Notice of Interest in Advancing Research about the Effects of Opioids and Opioid Antagonists on the Fetal and Neonatal Brain Development

Notice Number: NOT-DA-17-067

Key Dates
Release Date: February 12, 2018

Related Announcements

Issued by
National Institute on Drug Abuse (NIDA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)


In response to the current opioid epidemic, NIDA and NICHD are giving high programmatic priority to fund research on the effect of maternal opioid exposure on embryonic, fetal, post-natal brain development and other health outcomes.
It has been reported that the prevalence of opioid use disorders among pregnant women has increased from 1.7 per 1,000 delivery admissions in 1998 to 3.9 per 1,000 in 2011. The incidence of neonatal opioid withdrawal syndrome (NOWS) has increased approximately 400% nationally, from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 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 NOWS, a five-fold increase during that period where data are available. As part of the standard of care, opioid dependent pregnant women are treated with the opioid agonist methadone, partial agonist buprenorphine, and in rare cases, the antagonist naltrexone. In addition, fetal exposure to opioids may occur as a result of maternal prescription opioid use.
NOWS is just one of the sequela of in utero opioid exposure. Infants born to mothers who were exposed to opioids can be preterm, and exhibit low birth weight, thinner cortices, reduced cognitive ability, and physical and behavioral deficits. In addition, studies have identified long term social, psychological and behavioral abnormalities and deficits among children associated with maternal opioid exposure, including lower IQ scores, poor social skills, and 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.
The purpose of this Notice is to inform the scientific community of the interest of NIDA and NICHD in advancing scientific knowledge about the consequences of opioid agonist or antagonist exposure during pregnancy on embryonic, fetal and post-natal brain and behavioral development, as well as other health outcomes and the mechanisms underlying these consequences.
Areas of programmatic interest to NIDA include, but are not limited to:

  • Effects of different medication-assisted therapies (e.g., methadone, buprenorphine, naltrexone) on NOWS. 
  • Effect of severity of NOWS on brain, cognition, and behavior in neonates, adolescents, and adults.
  • Impact of maternal opioid exposure on children's stress responses.
  • Effect of social attachment as treatment of NOWS, as well as how social attachment in neonates is affected by the exposure to opioids.
  • Effects of maternal opioid exposure on child motor and cognitive development.
  • Effects of neonatal exposure to opioids on social/emotional development, e.g., play, cooperation, empathy, conflict, hostility, violence and aggression.
  • Role of sex/gender in outcome measures regarding severity of NOWS and impact on brain and behavioral development.
  • The genomic and genetic factors, including gene regulation and gene expression, associated with the incidence and severity of NOWS.
  • Impact of opioid agonists and antagonists, such as buprenorphine and naltrexone, on the developing brain at embryonic, fetal and early childhood stages, including brain morphology, neuroanatomy, connectivity, as well as the cellular and molecular mechanisms in neuronal differentiation, migration, synaptogenesis and neural circuit activities.
  • Effects of maternal opioid agonist and antagonist exposure on neural and glial interactions during synaptogenesis and synaptic pruning, particularly in neural circuits or brain regions related to substance abuse.
Areas of programmatic interest to NICHD include obstetric and pediatric clinical studies focused on the following research topics:
  • Structuring of prenatal care to optimize pregnancy outcomes in women with opioid use disorder.
  • Assessment of fetal well-being during pregnancy in women with opioid use disorder to optimize neonatal outcomes.
  • Complications of pregnancy associated with opioid use disorders and treatments to improve pregnancy outcomes for neonates and mothers.
  • Pharmacokinetic and pharmacodynamic studies of medications to treat opioid use disorder in pregnant and lactating women and neonates to optimize dosing.  Of interest are studies of which medications work best for which patient populations (precision medicine) and studies focused on the use and effects of these medications.
  • Studies of postpartum care and support for women with opioid use disorder to optimize maternal and neonatal outcomes.
  • Studies of safe and effective outpatient management strategies for neonatal opioid withdrawal syndrome including weaning protocols and optimal follow-up.
Areas of programmatic interest to both NIDA and NICHD include obstetric and pediatric clinical studies focused on the following research topics:
  • Clinical trials of medication assisted treatment compared with alternative therapy, such as combination medications, opioid antagonists, or medically supervised withdrawal.  Outcomes of interest include: neonatal outcomes, loss to follow-up rates, maternal overdose, and relapse rates to illicit opioid use.
  • Studies in neonates of the additive effect of alcohol, cigarettes, cannabis, benzodiazepines, and other substances of abuse in women with opioid use disorder.
  • Studies of methods for screening, identifying and assessing neonatal opioid withdrawal syndrome. Examples include development of a biomarker that reflects physiologic state, "lab on a chip" for rapid screening, development of predictive assays for which babies will develop neonatal opioid withdrawal syndrome, require treatment and treatment response.
  • Studies of treatment of neonatal opioid withdrawal syndrome.  Examples include non-pharmacologic care, timing of initiation of medication, optimal initial medication, indications for second medication and different environments for neonates, including foster care or multiple care-giving environments.
Please contact Dr. Da-Yu Wu and Dr. Ann Anderson at NIDA or Dr. Uma Reddy at NICHD to discuss the specific aims of your application and the appropriate funding opportunity mechanism to use.


Please direct all inquiries to:

Da-Yu Wu, PhD
National institute on Drug Abuse
Telephone: 301-435-4649
Ann Anderson, MD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5916
Uma M. Reddy, MD, MPH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1074