Development and validation of a prognostic model to predict birth weight: individual participant data meta-analysis.

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.

Design: Individual participant data meta-analysis.

Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.

Laboratory performance of genome-wide cfDNA for copy number variants as compared to prenatal microarray.

Background: Noninvasive prenatal testing (NIPT) allows for screening of fetal aneuploidy and copy number variants (CNVs) from cell-free DNA (cfDNA) in maternal plasma. Professional societies have not yet embraced NIPT for fetal CNVs, citing a need for additional performance data. A clinically available genome-wide cfDNA test screens for fetal aneuploidy and CNVs larger than 7 megabases (Mb).

Modified multiple marker aneuploidy screening as a primary screening test for preeclampsia.

Background: Abnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth.

Building the What Comes Next Cohort for and testing: a descriptive analysis.

Background: Our understanding of how testing for and mutations of the and genes affect cancer risk and the use of risk-reduction strategies comes largely from studies of women recruited from specialized genetics clinics. Our aim was to assemble a generalizable cohort of women who underwent testing (the What Comes Next Cohort), irrespective of test result, to enable study of health care utilization and outcomes after testing.

Methods: This descriptive study included adult women (≥ 18 yr) who met at least 1 of 13 provincial criteria for / testing and who underwent genetic testing at sites in Ontario, Canada, from 2007 to 2016.

Prenatal screening for trisomy 21: a comparative performance and cost analysis of different screening strategies.

Background: Prenatal screening for chromosome aneuploidies have constantly been evolving, especially with the introduction of cell-free fetal DNA (cfDNA) screening in the most recent years. This study compares the performance, costs and timing of test results of three cfDNA screening implementation strategies: contingent, reflex and primary.

Methods: We modelled enhanced first trimester screening (eFTS) as the first-tier test in contingent or reflex strategies.

Cognitive markers of dementia risk in middle-aged women with bilateral salpingo-oophorectomy prior to menopause.

Oophorectomy prior to menopause is associated with late-life dementia. Memory decline may start within 6 months after oophorectomy in middle-aged women, suggested by lower verbal and working memory performance. Unknown is whether such changes persist beyond 6 months, and whether they are reversed by estradiol.

Prenatal Biochemical Screening and a Woman's Long-Term Risk of Cancer: A Population-Based Cohort Study.

Background: Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman's subsequent risk of hormone-sensitive cancer.

Methods: This population-based cohort study included women aged 12-55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993-2011, where universal health care is available.

Risk of Severe Maternal Morbidity or Death in Relation to Prenatal Biochemical Screening: Population-Based Cohort Study.

Objective: This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality.

Study Design: This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated.

New insights into DNA methylation signatures: SMARCA2 variants in Nicolaides-Baraitser syndrome.

Background: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures.

Methods: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array.

International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation.

Background: Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017).

Methods: Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries.

Hormone Levels in Pregnancy and Subsequent Risk of Maternal Breast and Ovarian Cancer: A Systematic Review.

Objective: Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers.

Methods: Two reviewers independently conducted a literature search of MEDLINE and EMBASE databases from January 1970 to August 2017.

BAFopathies' DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes.

Real-world health services utilisation and outcomes after and testing in Ontario, Canada: the What Comes Next Cohort Study protocol.

Introduction: Women who have pathogenic mutations in the and genes are at greatly increased risks for breast and ovarian cancers. Although risk-reduction strategies can be undertaken by these women, knowledge regarding the uptake of these strategies is limited. Additionally, the healthcare behaviours of women who receive inconclusive test results are not known.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of -related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine.

Enhanced First Trimester Aneuploidy Screening with Placental Growth Factor and Alpha Feto-Protein: Detection of Trisomies 18 and 13.

Objectives: To assess the performance of first trimester combined screening (FTS) when enhanced with placental growth factor and alpha feto-protein in the detection of trisomies 18 and 13.

Methods: A retrospective case-control study. Marker parameters were derived using frozen serum samples.

Prenatal biochemical screening and long term risk of maternal cardiovascular disease: population based cohort study.

Objective: To examine whether abnormal prenatal biochemical screening results are associated with an increased risk of premature cardiovascular disease after pregnancy.

Design: Population based cohort study.

Setting: The entire province of Ontario, Canada, where healthcare is universally available.

Physical activity during adolescence and young adulthood and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

Background: Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer.

Methods: We conducted a case-control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk.

Genetic assessment wait time indicators in the High Risk Ontario Breast Screening Program.

Background: The Ontario Breast Screening Program (OBSP) expanded in July 2011 to screen high-risk women aged 30-69 with annual MRI and mammography. This study evaluated wait time (WT) indicators along the genetic assessment (GA) pathway for women referred to the High Risk OBSP.

Methods: Information was collected for 27,170 women referred to the High Risk OBSP from July 2011 to June 2015 and followed for GA until June 2016.

Enhanced First Trimester Screening for Trisomy 21 with Contingent Cell-Free Fetal DNA: A Comparative Performance and Cost Analysis.

Objective: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system.

Feasibility of computerized working memory training in individuals with Huntington disease.

Objectives: Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population.

Supporting genetics in primary care: investigating how theory can inform professional education.

Evidence indicates that many barriers exist to the integration of genetic case finding into primary care. We conducted an exploratory study of the determinants of three specific behaviours related to using breast cancer genetics referral guidelines effectively: 'taking a family history', 'making a risk assessment', and 'making a referral decision'. We developed vignettes of primary care consultations with hypothetical patients, representing a wide range of genetic risk for which different referral decisions would be appropriate.

First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor, and α-fetoprotein.

Objective: The aim of this study was to assess the screening performance for Down syndrome using first trimester combined screening (FTS) and two additional markers, serum placental growth factor (PlGF) and α-fetoprotein (AFP).

Methods: This is a retrospective case-control study of 137 pregnancies affected by Down syndrome and 684 individually matched unaffected pregnancies. Stored serum samples were tested for all four markers, and results were expressed as multiples of the gestation-specific median (MoM).

Pilot Testing of a Psycho-educational Telephone Intervention for Women Receiving Uninformative BRCA1/2 Genetic Test Results.

Evidence suggests that women who receive uninformative results for breast and ovarian cancer (BRCA1/2) gene mutations may experience as much distress as women whose results indicate the presence of a gene mutation. No intervention to reduce distress after receipt of uninformative results has yet been tested. The purpose of this study was to test the feasibility and preliminary effects of a psycho-educational telephone (PET) intervention to reduce distress in women who receive uninformative BRCA1/2 results.