Meconium Specimens Research Articles

The detection of caffeine and cotinine in umbilical cord tissue using liquid chromatography–tandem mass spectrometry

A liquid chromatography-tandem mass spectrometry method for the simultaneous detection of cotinine and caffeine in umbilical cord was fully validated. The analytes were quantified using multiple reaction monitoring and corresponding stable isotope internal standards (cotinine-d3 and caffeine-13C3). The method demonstrated acceptable imprecision (<12%) and bias (<13%). The limit of detection was 4 ng g−1 and 40 ng g−1 for cotinine and caffeine, respectively. The determined relative matrix effects for cotinine and caffeine were 3.0% and 3.2%, respectively. The method was used to successfully analyze two authentic umbilical cords that were matched with corresponding meconium specimens that had been analyzed for cotinine and caffeine using a previously published method. A simple, one-step collection procedure and the availability of specimen for every donor make umbilical cord a simple alternative for newborn toxicology.

Drugs of Abuse Detection in Meconium: A Comparison Between ELISA and Biochip Microarray

The results of meconium specimens and fortified samples screened for drugs of abuse by both enzyme-linked immunosorbent assay (ELISA, Immunalysis) and biochip microarray (Randox) methods were compared. The ELISA method was semi-automated using a TECAN Genesis. The Randox assay used the Randox Evidence Investigator system. Previously validated gas chromatography-mass spectrometry (GC-MS), GC-GC-MS, or liquid chromatography-MS-MS methods were used for confirmation and quantitation. Results from the two techniques compared well. Agreement of the Randox assay was greater than 90% when compared to the ELISA assay for all drug classes except cannabinoids (88%). Specificity of the biochip assay was slightly better for amphetamines and cocaine.

Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome

Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Prospective clinical study. An urban drug treatment facility treating pregnant and post-partum women and their children. Forty-nine opioid-dependent pregnant women received 30-110 mg methadone daily. Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid and cocaine were also found in 36.7 and 38.8 of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.

Broad-spectrum drug screening of meconium by liquid chromatography with tandem mass spectrometry and time-of-flight mass spectrometry

Analysis of the major drugs of abuse in meconium has been established in clinical practice for detecting fetal exposure to illicit drugs, particularly for the ready availability of the sample and ease of collection from diapers, compared with neonatal hair and urine. Very little is known about the occurrence and detection possibilities of therapeutic and licit drugs in meconium. Meconium specimens (n = 209) were collected in delivery hospitals, from infants of mothers who were suspected to be drug abusers. A targeted analysis method by liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) was developed for abused drugs: amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, morphine, codeine, 6-monoacetylmorphine, oxycodone, methadone, tramadol, buprenorphine, and norbuprenorphine. A separate LC-MS/MS method was developed for 11-nor-∆(9)-tetrahydrocannabinol-9-carboxylic acid. A screening method based on LC coupled to time-of-flight MS was applied to a broad spectrum of drugs. As a result, a total of 77 different compounds were found. The main drug findings in meconium were as follows: local anesthetics 82.5% (n = 172), nicotine or its metabolites 61.5% (n = 129), opioids 48.5% (n = 101), stimulants 21.0% (n = 44), hypnotics and sedatives 19.0% (n = 40), antidepressants 18.0% (n = 38), antipsychotics 5.5% (n = 11), and cannabis 3.0% (n = 5). By revealing drugs and metabolites beyond the ordinary scope, the present procedure helps the pediatrician in cases where maternal denial is strong but the infant seems to suffer from typical drug-withdrawal symptoms. Intrapartum drug administration cannot be differentiated from gestational drug use by meconium analysis, which affects the interpretation of oxycodone, tramadol, fentanyl, pethidine, and ephedrine findings.

Rates of fetal alcohol exposure among newborns in a high-risk obstetric unit

Meconium fatty acid ethyl esters (FAEEs) are sensitive and specific biomarkers for prenatal alcohol exposure (PAE) in pregnancy. We recently reported a 2.5% rate of FAEE positive meconium in a general population sample of infants born in the region of Grey-Bruce, Ontario. Women in this region with high-risk pregnancies are transferred to a tertiary care facility in London, Ontario. The objective of this study was to determine, in a population-based sample, whether high-risk pregnancies are associated with an increased risk of in utero alcohol exposure. Grey-Bruce residents transferred to the high-risk obstetric unit of St. Joseph's Health Care in London, Ontario were identified and consented to this anonymous prevalence study. Meconium was collected and analyzed for FAEE using gas chromatography with mass spectrometry. The prevalence of FAEE positive meconium was compared with the population-based prevalence in the Grey-Bruce. Fifty meconium specimens were collected from August 1, 2006 to July 31, 2007. Fifteen (30%) specimens tested positive for FAEE. The results indicate that infants born in the high-risk obstetric unit had a 12-fold higher risk of screening positive for second and third trimester alcohol exposure compared with infants born in the general population of Grey-Bruce (relative risk = 12.04, 95% confidence interval = 6.40–22.65, P < .0001). These results suggest that the high-risk pregnancies should be screened for PAE and followed-up for potential diagnosis of fetal alcohol spectrum disorder.

Effect of hydrolysis on identifying prenatal cannabis exposure

Identification of prenatal cannabis exposure is important due to potential cognitive and behavioral consequences. A two-dimensional gas chromatography-mass spectrometry method for cannabinol, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8beta,11-dihydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) quantification in human meconium was developed and validated. Alkaline, enzymatic, and enzyme-alkaline tandem hydrolysis conditions were optimized with THC- and THCCOOH-glucuronide reference standards. Limits of quantification ranged from 10 to 15 ng/g, and calibration curves were linear to 500 ng/g. Bias and intra-day and inter-day imprecision were <12.3%. Hydrolysis efficiencies were analyte-dependent; THC-glucuronide was effectively cleaved by enzyme, but not base. Conversely, THCCOOH-glucuronide was most sensitive to alkaline hydrolysis. Enzyme-alkaline tandem hydrolysis maximized efficiency for both glucuronides. Identification of cannabinoid-positive meconium specimens nearly doubled following alkaline and enzyme-alkaline hydrolysis. Although no 11-OH-THC glucuronide standard is available, enzymatic hydrolysis improved 11-OH-THC detection in authentic specimens. Maximal identification of cannabis-exposed neonates and the widest range of cannabis biomarkers are achieved with enzyme-alkaline tandem hydrolysis.

Opioid Detection in Maternal and Neonatal Hair and Meconium: Characterization of an At-Risk Population and Implications to Fetal Toxicology

Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of a reliable self-report. We aimed to characterize an at-risk neonatal population for opioid exposures as well as other drugs of abuse and alcohol. From June 2007 to January 2009, 563 neonatal hair and 1318 meconium specimens were assessed for opioids and were positive in 11.4% and 17.0%, respectively. Neonates testing positive for opioids in hair or meconium analysis were also more likely to test positive for other licit and illicit substances (odds ratiohair, 1.75; 95% confidence interval, 1.03-2.97; odds ratiomeconium, 1.61; 95% confidence interval, 1.16-2.22). Specifically, a positive neonatal hair test for opioids also predicted a positive result for oxycodone. In addition, a positive meconium test result for opioids was associated with positive results for cocaine, oxycodone, methadone, benzodiazepines, and fatty acid ethyl esters (alcohol). Finally, there was a significant correlation between maternal and neonatal hair test results for opioids (Spearman rank rho = 0.657, P = 0.03). Understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.

Nicotine and metabolites in meconium as evidence of maternal cigarette smoking during pregnancy and predictors of neonatal growth deficits

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.

Identification of Prenatal Amphetamines Exposure by Maternal Interview and Meconium Toxicology in the Infant Development, Environment and Lifestyle (IDEAL) Study

The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by gas chromatography mass spectrometry. Tobacco exposure was equally detected by immunoassay cotinine screening and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use or frequency or route of MAMP use. Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women stopped MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.

Phthalate Levels and Low Birth Weight: A Nested Case-Control Study of Chinese Newborns

To assess maternal-fetal exposure to phthalates and investigate whether in utero phthalate exposure is associated with low birth weight (LBW). A total of 201 newborn-mother pairs (88 LBW cases and 113 controls) residing in Shanghai were enrolled in this nested case-control study during 2005-2006. Maternal blood, cord blood, and meconium specimens were collected and analyzed for phthalates by high-performance liquid chromatography-mass spectrometry. Nonparametric tests were used to compare demographic characteristics in cases and controls. Conditional logistic regression and Spearman correlation were used to analyze the association between phthalate exposure and LBW. No significant differences in gestational age, prepregnancy body mass index, prenatal care, vitamin supplementation, or socioeconomic levels were found between the LBW and control infants. More than 70% of the biosamples had quantifiable levels of phthalates, with higher levels in the LBW infants compared with the controls. Prenatal di-n-butyl phthalate (DBP) exposure was associated with LBW, and di-2-ethylhexyl phthalate (DEHP) was negatively associated with birth length. After adjusting for the potential confounders, DBP concentrations in the highest quartile were associated with an increased risk of LBW. Newborns in China are ubiquitously exposed to phthalates; significantly higher phthalate levels were detected in LBW cases compared with controls. In utero DBP and DEHP exposures were associated with LBW in a dose-dependent manner. Prenatal phthalate exposure may be a risk factor for LBW.

Evaluation of a New ELISA Kit for the Detection of Benzodiazepines in Meconium

Two versions of enzyme-linked immunosorbent assay (ELISA) kits designed for the detection of benzodiazepine drugs and metabolites (Immunalysis) were evaluated for use with meconium specimens. One was an older kit, and one was a new replacement kit developed for better detection of several commonly prescribed benzodiazepines and metabolites. The kits were evaluated by analyzing 68 patient specimens previously analyzed by liquid chromatography-tandem mass spectrometry and eight quality control samples. In addition to the recommended calibrator (oxazepam), clonazepam was evaluated as an alternate calibrator for the new kit. Detection and sensitivity for some analytes was improved using the new ELISA kit, but was reduced for others. The new kit using clonazepam as the calibrator provided the most sensitive assay for detection of the 11 benzodiazepines and metabolites reported here.

Comparison of Drugs of Abuse Detection in Meconium by EMIT(R) II and ELISA

The results of meconium specimens and fortified samples screened for drugs of abuse by both enzyme multiplied immunoassay technique (EMIT((R) )II) and enzyme-linked immunosorbent assay (ELISA) methods were compared. The sample preparation for the ELISA screen was a simple buffer extraction versus a lengthy and more laborious sample preparation procedure for the EMIT II screen. The ELISA method was automated using a TECAN Genesis. The EMIT II analysis was automated with an Olympus AU400e. The opioid screen was calibrated with hydromorphone and the benzodiazepine screen was calibrated with clonazepam to maximize detection for these analytes. Previously validated gas chromatography-mass spectrometry (GC-MS), two-dimensional GC-MS, or liquid chromatography-tandem MS methods were used for confirmation. Results from the two techniques compared well. Agreement of the ELISA assay was greater than 90% when compared to EMIT II for all drug classes except barbiturates and benzodiazepines. ELISA appears to be more sensitive than EMIT II for the detection of amphetamines, methadone, propoxyphene, and cocaine. ELISA compared well to EMIT II for cannabinoids, opioids, and PCP. Specificity of the ELISA assay was slightly better for PCP and opioids. EMIT II appears to be more sensitive for the detection of barbiturates and benzodiazepines. The ELISA method reduced turnaround time by 50% compared to the EMIT II method.

Cross-Reactivity of Phentermine with an Immunoassay Designed to Detect Amphetamine in a Meconium Specimen

Neonates exposed to drugs of abuse in utero can experience prenatal drug dependence leading to withdrawal symptoms and a number of other health problems (1). Early detection of exposure is critical to guide necessary treatment and improve outcomes for these children. Meconium begins to form in the digestive tract at 12–16 weeks gestation. Drugs and metabolites collect in meconium beginning at about 5 months gestation. Thus, meconium testing can identify exposure to drugs during the last 4 months of a full-term pregnancy (2). Our laboratory uses ELISA reagents (Immunalysis) to detect drugs of abuse in meconium. Poor specificity of immunoassay reagents for amphetamines is well characterized and as a result, specimens that test positive for amphetamines by immunoassay are routinely tested by a second analytical method to prevent false-positive results. Our ELISA screen for meconium has separate detection antibodies for amphetamine and methamphetamine. The ELISA cutoff for these drugs is 20 ng/g. All positive screen results are confirmed by GC-MS. We report the investigation of an unconfirmed positive amphetamine result. ELISA assay of the meconium specimen …

Novel Biomarkers of Prenatal Methamphetamine Exposure in Human Meconium

Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine (MAMP) and amphetamine (AMP) have previously been observed in meconium of MAMP-exposed neonates; the presence of other metabolites has not been investigated. Detection of such analytes may lead to more sensitive identification and thus improved medical treatment of affected infants. Forty-three MAMP-positive meconium specimens were analyzed for newly identified MAMP biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to MAMP adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetamine and MAMP prenatal exposure, 3,4-methylenedioxymethamphetamine, its metabolites, and related sympathomimetic amines were assayed. MAMP, AMP, and unconjugated p-hydroxymethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetamine and norephedrine also were identified. It is possible that one of these additional analytes could be important for predicting toxicity or maternal or neonatal outcome measures in fetuses exposed to MAMP at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than MAMP and AMP in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of MAMP-exposed neonates. Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to MAMP.

Quantitation of Benzodiazepines in Urine, Serum, Plasma, and Meconium by LC-MS-MS

A single method for confirmation and quantitation of a panel of commonly prescribed benzodiazepines and metabolites, alpha-hydroxyalprazolam, alpha-hydroxyethylflurazepam, alpha-hydroxytriazolam, alprazolam, desalkylflurazepam, diazepam, lorazepam, midazolam, nordiazepam, oxazepam, temazepam, clonazepam, and 7-aminoclonazepam, was developed for three specimen types, urine, serum/plasma, and meconium. Quantitation was by liquid chromatography tandem-mass spectrometry (LC-MS-MS) using a Waters Alliance-Quattro Micro system. The instrument was operated in multiple reaction monitoring mode with an electrospray ionization source in positive ionization mode. The method was evaluated for recovery, imprecision, linearity, analytical measurement range, specificity, and carryover. Average recovery and imprecision (within-run, between-run, and total % CV) were within +/- 15% of the target concentrations for urine (10 to 5000 ng/mL) and serum/plasma (10 to 2500 ng/mL) and within +/- 20% for meconium (10 to 5000 ng/g). In all, 205 patient specimens were analyzed, and the results compared to a previous in-house gas chromatography-MS method or LC-MS-MS results from an outside laboratory. Oxazepam glucuronide was evaluated as a hydrolysis control for the urine and meconium specimens.

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium With Neonatal Outcomes

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.

Prevalence of Fetal Ethanol Exposure in a Regional Population-Based Sample by Meconium Analysis of Fatty Acid Ethyl Esters

Challenges in identifying children exposed prenatally to ethanol necessitate the development of a biomarker for neonates at risk for fetal alcohol spectrum disorder. Meconium fatty acid ethyl esters (FAEE), products of nonoxidative ethanol metabolism, have been established as a novel biomarker of fetal ethanol exposure. We present the first application of this biomarker to a population-based sample in Canada. Six-hundred eighty-two meconium specimens were anonymously collected in the region of Grey Bruce, Ontario, Canada. Meconium FAEE were extracted by liquid-liquid and solid-phase extraction and analyzed by gas chromatography with flame-ionization detection confirmed by gas chromatography with mass spectrometry. We measured ethyl palmitate (E16:0), ethyl palmitoleate (E16:1), ethyl stearate (E18:0), ethyl oleate (E18:1), ethyl linoleate (E18:2), ethyl linolenate (E18:3), and ethyl arachidonate (E20:4). Seventeen of 682 meconium samples tested positive for significant prenatal ethanol exposure (>2.0 nmol/g). FAEE analysis detected fivefold more ethanol-exposed pregnancies than standard postpartum questionnaires in this population (2.5% versus 0.5%) (P < 0.001). The prevalence of ethanol-exposed pregnancies was consistent with Centers for Disease Control and Prevention estimates of "frequent" prenatal drinking and previously published estimates of fetal alcohol spectrum disorder disease prevalence in the general North American population. The FAEE concentrations of negative (95% confidence interval, 0.38-0.49 nmol/g) versus positive (95% confidence interval, 7.74-151.28 nmol/g) samples were distinct, further demonstrating the specificity of this biomarker in determining significant prenatal ethanol exposure. Meconium FAEE analysis demonstrates a fivefold increase in sensitivity over currently used methods of self-report-based screening in Ontario for the detection of ethanol-exposed pregnancies in a clinical setting.

Determination of cocaine and heroin with their respective metabolites in meconium by gas chromatography‐mass spectrometry

The analysis of meconium specimens is a relatively accurate method for the detection of fetal exposure to drugs. The purpose of this study was to develop and validate a method for meconium sample preparation for a gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cocaine, benzoylecgonine, codeine, morphine and 6-monoacetylmorphine. The analytes were initially extracted from the matrix by methanol. Subsequently a solid-phase extraction with Waters Oasis HLB cartridges was applied. Analytes were determined in GC-MS single monitoring mode. The method was validated in the range 40-2000 ng g(-1) using 0.5 g of meconium per assay. The detector response was linear over the studied range, and limits of quantitation and detection were found to be acceptable. Intra- and inter-batch coefficients of variation oscillated between 2.54% and 20.5%, and mean relative errors were in the range 0.79%-19.9%. The recoveries were higher than 42.1% in all cases. Finally the method was applied to analysis of meconium in newborns to assess fetal exposure to cocaine and opiates.

Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium

We assessed the agreement of testing for fetal exposure to illicit drugs contrasting paired specimens of meconium vs umbilical cord tissue. We obtained paired samples of meconium and umbilical cord tissue from 118 pregnancies with high suspicion of illicit drug use by the mothers. Each specimen was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine using drug class-specific immunoassays. The agreement of drug screening results between cord and meconium was above 90% for all drugs tested. Meconium identified 21 cases as positive for amphetamines. The paired cord identified 20 of these, and in addition identified three other positives that the meconium labeled as negative. Gas chromatography-mass spectrometry confirmed these three cord samples as methamphetamine positive. Meconium identified 97 samples that were negative for amphetamines, while the cord identified 94 of these as negative but three as positive. Agreement of cord with meconium for amphetamines was 96.6%. The concordance for opiates was 94.9%, for cocaine was 99.2%, and for cannabinoids was 90.7%. Umbilical cord tissue performs as well as meconium in assessing fetal drug exposure to amphetamines, opiates, cocaine, and cannabinoids. Results of studies using the cord may have a more rapid return to the clinician, because waiting for meconium to be passed sometimes requires several days. Moreover, in some cases the meconium is passed in utero making collection impossible, whereas cord should always be available for drug testing.

Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: Preliminary results of the “Meconium Project”

For the first time in Europe, the “Meconium Project” aimed to estimate the prevalence of drug use by pregnant women and the effects of exposure to illicit drugs during pregnancy on the fetus and infant. Between October 2002 and February 2004, 1151 (79%) dyads among the 1439 mother–infant dyads from the Hospital del Mar, Barcelona, Spain, met eligibility criteria and agreed to participate in the study. We present preliminary results on the first 830 meconium samples and 549 mother–infant dyads, for which statistical analysis of socio-economic and demographic characteristics and newborn somatometry was completed. The meconium analysis showed an overall 7.9% positivity for drugs of abuse, with 6-monoacetylmorphine and cocaine being the analytes, most frequently found in samples positive for opiates and cocaine. Structured interview disclosed 1.3, 1.8 and 1.3% of mothers exposed to opiates, cocaine and both drugs, while only one mother declared ecstasy consumption. Meconium analysis showed that prevalence of opiates, cocaine and combined drugs exposure was 8.7, 4.4 and 2.2%, respectively, and confirmed the case of ecstasy use. Arecoline, the main areca nut alkaloid, was found in meconium specimens from four Asiatic newborns, whose mothers declared beetle nut consumption during pregnancy. Parental ethnicity was not associated with drug use, nor was the social class, although a higher tendency toward drug consumption was observed in professional and partly skilled mothers. Drug consuming mothers showed a higher number of previous pregnancies and abortions ( p < 0.05) when compared to non-consumer mothers (meconium negative test), probably due to a lack of family planning. Consumption of opiates and cocaine during pregnancy was associated with active tobacco smoking, a higher number of smoked cigarettes and cannabis use. Exposure status and smoking behavior correlated with significantly lower birth weight in newborns from mothers exposed only to cocaine and to opiates and cocaine simultaneously. Of the four newborns exposed to arecoline, one showed a low birth weight, low intrauterine growth, hyporeflexia and hypotonia.