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Advancing Research of Effect of Maternal Opioid Exposure on Developing Brain

Revised October 2017

NIDA is interested in funding research on the effect of maternal opioid exposure on embryonic, fetal and post-natal brain development.

It has been reported that the prevalence of opioid abuse or dependence among pregnant women has increased from 1.7 per 1,000 delivery admissions in 1998 to 3.9 per 1000 in 2011. As part of standard of care opioid dependent pregnant women are administered either the long-acting opioid agonist, methadone or the partial agonist, buprenorphine (BUP). Preventing episodic exposure and withdrawal from acute opioids decreases the incidence of Intrauterine fetal demise, neonatal death, and prematurity. Upon delivery, the newborn exposed to opioids during gestation undergoes withdrawal that is referred to as neonatal abstinence syndrome (NAS). The incidence of NAS has increased approximately 400% nationally, from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1000 births in 2012, with some states reporting rates in excess of 30 per 1,000 hospital births. The 2012 data showed 22000 infants born with diagnosed NAS, a five-fold increase for that decade where data is available.

NAS is just one of the sequela of in utero opioid exposure. Infants born to opioid abusing mothers can be preterm, and exhibit low birth weight, thinner cortices, reduced cognitive ability, and physical and behavioral deficits. In addition, studies have begun to identify long term social, psychological and behavioral abnormalities and deficits among children associated with maternal opioid exposure, including lower IQ scores, poor social skills, and with disruptive behaviors. The mechanisms underlying these deficits are not well understood.   Factors such as genetics, polydrug exposure, environmental toxins, stress, and maternal care are likely to influence developmental outcomes in opioid exposed embryos and fetuses.

Areas of programmatic interest to NIDA include, but not limited to:

  • Outcome comparisons of maternal opioid use to different medication assisted therapies in infants diagnosed of NAS.
  • Long term impact of the severity of NAS on brain, cognitive and behavioral outcomes.
  • Impact of maternal opioid exposure on child stress responses.
  • In addition to NAS, impact of opioids to the developing brain during embryonic, fetal and early childhood stages.
  • Effects of maternal opioid exposure on child motor and cognitive development.
  • Incidences of disorders in development and maintenance of social behavior, e.g., play, cooperation, empathy, conflict, hostility, violence and aggression in early childhood after pre- and postnatal opioid exposure.
  • Role of sex/gender in outcome measures regarding severity of NAS and impact of brain and behavioral development.
  • The genomic and genetic factors, including gene regulation and gene expression, associated with the incidence and severity of NAS.
  • Effects of maternal opioid exposure on brain morphology, neuroanatomy, connectivity.
  • The cellular and molecular mechanisms by which maternal opioid exposure affects brain development, including neuronal differentiation, migration, synaptic formation and neural circuit activities.
  • Effects of maternal opioid exposure on neural and glial interactions during synaptogenesis and synaptic pruning particularly in neural circuits or brain regions related to substance abuse.

Please contact Dr. Da-Yu Wu to discuss the specific aims of your application and the appropriate funding opportunity mechanism to use.

This page was last updated October 2017

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