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Background: The use of psychoactive substances (PSs) during pregnancy is a major public health concern because of their increasing prevalence worldwide. This study examined the understudied issue of gestational PS consumption in a cohort of Argentine delivering mothers., Methods: A cross-sectional pilot study involving 51 women receiving delivery care was conducted at the Santa Rosa Hospital in La Pampa, Argentina. Information on maternal sociodemographic characteristics, pregnancy history, and drug use was obtained through standardized interviews. Maternal hair samples were analyzed for alcohol, tobacco, licit, illicit, and prescription substance biomarkers using ultra-high-performance liquid chromatography high-resolution mass spectrometry and gas chromatography mass spectrometry., Results: During pregnancy, 49.0% of participants reported alcohol consumption, 25.5% reported tobacco use, and 23.5% reported cannabis use. Hair samples from 56.9% of the women were positive for illicit PSs, with the most frequent being cocaine (41.2%) and cannabis (15.7%). Among the women, 47.1% consumed alcohol during pregnancy. Of the 24 women with hair ethyl glucuronide ≥5 pg/mg, 33.3% drank until the end of gestation and 58.3% started a social drinking habit in the second half. The analysis also detected prescription substances (anticonvulsants, antidepressants, methadone, opioids, antihistamines, antiemetics, and analgesics), caffeine (70.6%), lidocaine, and levamisole, some of which were cocaine or opioid adulterants., Conclusions: This is the first study to objectively assess the consumption of licit and illicit PSs during pregnancy in Argentina. In contrast to most nearby countries, cocaine was the most detected illicit PS in this cohort of Argentine delivering women. This finding highlights the importance of regular monitoring of local trends in PS use during pregnancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioral, and/or learning disabilities that are included in the term fetal alcohol spectrum disorder. The measurement of ethylglucuronide (EtG) in alternative biological matrices, including neonatal and maternal hair, neonatal meconium, and maternal nails, is receiving increasing interest for the accurate evaluation of the in utero exposure to alcohol., Objective: To evaluate the correlation between EtG in maternal hair and nails with EtG in neonatal meconium to further explore the suitability of these biomarkers in disclosing prenatal exposure to ethanol., Methods: A total of 151 maternal hair strands (0-6 cm), nail clips (2-6 mm), and corresponding neonatal meconium and nails samples were obtained from neonatal wards of 4 Mediterranean public hospitals: Rome, Florence, and Belluno in Italy and Barcelona in Spain. Hair, nails, and meconium were analyzed for the presence of EtG by validated liquid chromatography mass spectrometry assay. Meconium was also analyzed for the presence of fatty acid ethyl esters (FAEEs) as a complementary biomarker of potential in utero exposure to alcohol., Results: Eighteen newborns resulted in utero exposed to maternal alcohol consumption by FAEE testing in meconium with EtG values between 0.5 and 1.5 nmol/g. Unfortunately, none of these cases were confirmed by the presence of EtG in maternal hair and nails samples, which resulted all negative to this biomarker., Discussion and Conclusions: The results confirm that FAEEs and EtG in meconium are the best biomarkers to assess in utero exposure to maternal alcohol. EtG in hair and nails are not good biomarkers to disclose alcohol consumption lower than on daily basis and lower than 1-2 alcoholic units per day.

The pharmacokinetics of methylphenidate (MPH), a prescription amphetamine derivative used in the treatment of attention-deficit hyperactivity disorder, has been amply described in conventional biological matrices. Recently, the excretion of MPH and its principal metabolite, ritalinic acid (RA) in oral fluid and plasma after a single drug administration has been described. The aim of this study was to describe the excretion of MPH and RA in sweat after the administration of a single dose of either fast-release or extended-release MPH. Three male subjects received 2 simultaneous oral doses of 10 mg fast-release MPH, and 1 male subject received one dose of 20 mg extended-release MPH. Sweat patches were applied to the back of each participant and removed at timed intervals. MPH and RA were determined in patches using a previously validated liquid chromatography-electrospray ionization mass spectrometric method. MPH was detected in sweat after the administration of fast- and extended-release formulations. For the fast-release formulation, MPH appeared in the sweat patches 2 hours after administration with a maximum of 15.9 nanogram per patch, reached after 24 hours. Mean total MPH excreted was 0.02 mg (about 0.08% of the administered dose). For the extended-release formulation, MPH appeared in the sweat 5 hours after administration and reached a maximum of 34.3 nanogram per patch after 24 hours. Mean total MPH excreted was 0.04 mg (about 0.18% of the administered dose). RA was not detected in either of the sweat patches probably because of its acidic properties. Measuring MPH in sweat patches can be a viable alternative to urine testing for noninvasive monitoring of use and misuse of the drug.

The detection of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in meconium has been investigated recently as an alternative to meconium fatty acid ethyl esters (FAEEs) measurement as an objective estimate of prenatal alcohol exposure, independent of maternal self-reporting. We report the results of the first study conducted to investigate the concentrations of EtG and EtS in meconium from newborns with and without intrauterine exposure to ethanol, defined by questionnaire and meconium FAEEs concentration. FAEEs, EtG, and EtS were quantified by liquid chromatography tandem mass spectrometry in meconium samples obtained from the Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (n = 80) and from the Hospital del Mar in Barcelona, Spain (n = 105). Median EtG and EtS values in meconium from newborns without intrauterine exposure to ethanol varied between 0.100 and 0.140 nmol/g and 0.010 and 0.020 nmol/g in Reggio Emilia and Barcelona samples, respectively. In meconium from newborns with uncertain prenatal ethanol exposure, the EtG median value was 0.160 nmol/g in the Italian cohort and 0.250 nmol/g in the Spanish one. The median EtS concentration was 0.020 in both cohorts. EtG and EtS median values in 5 meconium samples from newborns of heavily drinking mothers were 7.240 nmol/g and 0.033 nmol/g, respectively. A positive cutoff of 2.0 nmol/g for EtG yielded the best sensitivity and specificity (100%) to discriminate for true prenatal exposure to ethanol. It was not possible to establish a proper cutoff for EtS because of the low number of positive samples. Based on our results, meconium EtG can be proposed as an alternate biomarker for intrauterine alcohol exposure. In contrast to the 7 FAEEs, EtG is just one molecule that could be screened in meconium samples from all newborns by a simple, low-cost, easy-to-perform immunoassay, which can be routinely applied in neonatology wards for the early diagnosis of prenatal exposure to ethanol.

A liquid chromatography tandem mass spectrometric (LC-MS/MS) method with postcolumn addition of acetonitrile for the determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in meconium was developed and validated using pentadeuterated EtG and pentadeuterated EtS as internal standards. The analytes were extracted from the matrix by acetonitrile, concentrated by solid phase extraction, separated using a reversed-phase chromatographic column, and quantified within 9 minutes. Lower limits of quantification were 5 and 1 ng/g meconium for EtG and EtS, respectively. Calibration curves were linear from lower limits of quantifications to 500 ng/g, with a minimum r > 0.999. At 3 concentrations spanning the linear dynamic range of the assay, mean recoveries ranged between 78.7% and 96.8% for EtG and between 72.1% and 95.6% for EtS. Inaccuracy was better than 8.1%, with intra-assay and interassay imprecision better than 7.2% and 10.5%, respectively. Matrix effects (ion suppression/enhancement) were found to be negligible. The analytes of interest were stable at room temperature, at 4 degrees C, when exposed to 3 freeze-thaw cycles, and when stored at -20 degrees C for up to 6 months. This sensitive and specific method was used to assess the presence of these alcohol biomarkers in meconium samples from 2 different city cohorts.

The premature newborn of a mother who reported drinking mate during pregnancy presented with increased jitteriness and irritability, high-pitched cry, hypertonia in the limbs, and brisk tendon reflexes consistent with neonatal withdrawal syndrome. High concentrations of caffeine and theobromine were detected in various maternal and neonatal biological matrices (placenta, cord serum, neonatal urine, maternal and neonatal hair, meconium, and breast milk), demonstrating both acute and chronic prenatal and postnatal exposure to these methylxanthines, contained in high amounts in homemade mate. Symptoms progressively disappeared at 84 hours of age, although intermittent irritability was still present when the infant was discharged at 24 days of age. Fluctuating caffeine (and theobromine) content in different breast milk feeds likely generated the baby's irritability, due to either the physiological stimulatory effects of the methylxanthines or postnatal withdrawal syndrome as the substances cleared from the body. The mother was strongly advised to initiate a considerable, progressive, constant reduction of mate consumption to a maximum of 2 cups a day for the duration of breastfeeding.

A rapid and simple procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11-hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta-THC) and deuterated THC-COOH as internal standards. The biological matrix was subjected to liquid-liquid extraction after enzyme hydrolysis for conjugated analytes.Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The method was validated in the range 20 to 500 microg/g using 1g of meconium per assay. The method was applied to the analysis of meconium in a cohort of newborns to assess eventual fetal exposure to cannabis. Within positive samples, THC-COOH and THC-OH (range: 33.7 to 182.1 and 20.7 to 493.3 microg/g, respectively) were both present in the majority of cases with only 1 specimen with THC-OH as the most abundant metabolite and 2 with THC only.

Accidental ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) was detected in an infant admitted at the Pediatric Emergency Department by drug testing in urine. Concentrations of MDMA and its principal metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) in the infant's hydrolyzed urine were 11.7 mg/L and 34.4 mg/L, respectively. Apparent febrile convulsions and cardiovascular side effects resolved within 1 day after treatment with benzodiazepines. Chronic exposure to cocaine was evidenced by segmental hair analysis. Continuous maternal denial of the presence of any drug in the household made diagnosis of accidental ingestion of MDMA and chronic exposure to cocaine problematic. Periodic clinical and laboratory follow-ups were requested to check eventual long-term effects of exposure to illicit drugs and discontinuation of the child from exposure to dangerous environments.