus childhood-onset diseases with or without medical actionability. Of the 106 participants, 72 (68%) consented to receive additional findings with 29 (27.4%) selecting choice B and 43 (40.6%) opting for choice C. Family size, ethnicity, and age of infant at time of recruitment were the significant predictors of choice. Parents who opted to have additional findings analysis demonstrated less anxiety and decisional conflict. These data provide evidence from a culturally diverse population that choice around additional findings is important and the age of the infant when this choice is offered impacts on their decision. We found no evidence that offering different levels of genomic information to parents of newborns has a negative psychological impact.
- Published
- 2020
25. Maternity health care professionals' views and experiences of fetal genomic uncertainty: A review
- Author
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Celine Lewis, Jane Halliday, Lisa Hui, and Emma Jane Szepe
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Attitude of Health Personnel ,Genetic counseling ,education ,Prenatal diagnosis ,030105 genetics & heredity ,Midwifery ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Physicians ,Prenatal Diagnosis ,Health care ,medicine ,Humans ,Uncertain significance ,Genetics (clinical) ,030219 obstetrics & reproductive medicine ,Whole Genome Sequencing ,business.industry ,Uncertainty ,High-Throughput Nucleotide Sequencing ,Physicians, Family ,Obstetrics and Gynecology ,Genomics ,Microarray Analysis ,medicine.disease ,Obstetrics ,Family medicine ,Medical genetics ,Female ,business ,Psychosocial ,Postpartum period - Abstract
The field of prenatal screening and diagnosis for fetal anomalies has been marked by a rapid succession of technological advances, including most notably, chromosomal microarray analysis and next generation sequencing. Despite the diagnostic advantages of these technologies, their incorporation into prenatal testing has created additional challenges of revealing genomic variants of unknown or uncertain significance, and secondary findings. While detailed post-test counselling about uncertain variants is best performed by medical geneticists, many of the screening and diagnostic tests that lead to this information are actually ordered by general maternity health care professionals (HCPs), such as obstetricians, midwives and family physicians. Maternity HCPs support pregnant women through to the conclusion of their pregnancy and the postpartum period, and thus are close observers of the psychosocial impart of fetal genomic uncertainty on women and their families. Whilst there have been many studies exploring the handling of genomic uncertainty by genetics HCPs there has been relatively less attention paid to maternity HCPs without speciality training in genetics. This review explores the current literature surrounding non-genetic maternity HCPs' views and experiences of genomic uncertainty and returning uncertain results in the prenatal setting. This article is protected by copyright. All rights reserved.
- Published
- 2020
26. State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions
- Author
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Lulu Loughry, Cecilia Pynaker, Mary White, Jane Halliday, and Lisa Hui
- Subjects
Obstetrics and Gynecology ,Genetics (clinical) - Abstract
To analyze population-based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non-invasive prenatal testing (NIPT).Retrospective state-wide data for all prenatal diagnoses performed25 weeks gestation from 2005 to 2020 in Victoria, Australia. Non-invasive prenatal testing became locally available from 2012. The prenatal diagnosis rates of SCA as proportions of all prenatal diagnostic tests and all births were calculated. Statistical significance was assessed with the χ46,518 amniocentesis and chorionic villus sampling were performed during the study period, detecting 617 SCAs. There was a significant increase in the rate of prenatal SCAs from 5.8 per 10,000 births in 2005 to 8.7 per 10,000 births in 2020 (p 0.0001). This increase was predominantly due to 47,XXY cases, 91% of which were ascertained via positive NIPT for this condition in 2020. The prenatal diagnosis rate of 47,XXY significantly increased from 0.8 per 10,000 births in 2005 to 4.3 per 10,000 births in 2020 (p 0.0001).Screening for SCAs using NIPT has directly led to an increase in their prenatal diagnosis on a population-wide basis, especially 47,XXY. This has implications for clinician education, genetic counselling, and pediatric services.
- Published
- 2021
27. Sex- and tissue-specific effects of binge-level prenatal alcohol consumption on DNA methylation at birth
- Author
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Joanne Ryan, Evelyne Muggli, Jane Halliday, Jeffrey M. Craig, Sharon Lewis, Yuk Jing Loke, Richard Saffery, and Elizabeth J Elliott
- Subjects
Male ,Cancer Research ,animal structures ,Alcohol Drinking ,Offspring ,Placenta ,Physiology ,Biology ,Pregnancy ,Genetics ,medicine ,Tissue specific ,Humans ,Epigenetics ,Ethanol ,Infant, Newborn ,DNA Methylation ,Differentially methylated regions ,medicine.anatomical_structure ,Fetal Alcohol Spectrum Disorders ,Prenatal alcohol exposure ,Prenatal Exposure Delayed Effects ,DNA methylation ,Female ,Prenatal alcohol - Abstract
Background: Binge-level prenatal alcohol exposure (PAE) causes developmental abnormalities, which may be mediated in part by epigenetic mechanisms. Despite this, few studies have characterised the association of binge PAE with DNA methylation in offspring. Methods: We investigated the association between binge PAE and genome-wide DNA methylation profiles in a sex-specific manner in neonatal buccal and placental samples. Results: We identified no differentially methylated CpGs or differentially methylated regions (DMRs) at false discovery rate
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- 2021
28. Study protocol: childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort study
- Author
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Cecilia Pynaker, Jane Halliday, Joanne Kennedy, Sharon Lewis, Susan P. Walker, Lisa Hui, and David J. Amor
- Subjects
Pediatrics ,medicine.medical_specialty ,Population ,Prenatal diagnosis ,RJ1-570 ,Cohort Studies ,Study Protocol ,Genomic copy number variant ,Pregnancy ,Humans ,Medicine ,Variants of uncertain significance ,Toddler ,Child ,education ,Genetic testing ,education.field_of_study ,Childhood outcomes ,Wechsler Preschool and Primary Scale of Intelligence ,medicine.diagnostic_test ,business.industry ,Australia ,Infant ,Genomics ,Microarray Analysis ,Vineland Adaptive Behavior Scale ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,Postnatal outcomes ,business ,Chromosomal microarray analysis ,Cohort study - Abstract
Abstract Background The implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. Methods This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. Discussion This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. Trial registration ACTRN12620000446965p; Registered on April 6, 2020.
- Published
- 2021
29. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health
- Author
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Nora Fernandez-Jimenez, Ruby Fore, Ariadna Cilleros-Portet, Johanna Lepeule, Patrice Perron, Tuomas Kvist, Fu-Ying Tian, Corina Lesseur, Alexandra M. Binder, Manuel Lozano, Jordi Martorell-Marugán, Yuk J. Loke, Kelly M. Bakulski, Yihui Zhu, Anne Forhan, Sara Sammallahti, Todd M. Everson, Jia Chen, Karin B. Michels, Thalia Belmonte, Pedro Carmona-Sáez, Jane Halliday, M. Daniele Fallin, Janine M. LaSalle, Jorg Tost, Darina Czamara, Mariana F. Fernández, Antonio Gómez-Martín, Jeffrey M. Craig, Beatriz Gonzalez-Alzaga, Rebecca J. Schmidt, John F. Dou, Evelyne Muggli, Marina Lacasaña, Martine Vrijheid, Carmen J. Marsit, Margaret R. Karagas, Katri Räikkönen, Luigi Bouchard, Barbara Heude, Loreto Santa-Marina, Mariona Bustamante, Marie-France Hivert, Jose Ramon Bilbao, Child and Adolescent Psychiatry / Psychology, Department of Psychology and Logopedics, and Developmental Psychology Research Group
- Subjects
Risk ,Epigenomics ,515 Psychology ,Placenta ,Medicine (miscellaneous) ,Birth-weight ,Mothers ,Cohort profile ,Reproductive health and childbirth ,Associations ,General Biochemistry, Genetics and Molecular Biology ,Exposure ,Body Mass Index ,SDG 3 - Good Health and Well-being ,Pregnancy ,Genetics research ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Obesity ,Variant ,Gain ,Aetiology ,Child ,Newborns ,Nutrition ,Pediatric ,Human Genome ,Infant, Newborn ,Child Health ,Infant ,Perinatal Period - Conditions Originating in Perinatal Period ,DNA Methylation ,Newborn ,Good Health and Well Being ,Female ,General Agricultural and Biological Sciences - Abstract
Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenomewide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings., French Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences de l'Univers (INSU), Swiss National Science Foundation (SNSF), European Commission, Ministry of Science and Innovation, Spain (MICINN), Spanish Government FJC2018-036729, European Development Fund, European Social Fund (ESF)
- Published
- 2021
30. Trajectories of Prenatal Alcohol Consumption in An Australian Population-Based Cohort of Pregnant Women - A Data Driven Approach
- Author
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Anthony J. Penington, Evelyne Muggli, Sharon Lewis, Deanne K. Thompson, Stephen Hearps, Alicia J. Spittle, Peter J. Anderson, Jane Halliday, Della Forster, and Elizabeth J Elliott
- Subjects
Consumption (economics) ,Australian population ,business.industry ,Environmental health ,Cohort ,Medicine ,business ,Prenatal alcohol - Abstract
Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health interventions to prevent adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 grams (low discontinued) to 184 grams of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of fetal risk. Improved understanding of factors that contribute to alcohol consumption in pregnancy in specific sub-populations is critical when developing prevention strategies. Maternal characteristics associated with different trajectories can inform the strategic development of such initiatives.
- Published
- 2021
31. Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth
- Author
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Mariana F. Fernández, Evelyne Muggli, Marie-France Hivert, Jane Halliday, Patrice Perron, Beatriz González-Alzaga, M.-A. Charles, Todd M. Everson, Mariona Bustamante, Emily R Baker, J Sunyer, Johanna Lepeule, Barbara Heude, Jia Chen, Emie Seyve, Luigi Bouchard, Antonio Gómez-Martín, Marina Lacasaña, Jordi Martorell-Marugán, Andres Cardenas, Carmen Iñiguez, Nora Fernandez-Jimenez, Yuk Jing Loke, Corina Lesseur, Margaret R. Karagas, Carmen J. Marsit, Thalia Belmonte, Ke Hao, Pedro Carmona-Sáez, Stephanie J. London, Jeffrey M. Craig, Maya A. Deyssenroth, Marta Vives-Usano, and Jörg Tost
- Subjects
Epigenomics ,Maternal smoking ,Placenta ,General Physics and Astronomy ,Reproductive health and childbirth ,Bioinformatics ,Low Birth Weight and Health of the Newborn ,Epigenesis, Genetic ,Fetal Development ,Pregnancy ,Infant Mortality ,Fetal growth ,2.1 Biological and endogenous factors ,Aetiology ,Pediatric ,Multidisciplinary ,Smoking ,Cord blood ,DNA methylation ,Epigenetics ,Female ,medicine.symptom ,Science ,1.1 Normal biological development and functioning ,Inflammation ,Fetus -- Trastorns del creixement ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Genetic Heterogeneity ,Genetic ,Preterm ,Underpinning research ,Tobacco ,medicine ,Genetics ,Humans ,Conditions Affecting the Embryonic and Fetal Periods ,Nucleotide Motifs ,Hormone activity ,dNaM ,General Chemistry ,Epigenome ,DNA Methylation ,Perinatal Period - Conditions Originating in Perinatal Period ,medicine.disease ,Embarassades -- Consum de tabac ,Good Health and Well Being ,Risk factors ,Epigenesis - Abstract
We would like to thank all the families that participated in these studies for their generous contribution. Detailed acknowledgements and funding can be found in Sup plementary Material., Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-021-24558-y, Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth. Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth., Canadian Institutes of Health Research (CIHR) MOP 115071, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Environmental Health Sciences (NIEHS) P30 ES019776 - R01 ES022223 - P01 ES022832, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of General Medical Sciences (NIGMS) P20 GM104416, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R01 MH094609
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- 2021
32. Reproductive and Metabolic Health of Young Men Conceived Using ICSI
- Author
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Sarah CATFORD, Jane HALLIDAY, Sharon LEWIS, Moira O’BRYAN, David HANDELSMAN, Roger HART, John MCBAIN, Luk ROMBAUTS, David AMOR, Richard SAFFERY, and Robert MCLACHLAN
- Abstract
Background: Use of ICSI has escalated globally. Concerns include: 1) heritability of infertility, 2) effects of poor-quality spermatozoa on offspring health, 3) epigenetic effects of ICSI procedure. Aim: Compare reproductive and metabolic health of ICSI-conceived men to IVF-conceived and spontaneously conceived (SC) controls. Method: This study is part of a larger project investigating the health and development, reproductive and metabolic health, and epigenetic profiles of ICSI-conceived men (aged 18-25 years). Age-matched IVF-conceived controls were sourced from the Clinical review of the Health of 22–35-year-olds conceived with and without ART (CHART) study; SC controls were derived from the Western Australian Pregnancy Cohort (Raine) study. In subgroup analyses, ICSI-conceived men of fathers with spermatogenic failure (STF-ICSI) were compared with ICSI-conceived men whose fathers had an obstructive cause of infertility, and IVF- and SC controls. Semen parameters and serum reproductive hormones were compared between 120 ICSI-conceived men and 356 SC controls. Resting systolic and diastolic blood pressure (BP), height, weight, BMI, body surface area, and serum metabolic markers were compared between 121 ICSI-conceived men, and 74 IVF-conceived and 688 SC controls. Results: We found no compelling evidence of poorer reproductive health in ICSI-conceived men compared to age-matched SC controls, including a subgroup of STF-ICSI-conceived men. There was no correlation in any of the semen parameters between ICSI fathers and sons, including STF-ICSI father-son pairs. ICSI-conceived men compared with SC controls had higher resting diastolic BP and higher homeostasis model assessment for insulin resistance (HOMA-IR), but a similar proportion had insulin resistance. Metabolic parameters of ICSI-conceived men and IVF-conceived controls were comparable. Conclusion: This study is the largest to date and indicates comparable reproductive health of ICSI-conceived men, including men whose fathers had STF, to a similarly aged population-representative cohort of SC men. It shows few metabolic differences between ICSI-conceived men, and IVF-conceived and SC controls.
- Published
- 2022
33. Reproductive Health of Adults Conceived by IVF and GIFT
- Author
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Sharon LEWIS, Joanne KENNEDY, Anne GLYNN, Karin HAMMARBERG, David AMOR, Martha HICKEY, John MCBAIN, Sarah BIGGS, and Jane HALLIDAY
- Abstract
Background: We have an established cohort of singleton adults conceived by IVF and GIFT born from January 1982 to December 1992, and matched controls conceived without assisted reproduction (non-ART). They have participated in two previous studies: 1) a telephone interview study when aged 21 years on average and 2) a clinical review 6 years later. As these adults are reaching the average age of first-time parents, it is important to determine their reproductive health. Aim: To examine the reproductive health of IVF/GIFT-conceived adults compared to non-ART controls. Method: Contact details were confirmed via email or the Australian Electoral Roll. Participants were asked to complete a 15-minute online questionnaire hosted in REDCap with questions about fertility and reproductive health, well-being, self-reported health status, demographics and important potential outcome modifiers. Data were analysed using chi-squared and [Formula: see text]-tests. Results: 231 IVF (60%), 74 GIFT (65%) and 153 non-ART (41%) control participants completed the questionnaire. As there were no outcome differences between IVF and GIFT, their results are combined. The overall median age of the IVF/GIFT group and controls was 31.3 years, and 63% were female in both groups. In both groups just over a third had already given birth, with 15% and 18% respectively reporting having had medical advice for fertility concerns. Endometriosis was the only condition more common in IVF/GIFT-conceived females compared to female controls (16% versus 8%, p=0.07). There were no differences between IVF/GIFT and non-ART conceived women on other female reproductive conditions such as PCOS (18% and 16% respectively) and painful periods (26% and 30% respectively). All male conditions such as undescended testes, sperm parameters or erectile disorders were rare in both groups. Conclusion: As IVF/GIFT-conceived individuals reach the average childbearing age of 31 years, they appear to have no substantial adverse outcomes related to their reproductive health or fertility.
- Published
- 2022
34. Opportunities and Challenges Arising from the Australian Male Infertility Exposure (AMIE) Study
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Sarah BIGGS, Sharon LEWIS, Joanne KENNEDY, Georgina CHAMBERS, Robert MCLACHLAN, Moira O’BRYAN, Simon von SALDERN, Roger HART, Shadi KHASHABA, William LEDGER, Christopher NICOL, Luk ROMBAUTS, Kate STERN, Anusch YAZDANI, and Jane HALLIDAY
- Abstract
Background: A four-stream research program, Men and Infertility over the Lifecourse, is funded by the MRFF to address the medical, personal and social cost of idiopathic male infertility. This program includes a national case control study: AMIE. Designing and implementing AMIE poses both opportunities and challenges.
- Published
- 2022
35. INTRATUMORAL T‐CELLS HAVE A DIFFERENTIAL IMPACT ON FDG‐PET PARAMETERS IN FOLLICULAR LYMPHOMA
- Author
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Sarah-Jane Halliday, Maher K. Gandhi, Karthik Nath, Mohamed Shanavas, Annette Hernandez, Dipti Talaulikar, Sanjiv Jain, L. M. de Long, Colm Keane, Joshua W.D. Tobin, Robert Bird, Judith Trotman, Hennes Tsang, Soi-C. Law, Jay Gunawardana, Muhammed B. Sabdia, Donna Cross, and Phillip Law
- Subjects
Cancer Research ,PET-CT ,Pathology ,medicine.medical_specialty ,business.industry ,Follicular lymphoma ,Hematology ,General Medicine ,medicine.disease ,Oncology ,Indolent Non-Hodgkin Lymphoma ,medicine ,business ,Differential impact - Published
- 2021
36. A new technique of endoscopic decompression of suprasellar craniopharyngioma cyst
- Author
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Jane Halliday and Simon Cudlip
- Subjects
Male ,medicine.medical_specialty ,Decompression ,Ventricular system ,030218 nuclear medicine & medical imaging ,Craniopharyngioma ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Pituitary Neoplasms ,Cyst ,Central Nervous System Cysts ,Third Ventricle ,Third ventricle ,medicine.diagnostic_test ,business.industry ,Aseptic meningitis ,Endoscopy ,Interventional radiology ,Decompression, Surgical ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Female ,Neurology (clinical) ,Neurosurgery ,business ,030217 neurology & neurosurgery - Abstract
Craniopharyngiomas represent a unique management challenge. Aggressive surgical management has traditionally been associated with high rates of morbidity. Modern surgical techniques, and increasing practice of subtotal resection followed by radiosurgery, have reduced morbidity and mortality rates. One cause of postoperative morbidity, and indeed mortality, is aseptic meningitis from spill-out of craniopharyngioma cyst contents. We have developed a surgical technique for the management of large craniopharygngioma cysts extending into the third ventricle, to reduce this risk. We describe a technique of using an epidural catheter, inserted into the working channel of a neuroendoscope, to decompress the cystic portion of a craniopharyngioma cyst before opening the cyst wall widely, preventing spill-out of large volumes of cyst content into the ventricular system. We have had no cases of aseptic meningitis, nor any complications, from use of the described technique. We believe that this is a safe and effective technique of decompression and fenestration of large suprasellar craniopharyngioma cysts that reduces rates of aseptic meningitis and the associated morbidity and mortality from this.
- Published
- 2019
37. Health of adults aged 22 to 35 years conceived by assisted reproductive technology
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Jane Halliday, Michael Cheung, Liam Welsh, Richard Saffery, Markus Juonala, Sharon Lewis, Joanne Kennedy, David J. Amor, Stephen Hearps, John McBain, David Burgner, Robert I McLachlan, Karin Hammarberg, Lex W. Doyle, and Sarath Ranganathan
- Subjects
Adult ,Male ,0301 basic medicine ,Spirometry ,Pediatrics ,medicine.medical_specialty ,Reproductive Techniques, Assisted ,Victoria ,Health Status ,Respiratory Tract Diseases ,Risk Assessment ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Humans ,Medicine ,Respiratory function ,Young adult ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Age Factors ,Obstetrics and Gynecology ,Odds ratio ,Anthropometry ,Treatment Outcome ,030104 developmental biology ,Blood pressure ,Reproductive Medicine ,Cardiovascular Diseases ,Cohort ,Female ,business ,Cohort study - Abstract
Objective To determine the health outcomes for adults aged 22–35 years old who were conceived via assisted reproduction technology (ART) compared with adults of the same age conceived without use of ART. Design Cohort study. Setting Not applicable. Patient(s) Adult men and women aged 22–35 years who were conceived with and without use of ART. Intervention(s) Questionnaire and clinical review. Main Outcome Measure(s) Vascular structure (carotid artery intima-media thickness, pulse wave velocity), vascular function (blood pressure), metabolic markers (fasting blood glucose, insulin, and standard lipid profiles), anthropometric measurements, and respiratory function (spirometry). Result(s) The mean age of the 193 ART and 86 non-ART participants was 27.0 and 26.9 years, respectively. There were no substantial intragroup differences in demographics or vascular intermediate phenotypes, metabolic parameters, or anthropometric measures, before or after adjusting for perinatal factors and a quality of life measure with four domains. Diastolic blood pressure was lower in the ART men than the non-ART men (adjusted mean difference −4.4 mm Hg, 95% CI, −8.7 to −0.1). The ART group reported a higher prevalence of ever having asthma, (40.8% vs. 28.6%; odds ratio 1.7; 95% CI, 1.0–3.0), but expiratory flow rates were similar. Conclusion(s) This study of the health of 193 adults conceived via ART, the largest to date globally, found no evidence of increased vascular or cardiometabolic risk, or growth or respiratory problems in the ART group compared with a non-ART group from the same source population. Follow-up observation for reproductive and later-onset adverse health effects remains important.
- Published
- 2019
38. Population‐based trends in invasive prenatal diagnosis for ultrasound‐based indications: two decades of change from 1994 to 2016
- Author
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A Poulton, Emily Lostchuck, Jane Halliday, and Lisa Hui
- Subjects
Adult ,medicine.medical_specialty ,DNA Copy Number Variations ,Victoria ,Aneuploidy ,Chorionic villus sampling ,Prenatal diagnosis ,Ultrasonography, Prenatal ,Pregnancy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Advanced maternal age ,Retrospective Studies ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,medicine.disease ,Chorionic Villi Sampling ,Reproductive Medicine ,Cell-free fetal DNA ,Population Surveillance ,Amniocentesis ,Female ,Down Syndrome ,Trisomy ,business ,Cell-Free Nucleic Acids ,Maternal Age - Abstract
To assess trends in ultrasound-indicated prenatal diagnostic testing performed over the past two decades in the Australian state of Victoria, in the context of rapidly changing practices in aneuploidy screening and chromosome analysis.This was a retrospective analysis of all ultrasound-indicated prenatal diagnostic testing (amniocentesis and chorionic villus sampling) performed in the state of Victoria between 1994 and 2016. Ultrasound indications for testing included: fetal structural abnormality, fetal death, fetal growth restriction, abnormal amniotic fluid volume, genetic 'soft marker' and unspecified ultrasound abnormality. Maternal age, indication for testing, type of diagnostic procedure, gestational age, type of chromosome analysis (G-banded karyotyping or chromosomal microarray (CMA)) and test results were obtained. Diagnostic yield (i.e. percentage of tests yielding a major abnormality) was analyzed by year, maternal age and gestational age. Statistical analysis was performed using the χDuring the 23-year study period, 1 533 317 births were recorded and 16 152 diagnostic procedures were performed for the primary indication of ultrasound abnormality. In recent years, ultrasound abnormality became the most common indication for prenatal invasive testing (29.4% of diagnostic tests between 2013 and 2016) due to a steep decline in testing for other indications such as positive result on combined first-trimester screening or advanced maternal age alone. In 2016, over 95% of ultrasound-indicated procedures were performed with CMA; among these, pathogenic copy number variant (CNV) was the most common (3.5%) abnormality detected, followed by trisomy 21 (2.8%). The diagnostic yield of ultrasound-indicated tests performed 16 weeks was significantly higher than that of tests performed after 20 weeks (31.5% vs 9.0%).Ultrasound-indicated invasive testing is contributing to prenatal diagnosis in new ways in the genomic era. A pathogenic CNV is now the most likely diagnosis after ultrasound-indicated testing, rather than trisomy 21 or other whole-chromosome aneuploidy. Despite steady improvements in first-trimester screening for aneuploidy, the diagnostic yield of ultrasound-indicated tests 20 weeks has remained stable due to increased utilization of CMA. Procedures performed for structural abnormalities 16 weeks continue to have the highest diagnostic yield, supporting the benefits of early fetal structural assessment at 11-13 weeks. Copyright © 2018 ISUOG. Published by John WileySons Ltd.
- Published
- 2019
39. Pooling and patient satisfaction in non-instrumented lumbar decompressive surgery
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Jane Halliday and Daniel Holsgrove
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Adult ,Male ,musculoskeletal diseases ,Waiting time ,medicine.medical_specialty ,Databases, Factual ,Waiting Lists ,genetic structures ,Decompression ,Pooling ,Neurosurgical Procedures ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Lumbar ,Decompressive surgery ,medicine ,Humans ,Registries ,Elective surgery ,Aged ,Retrospective Studies ,Lumbar Vertebrae ,business.industry ,General Medicine ,Middle Aged ,Decompression, Surgical ,Surgery ,Elective Surgical Procedures ,Patient Satisfaction ,030220 oncology & carcinogenesis ,Female ,Neurology (clinical) ,business ,Procedures and Techniques Utilization ,030217 neurology & neurosurgery - Abstract
To determine the effect of pooling of patients for elective non-instrumented lumbar decompression on patient satisfaction and waiting times.We performed a retrospective review of Spine Tango and Theatre Databases of our Neurosurgical unit for patients who underwent elective primary non-instrumented lumbar decompression between January 2012 and 2016. Patient satisfaction scores at 3 and 12 months post-surgery were collected from the Spine Tango Registry, and patients categorised as pooled/non-pooled by searching theatre databases to determine their named listing and operating consultants. Results were analysed numerically and by performing chi-squared testing to determine if pooling affected patient satisfaction. Theatre records were analysed between January 2004-2006, January 2009-2011 and 2014-2016 to determine what effect implementation of the 18-week wait target system (2009) and of our pooled system (2012) had on waiting times to operation for patients undergoing elective primary non-instrumented lumbar decompression.There is no significant difference in patient satisfaction levels between pooled and non-pooled patients at 3 (p = .052) and 12 months (p = .5) post primary elective lumbar decompression (significance p .05). There was no difference in average waiting time between the pooled and non-pooled groups. Both setting of 18-week targets and pooling improved waiting times. Setting of 18-week targets affected average waiting times markedly while pooling most notably reduced the variability in waiting times between patients for the same procedure.Pooling of patients for elective non-instrumented lumbar decompression in our unit has improved waiting times, particularly the variability in them, with no detriment to patient satisfaction. We would recommend other units to consider developing a system of pooling such as ours, to help maximise use of their current resources and avoid highly variable waiting times for patients for the same procedure within the same department.
- Published
- 2018
40. Neurovascular neurosurgery
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Amr Mohamed, Jane Halliday, and Umang J. Patel
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Surgery - Published
- 2018
41. Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing
- Author
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A Poulton, Lisa Hui, Allanah Howard-Bath, and Jane Halliday
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Victoria ,Sex Chromosome Disorders of Sex Development ,Population ,Turner Syndrome ,Aneuploidy ,Chorionic villus sampling ,Trisomy ,Prenatal diagnosis ,030105 genetics & heredity ,Ultrasonography, Prenatal ,03 medical and health sciences ,Klinefelter Syndrome ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,XYY Karyotype ,medicine ,Humans ,Advanced maternal age ,education ,Sex Chromosome Aberrations ,Genetics (clinical) ,Retrospective Studies ,Chromosomes, Human, X ,education.field_of_study ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Mosaicism ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Chorionic Villi Sampling ,Cell-free fetal DNA ,Amniocentesis ,Female ,business - Abstract
OBJECTIVE: To assess the impact of non-invasive prenatal testing (NIPT) on trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) in a population with >73,000 annual births. METHOD: Retrospective population-based cohort study from 1986-2016 of all women undergoing prenatal diagnosis before 25 weeks gestation in the Australian state of Victoria. Statistical significance was tested using the chi-square test for trend or proportions. RESULTS: There were 2,043,345 births and 842 SCA diagnoses from 1986-2016. The percentage of prenatal diagnostic tests leading to a SCA diagnosis increased significantly from 0.95% in 2010 to 2.93% in 2016 (p
- Published
- 2018
42. Safety of Transsphenoidal Pituitary Surgery during the COVID-19 Pandemic and Comparison to the Prepandemic Era
- Author
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Meriem Amarouche, Anouk Borg, Jane Halliday, and SImon A. Cudlip
- Subjects
03 medical and health sciences ,0302 clinical medicine ,030217 neurology & neurosurgery - Published
- 2021
43. The Annual Report on Prenatal Diagnostic Testing in Victoria, 2019
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Pynaker, Cecilia, Loughry, Lulu, LISA HUI, and JANE HALLIDAY
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Health Sciences ,human activities - Abstract
This annual report from the Victorian Prenatal Diagnosis Database (VPDD) summarises the results of fetal chromosome testing in Victoria during 2019. Victoria has approximately 76,111 confinements annually, and a median maternal age of 32 years (Australian Bureau of Statistics; https://www.abs.gov.au/).The VPDD has been collecting state-wide data on prenatal diagnostic procedures since 1976. We acknowledge our long-standing collaborators - the Victorian Clinical Genetics Service (VCGS) and Monash Medical Centre (current contributors), Melbourne Pathology and Australian Clinical Labs (former contributors).
- Published
- 2021
- Full Text
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44. Effects of Assisted Reproductive Technology on Offspring Growth and Adiposity from Infancy to Early Adulthood: Coordinated Analysis of 26 Multinational Cohort Studies
- Author
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Ahmed Elhakeem, Amy E. Taylor, Hazel M. Inskip, Jonathan Huang, Muriel Tafflet, Johan L. Vinther, Federica Asta, Jan S. Erkamp, Luigi Gagliardi, Kathrin Guerlich, Jane Halliday, Margreet W. Harskamp-van Ginkel, Jian-Rong He, Vincent W.V. Jaddoe, Sharon Lewis, Gillian M. Maher, Yannis Manios, Toby Mansell, Fergus McCarthy, Sheila W. McDonald, Emanula Medda, Lorenza Nisticò, Angela Pinot de Moira, Maja Popovic, Irwin K.M. Reiss, Carina Rodrigues, Theodosia Salika, Ash Smith, Maria A. Stazi, Caroline Walker, Muci Wu, Bjørn Olav Åsvold, Henrique Barros, Sonia Brescianini, David Burgner, Jerry K.Y. Chan, Marie-Aline Charles, Johan G. Eriksson, Romy Gaillard, Veit Grote, Siri E. Håberg, Barbara Heude, Berthold Koletzko, Susan Morton, George Moschonis, Deirdre Murray, Desmond O'Mahony, Daniela Porta, Xiu Qiu, Lorenzo Richiardi, Franca Rusconi, Richard Saffery, Suzanne C. Tough, Tanja G.M. Vrijkotte, Scott M. Nelson, Anne-Marie Nybo Andersen, Maria C. Magnus, and Deborah A. Lawlor
- Published
- 2021
45. Exome Sequencing for Isolated Congenital Hearing Loss: A Cost‐Effectiveness Analysis
- Author
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Ilias Goranitis, Lilian Downie, Melissa Martyn, David J. Amor, Jane Halliday, and Sharon Lewis
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Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Hearing loss ,Cost effectiveness ,Cost-Benefit Analysis ,Hearing Loss, Sensorineural ,Comparative effectiveness research ,Genomics ,030105 genetics & heredity ,Congenital hearing loss ,03 medical and health sciences ,Exome Sequencing ,medicine ,Humans ,Genetic Testing ,Exome sequencing ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Australia ,Infant ,Standard of Care ,Health Care Costs ,Cost-effectiveness analysis ,030104 developmental biology ,Otorhinolaryngology ,Female ,medicine.symptom ,business - Abstract
OBJECTIVES/HYPOTHESIS: To assess the relative cost-effectiveness of exome sequencing for isolated congenital deafness compared with standard care. STUDY DESIGN: Incremental cost-effectiveness and cost-benefit analyses were undertaken from the perspective of the Australian healthcare system using an 18-year time horizon. METHODS: A decision tree was used to model the costs and outcomes associated with exome sequencing and standard care for infants presenting with isolated congenital deafness. RESULTS: Exome sequencing resulted in an incremental cost of AU$1,000 per child and an additional 30 diagnoses per 100 children tested. The incremental cost-effectiveness ratio was AU$3,333 per additional diagnosis. The mean societal willingness to pay for exome sequencing was estimated at AU$4,600 per child tested relative to standard care, resulting in a positive net benefit of AU$3,600. Deterministic and probabilistic sensitivity analyses confirmed the cost-effectiveness of exome sequencing. CONCLUSIONS: Our findings demonstrate the cost-effectiveness of exome sequencing in congenital hearing loss, through increased diagnostic rate and consequent improved process of care by reducing or ceasing diagnostic investigation or facilitating targeted further investigation. We recommend equitable funding for exome sequencing in infants presenting with isolated congenital hearing loss. LEVEL OF EVIDENCE: N/A. Laryngoscope, 131:E2371-E2377, 2021.
- Published
- 2020
46. Safety of Endoscopic Transsphenoidal Pituitary Surgery during the COVID-19 Pandemic and Comparison to the Pre-Pandemic Era
- Author
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Orlando J. Warner, Simon Cudlip, Jane Halliday, Anouk Borg, Meriem Amarouche, Samin Rashid, and John Eraifej
- Subjects
Transsphenoidal surgery ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Endoscope ,business.industry ,medicine.medical_treatment ,General surgery ,Pituitary tumors ,medicine.disease ,Antigen test ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Pandemic ,Medicine ,030212 general & internal medicine ,Neurology (clinical) ,business ,Pituitary surgery ,030217 neurology & neurosurgery - Abstract
Objectives: Safe provision of transsphenoidal surgery for pituitary tumors (TSS) has been significantly disrupted by theCOVID-19 pandemic. We assess whether there was any compromise to patient and staff safety from COVID-19 fromundertaking TSS during the COVID-19 pandemic in our institution. Methods: We retrospectively review all the cases performed between the March 1 and September 11, 2020 and comparedour findings to the cases performed between March 1 and September 11, 2019. In doing so, we aim to assess the impact ofthe COVID-19 pandemic on our service. We review individual patient records to identify any COVID-19 relatedcomplications during or after their inpatient stay and evaluate any COVID-19 confirmed cases among staff involved in theseoperations. Results: Twenty-seven patients had TSS since March 2020 versus 39 during the same period in 2019. Of the patientstreated during the COVID-19 pandemic, 10 required urgent TSS for apoplexy or visual compromise, 10 needed expeditedsurgery and seven had elective procedures. Average duration of GA was 43 minutes (vs. 25 minutes in 2019), surgery 78minutes (vs. 79 minutes in 2019). The length of stay postsurgery was 2 days on average ([range: 1-9 days] vs. 3.6 days in2019 [range: 1-27 days]). No COVID-19 related complications were seen, no new infections developed and no staffinvolved contracted COVID-19. Measures taken to minimize risk included patients self-isolating prior to surgery andpreoperative COVID-19 testing with all patients operated on after April 2020 having received a COVID-19 antigen test at 1to 4 days before the date of their surgery. Theater and anesthetic process followed Trust COVID-19 guidance and physicalmeasures to reduce the spread of aerosols generated were used (clear sheet applied over the patient with small openingsfor instruments and endoscope ([ Fig. 1 ]), nasal latex slits ([ Fig. 2 ]), and full PPE (whenever necessary). Conclusion: We did not see any patient or staff COVID-19 complications or have any new COVID-19 cases contracted byundertaking transphenoidal surgery during the COVID-19 pandemic for pituitary tumors (TSS), with appropriate testing andprecautions in place. Anesthetic time did increase for these cases but there again were no compromises to patient safety orrecovery from this.
- Published
- 2020
47. CSF rhinorrhoea after endonasal intervention to the anterior skull base (CRANIAL): proposal for a prospective multicentre observational cohort study
- Author
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Simon Cudlip, Rafid Al-Mahfoudh, Neil Donnelly, Alex Paluzzi, David Choi, Nicholas Thomas, Kismet Hossain-Ibrahim, Peter D. Lacy, Raj Bhalla, Mahmoud Kamel, Sinan Al-Barazi, Iain Robertson, Mohammad Habibullah Khan, Angelos G. Kolias, Patrick Statham, Ramesh Nair, Georgios Solomou, James R. Tysome, Adam Williams, Sam Muquit, Benjamin Stew, Daniel M Fountain, Rishi Sharma, Simon Shaw, Shahzada Ahmed, Jonathan Hempenstall, Richard Mannion, Brendan Hanna, Ivan Cabrilo, Rory J Piper, Graham Dow, Showkat Mirza, Bhavna Ramachandran, Mark Hughes, Pragnesh Bhatt, Andrew J. Martin, Kanna K. Gnanalingham, Andrew F. Alalade, Nick Phillips, Simon Stapleton, P.E. Ross, Claire Nicholson, Jane Halliday, Benjamin E. Schroeder, Parag Sayal, Dimitris Paraskevopoulos, Alice O’Donnell, Eleni Maratos, Mohsen Javadpour, Anuj Bahl, Bhaskar Ram, Anastasios Giamouriadis, Omar N. Pathmanaban, Nigel Mendoza, Hani J. Marcus, Neil Dorward, Thomas Santarius, Jonathan Pollock, Philip Weir, Saurabh Sinha, Catherine Gilkes, Joan Grieve, Vikesh Patel, Georgios Tsermoulas, Alistair Jenkins, David Bennett, Danyal Z Khan, Nijaguna Mathad, Caroline Hayhurst, Alireza Shoakazemi, and Soham Bandyopadhyay
- Subjects
medicine.medical_specialty ,Cerebrospinal Fluid Rhinorrhea ,CSF ,Transsphenoidal approach ,neuroendoscopy ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Pituitary adenoma ,Medicine ,Humans ,Prospective Studies ,CSF leak ,Anterior skull base ,Retrospective Studies ,Skull Base ,Cerebrospinal Fluid Leak ,business.industry ,General Medicine ,medicine.disease ,Surgery ,pituitary surgery ,Cerebrospinal fluid ,030220 oncology & carcinogenesis ,Neurology (clinical) ,skull base tumours ,business ,Pituitary surgery ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. Methods: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. Ethics and dissemination: Formal institutional ethical board review was not required owing to the nature of the study–this was confirmed with the Health Research Authority, UK. Conclusions: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.
- Published
- 2020
48. Association of Assisted Reproductive Technologies with offspring cord blood DNA methylation across cohorts
- Author
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Richard Saffery, Stephanie J. London, Maria C. Magnus, James Jungius, Christian M. Page, Jane Halliday, Hannah R Elliott, Caroline L Relton, Siri E. Håberg, Boris Novakovic, Debbie A Lawlor, Sharon Lewis, and Doretta Caramaschi
- Subjects
Longitudinal study ,CpG site ,Offspring ,Cord blood ,DNA methylation ,Cohort ,Reproductive technology ,Biology ,Cohort study ,Demography - Abstract
Study questionIs DNA methylation at birth associated with having been conceived by assisted reproductive technologies (ART)?Summary answerThis study shows does not provide strong evidence of an association of conception by ART with variation in infant blood cell DNA methylation.What is known alreadyAssisted reproductive technologies (ART) are procedures used to help infertile/subfertile couples conceive. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with ART could reveal new insights into the biological effects of ART and potential adverse offspring outcomes.Study designWe investigated the association of DNA methylation and ART using a case-control study design (N=205 ART cases and N=2439 non-ART controls in discovery cohorts; N=149 ART cases and N=58 non-ART controls in replication cohort).Participants/materials, settings, methodWe assessed the association between ART and DNA methylation at birth in cord blood (205 ART conceptions and 2439 naturally conceived controls) at >450000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N=149 ART conceptions and N=58 controls).Main results and the role of chanceThe ALSPAC and MoBa meta-analysis revealed evidence of association between conception by ART and DNA methylation (false-discovery-rate-corrected p-value < 0.05) at 5 CpG sites which are annotated to 2 genes. Methylation at 3 of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of ART-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling.Limitations, reasons for cautionsWhile insufficient power is likely, heterogeneity in types of ART and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to ART.Wider implications of the findingsART-conceived newborns present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health.
- Published
- 2020
49. Surgical Issues in the Management of Head-Injured Patients
- Author
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Jane Halliday, Peter C. Whitfield, and Puneet Plaha
- Published
- 2020
50. LAG3: a novel immune checkpoint expressed by multiple lymphocyte subsets in diffuse large B-cell lymphoma
- Author
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Sarah Jane Halliday, Ken H. Young, Anthony J. Gill, Mark P. Hertzberg, Clare Gould, Gayathri Thillaiyampalam, William Stevenson, Simone Birch, Muhammed B. Sabdia, Xiaohong Tan, Zijun Y. Xu-Monette, Maher K. Gandhi, Lilia Merida de Long, Emad Uddin Abro, Annette Hernandez, Dipti Talaulikar, Sanjiv Jain, Robert Bird, Colm Keane, Joshua W.D. Tobin, Grace Gifford, Donna Cross, Soi Cheng Law, and Sara Gabreilli
- Subjects
CD20 ,Tumor microenvironment ,LAG3 ,Lymphoid Neoplasia ,biology ,Hematology ,CD8-Positive T-Lymphocytes ,medicine.disease ,Lymphocyte Activation Gene 3 Protein ,Immune checkpoint ,International Prognostic Index ,Lymphocytes, Tumor-Infiltrating ,Antigen ,Antigens, CD ,medicine ,biology.protein ,Cancer research ,Tumor Microenvironment ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Diffuse large B-cell lymphoma ,Hepatitis A Virus Cellular Receptor 2 ,CD8 - Abstract
Blockade of the PD-1 axis has modest efficacy in diffuse large B-cell lymphoma (DLBCL), but data regarding LAG3 are sparse. The impact of LAG3 digital gene expression was tested in 309 patients with DLBCL treated with standard chemoimmunotherapy. Cellular distribution of LAG3 protein was determined by immunohistochemistry and flow cytometry. In tumor-infiltrating lymphocytes (TILs), LAG3 expression was highest on CD4+ regulatory T cells (Tregs) and was also highly expressed on CD8+ T cells compared with CD4+ non-Tregs (both P = .008). LAG3high TILs were enriched in PD-1 and TIM-3. LAG3 was also expressed on a proportion of malignant B cells, and these patients had significantly higher LAG3 messenger RNA in their biopsies (P = .03). LAG3high gene expression was associated with inferior survival in discovery/validation cohorts, independent of cell of origin and the international prognostic index. Patients who were PD-L1high were fivefold more likely to be LAG3high (P < .0001). Patients who were LAG3high/PD-L1high had an inferior progression-free survival (P = .011) and overall survival (P = .005) compared with patients who were LAG3low/PD-L1high. Digital spatial protein analysis confirms LAG3 expression on T cells and, surprisingly, tumor-associated macrophages (TAMs) at higher levels than found on CD20+ B cells in the tumor microenvironment. LAG3 is frequently expressed on CD4+ Tregs and CD8+ TILs, typically with other immune checkpoints, and is also present in a proportion of malignant B cells in DLBCL and in areas enriched for TAMs. LAG3high expression is associated with poor outcome independent of conventional prognosticators.
- Published
- 2020
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