Referral networks for pediatric patients with genetic conditions: The perspective of occupational therapists.

Families of children with developmental delays but no diagnosed genetic condition may benefit from connection to genetic systems of care. This work examines the role of occupational therapy as a space for families of pediatric patients to gain access to genetic services. Between September 2021 and February 2022, we interviewed 20 occupational therapists in New England who work primarily with pediatric patients.

Assessment of a Simplified Cell-Free DNA Method for Prenatal Down Syndrome Screening.

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.

Prenatal cell-free DNA screening test failures: a systematic review of failure rates, risks of Down syndrome, and impact of repeat testing.

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.

The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population.

Objective: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population.

Methods: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures.

Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies.

Purpose: We sought to compare measurements of circulating cell-free DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies.

Methods: Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and karyotype results were available for analysis.

The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies.

Maternal plasma contains circulating cell-free DNA fragments originating from both the mother and the placenta. The proportion derived from the placenta is known as the fetal fraction. When measured between 10 and 20 gestational weeks, the average fetal fraction in the maternal plasma is 10% to 15% but can range from under 3% to over 30%.

Feasibility of using plasma rather than serum in first and second trimester multiple marker Down's syndrome screening.

Objective: To compare maternal plasma with serum for measuring markers currently used in first and second trimester screening for Down's syndrome.

Setting: A laboratory-based investigation of two sample types in assays used in prenatal screening for Down's syndrome.

Methods: A paired data-set included both plasma and serum from 101 pregnant women.

DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations.

Objective: Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies. If MPSS testing is offered clinically, it is important to know if these trisomies will also be identified in multiple pregnancies.

Method: Among a cohort of 4664 high-risk pregnancies, maternal plasma samples were tested from 25 twin pregnancies (17 euploid, five discordant and two concordant for Down syndrome; one discordant for trisomy 13) and two euploid triplet pregnancies [Correction made here after initial online publication.

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.

Purpose: To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13.

Methods: Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.

Mid-gestational maternal free thyroxine concentration and offspring neurocognitive development at age two years.

Context: Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy.

Objective: The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy.

Design: This was an observational, nested case-control study.

DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.

Purpose: Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.

Methods: A blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome.

Maternal urine and serum steroid measurements to identify steroid sulfatase deficiency (STSD) in second trimester pregnancies.

Objective: To document the performance of second trimester maternal urine and serum steroid measurements for detecting fetal steroid sulfatase deficiency (STSD).

Methods: We studied detection rate and false positive rate (DR, FPR) of analytes in maternal urine [combinations of 16alpha-OH-dehydroepiandrosterone sulfate (16alpha-OH-DHEAS), 11beta-hydroxyandrosterone, total estriol] and serum [combinations of 16alpha-OH-DHEAS, 11beta-hydroxyandrosterone, total estriol, unconjugated estriol (uE3)]. Samples were obtained from pregnancies which were screen positive for Smith-Lemli-Opitz syndrome (SLOS).

A genetic history questionnaire-based system in primary prenatal care to screen for selected fetal disorders.

DNA (and other) diagnostic tests are now available for a number of serious, but uncommon, fetal disorders. We designed and evaluated a screening system for this purpose in primary care, coupled with targeted information for practitioners and patients. We developed a 15-question family history form for completion by office staff or patients, addressing conditions for which definitive diagnosis was available, linked to secondary questionnaires to follow up on "yes" answers.

Identifying Smith-Lemli-Opitz syndrome in conjunction with prenatal screening for Down syndrome.

Background: Smith-Lemli-Opitz syndrome (SLOS) is a rare hereditary disorder of cholesterol metabolism. We examine the feasibility of identifying SLOS as a part of a routine prenatal screening and evaluate diagnostic testing in maternal urine (or serum), in addition to amniotic fluid.

Methods: Our SLOS risk algorithm utilized three Down syndrome screening markers (estimated 62% detection rate; 0.

Screening for thyroid disorders during pregnancy: results of a survey in Maine.

Objective: Guidelines regarding prenatal screening for thyroid deficiency are conflicting, and current practice in primary care settings is unknown. Our survey sought to determine the: 1) extent of screening in Maine; 2) factors associated with screening; and 3) laboratory cut-off levels used.

Study Design: In 2004 we surveyed 61 prenatal care practices, representing 246 practitioners and 85% of Maine deliveries.

Integrated serum screening for Down syndrome in primary obstetric practice.

Objectives: Integrated serum screening for Down syndrome is potentially more effective than current second-trimester screening. We report results of an intervention trial of integrated serum screening that involved 229 primary prenatal care practitioners throughout Maine.

Methods: Women provided a first-trimester serum (for PAPP-A) followed by a second-trimester serum (for AFP, uE3, hCG, and DIA).

Patient and health professional acceptance of integrated serum screening for Down syndrome.

Integrated testing for Down syndrome combines first trimester maternal serum and nuchal translucency (NT) measurements with second trimester maternal serum measurements into a single second trimester Down syndrome risk. A variant of integrated testing, the integrated serum test, requires only the serum measurements and may be more suitable for widespread use in the general pregnancy population. Concern has been voiced that women will find the delay associated with waiting for screening results unacceptable for either fully integrated (including NT measurements) or integrated serum testing.

Cystic fibrosis prenatal screening in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

For over a decade, prenatal screening for cystic fibrosis (CF) has been considered a model for the integration of genetic testing into routine medical practice. Data from pilot studies and public policy discourse have led to recommendations by some professional organizations that CF screening should be offered or made available to pregnant women and their partners, and to couples planning a pregnancy. It is crucial that genetic counselors gain thorough understanding of the complexities of CF and the implications of positive test results, so that they may serve as a reliable, educated referral base and resource for health care providers and their patients.