Publications by authors named "Glenn E Palomaki"
Article Synopsis
- Genomic reports in molecular diagnostics are often narrative and inconsistent in content and format, despite existing regulatory guidelines.
- A study evaluated 69 reports from 31 laboratories across five disciplines, finding that most met compliance but exhibited variability in how required elements were presented.
- The findings highlight a need for improved consistency in report formatting to enhance communication of genetic test results to healthcare providers and patients.
Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals.
Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy.
Background: Maternal serum alpha-fetoprotein (AFP) levels are used in screening for open neural tube defects (ONTD). Historical reports show that AFP levels and maternal weights are higher in self-reported Black than White individuals, but recent reports question the need to account for these variables in screening. Our study compares screening performance with and without accounting for race.
View Article and Find Full Text PDFObjective: Determine current analytical methods and number of cell-free (cf) DNA prenatal screening tests performed for common trisomies.
Methods: The College of American Pathologists 2022-B Noninvasive Prenatal Testing exercise was distributed in December 2022 to 93 participants in 22 countries. Supplemental questions included the number of tests performed in a recent month and the proportion of samples originating outside the United States (US).
Article Synopsis
- * The study analyzed data from 65,559 participants across 25 cohorts, focusing on risk factors like maternal age, BMI, and antibody positivity while excluding those with pre-existing thyroid issues.
- * Results indicated a screening rate of 58% among high-risk cohorts, with minimal variation in risk for hypothyroidism based on age and BMI, and TPOAb/TgAb positivity significantly correlated with higher risks for overt and subclinical hypothyroidism.
Article Synopsis
- Guidelines recommend using specific thyroid hormone reference intervals during pregnancy, but these are often not available, leading to alternative diagnostic methods.
- A study analyzed data from over 52,000 women and found that these alternative methods had low sensitivity (0.63-0.82) and high false discovery rates (0.11-0.35) compared to trimester-specific reference intervals.
- The results indicate that using alternative approaches for thyroid hormone testing in pregnancy can result in significant misdiagnosis, highlighting the need for better strategies for detecting thyroid dysfunction in pregnant women.
Article Synopsis
- - A study investigated a rolling circle amplification (RCA) method using cell-free DNA for screening trisomies, revealing a problematic 1% false positive rate and variable assay performance, prompting a multi-center review.
- - Data from multiple labs showed significant improvement in the precision of results over time, with the percentage of runs exceeding standard deviation caps for multiple chromosomes decreasing sharply after reformulations in reagents and software updates.
- - The refined method achieved high detection rates (98.4%) and drastically reduced false positive rates (0.3%), making it competitive with other screening techniques while minimizing test failure after re-testing.
Objective: Limited data are available on the performance of SARS-CoV-2 antibody assays and data collected during pregnancy vary widely. The objective of this study was to estimate the seroprevalence of antibodies against SARS-CoV-2 in pregnant individuals in Rhode Island and to evaluate whether the prevalence differed by month of collection, age, county of residence, or economic status as estimated by zip code.
Methods: Pre-pandemic (2019) and early pandemic (2020) serum samples, collected for prenatal screening between 15 and 22 weeks of gestation, were analyzed utilizing two SARS-CoV-2 immunoglobulin G (IgG) automated assays that targeted the viral nucleocapsid (anti-N) or spike (anti-S) receptor binding domain proteins.
Background: Prenatal screening for common trisomies via cell-free (cfDNA) is usually implemented by technologies utilizing massively parallel sequencing, stringent environmental controls, complex bioinformatics, and molecular expertise. An alternative and less complex methodology utilizes rolling circle amplification (RCA). Further evaluation of its performance and related requirements are warranted.
View Article and Find Full Text PDFContext: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology.
Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts.
Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021.
The Association for Molecular Pathology Variant Interpretation Testing Among Laboratories (VITAL) Working Group convened to evaluate the Standards and Guidelines for the Interpretation of Sequence Variants implementation into clinical practice, identify problematic classification rules, and define implementation challenges. Variants and associated clinical information were provided to volunteer respondents. Participant variant classifications were compared with intended consensus-derived classifications of the Working Group.
View Article and Find Full Text PDFArticle Synopsis
- Preeclampsia is linked to poor placentation and insufficient blood flow due to decreased angiogenesis, with vitamin D potentially playing a role in pregnancy outcomes.
- A study compared serum samples from women with preeclampsia to those without and found that preeclamptic women had significantly lower vitamin D levels, along with higher levels of anti-angiogenic factors sFlt-1 and endoglin.
- These results suggest that monitoring and potentially improving vitamin D levels could be a target for understanding and addressing preeclampsia.
Article Synopsis
- * In 2020, 56 laboratories reported screening over 1.1 million pregnancies, with a notable drop in testing numbers and a decrease in the number of labs offering these tests compared to eight years earlier.
- * The significant decline in traditional serum screening (up to 72%) was attributed to the rise of cell-free DNA testing, which saw a substantial increase in usage during the same period.
Article Synopsis
- - The study investigates whether women with BRCA mutations experience greater declines in ovarian reserve after chemotherapy, linked to DNA damage from the treatment and the mutations' role in DNA repair deficiency.
- - In a cohort of 108 breast cancer patients, results showed that women with BRCA mutations had significantly lower levels of antimüllerian hormone (AMH) before and after chemotherapy, indicating accelerated ovarian aging and impaired recovery compared to those without mutations.
- - The findings suggest that women with BRCA mutations may need to focus more on fertility preservation options after chemotherapy due to increased risk of losing ovarian reserve, highlighting the broader implications of DNA repair deficiency in aging and infertility.
Objective: To examine whether accounting for a woman's age and body mass index (BMI) would improve the ability of antimüllerian hormone (AMH) to distinguish between women with (cases) and without (controls) polycystic ovarian syndrome (PCOS).
Design: An opportunistic case-control dataset of reproductive age women having evaluations for PCOS as defined by National Institutes of Health criteria.
Setting: Two medical centers in the United States enrolled women.
Purpose: Summarize and interpret results from exercises distributed to laboratories offering cell-free (cf) DNA screening for Down syndrome.
Methods: The College of American Pathologists distributed three patient-derived plasma specimens twice in 2018. Sequencing platforms, test methods, results, and responses to supplemental questions were collected.
Objective: To determine whether differences exist in angiogenic placental growth factor (PlGF) and antiangiogenic soluble vascular endothelial growth factor receptor 1 (sVEGFR-1; both being early markers of placental ischemic disease) in oocyte-donation (OD) pregnancies, compared with autologous in vitro fertilization (aIVF) and spontaneous pregnancies.
Design: Case-control study of residual second-trimester serum samples from women undergoing prenatal screening.
Setting: Academic medical center.
Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the relationship between maternal body mass index (BMI) and peripheral deiodinase activity, especially focusing on how these factors relate to glucose and C-peptide levels in pregnant women.
- It analyzes data from a subset of 600 non-Hispanic white women, assessing thyroid hormone levels and comparing outcomes in women with and without gestational diabetes mellitus (GDM).
- Findings reveal that higher maternal BMI correlates with increased deiodinase activity and higher levels of glucose, indicating that while deiodinase activity contributes to glucose levels, it only accounts for a small portion of the variation.
Purpose: We systematically reviewed the published literature on test failure rates for the sequencing of cell-free DNA (cfDNA) in maternal plasma to identify Down syndrome.
Methods: We searched peer-reviewed English publications with diagnostic results on all pregnancies that provided test failure rates. Data on the odds of failure in Down syndrome and euploid pregnancies and the impact of repeat testing were extracted.