Neurophysiological monitoring in neonatal abstinence syndrome from cocaine.

INTRODUCTION: Neonatal abstinence syndrome (NAS) in a newborn is a result of the sudden discontinuation of exposure to psychotropic drugs abused by the mother during pregnancy. Since forty decades, the standardized Finnegan Neonatal Abstinence Scoring Tool (FNAST) documents the infant withdrawal, and initiate the appropriate treatment regimen, when elevated scored are reported. Whereas FNAST is successfully applied for opioids NAS, in case of other psychotropic drugs and especially cocaine, the tool is not always efficacious or predictive. METHODS: Continuous v-Electroencephalography (vEEG) provides particularly useful information about brain cortical functioning and evaluation of background activity in normal newborns. vEEG allows to properly study and identify clinical manifestations as physiological motor paroxysms, that disappear from birth to infant age in correlation with the neurological development. Due to its feature to be a non-invasive tool continuous vEEG monitoring could be used to describe some clinical manifestations and assess if they can be correlated to possible injuries in critical neonates as those exposed in utero to psychoactive drugs presenting NAS. RESULTS: An example for the potential use of such methodology is discussed in a case of NAS due to prenatal exposure to cocaine as a complementary tool for the evaluation of behavioural state and clinical and neurological signs in newborns in utero exposed to psychoactive drugs, excluding epileptic phenomena. DISCUSSION: Video-EEG recording could be considered an important and objective tool that allows the evaluation of behavioural state and clinical and neurological signs in newborns in utero exposed to psychoactive drugs and the neurophysiological definition of signs and symptoms, which cannot be evaluated by FNAST such as startles and its variability during subsequent days after birth, subclinical seizures or brain injuries.

Screening for Opioid and Stimulant Exposure In Utero Through Targeted and Untargeted Metabolomics Analysis of Umbilical Cords.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Urine Comprehensive Drug Screen, Low Birth Weight and Withdrawal Symptoms in a Neonatal Unit: A Case Control Study.

OBJECTIVE: Maternal drug abuse may influence neonatal outcomes. We compared neonatal outcomes of patients with urine screened positive for commonly abused drugs (CAD) versus those who were screened negative, and reviewed the pattern of drugs detected at a university teaching hospital. METHODS: Urine samples collected from babies with suspected illicit drug exposure who were admitted to the neonatal unit were sent for comprehensive drug screen (CDS) performed by liquid chromatographytime- of-flight mass spectrometry (LC-TOF/MS). The screening library can detect more than 300 drugs and their metabolites. Fluorescence polarization immunoassay (FPIA) was also used to screen for cannabinoids which were not detected by the present LC-TOF/MS method. Symptoms suggestive of drug exposure and history of maternal substance misuse were recorded. RESULTS: Commonly abused drugs (CAD) including methadone, morphine, codeine, methamphetamine, ketamine, midazolam and heroin were present in the urine specimens of 46 (24.2%) of 190 neonates. Eighty-one (42.6%) urine samples screened positive for other drugs, which include antibiotics, lidocaine and pethidine administered during delivery. Drugs were undetectable in 33.2% samples. Urine positive for CAD was independently associated with maternal history of substance misuse (0.0001), birth-weight 2.5 kg (OR 2.9,0.01), neonatal withdrawal symptomatology (OR=8.89, 0.0001); but not with risk of preterm delivery. Logistic regression demonstrated that neonates with maternal history of substance misuse and CAD positivity were 5.99 (p=0.021) and 5.91 (0.0005) times more likely to have withdrawal symptoms. CONCLUSIONS: CADs are isolated in the CDS of nearly one-fourth of neonates. Neonates with maternal history of CAD exposure as evidenced by positive urine CDS are associated with low birth weight, and symptoms of drug withdrawal.

[Drug withdrawal in newborns - clinical data of 49 infants with intrauterine drug exposure: what should be done?]. / Drogenentzug beim Neugeborenen - klinische und soziodemografische Daten von 49 Neugeborenen drogenabhängiger Mütter: Was kann und soll getan werden?

BACKGROUND: Infants of drug abusing mothers are at high risk to suffer from neonatal abstinence syndrome (NAS). Depending on the drug signs of neonatal withdrawal vary but mainly include central nervous system irritability. NAS causes long duration of hospital stay. Severe withdrawal signs are seen in infants exposed to methadone, infants exposed to other opioids like heroin or buprenorphine have been shown to be less symptomatic. Between the years 1997 and 2003 following the border opening there was a dramatic increase in drug exposed newborns seen in the area of Leipzig (East Germany). METHODS: In a retrospective study maternal and infant characteristics, severity of symptoms, duration of withdrawal and hospital stay, duration and kind of treatment as well as modalities for release from hospital were analyzed. RESULTS: From 1997 to 2003 49 drug exposed newborns were admitted to our neonatal care unit. There was an increase of the number of affected infants within these years ( ). Maternal drug abuse (n=48) included mainly methadone (n=33), in second line heroine and benzodiazepines, in a few cases also cocaine and cannabinoides. 3 mothers received substitution therapy with buprenorphine. Additional drug use to substitution therapy was seen in 15 mothers. Drugs of abuse were detected in infant urine specimen (36/48). 35 of exposed newborns showed signs of NAS (incidence of NAS 71%). For evaluation of withdrawal signs and conduction of therapy the Finnegan score was used. As first line pharmacological treatment phenobarbitone was administered (n=42), secondary morphine was used (n=14, treatment failure 33%). Mean duration of hospital stay was 21 days. Mean duration of pharmacological treatment was 14 days with longer duration for methadone exposed infants vs. non-methadone exposed infants (16 vs. 10 days). Hospital stay was longer for non-methadone exposed infants. Maternal intake of more than 20 mg methadone per day vs. up to 20 mg per day caused longer duration of hospital stay (28 vs. 20 days, p=0,015). CONCLUSION: Long duration of hospital stay and pharmacological treatment call for optimised principal guide lines for diagnosis, treatment and long term follow-up. The results also underline the need for further research for an effective pharmacological treatment.

Modification of screening immunoassays to detect sub-threshold concentrations of cocaine, cannabinoids, and opiates in urine: use for detecting maternal and neonatal drug exposures.

Testing for drugs of abuse in urine is commonplace in emergency departments and neonatal units. However, the clinical sensitivity of immunochemical screening methods is limited by the threshold concentrations used to distinguish between positive and negative specimens. Immunochemical screening methods for cocaine metabolite (benzoylecgonine), cannabinoids, and opiates in urine were recalibrated to detect drugs at lower threshold concentrations. The precision and linearity of the signals at the modified thresholds were verified by diluting drug-positive urine specimens to concentrations below the conventional cutoff concentration and measuring the rate signals in triplicate. To assess the clinical performance of the modified methods, specimens that tested negative using the unmodified assays were re-screened at the lower threshold, and specimens that re-screened positive were submitted for gas chromatographic/mass spectrometric (GC/MS) confirmation. Reproducibility of sub-threshold measurements was comparable to the unmodified assays, and rate separations between successive dilutions were sufficient to give semi-quantitative results. Using the lower thresholds, drugs were detected in 4-5% of the subjects that had screened negative at the conventional threshold concentration. GC/MS analysis confirmed the presence of cannabinoids and cocaine metabolite in 74% and 84%, respectively, of urine specimens that re-screened positive. Morphine, codeine, hydromorphone, or hydrocodone was detected by GC/MS analysis in 31% of opiate-positive re-screens.

Comparison of a rocking bed and standard bed for decreasing withdrawal symptoms in drug-exposed infants.

PURPOSE: To determine if the use of a mechanical rocking bed with maternal intrauterine sounds would decrease symptoms of withdrawal and promote neurobehavioral adaptation in drug-affected infants. METHODS: This was a repeated measures experimental design, with infants randomized to a standard bed or a rocking bed. The sample consisted of 14 full-term infants who were prenatally exposed to methadone plus other illicit drugs. RESULTS: Infants receiving the rocking bed therapy experienced a significant increase in withdrawal symptoms and sleep deprivation and displayed suboptimal neurobehavioral functioning on day 7 of life. IMPLICATIONS: The results suggest that the use of a mechanical rocking bed may be overstimulating for these fragile infants during the acute period of withdrawal.

[Value of toxicological research in newborn infants of addicted mothers by the study of several samples (urine, meconium, hair)]. / Intérêt des recherches toxicologiques chez les nouveau-nés de mères toxicomanes par l'étude de plusieurs échantillons (urines, méconium, cheveux).

BACKGROUND: 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. POPULATION AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Urine, meconium and hair testing versus urine testing alone increase the sensitivity of laboratory analysis for detection of prenatal drug exposure.

Methadone levels and neonatal withdrawal.

The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone.

Auditory brainstem-evoked potentials in term infants born to mothers addicted to opiates.

A series of 20 normal newborn term infants and 12 infants born to mothers who had abused opiates during pregnancy were studied. Auditory brainstem-evoked potentials were used to describe neurophysiologic dysfunction in a group of drug-addicted term infants. Significant differences in the auditory brainstem-evoked potentials were found between the two groups. Specifically, a decrease in the central conduction times was noted for the I-III interpeak interval, suggesting neurophysiologic dysfunction in the area of the pons and cerebellum.

Urine drug screening in mothers and newborns.

A retrospective analysis of comprehensive urine drug screening was performed during a 13-month period on specimens submitted from the Neonatal Nursery and Obstetrics/Gynecology wards at San Francisco (Calif) General Hospital (mothers, N = 601; newborns, N = 339). Of mothers and newborns, respectively, 19.2% and 15.3% of all admissions during this period were screened; 68.2% and 63.1% of urine samples submitted were positive for any drug; 38.8% and 21.1% of screens were positive for more than one drug; and 45.8% and 41.6% were positive for cocaine. In mother-newborn pairs (N = 191) where urine samples were submitted within 4 days of each other, an 84% concordance was shown for cocaine and 67% for methadone, but concordance was much less for other drugs (less than 21%). These results indicate that cocaine was the most common drug detectable in the peripartum period and that both mothers and newborns should be tested to confirm the suspicion of drug effect or withdrawal in the newborn.