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Detection of maternal prenatal opiate/opioid use up to 5 months before birth
Opiates are naturally occurring alkaloids that are derived from the opium poppy and demonstrate analgesic effects. Opioids are derived from natural and semisynthetic alkaloids of opium or synthetic compounds(1):
-Codeine is a naturally occurring opioid agonist often incorporated into formulations along with acetaminophen or aspirin to increase its analgesic effect.(2) Codeine is metabolized to morphine and subsequently undergoes glucuronidation and sulfation.
-Morphine is an opioid receptor agonist that is used for major pain analgesia.(2) It has been shown to distribute widely into many fetal tissues,(4) and has been detected in meconium.
-Hydrocodone is a semisynthetic analgesic derived from codeine. Hydrocodone is 6 times more potent than codeine and is prescribed for treatment of moderate-to-moderately severe pain.(2) Hydrocodone undergoes O-demethylation in vivo, forming hydromorphone.
-Hydromorphone, a semisynthetic derivative of morphine, is an opioid analgesic. It is 7 to 10 times more potent than morphine, its addiction liability is similar to morphine.(2)
-Oxycodone, a semisynthetic narcotic derived from thebaine. It is metabolized by O-demethylation, forming oxymorphone.(2)
-Oxymorphone is a semisynthetic opioid derivative of thebaine and is indicated for moderate-to-severe pain.(2)
-Heroin, a semisynthetic derivative of morphine, is rapidly deacetylated in vivo to the active metabolite 6-monoacetlymorphine (6-MAM), which is further hydrolyzed to morphine.(2)
Opiates have been shown to readily cross the placenta and distribute widely into many fetal tissues. Opiate use by the mother during pregnancy increases the risk of prematurity and small size for gestational age. Furthermore, heroin-exposed infants exhibit an early onset of withdrawal symptoms compared to methadone-exposed infants. These infants demonstrate a variety of symptoms including irritability, hypertonia, wakefulness, diarrhea, yawning, sneezing, increased hiccups, jitteriness, excessive sucking, and seizures. Long-term intrauterine drug exposure may lead to abnormal neurocognitive and behavioral development as well as an increased risk of sudden infant death syndrome.
The disposition of opiates and opioids in meconium, the first fecal material passed by the neonate, 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. The first evidence of meconium in the fetal intestine appears at approximately the 10th to 12th week of gestation, and slowly moves into the colon by the 16th week of gestation. Therefore, the presence of drugs in meconium has been proposed to be indicative of in utero drug exposure during the final 4 to 5 months of pregnancy, a longer historical measure than is possible by urinalysis.
Positives are reported with a quantitative LC-MS/MS result.
Codeine by LC-MS/MS: 50 ng/g
Hydrocodone by LC-MS/MS: 50 ng/g
Hydromorphone by LC-MS/MS: 50 ng/g
Morphine by LC-MS/MS: 50 ng/g
Oxycodone by LC-MS/MS: 50 ng/g
Oxymorphone by LC-MS/MS: 50 ng/g
The presence of any of the following opiates (codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) at > or =50 ng/g or 6-monoacetlymorphine at > or =10 ng/g indicates the newborn was exposed to opiates/opioids during gestation.
Since the evidence of illicit drug use during pregnancy can be cause for separating the baby from the mother, a kit is available that includes all the materials necessary to complete chain-of-custody to ensure that the test results are appropriate for legal proceedings.
1. Gutstein HB, Akil H: Opioid analgesics. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by LL Brunton, JS Lazo, KL Parker. 11th edition. McGraw-Hill Companies Inc, 2006. Available at URL: www.accessmedicine.com/content.aspx?aID=940653
2. Disposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt. Foster City, CA. Biomedical Publications, 2008, pp 355-360; 730-735; 745-747; 750-752; 1057-1064; 1166-1168; 1470-1171
3. Ostrea EM Jr, Lynn SM, Wayne RN, Stryker JC: Tissue distribution of morphine in the newborns of addicted monkeys and humans. Clinical implications. Dev Pharmacol Ther 1980;1:163-170
4. Szeto HH: Kinetics of drug transfer to the fetus. Clin Obstet Gynecol 1993;36:246-254
5. Kwon TC, Ryan RM: Detection of intrauterine illicit drug exposure by newborn drug testing. National Academy of Clinical Biochemistry. Clin Chem 1997;43:235-242
6. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477
7. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv 2005;60:45-56