Prenatal substance use remains a significant public health concern, with defined consequencesestablished in the neonatal period and additional health consequences identified at birth andthrough adolescence. Tobacco and alcohol remain the most frequently used substances duringpregnancy, followed by marijuana, methamphetamine, opiates and cocaine. Estimates from theNational Survey on Drug Use and Health suggest that over five percent of pregnant women useone or more illicit substances. Prenatal exposure to substances of abuse can not only causeneonatal abstinence syndrome (NAS) and other complications at birth, but can also lead to anumber of neurobehavioral and cognitive developmental disabilities in adolescence. Epigeneticmechanisms, including DNA methylation, provide a mechanistic link between prenatal exposureand health consequences following the prenatal period. Alterations to the epigenome duringprenatal development, due to environmental exposure to toxins or drugs, can induce lastingepigenetic changes that can induce physiological changes to the fetus. While multiple studieshave already established unique methylation signatures related to prenatal exposure to tobaccoand alcohol, there are no reported human epigenetic studies on the impact of prenatal exposureto illicit drugs on the fetal epigenome and how these perturbations impact subsequentdevelopmental consequences. Research to understand the epigenetic predisposition resultingfrom drug exposures and identification of biomarkers specific to each substance is necessary toidentify affected neonates and tailor effective treatment interventions. This Phase I proposal willbe the first study to evaluate whole epigenome methylation signatures from newborns withknown exposure to substances of abuse in utero, identify specific methylation sites that aresignificantly differentiated from non-exposed controls, and examine the correlation with birthoutcomes in newborns including severity of NAS. The differential patterns of DNA methylationidentified will be examined in a Phase II study to examine the correlation between fetalexposure to illicit drugs, methylation patterns in exposed newborns versus healthy controls,NAS severity, and developmental outcomes as the infants mature. Our long-term goal is toexamine a correlation between identified epigenetic changes and an increased risk of thedevelopmental disabilities associated with prenatal exposure to illicit drugs. Establishment of anepigenetic biomarker of fetal exposure to illicit drugs using neonatal blood spots would be morebeneficial than current screening methods in its ability to predict fetal damage at a very earlytime point allowing for prompt diagnosis and early intervention.
Public Health Relevance Statement: PROJECT NARRATIVE
Prenatal substance use remains a significant public health concern, with defined consequences
established in the neonatal period and additional health consequences identified at birth (NAS)
and through adolescence. Alterations to the epigenome during prenatal development, due to
environmental exposure to toxins or drugs, can induce lasting epigenetic changes that can
induce physiological changes to the fetus and the maturing infant. This Phase I proposal will be
the first human study to evaluate whole epigenome methylation signatures from newborns with
known exposure to specific substances of abuse in utero and to identify specific methylation
sites that are significantly differentiated and may serve as potential epigenetic biomarkers of
prenatal substance exposure using routinely collected newborn dried blood spots.
Project Terms: Adolescence ; 12-20 years old ; adolescence (12-20) ; Adult ; 21+ years old ; Adult Human ; adulthood ; Affect ; Alcohols ; Alcohol Chemical Class ; Animals ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Birth ; Parturition ; Blood ; Blood Reticuloendothelial System ; Child ; 0-11 years old ; Child Youth ; Children (0-21) ; youngster ; Developmental Disabilities ; Child Development Disorders ; Cocaine ; Diagnosis ; Disease susceptibility ; Diathesis ; liability to disease ; DNA ; Deoxyribonucleic Acid ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Embryonic Development ; Embryo Development ; Embryogenesis ; Environmental Exposure ; Exhibits ; Fetal Development ; Developing fetus ; Fetus ; Genetic Screening ; Genome ; Goals ; Health ; Human ; Modern Man ; Incidence ; Infant ; Newborn Infant ; 0-4 weeks old ; Newborns ; newborn child ; newborn children ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Marijuana ; marihuana ; Methamphetamine ; Crystal Meth ; Deoxyephedrine ; Desoxyephedrine ; Methylamphetamine ; N-Methylamphetamine ; Methods ; Methylation ; Mothers ; Neonatal Abstinence Syndrome ; Neonatal Opioid Withdrawal Syndrome ; Neonatal Substance Withdrawal ; Neonatal Withdrawal Syndrome ; newborn abstinence syndrome ; Phenotype ; Pregnancy ; Gestation ; Pregnant Women ; expectant mother ; expecting mother ; pregnant mothers ; Program Development ; Public Health ; Research ; research and development ; Development and Research ; R & D ; R&D ; Risk ; medical specialties ; Specialty ; Surveys ; Survey Instrument ; Teratogens ; Teratogenic ; Teratogenicity ; Testing ; Time ; Tobacco ; Toxicology ; Toxin ; Umbilical cord structure ; Umbilical Cord ; United States ; bisulfite ; hydrogen sulfite ; hydrosulfite ; Illicit Drugs ; base ; DNA analysis ; Site ; Phase ; Physiological ; Physiologic ; Link ; Predisposition ; Susceptibility ; Opioid ; Opiates ; Drug usage ; drug use ; Early Intervention ; Spottings ; Exposure to ; DNA Methylation ; Life ; Severities ; Scanning ; Pattern ; fetal ; toxicant ; unborn ; prenatal ; substances of abuse ; Substance of Abuse ; Reporting ; Drug Exposure ; Sampling ; exposed in utero ; fetal exposure ; in utero exposure ; intra-uterine environmental exposure ; intrauterine environmental exposure ; prenatally exposed ; prenatal exposure ; Property ; Intervention Strategies ; interventional strategy ; Intervention ; Tissue Sample ; Cognitive ; Enrollment ; enroll ; Epigenetic Process ; Epigenetic ; Epigenetic Change ; Epigenetic Mechanism ; Modification ; Development ; developmental ; Behavioral ; in utero ; pyrosequencing ; tobacco exposure ; exposure to tobacco ; neonate ; neurobehavioral ; fetal drug exposure ; gestational drug exposure ; prenatal drug exposure ; prenatally drug exposed ; Outcome ; Neonatal ; human study ; Population ; prenatal health ; drug testing ; drug detection ; alcohol exposure ; alcohol exposed ; ethanol exposed ; ethanol exposure ; exposed to alcohol ; exposed to ethanol ; exposure to alcohol ; exposure to ethanol ; critical period ; minimally invasive ; effective therapy ; effective treatment ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; phase 1 study ; Phase I Study ; phase 2 study ; phase II study ; epigenetic marker ; epigenetic biomarker ; screening ; epigenome ; methylation pattern ; specific biomarkers ; biomarker identification ; marker identification ; whole genome ; entire genome ; full genome ; illicit drug use ; neonatal period ; fetal substance exposure ; prenatal substance exposure ; substance use ; substance using ;
