morphine and Neonatal-Abstinence-Syndrome

Illicit drug use during pregnancy is a concern worldwide, with many international studies describing attempted strategies to mitigate this problem. Drug misuse during pregnancy is associated with significant maternal as well as perinatal complications, which include a high incidence of stillbirths, fetal distress, neonatal abstinence syndrome (NAS) and increased neonatal mortality. Unfortunately, the identification of a drug-exposed mother or neonate is challenging. Maternal disclosure of drug use is often inaccurate, principally due to psychosocial factors including behavioral denial or the fear of the consequences resulting from such admissions. Likewise, many infants who have been exposed to drugs in utero may appear normal at birth and initially show no overt manifestations of drug effects. Thus, the identification of the drug-exposed infant requires a high index of clinical suspicion. Conversely, analytical testing is an objective means of determining drug exposure when it may be necessary to document proof of the infant's exposure to illicit drugs. The review will discuss the different matrices that are most commonly used for testing (e.g., maternal urine, neonatal urine, meconium, and umbilical cord), the strengths and limitations for each matrix, which drugs and metabolites are appropriate for testing, the various testing methods, and the advantages and disadvantages of each method.

Topics: Female; Hospitalization; Humans; Illicit Drugs; Infant, Newborn; Meconium; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Substance-Related Disorders

The management of the infant exposed to drugs in utero poses significant challenges. Symptoms and signs of neonatal abstinence syndrome (NAS) are non-specific but most commonly associated with withdrawal from maternal opioids. A high index of suspicion is required when presented with an infant who could be manifesting symptoms of NAS. In the absence of a reliable history of maternal drug exposure, analysis of neonatal meconium or urine may be indicated. Approximately 90% of infants exposed to opioids will exhibit signs of NAS, although a smaller proportion will require pharmacological treatment. Although few studies have evaluated the advantages of different therapeutic agents and strategies, opioid withdrawal is best treated initially with opioid medication. Supportive care of the infant should include assessment of the adequacy of feeding, evaluation of social circumstances (particularly child protection issues) and surveillance for transmission of viral infection.

Topics: Female; Humans; Infant, Newborn; Meconium; Neonatal Abstinence Syndrome; Pregnancy

Topics: Adolescent; Adult; Animals; Biomarkers; Blood Chemical Analysis; Chromatography; Clinical Laboratory Techniques; Drug and Narcotic Control; Ethanol; Female; Fetus; Hair; Humans; Immunoassay; Infant, Newborn; Macaca mulatta; Mass Screening; Meconium; Neonatal Abstinence Syndrome; Pregnancy; Specimen Handling; Substance Abuse Detection; Substance Withdrawal Syndrome; Urine

Recent reports indicate that cocaine metabolites have biologic activity and could be toxic. To explore this possibility, two studies were initiated. The first study aimed to define the distribution of cocaine species by quantifying levels of cocaine and its metabolites norcocaine, benzoylecgonine, and benzoylnorecgonine in newborn cord blood and meconium. The second study sought to determine whether they produced a clinical effect. Compared to cord blood, meconium had a greater number of metabolites and a higher concentration of cocaine metabolites, including the previously undetectable norcocaine and benzoylnorecgonine derivatives. Benzoylecgonine was the most common species found in both sources and was usually lower in concentration in blood. An inverse relation existed between meconium benzoylecgonine levels and the serum catabolic enzyme pseudocholinesterase, implying genetic variability in cocaine metabolism. To determine whether cocaine and/or its metabolites could be linked to a distinct clinical state, a second study focusing on newborn behavior was performed with an independent large cohort of cocaine-exposed infants. Neonates with increased signs of "neuroexcitation" had benzoylecgonine and no cocaine in urine, whereas lethargic neonates had detectable urinary cocaine. These findings support the hypothesis that cocaine metabolites, especially benzoylecgonine, may play a role in altering newborn behavior and produce a clinical syndrome distinct from that related to the parent compound.

Topics: Butyrylcholinesterase; Central Nervous System Diseases; Cocaine; Female; Fetal Blood; Fever; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Neonatal Abstinence Syndrome; Pregnancy; Prospective Studies; Respiratory Distress Syndrome, Newborn

The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure.. Subjects comprised 19 opioid-dependent pregnant women from 2 clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared with those in placenta and meconium, and urine specimens collected throughout gestation.. Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine- and opiate-positive specimens than did umbilical cord.. Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict the NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pyrrolidines; Umbilical Cord

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.

Topics: Adult; Buprenorphine; Cocaine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Maternal Behavior; Maternal-Fetal Exchange; Meconium; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Nicotine; Opiate Alkaloids; Opioid-Related Disorders; Pregnancy; Smoking

Neonatal abstinence syndrome is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of neonatal abstinence syndrome has tripled over the past decade. The current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs.. A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography-mass spectrometry. Drugs were identified using the National Institute of Standards and Technology database, and an analytical method was developed and validated using secondary liquid chromatography-mass spectrometry instrument for positive confirmation and quantitative analysis.. Twenty-one random umbilical cords from women were tested: 4 were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; 3 were positive for cotinine, the metabolite of nicotine; and 5 were positive for acetyl norfentanyl.. Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be used to develop a reliable complementary testing method for meconium toxicology screens.

Topics: Analgesics, Opioid; Central Nervous System Stimulants; Chromatography, Liquid; Cocaine; Female; Humans; Meconium; Metabolomics; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Prospective Studies; Substance Abuse Detection; Tandem Mass Spectrometry; Umbilical Cord

Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential.

Topics: Female; Follow-Up Studies; Humans; Infant, Newborn; Meconium; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Substance Abuse Detection

The neonatal abstinence scoring system proposed by Finnegan is used widely in neonatal units to initiate and to guide therapy in babies of opiate-dependent mothers. The purpose of this study was to assess the variability of the scores in newborns and infants not exposed to opiates during the first 3 days of life and during 3 consecutive days in weeks 5 or 6.. Healthy neonates born after 34 completed weeks of gestation, whose parents denied opiate consumption and gave informed consent, were included in this observational study. Infants with signs or symptoms of disease or with feeding problems were excluded. A modified scoring system was used every 8 hours during 72 hours by trained nurses; 102 neonates were observed for the first 3 days of life and 26 neonates in weeks 5-6. A meconium sample and a urine sample at weeks 5-6 were stored from all infants to be analysed for drugs when the baby scored high. Given a non-Gaussian distribution the scores were represented as percentiles.. During the first 3 days of life median scores remained stable at 2 but the variability increased, with the 95th percentile rising from 5.5 on day 1 to 7 on day 2. At weeks 5-6 median values were higher during daytime (50th percentile = 5, 95th percentile = 8) than night-time (50th percentile = 2, 95th percentile = 6, P = 0.02).. Scores increase from days 1-3 to weeks 5-6 and show day-night cycles with 5-6 weeks. Values above 8 can be considered pathological. This data may help to raise suspicion of narcotic withdrawal and to guide therapy.

Topics: Humans; Infant, Newborn; Meconium; Medical History Taking; Neonatal Abstinence Syndrome; Reference Values; Time Factors

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.

Topics: Adult; Analgesics, Opioid; Cocaine; Cocaine-Related Disorders; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Meconium; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Prospective Studies; Substance Abuse Detection; Young Adult

Different biological matrices are suitable for drug testing in newborns presenting with an acute withdrawal syndrome.. The newborn of a mother reporting alprazolam use during pregnancy presented with respiratory distress and clinical features consistent with neonatal withdrawal syndrome or neonatal sepsis of vertical transmission. Alprazolam and its main metabolite (alpha-hydroxyalprazolam) were detected in cord serum, neonatal urine and also in neonatal hair, meconium and placenta, accounting for both acute and chronic exposure to this benzodiazepine during intrauterine life. At the same time, the clinical diagnosis of neonatal sepsis was confirmed by isolation of Streptococcus agalactiae from otic cultures. The infant received oxygen therapy and antibiotic treatment and recovered completely at the age of 11 days. Although no congenital anomalies or behavioral alterations were diagnosed during hospitalization, periodic follow-ups were requested to check for potential long-term effects of prenatal exposure to alprazolam.

Topics: Adult; Alprazolam; Anti-Anxiety Agents; Diagnosis, Differential; Female; Fetal Blood; Hair; Humans; Infant, Newborn; Male; Maternal Exposure; Maternal-Fetal Exchange; Meconium; Neonatal Abstinence Syndrome; Oxygen Inhalation Therapy; Placenta; Pregnancy; Sepsis; Streptococcal Infections; Streptococcus agalactiae; Substance Abuse Detection; Treatment Outcome; Urine

The betel nut is commonly used as a drug by Asian populations. A high prevalence of adverse pregnancy outcomes has been reported in women who chewed betel quid during gestation. The hypothesis that chronic exposure of the fetus to arecoline (the principal alkaloid of the areca nut) is the cause was investigated in a clinical observational study on six newborns from Asian mothers who chewed betel nut during pregnancy.

Topics: Areca; Arecoline; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Neonatal Abstinence Syndrome; Placenta; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects

Recently, interest in hair analysis in such fields as drug abuse, driving, or for clinical purposes (determination of drug-exposed neonates especially) has grown because of the highly sensitive method of detection (GC-MS) that can now be applied. Neonates born to drug-addicted mothers can suffer from neonatal withdrawal syndrome (NWS), which requires morphine treatment in its severe forms. To assess and measure toxicologic factors predicting the appearance and the severity of this syndrome, matrices such as urine, meconium, and hair are necessary. Cannabinoids, opiates, cocaine (and its metabolites), and methadone in particular were determined in the various matrices collected in 17 mother/neonate pairs. An immunologic screening method was used, and quantification was achieved with GC-MS. In spite of some bias (color, length, race) that might hinder an accurate interpretation, the results of hair analysis makes it possible to confirm a fetal drug exposure and to reinforce the diagnosis of the NWS observed, particularly when results obtained in other matrices are negative. Hair analysis contributes to our ability to predict a NWS.

Topics: Cannabinoids; Cocaine; Female; Gas Chromatography-Mass Spectrometry; Hair; Humans; Infant, Newborn; Meconium; Methadone; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Substance Abuse Detection

Urinary detection of prenatal drug exposure in the neonate may give false-negative results. We report our experience on meconium and hair testing, in addition to urine testing in order to improve diagnosis of fetal drug exposure.. Thirty-one infants (aged 1-45 days) whose mothers were confirmed (n = 12) or suspected (n = 19) to be drug-addicted were included in the study. One or more specimens of urine, meconium or hair were collected in the 31 infants, two of the specimens in 17 and three in six. Drugs and their metabolites were detected by immunoenzymologic techniques and positive results were confirmed by gas-exchange chromatography. All the mothers and families were interviewed during admission and the information was compared to those provided by medical and social services; the results of laboratory analysis were not known by the investigators at this time of the study.. The maternal drug addiction was confirmed after clinical investigation in 18 cases including the 12 cases detected by prenatal interview (group 1), and recused in 13 other cases (group 2). In group 1, nine infants of 12 had a positive urine test (seven opiate, one cocaine, one cannabis), 11 of 11 a positive meconium test (nine opiate, one cocaine, one cannabis), ten of 19 a positive hair test (eight opiate, one cocaine, one cannabis); all infants in this group had at least one positive result. In group 2, all tests were negative except one urine test positive for opiate after cesarean delivery performed under anesthesia including opiate analgesia.. Urine, meconium and hair testing versus urine testing alone increase the sensitivity of laboratory analysis for detection of prenatal drug exposure.

Topics: Cannabis; Cocaine; Female; Hair; Humans; Infant; Infant, Newborn; Male; Maternal-Fetal Exchange; Meconium; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Substance-Related Disorders

For purposes of mass drug screening, the procedure for analysis of meconium for drugs was modified into a one-step extraction and analysis by enzyme immunoassay. The accuracy of this modified method was tested by comparing the results of simultaneous analysis of 61 meconium samples for cocaine opiate and cannabinoid metabolites by both the original and the modified methods. In 61 samples analyzed, opiate was detected in 8 (13%) samples by the original method and in 9 (15%) by the modified method; cocaine was detected in 39 (64%) samples by the original method and in 39 (64%) by the modified method. The concordance between the negative and positive results of the modified versus the original methods was 98% and 100%, respectively, for opiate and 95% and 98%, respectively, for cocaine. Only one sample was positive for cannabinoid. Thus a comparison of positive results for cannabinoid was not done; however, all the negative results obtained by the modified method were confirmed by the original method. The clinical experience of mass meconium drug testing using the modified method in 1991 is also reported. In four centers tested (total tests = 4409), the prevalence of presence of drug was consistent with the high- or low-risk status of the population. This simplified, rapid procedure can be performed in most clinical laboratories. This adaptation has made the meconium drug test feasible for large-scale clinical and research use.

Topics: Cannabinoids; Cocaine; Female; Humans; Infant, Newborn; Meconium; Morphine; Narcotics; Neonatal Abstinence Syndrome; Neonatal Screening; Pregnancy; Pregnancy Complications; Substance-Related Disorders

The number of newborn infants with symptoms suggesting drug withdrawal is increasing. As only part of prenatally exposed infants show typical drug withdrawal, and drug-use reported by addicted mothers is often unreliable the prevalence of neonates that were exposed to illicit drugs before birth is unknown. The purpose of this study was to evaluate prospectively the prevalence of drugs in meconium and to define risk factors for intrauterine drug exposure.. During a period of 4 months meconium was collected twice in 420 nonselected newborn infants. Meconium was analysed with a modified test developed for toxicology screening in urine. Information on pre- and postnatal risk factors including drug-use during pregnancy was obtained.. Among 415 mothers four reported illicit drug use and ten licit drug use during late pregnancy. In all these infants meconium drug test was positive. After exclusion of these infants and of five second twins 401 infants with negative drug history remained. 45 of them (11%) had one or two drugs in the meconium: opiate 17x, amphetamine 16x, barbiturate 15x, benzodiazepine 3x, cannabinoid 2x, cocaine 1x (in 9 infants two substances were detected). None was positive for LSD or phencyclidine. The infants with positive drug tests had the following risks compared to those with negative tests: prematurity (odds ratio 2.3, 95% confidence interval 1.3-4.3). Microcephaly or macrocephaly (2.0:1.01-4.1), Apgar-Score below 5 at 1 min (2.4:1.5-5.4), Apgar score below 7 at 10 min (4.0: 1.6-9.9), mother academic (2.8:1.2-6.2).. Newborn infants may have been exposed to illicit drugs in utero even if their mothers deny drug use and even if they do not show withdrawal symptoms. Prematurely born infants and infants with problems in postnatal adaptation have an increased risk of having been exposed to drugs.

Topics: Birth Weight; Cross-Sectional Studies; Female; Gestational Age; Humans; Illicit Drugs; Incidence; Infant, Newborn; Meconium; Neonatal Abstinence Syndrome; Neonatal Screening; Pregnancy; Psychotropic Drugs; Socioeconomic Factors; Switzerland

The number of newborn infants exposed to drugs in utero is on the increase in many European countries. As drug use reported by addicted pregnant women is unreliable there is a need for an accurate test to determine the drugs to which an infant has been exposed in utero. The purpose of this study was to evaluate the reliability of toxicology testing in meconium compared with traditional urine testing.. From twenty newborn infants born to drug-dependent mothers, meconium and urine were collected as soon as possible after birth and tested for drugs with the same radioimmunoassay. Five neonates were premature (Gestational weeks less than 37), six were small and three microcephalic for gestational age.. Meconium was positive for drugs in 19 infants (95%) (Methadone 9, Morphine 9, Cocaine 6, Cannabis 4). Urine testing revealed the presence of drugs in 13 babies (65%) (Methadone 9, Morphine 6, Cocaine 4, Cannabis 1, Barbiturates 1). Five infants did not have any drug withdrawal, five had mild and ten severe withdrawal symptoms necessitating treatment with chlorpromazine and in four instances additional pethidine.. Meconium is not only easier to collect but also at least as reliable as urine for drug detection in neonates.

Topics: AIDS Serodiagnosis; Female; Humans; Illicit Drugs; Infant, Newborn; Male; Meconium; Neonatal Abstinence Syndrome; Neonatal Screening; Psychotropic Drugs; Risk Factors; Substance Abuse, Intravenous