TY - JOUR
AU - Ryan, Rita, M
AB - Abstract Identification of intrauterine drug-exposed newborns with toxicological screening may have benefits including close follow-up of the infant by both medical and social services. Applying specific written guidelines to select newborns for drug testing decreases bias and protects the physicians and hospitals involved. All drugs reported as positive should be confirmed by an appropriate second test. Urine and meconium testing are the best current options for identifying drug-exposed neonates. Urine testing sensitivity is low because of problems encountered in urine collections and the high thresholds used in current urine assays. The disadvantage to meconium testing is the increased labor and time required to work with this material. Testing of newborn hair is unlikely to be widely used until technically less demanding assays become available. Testing of amniotic fluid or gastric lavage is still in the developmental stages. Adopting lower urine assay thresholds for newborn samples would increase sensitivity and would be an appropriate modification of current methodologies. indexing terms: meconium, urine testing, hair analysis, gas chromatography–mass spectrometry, drug screening, immunoassays Intrauterine drug exposure (IUDE) remains a major health concern (1)(2).1 Prenatal cocaine use has been associated with placental abruption and premature labor (3)(4)(5)(6)(7)(8)(9). Intrauterine cocaine exposure has also been associated with an increased risk of prematurity, small for gestational age status, microcephaly, congenital anomalies including cardiac and genitourinary abnormalities, necrotizing enterocolitis, and central nervous system stroke or hemorrhage (3)(4)(5)(6)(7)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Infants born to mothers using amphetamines have many of the same problems as cocaine-exposed infants, including increased rates of maternal abruption, prematurity, and decreased growth parameters such as low birth weight (2). In addition to an increased risk of prematurity and being small for gestational age, striking withdrawal symptoms often requiring treatment are frequently observed in infants after in utero opioid exposure. Symptoms include irritability, hypertonia, wakefulness, jitteriness, diarrhea, increased hiccups, yawning and sneezing, and excessive sucking and seizures, with onset of withdrawal earlier in heroin-exposed babies compared with methadone-exposed infants (23)(24). Some intrauterine cocaine-exposed infants may manifest symptoms of withdrawal including hypertonicity, jitteriness, and seizures (7)(9)(15)(25)(26). Intrauterine amphetamine-exposed infants may also have similar postnatal symptoms including hypertonia, tremors, poor feeding, and abnormal sleep patterns (27). Long-term follow-up of IUDE infants suggests that in addition to the potential for difficult social situations, such as increased risk for child abuse and neglect (28)(29), abnormal neurocognitive and behavioral development may occur (18)(30)(31)(32)(33)(34), as well as an increased risk of sudden infant death syndrome (35)(36)(37)(38). guidelines for medically indicated newborn drug testing Identification of drug-using mothers before or early in pregnancy would be ideal, potentially avoiding intrauterine exposure. However, the physician with primary responsibility for the infant is not in a position to test mothers, but, rather, can only consider ordering a newborn drug test after IUDE may have occurred. Possible benefits of identifying IUDE infants could include programs for improvement of parenting skills, maternal drug treatment, home assistance, focused medical observation during the newborn period, restriction of breast-feeding, and close pediatric follow-up emphasizing developmental and social issues. In addition, currently unidentified problems caused by IUDE may be discovered in the future; beyond the immediate newborn period the opportunity to identify IUDE infants by urine testing is lost. With adequate testing and successful maternal treatment, there is also the potential for decreased postnatal infant exposure, which can have deleterious effects (39)(40)(41) and decreased risk of IUDE in future pregnancies. Drug testing is one of the only methods of identification of IUDE. Maternal history of drug use is often unreliable. If identification of IUDE infants is worthwhile, it is inadequate to rely on maternal self-reporting; for example, 24–63% of mothers with positive cocaine tests deny cocaine use (4)(21)(42)(43)(44). Even if the mother does admit to substance abuse, the accuracy of the recall about frequency of use, purity, and range of drugs used is often poor. Clinical diagnosis is complicated by the fact that some drug-exposed infants do not have immediate or specifically recognizable symptoms in the newborn period. A combination of maternal history, newborn clinical symptoms, and laboratory toxicological testing of the mother and newborn serve best to avoid significant underestimation of the incidence of in utero exposure determined by any one of these approaches independently. In addition, in many jurisdictions, a physician caring for a newborn suspected of IUDE is required to investigate and report the findings to the appropriate authorities. A positive maternal history of drug use or the demonstration of drug in maternal urine may not constitute sufficient evidence to indicate a report to child protective services. Definitive documentation of the presence of drug in the baby may be required. Possible maternal and infant risk factors can be culled from the current literature and then can be developed into specific guidelines to identify those infants for drug testing; this is more cost-effective than universal screening, which is currently not recommended (45). Also, a set of formal guidelines based on maternal history and newborn clinical findings removes the bias in physician-ordered drug tests, and fewer IUDE infants are missed. Guidelines protect the physician who orders the drug screening. When the ordering physician informs the mother that a drug test has been ordered for her baby, he or she can inform parents that all infants who meet these guidelines are screened as a matter of routine, and that they are not being “singled out” for other reasons. Physicians should document in the chart the indication for the infant drug test and that the mother has been informed that an infant sample has been sent to the laboratory for drug testing. The following guidelines were developed on the basis of previous studies in the literature: 1) Infants whose mothers have any of the following: (a) History of drug abuse in present or previous pregnancies; (b) limited prenatal care (<5 prenatal visits); (c) history of hepatitis B, AIDS, syphilis, gonorrhea, prostitution; (d) unexplained placental abruption; (e) unexplained premature labor. 2) Infants who have any of the following: (a) Unexplained neurologic complications (e.g., intracranial hemorrhage or infarction, seizures); (b) evidence of possible drug withdrawal (e.g., hypertonia, irritability, seizures, tremulousness, muscle rigidity, decreased or increased stooling); (c) unexplained intrauterine growth retardation. These guidelines were tested prospectively to be 89% sensitive in a population with mixed socioeconomic status (46) and confirmed the association of specific maternal characteristics with maternal cocaine use (6)(7)(42)(43)(47)(48)(49)(50)(51)(52). Note that adolescent pregnancy and a maternal history of genital herpes or Chlamydia infection are not included as risk factors because they have not been associated with increased maternal drug use either in our population or in most prior published reports. We include a full copy of our protocol as an aid to those faced with developing guidelines at their own institutions (see Appendix). laboratory testing of newborns for drugs of abuse Testing should aim at accurate and early identification of drug-exposed newborns. Drug or drug metabolite concentrations in newborn specimens can be below the detection limits of many of the clinical laboratory analytical techniques. Thin-layer chromatography and HPLC methods can detect the relatively high drug concentrations found in suspected drug overdose patients, but lack the sensitivity needed for newborn testing. Most testing protocols rely on nonisotopic immunoassays for the initial testing phase, rather than the more difficult and costly gas chromatography—mass spectrometry (GC-MS) procedures. The immunospecificity of immunoassays are generally directed toward a group of structurally closely related drugs or metabolites and not a specific drug. Therefore, a positive immunoassay result must be considered as presumptive for a group of drug compounds and should be subjected to confirmation testing for definitive identification. Confirmation testing, performed on a fresh aliquot, should be an assay that is based on an analytical principle different from that of the initial test, and one that is more specific and at least equally sensitive. Therefore, an initial result by an immunoassay should not be confirmed by another immunoassay, even if the latter has more selective immunospecificity or is a product of a different vendor. Confirmation of a positive result by an amphetamine or methamphetamine-specific immunoassay is best considered as an intermediary test that will be followed by a more definitive confirmation test. The laboratory should be familiar with the specificity of both initial and confirmation assays, and the drugs or medications that can cause significant interference, including those that are administered during the birthing process. If the initial result cannot be confirmed, a negative report must be issued. If confirmation testing is performed by a reference laboratory, it is good laboratory quality-assurance practice to save an aliquot of the specimen for retest if necessary. newborn urine testing Because the specimen of choice for toxicology analysis in most clinical laboratories is urine, many laboratories have applied their urine-based methodologies to testing newborns suspected of IUDE. Newborn urine is far from ideal for this purpose. The most serious drawbacks are the difficulty in urine collection and the critical timing needed for a successful collection (53). Positioning the collection bag and maintaining it in position to avoid loss through leakage can be a frustrating exercise, and may require 2–3 attempts before a suitable specimen is obtained. Very often multiple attempts still result in failure. Skin rashes as a reaction to the adhesive bag are common and further complicate the collection process. The urine collected may not be of sufficient quantity to permit both initial and confirmation testing because of collection difficulties and also as a result of the lower normal urine volume in newborns. Timing of specimen collection is critical for testing newborns. The time a urine specimen is finally collected may be outside the narrow window of detection. Many negative findings caused by delays in obtaining a specimen soon after birth can be attributed to late onset of withdrawal symptoms and belated arrival at the clinical suspicion of drug exposure as well as difficulties in urine collection (53). The various problems associated with specimen collection contribute to the underestimation of IUDE. thresholds for urine initial and confirmation tests Sensitivity of a urine drug-of-abuse test depends on the threshold (cutoff) chosen. The convention is to designate a result positive if it is equal to or greater than the threshold, and negative if it is less. There are no recommended thresholds for testing of clinical samples, usually urine, for drugs of abuse. Most clinical laboratories have adopted for maternal and infant urine testing programs the thresholds used in workplace drug testing (54). One reason is that reagent manufacturers have formulated and packaged their kits on the basis of standard workplace drug testing thresholds. Some of these thresholds have been shown to be too high for clinical testing, the consequence of which has been underestimation of drug exposure. Adopting lower thresholds (e.g., 80 μg/L for benzoylecgonine and 20 μg/L for cannabinoid metabolites) can dramatically improve detection rates (55)(56). Laboratories planning to use lower thresholds have to purchase or prepare their own threshold calibrators and controls, and the stated concentrations of these materials have to be confirmed. To meet regulatory requirements, laboratories also must undertake a thorough confirmation of these “modified” assays in terms of limits of linearity and precision around the threshold. meconium testing Meconium has been proposed as an alternative specimen to urine because of difficulties associated with urine testing. Meconium, the dark green viscous first stool of a newborn, is a collection of debris consisting of desquamated cells of the alimentary tract and skin, lanugo, fatty material from the vernix caseosa, amniotic fluid, and various intestinal secretions. The disposition of drug in meconium is not well understood. The proposed mechanism is that the fetus excretes drug into bile and amniotic fluid. Drug accumulates in meconium either by direct deposition from bile or through swallowing of amniotic fluid (47). Meconium appears to form in the second trimester; because it is not excreted, it contains drugs to which the fetus has been exposed. Therefore, the presence of drugs in meconium has been proposed to be indicative of in utero drug exposure in the month or more before birth, a longer historical measure than is possible by urinalysis (47). Most reports in the literature describe the detection of cocaine in meconium, but studies in which meconium was also analyzed for other drugs of abuse demonstrated that cocaine was detected at a much higher rate than marijuana, amphetamines, or opiates (47)(57)(58). Several studies reported that some infants whose urines were negative for cocaine had positive meconium, suggesting that meconium testing is more sensitive than urine testing (46)(47)(57)(58)(59)(60)(61)(62)(63). However, part of the improved detection rate relates to the method of analysis—urine by enzyme immunoassay (EIA) or fluorescence polarization immunoassay (FPIA) vs meconium by RIA or GC-MS, or the thresholds used (300 vs 80 μg/L for benzoylecgonine) rather than the type of specimen (urine vs meconium). When more sensitive urine analytical methods and lower cutoffs were used, infant urine and meconium analyses yielded equivalent results for identifying newborns who have been exposed to cocaine in utero (47)(56)(60). Meconium is easier to collect than urine, and the amount collected is usually sufficient for complete analysis, including confirmation. Meconium testing does have some limitations. Meconium is usually passed by full-term newborns within 24 to 48 h, after which transition from blackish-green color to yellow color indicates beginning of passing of neonatal stool (64). Infants with low birth weight (<1000 g) have been shown to pass their first meconium at a median age of 3 days (65). Thus, meconium collection can be missed because of delayed passage and also may not be available soon after birth for early detection of IUDE. In fact, in a large-scale study, only 77.6% of 3879 newborns had meconium available for analysis (58). In the clinical laboratory, meconium is an unfamiliar matrix, being a sticky material that is more difficult to work with than urine. Furthermore, processing of meconium for analysis requires weighing and extraction steps that are not needed for urine. An accurately weighed 0.1 to 1 g of meconium is generally used, and drug analyte has to be extracted from meconium into a medium that is compatible with the initial immunoassays. Extraction has been achieved by acidified water (47)(58) or saline (59), methanol (66), or acetonitrile (46). Improved assay sensitivity can be attained by evaporating the extract solvent either to dryness or a lower volume. A variety of immunoassays has been used for the initial testing of meconium extracts: EIA (63)(67), RIA (47)(58)(59), FPIA (46)(60)(61), and kinetic interaction of microparticles in solution (KIMS) (61). To improve sensitivity, thresholds for the extract should be set as low as possible and certainly lower than the workplace drug-testing thresholds. All urine drugs-of-abuse assays, if they are used with meconium extracts, must be investigated for possible effect of matrix on accuracy, precision, and assay linearity. Confirmation assays for meconium are more difficult than those for urine. Although HPLC has been used (68), it is GC-MS methods that have the lower assay detection limits necessary for identifying newborns with low drug concentration in meconium. Most published GC-MS procedures involve the extraction of the drug from meconium by solid-phase extraction columns after meconium has been dispersed in extraction solvent by rigorous vortex-mixing or sonication, and particulate materials sedimented by centrifugation (46)(66)(69)(70). Recoveries of drugs from meconium can be low (30–50%), which means that selection of proper internal standards is important. Fortunately, deuterated internal standards for most of drugs of abuse are now available. Some laboratories may find it easier to modify existing urine methodologies to perform at lower thresholds than to develop and confirm a new set of more difficult assays for meconium. It is recommended that laboratories contemplating meconium testing should consider first lowering the threshold of their urine assays before embarking on meconium testing because sensitivity of urine testing at lower urine thresholds has been reported to be comparable with that of meconium testing. hair testing Systemic drug exposure leads to incorporation of the drug into hair. Hair analysis has demonstrated the presence of drugs of abuse in the hair of drug users (71)(72). Nevertheless, the proposal to use hair testing in drug screening programs for the workplace has been controversial. Among the concerns expressed is the difficulty in identifying the presence of drug in hair caused by external application, i.e., environmental contamination (73)(74). Therefore, the presence of cocaine in hair is not necessarily an indication of drug use. Detection of benzoylecgonine in hair has been proposed to be a marker of active cocaine use (75), but unless very careful precautions are taken to control assay conditions, particularly pH during the extraction process, artificial production of benzoylecgonine will lead to a false-positive result (74). Testing of newborn hair to document IUDE, however, is an appropriate clinical application of hair testing (76). In testing newborn hair, environmental contamination is a not an issue if the newborn is tested during the immediate postdelivery period while still in the hospital and not after the newborn has been discharged to go home with a mother who is suspected of drug abuse. Literature reports on newborn hair testing are mostly related to cocaine exposure, although amphetamines, opiates, and methadone have been found in adult hair testing (77)(78)(79). Cocaine crosses the placenta and cocaine and its metabolite have been found in newborn hair. Hair present at birth grows during the third trimester; therefore detection of drug in newborn hair reflects maternal drug use during the last 3 months of pregnancy (76)(80). The quantity of benzoylecgonine in newborn hair correlates best with that in the proximal segment of the mother’s hair, which represents maternal hair growth in the 12 weeks or so before delivery (60). Hair analysis results will be positive for IUDE newborns whose urines are negative because their mothers abstained from drug use only for a few days before delivery. Unlike urine or meconium testing, the timing of hair collection is not critical. Hair collected even a few weeks after birth offers the likelihood of detecting gestational drug exposure, assuming environmental contamination can be ruled out. Hair analysis is technically much more involved than urine or meconium. Before extraction, hair samples require decontamination by washings with a variety of agents including methanol, ethanol, dichloromethane, acetone, detergent, or warm water (81). Drug is then extracted from hair by incubation with methanol, ethanol, acid, and proteinase or pronase. The low drug concentrations in hair are detectable by RIA only and the amount of neonatal hair needed is 2–5 mg (82). By using GC-MS assays with data acquisition in selected-ion monitoring mode, as little as 5–10 mg of adult hair is adequate (74), whereas a sophisticated research protocol base on tandem mass spectrometry will need only 1 mg of hair (83). GC-MS procedures requiring 50–100 mg of hair are more suitable for testing adult hair because most newborns do not have that much hair, and their mothers probably will object to extensive shaving of their babies for drug testing. Because hair analysis is technically demanding, the availability of newborn hair testing is limited to a few specialized laboratories. testing of other fluids Analysis of amniotic fluid for detection of IUDE is a largely unexplored option. Benzoylecgonine concentration in amniotic fluid has been shown to be higher than that in newborn urine, and more exposed newborns can be detected compared with urinalysis (84). Availability of amniotic fluid is an issue with patients who have premature rupture of membranes or rapidly advancing labor. Whether amniotic fluid testing has any clinical value as a measure of long-term exposure has not been studied. A recent report demonstrated the feasibility of using newborn gastric amniotic fluid for determining gestational cocaine exposure (44). In a small sample of 39 newborns, the detection rate of gastric fluid analysis was essentially that of meconium, and approximately twice that of urinalysis. It was not mentioned, however, whether the same or different thresholds had been used for the analysis of the three specimen types. The advantage of gastric fluid is the availability of this specimen soon after birth for rapid testing for drug exposure. The major disadvantages are that not all infants suspected of IUDE are identified at the time of birth, and that deep suction of a newborn for gastric secretions is not necessarily a routine procedure. The usefulness of gastric fluid analysis must await further studies. laboratory report The laboratory report should reflect accurately the laboratory analysis that has been performed, and should contain all the information necessary for proper interpretation of the analytical outcome. If the positive result reported is only the initial result because there is insufficient urine for confirmation, confirmation is pending, or the laboratory does not perform confirmation testing, the reason for reporting an unconfirmed positive result should clearly be stated. Physicians, nurses, and social workers have to know the scope and limitation of the drug test, and a result reported accurately and unambiguously is critical in reaching that goal. For example, testing for opiates for many laboratories is limited to codeine and morphine only, and a specimen containing opiates other than codeine or morphine (e.g., dihydrocodone or hydromorphone) should be reported as negative for codeine and morphine and not as negative for opiates. Furthermore, if a specimen contains codeine or morphine, the laboratory report also should state which opiate or opiates have been detected and confirmed: morphine only, or morphine and codeine. It is not sufficient to report opiates positive and confirmed because interpretations of the two results are different, as they suggest different sources for morphine (85). The same specimen can be either positive or negative depending on the threshold used. Therefore, the laboratory report should indicate all threshold concentrations for both initial and confirmation tests. This is particularly important if comparison of results from two laboratories is to be meaningful. guidelines for chain-of-custody documentation The documentation of the presence of an illicit drug in a newborn can be challenged by the mother or the family. Moreover, in many jurisdictions, reporting of the finding to state or local authorities is mandatory and, although infrequent, may result in the mother’s losing custody of her baby. Therefore, depending on the local environment and needs, testing of newborns for illicit drugs may require chain-of-custody documentation to prove the integrity of the test specimen has been maintained and to record all individuals who have handled the specimen and when. Document by signature all individuals, starting with the specimen collector, who have handled and have had custody of the specimen until the specimen is discarded. Record the time and reason of each transfer (change in custody) of the specimen. The collector should seal a specimen with tamper-proof tape and release specimen for transportation to the laboratory in a bag or package that is sealed also with tamper-proof tape. The chain of custody of each aliquot from aliquoting to discard should also be documented. Laboratory areas for specimen processing, analysis, and storage should be secure and access limited to authorized personnel only. Appendix guidelines for medically indicated newborn urine drug testing 1) Infants whose mothers have any of the following: (a) History of drug abuse in present or previous pregnancies; (b) limited prenatal care (<5 prenatal visits); (c) history of hepatitis B, AIDS, syphilis, gonorrhea, prostitution; (d) unexplained placental abruption; (e) unexplained premature labor. 2) Infants who have any of the following: (a) Unexplained neurologic complications (e.g., intracranial hemorrhage or infarction, seizures); (b) evidence of possible drug withdrawal (e.g., hypertonia, irritability, seizures, tremulousness, muscle rigidity, decreased or increased stooling); (c) unexplained intrauterine growth retardation. If any of these guidelines are met: (a) Nurses will automatically place a urine collection bag on the infant; (b) urine screen will not be sent until a physician writes the order. If a urine screen is sent, the physician writing the order must: (a) notify the infant’s attending physician (if not the same) that the screens are being sent; (b) document the indication for the screen in the infant’s hospital chart. If a urine screen is sent, the physician writing the order or the infant’s attending physician (if not the same) must: (a) notify the infant’s mother and tell her the indication for the screen; (b) notify the mother’s obstetrician that the screen is being sent; (c) notify social services that the screen is being sent. If social services had not been previously consulted because there were no other concerns, social services will simply review the chart and only talk to the mother after discussion with the mother’s obstetrician or infant’s physician. If the newborn drug screen is positive: (a) the physician of the newborn is responsible for notifying the mother of the results of the screen; (b) social services will evaluate the mother, her resources, home situation, and associated problems, and will assist the mother with rehabilitation programs, parenting courses, parent support groups, home health aides, public health nurses, and medical/mental health referrals as necessary as well as inform Child Protective Services; (c) HIV and hepatitis B status should be established in the mother and appropriate care of the infant should follow; (d) the infant should have close neurodevelopmental follow-up; (e) performance of a head ultrasound should be considered; (f) breast-feeding should not be permitted. Summary Hospitals involved in drug testing of newborns should have a set of carefully developed guidelines for selection of infants for testing and protocols for ordering the test and informing the family. Laboratory analysis should be performed on the basis of validated methodologies. It is important that all positive results are confirmed by a second test before reporting and that clinicians understand the reported results. Urine remains the most commonly used specimen for newborn drug testing. Urine testing has been reported to be less sensitive than meconium testing, although this may be caused by higher thresholds used in urine assays. However, urine is definitely more difficult to obtain. Meconium testing is hampered by the more labor-intensive and time-consuming preanalytical steps. More extensive testing of newborns by hair analysis must await the development of technically less demanding techniques, and testing of amniotic fluid or gastric lavage is still in the developmental stages. Urine and meconium testing remain the current options for identifying those newborns exposed to illicit drugs in utero. Lowering thresholds for urine assays by modifying existing methodologies would be an appropriate goal for those laboratories wishing to improve sensitivity. 1 Nonstandard abbreviations: IUDE, intrauterine drug exposure; GC-MS, gas chromatography–mass spectrometry; EIA, enzyme immunoassay; and FPIA, fluorescence polarization immunoassay. 1 Young SL, Vosper HJ, Phillips SA. Cocaine: its effects on maternal and child health. Pharmacotherapy 1992 ; 12 : 2 -17. PubMed 2 Bell GL, Lau K. Perinatal and neonatal issues of substance abuse. Pediatr Clin North Am 1995 ; 42 : 261 -281. Crossref Search ADS PubMed 3 Chasnoff IJ. Cocaine, pregnancy and the neonate. Women Health 1989 ; 15 : 23 -25. Crossref Search ADS PubMed 4 Chasnoff IJ, Griffith DR. Cocaine: clinical studies of pregnancy and the newborn. Ann N Y Acad Sci 1989 ; 562 : 260 -266. Crossref Search ADS PubMed 5 Cohen HR, Green JR, Crombleholme WR. Peripartum cocaine use: estimating risk of adverse pregnancy outcome. Int J Gynaecol Obstet 1991 ; 35 : 51 -54. Crossref Search ADS PubMed 6 Gillogley KM, Evans AT, Hansen RL, Samuels SJ, Batra KK. The perinatal impact of cocaine, amphetamine, and opiate use detected by universal intrapartum screening. Am J Obstet Gynecol 1990 ; 163 : 1535 -1542. Crossref Search ADS PubMed 7 Little BB, Snell LM, Klein VR, Gilstrap LC, III. Cocaine abuse during pregnancy: maternal and fetal implications. Obstet Gynecol 1989 ; 73 : 157 -160. PubMed 8 Ney JA, Dooley SL, Keith LG, Chasnoff IJ, Socol ML. The prevalence of substance abuse in patients with suspected preterm labor. Am J Obstet Gynecol 1990 ; 162 : 1562 -1567. Crossref Search ADS PubMed 9 Oro AS, Dixon SD. Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J Pediatr 1987 ; 111 : 571 -578. Crossref Search ADS PubMed 10 Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr 1986 ; 108 : 456 -459. Crossref Search ADS PubMed 11 Chavez GF, Mulinare J, Cordero J. Maternal cocaine use during early pregnancy as a risk factor for congenital urogenital anomalies. JAMA 1989 ; 262 : 795 -798. Crossref Search ADS PubMed 12 Czyrko C, Del Pin CA, O’Neill JA, Peckham GJ, Ross AJ, III. Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival. J Pediatr Surg 1991 ; 26 : 414 -421. Crossref Search ADS PubMed 13 Dixon SD, Bejar R. Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J Pediatr 1989 ; 115 : 770 -778. Crossref Search ADS PubMed 14 Downing GJ, Horner SR, Kilbride HW. Characteristics of perinatal cocaine-exposed infants with necrotizing enterocolitis. Am J Dis Child 1991 ; 145 : 26 -27. PubMed 15 Fulroth R, Phillips B, Duranc DJ. Perinatal outcomes of infants exposed to cocaine and/or heroin in utero. Am J Dis Child 1989 ; 143 : 905 -910. PubMed 16 Greenfield SP, Rutigliano E, Steinhardt G, Elder JS. Genitourinary tract malformations and maternal cocaine abuse. Urology 1991 ; 307 : 455 -459. 17 Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: perinatal outcomes. Am J Epidemiol 1991 ; 133 : 818 -825. Crossref Search ADS PubMed 18 Kelley SJ, Walsh JH, Thompson K. Birth outcomes, health problems, and neglect with prenatal exposure to cocaine. Pediatr Nurs 1991 ; 17 : 130 -136. PubMed 19 Lipshultz SE, Frassica JJ, Orav EJ. Cardiovascular abnormalities in infants prenatally exposed to cocaine. J Pediatr 1991 ; 118 : 44 -51. Crossref Search ADS PubMed 20 Sehgal S, Ewing C, Waring P, Findlay R, Bean X, Taeusch W. Morbidity of low-birthweight infants with intrauterine cocaine exposure. J Natl Med Assoc 1993 ; 85 : 20 -24. PubMed 21 Zuckerman B, Frank D, Hingson R, Amaro H, Levenson S, Kayne H, et al. Effects of maternal marijuana and cocaine use on fetal growth. N Engl J Med 1989 ; 320 : 762 -768. Crossref Search ADS PubMed 22 Lopez SL, Taeusch HW, Findlay RD, Walther FJ. Time of onset of necrotizing enterocolitis in newborn infants with known prenatal cocaine exposure. Clin Pediatr (Phila) 1995 ; 34 : 424 -429. Crossref Search ADS PubMed 23 Franck L, Vilardi J. Assessment and management of opioid withdrawal in ill neonates. Neonatal Netw 1995 ; 14 : 39 -48. 24 Finnegan LP, Kaltenbach K. Neonatal abstinence syndrome. Hoekelman RA eds. Primary pediatric care 3rd ed. 1996 : 1367 -1378 CV Mosby St Louis. . 25 Mastrogiannis DS, DeCavalas GO, Verma U, Tejani N. Perinatal outcome after recent cocaine usage. Obstet Gynecol 1990 ; 76 : 8 -11. PubMed 26 LeBlanc PE, Parekh AJ, Naso B, Glass L. Effects of intrauterine exposure to alkaloidal cocaine (’crack’). Am J Dis Child 1987 ; 141 : 937 -938. PubMed 27 Dixon SD. Effects of transplacental exposure to cocaine and methamphetamine on the neonate. West J Med 1991 ; 150 : 436 -442. 28 Regan DO, Ehrlich SM, Finnegan LP. Infants of drug addicts: at risk for child abuse, neglect and placement in foster care. Neurotoxicol Teratol 1987 ; 9 : 315 -319. Crossref Search ADS PubMed 29 Jaudes PK, Ekwo E, Van Voorhis J. Association of drug abuse and child abuse. Child Abuse Negl 1995 ; 19 : 1065 -1075. Crossref Search ADS PubMed 30 Chasnoff IJ, Griffith DR, Freier C, Murray J. Cocaine/polydrug use in pregnancy: two year follow-up. Pediatrics 1992 ; 89 : 284 -289. PubMed 31 Schneider JW, Chasnoff IJ. Motor assessment of cocaine/polydrug exposed infants at age 4 months. Neurotoxicol Teratol 1992 ; 14 : 97 -101. Crossref Search ADS PubMed 32 Singer L, Arendt R, Minnes S. Neurodevelopmental effects of cocaine. Clin Perinatol 1993 ; 20 : 245 -262. Crossref Search ADS PubMed 33 Streissguth AP, Grant TM, Barr HM, Brown ZA, Martin JC, Maycock DE, et al. Cocaine and the use of alcohol and other drugs during pregnancy. Am J Obstet Gynecol 1991 ; 164 : 1239 -1243. Crossref Search ADS PubMed 34 Van Baar AL, Soepatmi S, Gunning WB, Akkerhuis GW. Development after prenatal exposure to cocaine, heroin and methadone. Acta Paediatr Suppl 1994 ; 404 : 40 -46. PubMed 35 Chasnoff I, Hunt CE, Kletter R, Kaplan D. Prenatal cocaine exposure is associated with respiratory pattern abnormalities. Am J Dis Child 1989 ; 143 : 583 -587. PubMed 36 Ward SL, Bautista D, Chan L, Derry M, Lisbin A, Durfee MJ, et al. Sudden infant death syndrome in infants of substance-abusing mothers. J Pediatr 1990 ; 117 : 878 -881. 37 Kandall SR, Gaines J, Habel L, Davidson G, Jessop D. Relationship of maternal substance abuse to subsequent sudden infant death syndrome in offspring. J Pediatr 1993 ; 123 : 120 -126. Crossref Search ADS PubMed 38 Sylvestri JM, Long JM, Weese-Mayer DE, Barkov GA. Effect of prenatal cocaine on respiration, heart rate, and sudden infant death syndrome. Pediatr Pulmonol 1991 ; 11 : 328 -334. Crossref Search ADS PubMed 39 Kharasch SJ, Glotzer D, Vinci R, Weitzman M, Sargent J. Unsuspected cocaine exposure in young children. Am J Dis Child 1991 ; 145 : 204 -206. PubMed 40 Mirchandani HG, Mirchandani IH, Hellman F, English-Rider R, Rosen S, Laposata EA. Passive inhalation of free-base cocaine (’crack’) smoke by infants. Arch Pathol Lab Med 1991 ; 115 : 494 -498. PubMed 41 Rosenberg NM, Meert K, Marino D, Yee H, Kauffman RE. Occult cocaine and opiate exposure in children and associated physical findings. Pediatr Emerg Care 1995 ; 11 : 167 -169. Crossref Search ADS PubMed 42 Frank DA, Zuckerman BS, Amaro H, Aboague K, Bauchner H, Cabral H, et al. Cocaine use during pregnancy: prevalence and correlates. Pediatrics 1988 ; 82 : 888 -895. PubMed 43 Matera C, Warren WB, Moomjy M, Fink DJ, Fox HE. Prevalence of use of cocaine and other substances in an obstetric population. Am J Obstet Gynecol 1990 ; 163 : 797 -801. Crossref Search ADS PubMed 44 Garcia DC, Romero A, Garcia GC, Ostrea EM. Gastric fluid analysis for determining gestational cocaine exposure. Pediatrics 1996 ; 98 : 291 -293. PubMed 45 Committee on Substance Abuse. Drug-exposed infants. Pediatrics 1995;96:364–6.. 46 Ryan RM, Wagner CL, Schultz JM, Varley J, DiPreta J, Sherer DM, et al. Meconium analysis improves identification of intrauterine cocaine exposed infants. J Pediatr 1994 ; 125 : 435 -440. Crossref Search ADS PubMed 47 Ostrea EM, Jr, Brady MJ, Parks PM, Asensio DC, Naluz A. Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989 ; 115 : 474 -477. Crossref Search ADS PubMed 48 Schutzman DL, Frankenfield-Chernicoff M, Clatterbaugh HE, Singer J. Incidence of intrauterine cocaine exposure in a suburban setting. Pediatrics 1991 ; 88 : 825 -827. PubMed 49 McCalla S, Minkoff HL, Feldman J, Delke I, Salwin M, Valencia G, Glass L. The biologic and social consequences of perinatal cocaine use in an inner-city population: results of an anonymous cross sectional study. Am J Obstet Gynecol 1991 ; 164 : 625 -630. Crossref Search ADS PubMed 50 Chasnoff IJ, Landress HJ, Barrett ME. The prevalence of illicit-drug and alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida. N Engl J Med 1990 ; 322 : 1202 -1206. Crossref Search ADS PubMed 51 Vega WA, Kolody B, Hwang J, Moble A. Prevalence and magnitude of perinatal substance exposures in California. N Engl J Med 1993 ; 329 : 850 -854. Crossref Search ADS PubMed 52 Webber MP, Lambert G, Bateman DA, Hauser WA. Maternal risk factors for congenital syphilis: a case-control study. Am J Epidemiol 1993 ; 137 : 415 -422. Crossref Search ADS PubMed 53 Halstead AC, Godolphin W, Lockitch G, Segal S. Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns. Clin Biochem 1988 ; 21 : 59 -61. Crossref Search ADS PubMed 54 Mandatory guidelines for federal workplace drug testing programs. Fed Regist 1988;53:11979–89.. 55 Hicks JM, Morales A, Soldin SJ. Drugs of abuse in a pediatric outpatient population [Letter]. Clin Chem 1990 ; 36 : 1256 -1257. Crossref Search ADS PubMed 56 Casanova OQ, Lombardero N, Behnke M, Eyler FD, Conlon M, Bertholf RL. Detection of cocaine exposure in the neonate. Arch Pathol Lab Med 1994 ; 118 : 988 -993. PubMed 57 Lewis D, Moore C, Leikin JB, Kechavarz L. Multiple birth concordance of street drug assays of meconium analysis. Vet Hum Toxicol 1995 ; 37 : 318 -319. PubMed 58 Ostrea EM, Brady M, Gause S, Raymundo AL, Stevens M. Drug screening of newborns by meconium analysis: a large-scale, prospective, epidemiologic study. Pediatrics 1992 ; 89 : 107 -113. PubMed 59 Maynard EC, Amoruso LP, Oh W. Meconium for drug testing. Am J Dis Child 1991 ; 145 : 650 -652. PubMed 60 Callahan CM, Grant TM, Phipps P, Clark G, Novack AH, Streissguth AP, Raisys VA. Measurement of gestational cocaine exposure: sensitivity of infants’ hair, meconium, and urine. J Pediatr 1992 ; 120 : 763 -768. Crossref Search ADS PubMed 61 Lewis DE, Moore CM, Leikin JB, Koller A. Meconium analysis for cocaine: a validation study and comparison with paired urine analysis. J Anal Toxicol 1995 ; 19 : 148 -150. Crossref Search ADS PubMed 62 Bibb KW, Stewart DL, Walker JR, Cook VD. Drug screening in newborns and mothers using meconium samples, paired urine samples, and interviews. J Perinatol 1995 ; 15 : 199 -202. PubMed 63 Wingert WE, Feldman MS, Kim MH, Noble L, Hand I, Yoon JJ. A comparison of meconium, maternal urine and neonatal urine for detection of maternal drug use during pregnancy. J Forensic Sci 1994 ; 39 : 150 -158. PubMed 64 Gourley GR, Kreamer B, Arend R. Excremental studies in human neonates. Gastroenterology 1990 ; 99 : 1705 -1709. Crossref Search ADS PubMed 65 Verna A, Dhanireddy R. Time of first stool in extremely low birth weight (<1000 gm) infants. J Pediatr 1992 ; 122 : 626 -629. 66 Clark GD, Rosenzweig B, Raisys VA, Callahan CM, Grant TM, Streissguth AP. The analysis of cocaine and benzoylecgonine in meconium. J Anal Toxicol 1992 ; 16 : 261 -263. Crossref Search ADS PubMed 67 Ostrea EM, Romero A, Yee H. Adaptation of meconium drug test for mass screening. J Pediatr 1993 ; 122 : 152 -154. Crossref Search ADS PubMed 68 Murphey LJ, Olsen G, Konkol RJ. Quantitation of benzoylnorecgonine and other cocaine metabolites in meconium by high-performance liquid chromatography. J Chromatogr 1993 ; 613 : 330 -335. Crossref Search ADS PubMed 69 Lombardero N, Casanova O, Behnke M, Eyler FD, Bertholf RL. Measurement of cocaine and metabolites in urine, meconium, and diapers by gas chromatography/mass spectrometry. Ann Clin Lab Sci 1993 ; 23 : 385 -394. PubMed 70 Abusada GM, Abukhalaf IK, Alford DD, et al. Solid-phase extraction and GC/MS quantitation of cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma. J Anal Toxicol 1993 ; 17 : 353 -358. Crossref Search ADS PubMed 71 Moeller MR, Fey P. Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine) in human hair by GC/MS and its application to a methadone treatment program. Forensic Sci Int 1993 ; 63 : 185 -206. Crossref Search ADS PubMed 72 Baumartner WA, Hill VA, Blahd WH. Hair analysis for drugs of abuse. J Forensic Sci 1989 ; 34 : 1433 -1453. 73 Blank DL, Kidwell DA. Decontamination procedures for drugs of abuse in hair: are they sufficient?. Forensic Sci Int 1995 ; 70 : 13 -38. Crossref Search ADS PubMed 74 Wang WL, Cone EJ. Testing human hair for drugs of abuse. IV. Environmental cocaine contamination and washing effects. Forensic Sci Int 1995 ; 70 : 39 -51. Crossref Search ADS PubMed 75 Koren G, Klein J, Forman R, Graham K. Hair analysis of cocaine: differentiation between systemic exposure and external contamination. J Clin Pharmacol 1992 ; 32 : 671 -675. Crossref Search ADS PubMed 76 Koren G. Measurement of drugs in neonatal hair; a window to fetal exposure. Forensic Sci Int 1995 ; 70 : 77 -82. Crossref Search ADS PubMed 77 Moeller MR, Fey P. Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine) in human hair by GC-MS and its application to a methadone treatment program. Forensic Sci Int 1993 ; 63 : 185 -206. Crossref Search ADS PubMed 78 Staub C. Analytical procedures for determination of opiates in hair: a review. Forensic Sci Int 1995 ; 70 : 111 -123. Crossref Search ADS PubMed 79 Brewer C. Hair analysis as a tool for monitoring and managing patients on methadone maintenance. Forensic Sci Int 1993 ; 63 : 277 -283. Crossref Search ADS PubMed 80 Graham K, Koren G, Klein J, Schneiderman J, Greenwald M. Determination of gestational cocaine exposure by hair analysis. JAMA 1989 ; 262 : 3328 -3330. Crossref Search ADS PubMed 81 Selavka CM, Rieders F. The determination of cocaine in hair: a review. Forensic Sci Int 1995 ; 70 : 155 -164. Crossref Search ADS PubMed 82 Klein J, Forman R, Eliopoulos C, Koren G. A method for simultaneous measurement of cocaine and nicotine in neonatal hair. Ther Drug Monit 1994 ; 16 : 67 -70. Crossref Search ADS PubMed 83 Kidwell DA. Analysis of phencyclidine and cocaine in human hair by tandem mass spectrometry. J Forensic Sci 1993 ; 38 : 272 -284. PubMed 84 Jain L, Meyer W, Moore C, Tebbett I, Gauthier D, Vidyasagar D. Detection of fetal cocaine exposure by analysis of amniotic fluid. Obstet Gynecol 1993 ; 81 : 787 -790. PubMed 85 ElSohly MA, Jones AB. Morphine and codeine in biological fluids: approaches to source differentiation. Forensic Sci Rev 1989 ; 1 : 14 -22. © 1997 The American Association for Clinical Chemistry This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Detection of intrauterine illicit drug exposure by newborn drug testing
JF - Clinical Chemistry
DO - 10.1093/clinchem/43.1.235
DA - 1997-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/detection-of-intrauterine-illicit-drug-exposure-by-newborn-drug-sSXbr5n6W4
SP - 235
EP - 242
VL - 43
IS - 1
DP - DeepDyve
ER -