Clinical chemistry最新文献

Background: Hypertension, infection, hemorrhage, cardiovascular events, gestational diabetes, anemia, and miscarriage remain the primary cause of maternal mortality and morbidity. Despite advances in maternal health, there remains a gap in the ability to accurately diagnose, or predict the risk of, certain pregnancy-related conditions.

Content: Here, we discuss preterm delivery, preeclampsia, ectopic pregnancy, gestational diabetes, and detection of fetal anomalies. These are 5 examples of pregnancy-related conditions for which a significant diagnostic gap still exists. We note that many of the available tests used in this field promote a high negative predictive value (NPV), when tests with high positive predictive value (PPV) are needed to drive treatment.

Summary: To improve the modes of maternal testing, researchers need to establish the performance criteria necessary for the given condition. For low-prevalence conditions with potentially catastrophic outcomes, a single test needs extremely high sensitivity and specificity to achieve the PPV required to identify the small number of affected women who would benefit from intensive intervention. Alternatively, 2-step approaches could be used with a highly sensitive screen followed by a highly specific test. However, the solution to improving maternal morbidity and mortality is 2-fold: both affordable, effective, and rapid modes of testing; and safer, more effective treatments are needed.

Background: The field of pediatric cancer genetics has recently seen important advancements driven by collective international precision oncology trials and surveillance guideline development for childhood cancer predisposition syndromes (CPS). It is now recognized that 8%-18% of children with cancer will be identified with a pathogenic/likely pathogenic variant in a cancer predisposition gene. While progress has been significant, ongoing work is necessary to optimize the lifelong care of this growing population of individuals.

Content: This review provides an overview of the impact of 2 significant movements in the field of pediatric oncology: precision oncology trials utilizing paired tumor-germline sequencing and the development of expert-informed screening guidelines for the clinical care of children with childhood CPS. We summarize the influence these initiatives have had on patients and the clinical teams and institutions caring for them. We highlight current research that aims to elucidate the downstream effects of genetic testing and cancer surveillance for CPS to improve the efficacy of and access to CPS care as well as the psychosocial outcomes for patient and families living with a CPS. Finally, we discuss important areas of future research to better identify and care for this population across their lifespan.

Summary: A broadened or universal approach to testing for childhood CPS in pediatric oncology increases opportunities for early cancer detection and treatment for children and their family members. However, longitudinal studies on access to and the impact of this information and its consequences for families are needed for implementation into clinical practice.

Background: Preterm birth (PTB), or birth occurring before 37 weeks' gestation, remains a significant public health burden, accounting for 10% of live births annually in the United States and incurring substantial healthcare expenditures. Our understanding of the molecular mechanisms underlying spontaneous preterm birth (sPTB) has advanced across the previous 4 decades, yet precise prediction tools and prevention strategies are lacking.

Content: Numerous studies have identified potential anatomical and molecular risk factors for sPTB, including sonographic characteristics of the cervix; maternal serum circulating RNA and proteins; maternal urine metabolic byproducts; cervicovaginal cytokine, microbiome, and metabolome composition; amniotic fluid cytokines; umbilical cord blood leukocyte DNA methylation status; and placental transcriptome profiles. This review focuses on recent developments in sPTB biomarker determination among singleton gestations.

Summary: Herein, we synthesize and evaluate the test characteristics of candidate biomarkers of sPTB, concluding that no single biomarker can accurately predict sPTB. However, several individual or combined panels of biomolecules, including some commercially available, carry clinically significant predictive information. These biomarkers include cervical ultrasonography, the ratio of insulin-like growth factor-binding protein 4 to sex-hormone binding globulin, panels of urinary metabolites and amniotic fluid proteins, and maternal circulating cell-free RNA. Future integration of select biomarkers drawn from prospective validation cohorts into existing risk stratification strategies may enhance sPTB prediction, thereby identifying patients at greatest risk.

Background: Congenital heart defects (CHDs) are the most prevalent birth defects, contributing significantly to infant morbidity and mortality. While genetic factors account for a subset of CHDs, environmental exposures during critical periods of cardiac development are increasingly recognized as potential contributors.

Content: This review synthesizes current evidence linking per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, and other environmental contaminants to CHDs. We discuss epidemiological findings, biological mechanisms, exposure assessment methodologies, and future research directions, emphasizing the need for integrated approaches in understanding and mitigating environmental risks to fetal cardiac development.

Summary: This review emphasizes the need for integrated approaches in understanding and mitigating environmental risks to fetal cardiac development.

Background: Persistent disparities in prenatal care contribute to preventable maternal and fetal morbidity and mortality, particularly among high-risk and underserved populations. Clinical laboratories play a central role in early detection of prenatal gaps in care and stratifying pregnancy-related risk factors linked to other health conditions, yet their full potential remains underutilized.

Content: This review examines the integration of data analytics with laboratory information systems and electronic health records to proactively identify and address lapses in prenatal care. Structured laboratory data can drive clinical decision support, stratify risk in early pregnancy, and guide targeted interventions. Predictive analytics and population health tools are discussed as mechanisms to uncover disparities in access, optimize resource allocation, and inform system-level strategies. While there are critical challenges that must be addressed, including data interoperability, incomplete data sets, and ethical considerations such as patient autonomy and data privacy, data analytics can be leveraged to advance prenatal care.

Summary: By centering diagnostic data within the broader analytics framework, clinical laboratories are positioned to lead multidisciplinary efforts to deliver more equitable and effective maternal healthcare.

Background: Newborn screening (NBS) is a foundational public health program designed to identify severe but treatable conditions in presymptomatic newborns. Since Robert Guthrie introduced the phenylketonuria test in the 1960s, NBS has evolved from single-condition assays to multiplex platforms, enabling early diagnosis, intervention, and long-term follow-up. Understanding the historical, technological, and organizational aspects of NBS is critical to addressing the challenges posed by the integration of genomic technologies.

Content: Tandem mass spectrometry forms the backbone of current NBS, allowing cost-effective detection of multiple metabolites and expanding the scope of screening. NBS requires coordinated efforts among primary care providers, specialized teams, and state public health programs. Although the federal Recommended Uniform Screening Panel currently includes 64 conditions, adoption and implementation vary across states. Advances in genomic technologies, particularly next-generation sequencing (NGS), offer the potential to further expand NBS, complementing rather than replacing traditional functional screening. Integrating NGS raises challenges, including selection of disorders, management of variants of uncertain significance, presymptomatic diagnoses, and ethical and privacy considerations. Evidence is still needed to define the clinical utility, cost-effectiveness, and long-term outcomes of population-wide genomic screening.

Summary: NBS has transformed over the past 6 decades from single-condition testing to complex, multi-disorder programs. While genomic technologies promise further expansion, careful evaluation of clinical, ethical, and practical considerations is essential to ensure that NBS continues to provide timely, equitable, and beneficial care to all newborns.

Background: Prenatal cell-free DNA (cfDNA) screening has transformed the prenatal aneuploidy testing landscape testing since its clinical introduction in 2011. Leveraging placentally derived cfDNA fragments as fetal indicators in maternal plasma, cfDNA screening enables highly sensitive aneuploidy detection, most notably for trisomies 21, 18, and 13. With its superior performance compared to traditional screening approaches, cfDNA screening has been rapidly adopted into routine obstetric care worldwide.

Content: This review provides an overview of central laboratory foundations of prenatal cfDNA screening based on our in-house developed test experience and includes preanalytical, analytical, and postanalytical considerations. Key topics include specimen handling, quality management practices, an overview of assay platforms, and bioinformatic processing. We explore test performance characteristics such as sensitivity, specificity, and positive predictive value (PPV), as well as factors influencing test accuracy. We discuss critical topics such as interpreting discordant results, the significance of low fetal fraction, and the challenges of confined placental mosaicism and maternal health conditions, including malignancy. Additionally, we consider cfDNA screening expansion to genome-wide analysis with associated interpretive complexities.

Summary: Prenatal cfDNA screening has quickly become a cornerstone of modern prenatal care. Accurate test performance requires rigorous assay validation, quality assurance, and clear interdisciplinary communication. Understanding laboratory methods and limitations underlying tests is essential for accurate interpretation and appropriate clinical integration. This review highlights the rapid evolution of testing and its profound impact on prenatal screening. As adoption expands and clinical guidelines evolve, the laboratory role in ensuring analytical quality and accurate result interpretation is critical.