Detection of cotinine in newborn dried blood spots
ABSTRACT Maternal smoking while pregnant is a plausible risk factor for childhood cancers because many seem to initiate in utero and tobacco-specific carcinogens cross the placenta. Social desirability bias may affect maternal report of smoking in case-control studies and could explain inconsistently observed associations with offspring cancer. Detection of tobacco smoke biomarkers in dried blood spots (DBS), which are increasingly stored by newborn screening programs, may improve retrospective assessment of fetal tobacco exposure. As proof-of-principle, we examined cotinine in DBS of 20 infants enrolled in a pilot study of pregnancy among low-income women. We recruited 107 pregnant women (<30 weeks of gestation) from six Women, Infants, and Children clinics in Minneapolis and St. Paul in 1999. Blood samples obtained at enrollment were tested for total cotinine using gas chromatography/mass spectrometry. Women were then interviewed at 7 months of gestation to determine current smoking habits. DBS were obtained from the Minnesota Department of Health. We tested DBS from 10 infants whose mothers had detectable serum cotinine at baseline and 10 control infants whose mothers had none. One quarter of each DBS was assayed for cotinine using gas chromatography/mass spectrometry; levels were estimated assuming 50 muL blood per sample. Mean cotinine was 29 ng/mL (SD, 7.5), 45 ng/mL (SD, 9.7), and 9 ng/mL (SD, 7.4), respectively, among infants of all smokers, infants of four women who acknowledged smoking at 7 months of gestation, and infants of nonsmokers. These results suggest that DBS analysis may identify infants of women who smoke throughout pregnancy.
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ABSTRACT: About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e.g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology.Critical Reviews in Toxicology 03/2012; 42(3):230-43. DOI:10.3109/10408444.2011.650790 · 6.41 Impact Factor
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ABSTRACT: Approximately 10,700 children under the age of 15 years are newly diagnosed with cancer each year in the United States (American Cancer Society, 2008), including nearly 3,500 children with leukemia. Even with great advances in treatment over the last several decades, leukemia remains a major source of disease-related morbidity and mortality in children. Of the leukemias, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), comprise the vast majority in childhood, occurring at a frequency of approximately 76% and 18%, respectively (Ries et al. 1999). Other leukemias can occur in children, but are extremely rare, including biphenotypic or mixed lineage leukemia, chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), and chronic lymphocytic leukemia (CLL). This review focuses on the epidemiology of childhood ALL and AML. Below, we provide an overview of the classification systems used, including how these entities may help define the timing of when the leukemia might have occurred. Second, international and national data with regard to incidence and survival rates, along with trends, are described. Further, risk factors associated with childhood leukemia are discussed including inherited syndromes, exposures and conditions, and genetic susceptibility as measured through single nucleotide polymorphisms (SNPs). Finally, we discuss challenges and potential future directions that may lead to more fruitful understanding of the underlying causes of childhood leukemia.Archivos argentinos de pediatría 64(5):195-7. · 0.29 Impact Factor
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ABSTRACT: Previous studies from this laboratory have focused on the characterization of blood protein adducts formed in utero as a result of maternal smoking during pregnancy. These biological samples, obtained during the third trimester of pregnancy, at delivery, have clearly shown a correlation between maternal smoking histories and exposure of the fetus to tobacco smoke carcinogens, including 4-aminobiphenyl and benzo(a)pyrene. In the present study, we examined exposure of the fetus during the first trimester of pregnancy to various environmental carcinogens, particularly those found in tobacco smoke. Amniotic fluid samples were obtained from women undergoing routine amniocentesis between 16 and 20 weeks gestational age. Amniotic fluid, produced by the fetal lungs and kidneys, is an important part of pregnancy and fetal development and this fluid surrounds the fetus throughout pregnancy. In these studies, samples of amniotic fluid were obtained from nonsmokers as well as 0.5 pack per day smokers, 1.0 pack per day smokers, and greater than 2.0 pack per day smokers. Maternal smoking status was determined by questionnaire as well as assessment of amniotic fluid for cotinine via immunoassay. Amniotic fluid samples were extracted and analyzed for the presence of polycyclic aromatic hydrocarbons (PAHs). A clear correlation was found between levels of maternal smoking and PAHs in the amniotic fluid. Amniotic fluid 1-hydroxypyrene levels ranged from 1.54 ± 0.12 μ g/L in nonsmokers to 11.72 ± 0.67 μ g/L in women smoking greater than 2 pks/da, indicating approximately a 10X increase over nonsmokers. Similar results were found 3-hydroxybenzo(a)pyrene, 6-hydroxybenzo(a)pyrene, and 3,6-dihydroxybenzo(a)pyrene, metabolites of the carcinogen benzo(a)pyrene as well as with the 9-hydroxy and 9,10-dihydroxy metabolites of anthracene. The 5-hydroxymethyl metabolite of 5-methylchrysene was found to range in concentrations from 1.65 ± 0.11 μ g/L in nonsmokers to 12.67 ± 0.79 μ g/L in greater than 2 packs per day smokers.These results demonstrate that amniotic fluid can serve as a biological marker of exposure to tobacco related polycyclic aromatic hydrocarbons. Identification of potentially harmful compounds detected at an early stage of pregnancy may prevent subsequent exposures to the fetus and as a result decrease the risk of potential genotoxic as well as teratogenic events.Polycyclic Aromatic Compounds 01/2008; 28(1):39-66. DOI:10.1080/10406630701779434 · 0.83 Impact Factor