Opioid and polysubstance exposure

effects on metabolomics during

pregnancy

o Ahmad Aboaziza, MD; Devon Kuehn, MD; Sri Ravisankar, MD; Kim Kew, PhD; Kadesha
McIntyre, MS; Samantha Poppenfuses, BS; Dmitry Tumin, PhD
3/25/19
INTRODUCTION

šOpioid use has become increasingly

common among pregnant women in
the United States
šAs a result, there has been an
increased incidence of Neonatal
abstinence syndrome (NAS) in the
United States.
Rates of Infants Identified with Drug Withdrawal Syndrome by NC hospitals, per 100,000 Live Births.
Adapted from North Carolina State Center for Health Statistics, Injury Epidemiology and Surveillance Unit (2014)

Rates of Infants Identified with Drug Withdrawal Syndrome by NC hospitals, per 100,000 Live Births
 NAS BACKGROUND

NAS is array of signs and symptoms Condition in the neonate is characterized by

occurring after birth due to abrupt hyperactivity of the central and autonomic
discontinuation of intrauterine exposure to nervous systems.
substances taken by the mother.
 NUTRITIONAL IMPACTS

š It is known that decreases in folate and vitamin B12 increase the risk of a
variety of chromosomal breakage and aberrations, neural tube defects,
recurrent fetal losses, preterm delivery and low birth weight and a variety
of other detrimental outcomes
š Shrestha et al in a recent study has shown a negative impact of opioids
and polysubstance abuse during pregnancy on maternal dietary intake,
specifically vitamin A, vitamin B6, vitamin E, iron, folate, and choline.
š Currently there is a lack of research in regards to nutritional deficiencies
among drug exposed infants
HYPOTHESIS

Increased levels of prenatal opioid exposure will be

associated with decreased nutrient concentrations in the
umbilical cord of these infants.
 SPECIFIC AIMS

š To determine the influence of opioid and polysubstance drug use during

pregnancy on the status of key nutrients in fetal development by
assessing umbilical cord concentration of these nutrients
š To assess correlation between opioid and polysubstance exposure on
neonatal outcomes
 STUDY DESIGN

š A prospective, cohort study comparing nutritional deficiencies with

maternal drug exposure and neonatal outcome(Birth weight, NAS scores,
treatment requirement, LOS)
š Study population: pregnant women singleton neonate with a gestational
age ≥34 weeks
š 61 patients enrolled to date. 9 cords excluded from analysis for the
presence of suspected chorioamnioitis
š N=52 available for evaluation
 METHODS

š Demographic data on maternal substance abuse and pregnancy and neonatal data
including NAS and any treatment needed was collected from the medical record
š Within 1 hour of birth, cord samples were collected from mothers who had consented to
be in the study including the control mothers who had no prenatal drug exposure.
š The cords were rinsed of excess blood, weighed and cut in to uniform segments that
were stored at -80 until analyzed.
š Cord samples were homogenized, and extracted for analysis using solid phase or protein
precipitation.
š Liquid chromatography/mass spectroscopy used to measure global and targeted
metabolite and drug levels.
Concentration (ng/mL)

QUANTITATIVE RESULTS
 METABOLOMICS ANALYSIS

š Principal component-
discriminant analysis (PCA-DA)
š 985 metabolite features
detected
T-TEST RESULTS

Number of Features Significantly Different than the Control Group

Sample Group
(p-value ≤ 0.05)

Measured Cotinine Users 67

Measured Methadone Users 140

Measured THC Users 113

T-TEST RESULTS

T-test p-value 0.049* T-test p-value 0.035* T-test p-value 0.39

F o la t e DHA EPA

1500 1000 250

800 200

1000
600 150

400 100
500

200 50

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 PATHWAY ANALYSIS
NICOTINATE AND NICOTINAMIDE… 1
FOLATE BIOSYNTHESIS 1
NITROGEN METABOLISM 1
ARGININE AND PROLINE METABOLISM 2 Limonene
ALPHA-LINOLENIC ACID METABOLISM
Arginine &
1
PHENYLALANINE, TYROSINE AND…
Ornithine
1
LINOLEIC ACID METABOLISM 1
Tryptophan
GLYCOSYLPHOSPHATIDYLINOSITOL(GPI)-… 1
DRUG METABOLISM - OTHER ENZYMES 2 Glycerophosholipid
TERPENOID BACKBONE BIOSYNTHESIS 2
GLYCEROLIPID METABOLISM 2
HISTIDINE METABOLISM 3
GLYCEROPHOSPHOLIPID METABOLISM 3
TRYPTOPHAN METABOLISM 6
D-ARGININE AND D-ORNITHINE… 2
LIMONENE AND PINENE DEGRADATION 7

0 1 2 3 4 5 6 7 8
Tryptophan
Pathway Map
SUMMARY AND FUTURE WORK

š We found infants exposed to prenatal opioids had a measurable negative impact on

several nutritional metabolites which play a significant role in fetal development, in
particular, folate and DHA.
š We also identified a large number of diverse metabolic pathways that were substantially
different from controls. We are currently working on defining these differences further.
š Limitations to this study
š Time of exposure
š Amount of exposure
š Polysubstance interactions

š Potentially may lead to development nutritional guidelines to improve NAS outcomes.

 SPECIAL THANKS

o Devon Kuehn, MD
o Sri Ravisankar, MD
o Kim Kew, PhD
o Kadesha McIntyre, MS
o Samantha Poppenfuses, BS
o Dmitry Tumin, PhD
ACKNOWLEDGEMENTS

š Pediatric Association Society, April 29, 2019, Baltimore, MD

š Children’s Miracle Network (CMN) grant

 REFERENCES

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Martin C, Longinaker N, Mishka T. Recent trends in treatment admissions for prescription opioid abuse during pregnancy. J Subst Abuse Treat 2015;48:37–
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Shikhar Shrestha, Elizabeth Jimenez, Laura Garrison, Peter Pribis, Dennis W. Raisch, Julia M. Stephen & Ludmila N. Bakhireva (2018) Dietary Intake Among
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