morphine and hydroxycotinine

Smoking during pregnancy can have serious obstetric and fetal complications. Therefore, it is essential to identify in utero exposure to tobacco, being meconium the matrix of choice for this purpose. Meconium (n = 565) was analyzed for nicotine, cotinine and hydroxycotinine by LC-MS-MS. Then, tobacco meconium results were compared with smoking habits during pregnancy and neonatal outcomes measures (birth weight, length, head circumference, gestational age and Apgar scores). Although meconium analysis increased identification of in-utero exposure to tobacco (17.7% meconium positive specimens vs 13.5% mothers admitting tobacco use during pregnancy), there was a statistically significant relationship between meconium results and interview answers (P < 0.001). Birth weight was significantly lower for newborns with meconium positive results in males (P = 0.023) and females (P = 0.001), while for length significance was only observed in females (P = 0.001); however, when excluding meconium specimens positive for other drugs, a statistically significant difference was only found for female weight (P = 0.045). Meconium analysis proved to be more reliable for tobacco prenatal exposure detection than maternal interview. In addition, positive meconium results increased the probability for low birth weight, especially in females.

Topics: Chromatography, Liquid; Cotinine; Female; Humans; Infant, Newborn; Male; Mass Spectrometry; Maternal Exposure; Meconium; Nicotine; Pregnancy; Tobacco Smoke Pollution

To assess relationships between marker concentrations of tobacco in meconium and weekly self-reported maternal cigarette consumption, and prediction of neonatal growth outcomes.. Pregnant mothers (n = 119) from a longitudinal maternal smoking and infant neurobehavioral study (Behavior and Mood in Babies and Mothers [BAM BAM]) provided daily tobacco smoking histories. Nicotine, cotinine, and trans-3'-hydroxycotinine concentrations were quantified in 111 neonatal meconium specimens by liquid chromatography-tandem mass spectrometry.. Median self-reported third trimester smoking was 5.9 cigarettes per day among smokers. Meconium samples from infants born to non-smokers (n = 42) were negative for tobacco markers, while specimens from self-reported smokers (n = 41) were positive for (median, range) nicotine (50.1 ng/g, 3.9-294), cotinine (73.9 ng/g, 6.4-329), and trans-3'-hydroxycotinine (124.5 ng/g, 10.2-478). Quitters (n = 28) self-reported stopping smoking at gestational weeks 2-39. Four meconium specimens from quitters were positive for tobacco biomarkers. Reduced birth weight, length, and head circumference significantly correlated with presence of meconium markers but not with individual or total marker concentrations. Among quitters and smokers, reduced infant birth weight, head circumference, and gestational age correlated with total and average daily cigarette consumption in the second and third trimesters.. Smoking cessation or reduction during pregnancy improved neonatal outcomes. The window of detection for tobacco in meconium appears to be the third trimester; however, low exposure in this trimester failed to be detected. These results will aid physicians in educating women who are pregnant or thinking about becoming pregnant on the negative consequences of smoking during pregnancy. In addition, infants at risk can be identified at birth to assist early intervention efforts.

Topics: Adolescent; Adult; Biomarkers; Chromatography, Liquid; Cotinine; Female; Humans; Infant, Newborn; Longitudinal Studies; Maternal Exposure; Maternal-Fetal Exchange; Meconium; Nicotiana; Nicotine; Pregnancy; Prenatal Exposure Delayed Effects; Smoking; Tandem Mass Spectrometry; Young Adult

Umbilical cord tissue was studied as a means of detecting prenatal exposure to nicotine. This was accomplished by comparing the presence and concentration of nicotine as well as nicotine metabolites in both umbilical cord tissue and paired meconium samples with maternal smoking histories obtained by self-report. Nicotine and metabolites (cotinine, 3-hydroxycotinine, nornicotine, and anabasine) were detected and quantitated using liquid chromatography-tandem mass spectroscopy. Between June and September 2009, 19 women with a tobacco exposure history (either first- or second-hand tobacco smoke exposure during pregnancy) were consented for the study. A questionnaire was completed to document nicotine exposure during each trimester of pregnancy. All infants were delivered at term (38 weeks or greater) and paired umbilical cord tissue (10-cm segment or greater) and meconium were obtained. Nicotine and 3-hydroxycotinine were most prominent in meconium, whereas cotinine and 3-hydroxycotinine were most prominent in the umbilical cord. Concentrations of all three analytes were generally higher in meconium. Nornicotine was detected only in meconium, at very low concentrations, and anabasine was not detected in either specimen. All analyte concentrations were lowest when the mother stated she quit smoking early in pregnancy or had only second-hand exposure, and detection was poor if exposure was limited to the first or second trimesters. Although different nicotine and metabolite patterns exist in meconium versus umbilical cord tissue, this work indicates that either specimen can be used to detect third-trimester fetal nicotine exposure.

Topics: Anabasine; Central Nervous System Stimulants; Cotinine; Female; Humans; Infant, Newborn; Maternal Exposure; Maternal-Fetal Exchange; Meconium; Nicotine; Pregnancy; Smoking; Umbilical Cord

Nicotine (NIC), cotinine (COT) and trans-3'-hydroxycotinine (OHCOT) are the most prevalent and abundant tobacco biomarkers in meconium. We have developed and validated an accurate and precise method for the measurement of these analytes in meconium in which potassium hydroxide is used to digest the meconium sample, followed by solid phase extraction from the liquified sample. The precision of OHCOT, COT and NIC measurements (intra-day and inter-day) were 4.8-10.6%, 3.4-11.6% and 9.3-15.8%, respectively. Evaluation of accuracy indicated bias of -4.0, 2.0 and 0.8% for OHCOT at concentrations of 0.5, 2.5 and 7.5 ng/g. The accuracy estimates for COT at concentrations of 0.5, 2.5 and 7.5 ng/g are 4.0, 4.0 and 5.7%, respectively. For NIC at 2, 10 and 30 ng/g the accuracy was calculated to be 3.0, 5.0 and 5.1%, respectively. The linear range of standard solutions was 0.125-37.5 ng/mL for OHCOT and COT, and 0.75-150 ng/mL for NIC. This method was applied to the analysis of 374 meconium samples from infants of both smoking and nonsmoking mothers. Positive correlations with r(2)≥0.63 were observed between NIC and COT, COT and OHCOT, NIC and OHCOT, and NIC and (OHCOT+COT) in these samples.

Topics: Biomarkers; Chromatography, Liquid; Cotinine; Drug Stability; Female; Humans; Hydroxides; Infant, Newborn; Linear Models; Maternal Exposure; Meconium; Nicotine; Potassium Compounds; Reproducibility of Results; Sensitivity and Specificity; Smoking; Solid Phase Extraction; Tandem Mass Spectrometry

Amniotic fluid was collected from 78 pregnant women at birth additionally with their urine prior to delivery as well as neonatal urine and meconium. The smoking markers, nicotine and its metabolites cotinine and trans-3'-hydroxycotinine (OH-cotinine), were determined using high-performance liquid chromatography (HPLC). The self-reported smoking status during pregnancy determined by means of a questionnaire was verified by measurement of maternal urine. In all smokers, nicotine metabolites were detected in amniotic fluid and in 80% of them nicotine as well. However, the sum of the nicotine metabolites (Sum(met)) was significantly lower (p < .001) in amniotic fluid (704 +/- 464 nmol/L) than in meconium (921 +/- 588 nmol/L), neonatal urine (1139 +/- 813 nmol/L) and maternal urine (4496 +/- 3535 nmol/L). Concentrations of nicotine metabolites in amniotic fluid correlated well (p < .001) with that in the other specimen types. After environmental tobacco smoke (ETS) exposure, no nicotine or nicotine metabolites were detectable in amniotic fluid but only in maternal and neonatal urine. Analysis of amniotic fluid at birth lends itself to verifying smoking habits during pregnancy and clearly discriminating from ETS exposure, but it is not a suitable approach to differentiating between ETS exposure and non-exposure.

Topics: Adolescent; Adult; Amniotic Fluid; Biomarkers; Chromatography, High Pressure Liquid; Cotinine; Female; Humans; Infant, Newborn; Maternal Exposure; Maternal-Fetal Exchange; Meconium; Nicotine; Pregnancy; Smoking; Young Adult

Many women continue tobacco use during pregnancy despite known adverse consequences on neonatal growth and development. Testing meconium, the first neonatal feces, for tobacco biomarkers offers objective evidence of prenatal tobacco exposure. However, relationships between the amount, frequency, and timing of cigarette smoking during gestation and tobacco biomarker meconium concentrations and neonatal outcomes are unclear.. Eighty-seven pregnant women provided detailed self-reports of daily tobacco consumption throughout pregnancy. Nicotine, cotinine, and trans-3'-hydroxycotinine were quantified in neonatal meconium by liquid chromatography-tandem mass spectrometry.. Among nonsmokers, all meconium specimens were negative, whereas nearly all meconium specimens were positive if the mother self-reported tobacco use into the third trimester. Tobacco biomarker concentrations were significantly albeit weakly correlated with mean cigarettes per day in the third trimester. Reduced birth weight, gestational age, or head circumference were observed if meconium contained one or more tobacco biomarkers, but deficits did not correlate with biomarker concentrations.. While previously thought to reflect second and third trimester drug exposure, meconium appears to reliably identify only third trimester drug use. While a 10 ng/g nicotine, cotinine, or trans-3'-hydroxycotinine cutoff in meconium was previously proposed to differentiate tobacco-exposed from nonexposed or passively exposed neonates, improved maternal self-reporting techniques in this cohort suggest that a lower cutoff, equivalent to the analytic limits of quantification, is more appropriate.

Topics: Adolescent; Adult; Chromatography, Liquid; Cotinine; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Nicotine; Pregnancy; Pregnancy Trimesters; Smoking; Tandem Mass Spectrometry; Young Adult

The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure.. We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations) and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression.. We detected nicotine (80%), cotinine (69%), and trans-3'-hydroxycotinine (57%) in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight.. Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

Topics: Adult; Biomarkers; Birth Weight; Cohort Studies; Cotinine; Female; Humans; Infant, Newborn; Male; Maternal Exposure; Meconium; Nicotine; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Tobacco Smoke Pollution

Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes' concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans-3'-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in meconium, identify the best biomarkers of in utero tobacco exposure, compare meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration-outcome relationships.. We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in meconium from tobacco-exposed and nonexposed neonates by liquid chromatography-tandem mass spectrometry. We compared meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores.. Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference.. Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure.

Topics: Apgar Score; Biomarkers; Body Size; Chromatography, Liquid; Cotinine; Female; Gestational Age; Glucuronates; Humans; Hydrolysis; Infant, Newborn; Maternal Exposure; Maternal-Fetal Exchange; Meconium; Nicotine; Pregnancy; Smoking; Tandem Mass Spectrometry; Tobacco Smoke Pollution

There are no analytical methods that simultaneously quantify nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose-meconium concentration relationships exist, and whether nicotine meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5-500ng/g. Method applicability was evaluated with meconium collected from an in utero tobacco exposed infant.

Topics: Adult; Calibration; Chromatography, High Pressure Liquid; Cotinine; Female; Humans; Indicators and Reagents; Infant, Newborn; Mass Spectrometry; Meconium; Nicotine; Pregnancy; Quality Control; Reference Standards; Smoking; Tandem Mass Spectrometry

Meconium samples collected from 115 neonates were analysed for nicotine, cotinine and trans -3-hydroxycotinine (OH-cotinine) by means of high-performance liquid chromatography (HPLC) to identify prenatal smoke exposure. The self-reported maternal smoking status during pregnancy was determined by means of a questionnaire and verified by measurements in urine prior to childbirth. The total sum of nicotine and its metabolites (Sum(tot)) of the first passed meconium samples was 1560 +/- 1024 pmol/g in newborns of smoking mothers. Smoking of less than five cigarettes was clearly detected. Sum(tot) remained constant in all meconium samples passed by a neonate in succession. However, the proportion of nicotine decreased with the time of passage after birth and the OH-cotinine proportion increased, whereas cotinine hardly changed. Nicotine or its metabolites were not detectable in meconium (detection limit < 20 pmol/g), when the mothers were only exposed to environmental tobacco smoke (ETS) using the HPLC method. The hypothesis that the content of nicotine metabolites in meconium reflects long-term smoke exposure could not be confirmed in newborns whose mothers had quit smoking during the latter half of pregnancy. Determining Sum(tot) enables the intensity of continuous smoking during pregnancy to be estimated in all meconium samples passed by a newborn.

Topics: Adolescent; Adult; Chromatography, High Pressure Liquid; Cotinine; Data Interpretation, Statistical; Environmental Exposure; Female; Germany; Humans; Infant, Newborn; Maternal Exposure; Meconium; Nicotine; Pregnancy; Reproducibility of Results; Surveys and Questionnaires; Tobacco Smoke Pollution; Toxicology; Urinalysis

We measured nicotine metabolites (cotinine and trans-3'-hydroxycotinine) in meconium of infants of passive or active smokers as a direct marker of fetal exposure to tobacco smoke. Meconium was collected from 55 infants whose mothers were nonsmokers, passive smokers, or light or heavy active smokers. Nicotine metabolite concentration (NMC) in meconium was analyzed by radioimmunoassay and gas chromatography-mass spectrometry. Radioimmunoassay showed the following mean meconium NMCs (in nanograms per milliliter); nonsmoker, 10.9; passive smoker, 31.6; light active smoker; 34.7, and heavy active smoker, 54.6. Analysis of available samples by gas chromatography-mass spectrometry confirmed the presence of cotinine. Correlation between meconium NMC and the degree of maternal smoking was 0.54 (p < 0.001). Meconium NMCs in infants of passive and active smokers were significantly higher than in those of nonsmokers (p < 0.05). Meconium NMC in passive smokers was not significantly different from that in light active smokers (p > 0.05). Thus exposure of the fetus to tobacco smoke is substantial, even by passive maternal smoking. Meconium analysis for nicotine metabolites may be useful for clinical and research purposes.

Topics: Cotinine; Female; Fetus; Humans; Maternal-Fetal Exchange; Meconium; Nicotine; Pregnancy; Smoking; Tobacco Smoke Pollution