New meconium biomarkers of prenatal methamphetamine exposure increase identification of affected neonates.
BACKGROUND
Prenatal methamphetamine (MAMP) exposure is poorly reflected in neonatal meconium. Often, maternal self-reported MAMP use is not corroborated by positive results in amphetamines immunoassays of meconium, and even if initial test results are positive, they frequently are not confirmed for MAMP or amphetamine (AMP) by chromatographic analysis. The presence of the MAMP metabolites p-hydroxymethamphetamine (pOHMAMP), p-hydroxyamphetamine (pOHAMP), and norephedrine (NOREPH) in meconium may improve the identification of MAMP- and AMP-exposed neonates.


METHODS
Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography- tandem mass spectrometric reanalysis for these recently identified metabolites.


RESULTS
pOHAMP and NOREPH were detected only when MAMP and/or AMP were present and thus do not appear to be promising biomarkers of prenatal MAMP exposure. pOHMAMP, in contrast, identified 6 additional neonates whose mothers reported MAMP exposure, yet had a meconium sample screened as negative; pOHMAMP was more likely to be present if maternal MAMP use continued into the third trimester. Although the pOHMAMP results for meconium samples corroborated the maternal self-reports, the confirmation rate for positive meconium screening results did not improve with the inclusion of these new biomarkers.


CONCLUSIONS
pOHMAMP identified additional MAMP- exposed neonates; therefore, MAMP, AMP, and pOHMAMP should be included in meconium chromatographic analyses. Maximizing the identification of MAMP-exposed children requires improvement in immunoassay screening tests to reduce false-negative and false-positive results. Additional research will help clarify which AMP-related compounds, if any, contribute to unconfirmed positive results in screening tests. Furthermore, nonamphetamine compounds endogenous to the complex meconium matrix also may cross-react, making chromatographic confirmation of screening results essential.
Gray
Teresa R
TR
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
Kelly
Tamsin
T
LaGasse
Linda L
LL
Smith
Lynne M
LM
Derauf
Chris
C
Grant
Penny
P
Shah
Rizwan
R
Arria
Amelia
A
Haning
William
W
Della Grotta
Sheri
S
Strauss
Arthur
A
Lester
Barry M
BM
Huestis
Marilyn A
MA
D000697:Central Nervous System Stimulants / Q000032:analysis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008470:Meconium / Q000737:chemistry*; D008694:Methamphetamine / Q000032:analysis* / Q000378:metabolism*; D011247:Pregnancy; D015813:Substance Abuse Detection / Q000379:methods*
D000697:Central Nervous System Stimulants; D008694:Methamphetamine