Carbon monoxide (CO) is the leading cause of poisoning in the United States and is associated with high maternal and fetal mortality rates. Given the nonspecific signs and symptoms of toxicity, cases may go unsuspected or attributed to other etiologies. As CO adversely affects both mother and fetus, it is important for practitioners to recognize and treat poisoning in a timely manner. We seek to assist practitioners with understanding the physiology and recognizing the presentations of both acute and chronic CO poisoning, as well as provide information on diagnosis and treatment options. We also conducted a review of cases described in the literature during the past half century to show varying presentations and treatment methodologies. A qualitative literature search was conducted using PubMed and Google Scholar for articles published between 1970 and 2014 that assessed cases of CO poisoning during pregnancy. Excluded studies were not in English or contained nonhuman subjects. Nineteen published reports of CO poisoning during pregnancy described in varying levels of detail were found in the literature from 1971 to 2010. Carbon monoxide poisoning requires a high degree of suspicion. Diagnosis is made based on initial history and physical evaluation and assessment of environmental CO levels; presenting carboxyhemoglobin levels may be poor indicators of severity of disease. Oxygen therapy should be initiated promptly in all possible cases with consideration of hyperbaric oxygen therapy in cases of significant maternal exposure. Treatment requires a longer duration for fetal CO elimination than in the nonpregnant patients. Importantly, practitioners should educate pregnant patients on prevention.

Epithelial ovarian cancer is the most lethal gynecologic malignancy and has few reliable non-invasive tests for early detection or diagnosis. Recent advances in genomic techniques have bolstered the utility of cell-free DNA (cfDNA) evaluation from peripheral blood as a viable cancer biomarker. For multiple reasons, comparing alterations in DNA methylation is particularly advantageous over other molecular assays. We performed a literature review for studies exploring cfDNA methylation in serum and plasma for the early diagnosis of ovarian cancer. The data suggest that serum/plasma cfDNA methylation tests have strong diagnostic accuracies for ovarian cancer (median 85%, range 40–91%). Moreover, there is improved diagnostic performance if multiple genes are used and if the assays are designed to compare detection of ovarian cancer with benign pelvic masses. We further highlight the vast array of possible gene targets and techniques, and a need to include more earlier-stage ovarian cancer samples in test development. Overall, we show the promise of cfDNA methylation analysis in the development of a viable diagnostic biomarker for ovarian cancer.

Purpose: High-grade serous ovarian carcinoma (HGSOC) is the most lethal epithelial ovarian cancer (EOC) and is often diagnosed at late stage. In women with a known pelvic mass, surgery followed by pathologic assessment is the most reliable way to diagnose EOC and there are still no effective screening tools in asymptomatic women. In the current study, we developed a cell-free DNA (cfDNA) methylation liquid biopsy for the risk assessment of early-stage HGSOC. Experimental Design: We performed reduced representation bisulfite sequencing to identify differentially methylated regions (DMR) between HGSOC and normal ovarian and fallopian tube tissue. Next, we performed hybridization probe capture for 1,677 DMRs and constructed a classifier (OvaPrint) on an independent set of cfDNA samples to discriminate HGSOC from benign masses. We also analyzed a series of non-HGSOC EOC, including low-grade and borderline samples to assess the generalizability of OvaPrint. A total of 372 samples (tissue n = 59, plasma n = 313) were analyzed in this study. Results: OvaPrint achieved a positive predictive value of 95% and a negative predictive value of 88% for discriminating HGSOC from benign masses, surpassing other commercial tests. OvaPrint was less sensitive for non-HGSOC EOC, albeit it may have potential utility for identifying low-grade and borderline tumors with higher malignant potential. Conclusions: OvaPrint is a highly sensitive and specific test that can be used for the risk assessment of HGSOC in symptomatic women. Prospective studies are warranted to validate OvaPrint for HGSOC and further develop it for non-HGSOC EOC histotypes in both symptomatic and asymptomatic women with adnexal masses.