Brains Begin Before Birth Midwest Consortium
New National Consortium Will Study Long Term Effects of Prenatal Opioid Use
Researchers within Northwestern’s Institute for Innovations in Developmental Sciences (DevSci), in partnership with Ann & Robert H. Lurie Children’s Hospital and Washington University School of Medicine (WUSM), are leading a multi-pronged scientific approach to lay the groundwork for a future planned major national initiative to study the long term effects of prenatal opioid use and other adverse perinatal exposure on neurodevelopment and health of offspring. The project is designed as a developmental antecedent to the large national Adolescent Brain & Cognitive Development (ABCD) Study currently underway.
This transdisciplinary research team, comprised of scientists and clinicians from Northwestern’s DevSci, Lurie, and Washington University, was recently awarded a grant from the National Institutes of Health Helping to End Addiction Long-term (NIH HEAL) Initiative to conduct multisite pilot and feasibility studies addressing challenges to prenatal research on opioids and other adverse exposures.
About the NIH HEAL Initiative
As the U.S. opioid crisis becomes an urgent public health concern, the NIH launched the HEAL Initiative in 2018 to improve pain management, opioid addiction prevention and opioid treatment strategies. This year, the NIH awarded $945 million in total funding for grants, contracts, and cooperative agreements across 41 states to develop and apply transdisciplinary scientific solutions to the opioid crisis.
To support research that attends to the impact of this crisis on offspring neurodevelopment and health, the NIH established the HEALthy Brain and Child Development (HBCD) Phase I Study, reflecting the complex challenges to engagement and long-term follow-up of families struggling with opioid and corollary addictions and problems. The researchers will tackle problems by generating new data and best practice guidelines to recommend solutions to barriers to successfully conducting the planned Phase II study to follow. Under HBCD, DevSci has received an 18-month planning grant to address bioethical and scientific protocol issues key to successful launch of the large Phase II study.
Brains Begin Before Birth (B4) Midwest Consortium
Lauren Wakschlag, DevSci Director, and Professor & Vice Chair of the NUFSM Department of Medical Social Sciences, is the Northwestern PI of the Brains Begin Before Birth (B4) Midwest Consortium along with Washington University neuroscientist PIs, Cynthia Rogers and Chris Smyser. The rare scope of this transdisciplinary Midwestern partnership reflects DevSci’s unique strengths in catalyzing developmental team science by bringing together typically disparate scientific areas to solve real-world problems. The team includes scientists in the fields of neuroscience, bioethics, law, pediatric population health, maternal-fetal medicine, addiction psychiatry, developmental/clinical science, health policy, and child welfare.
Although many opioid-using women are of childbearing age and some are pregnant, prenatal exposure to opioids and other substances is an understudied aspect of the public health impact of the opioid epidemic. Delineating whether and how these exposures impact fetal and child neurodevelopment, how the postnatal environment may amplify or attenuate these effects, and how preventions can help exposed young children get a healthier start are all critical questions to address the impact of the epidemic.
However, a number of regulatory and scientific barriers impede research in this area. B4 intends to address this knowledge gap and provide national leadership addressing three major challenging areas to a high-quality, representative, national multi-site study in Phase II: legal/ethical considerations, engagement of participants in clinical care and research, and neurodevelopmental assessment. Widely varying policies across jurisdictions, namely Illinois (where opioid use is criminalized) and Missouri (where opioid use is not criminalized), affect the standard of care and research engagement of pregnant women who are using opioids and therefore have high-risk pregnancies.
For too long we have ‘protected’ pregnant women and fetuses from research in ways that leave them unable to benefit from research designed to address important health problems. Such problems do not spare these populations, and our research must include them.”
Seema Shah, Lurie site PI
WUSM’s collaboration adds depth of expertise in neonatal imaging analytics and harmonization, novel recruitment apps and biomarker collection. Moreover, the opportunity to recruit in Missouri offers circumstances in which opioid use during pregnancy is not criminalized, enabling a well-integrated network of preventive services not possible in Illinois.
Ethical Complexities
“Conducting studies examining how adverse exposure affects neurodevelopment facilitates a detailed, prospective examination of exposure patterns,” says Wakschlag. “Punitive policies like those in Illinois create a ‘don’t ask, don’t tell’ culture which is harmful to parents, children and clinicians because it limits clinicians’ opportunities to intervene and help. Furthermore, the punitive culture may fundamentally impede scientific investigation of the long-term impact of prenatal opioid and other substance exposure.”
Wakschlag also emphasizes the importance of harnessing all available research tools to generate the scientific evidence needed to advance clinical care to secure healthier futures for families who are faced with challenges to children’s health in the fetal, perinatal and early childhood periods.
Seema Shah, Associate Professor of Pediatrics in the Stanley Manne Children’s Research Institute and a pediatric bioethicist who is serving the Lurie Children’s site PI, will lead highly novel approaches to elucidate the effects that punitive laws may have on quality of care women and children receive and the ability to conduct research with the potential to benefit future generations of children.
For too long,” Shah says, “we have ‘protected’ pregnant women and fetuses from research in ways that leave them unable to benefit from research designed to address important health problems. Such problems do not spare these populations, and our research must include them.”
Seema Shah, JD
Recruitment, Neurodevelopmental Assessment, and Data Science
In addition to the bioethics research, DevSci will use innovative approaches to addressing other significant challenges with a number of innovative approaches. First, the team will develop novel ways to collect infant neuroimaging data in community settings for this hard-to-reach population. DevSci Neurodevelopmental Core Co-Director Elizabeth Norton, Assistant Professor of Communication Sciences and Disorders, and Core Scientist Michael Murias, Research Associate Professor of Medical Social Sciences, will develop and pilot a method for collecting EEG data in community settings as well as to examine how exposed infants differ in their brains’ ability to synchronize with biologic vs. foster mothers. This will draw on Lurie’s extensive community partnerships including Illinois Children’s Mental Health Partnership, Lurie Children’s Health Partners Care Coordination and the Illinois Perinatal Quality Collaborative.
Second, Norrina Allen, Associate Professor of Preventive Science and Co-Director of DevSci’s Data Science Hub, will draw on risk prediction methods innovated in cardiovascular epidemiology to specify those risk factors most informative for Phase II assessments to distinguish exposed children with poor vs. healthy outcomes.
Third, Shah and Sheila Krogh-Jespersen, Research Assistant Professor of Medical Social Sciences, will create novel recruitment materials blending their skills in behavioral economic framing and eye-tracking methods to identify recruitment methods that are most compelling and “eye-catching” for opioid-using mothers and others at risk.
A National Imperative
“By including funding to study the impact of opioid exposure in early childhood, NIH HEAL is bringing national attention to the challenges facing children exposed to opioids as their nervous systems are developing,” says Matthew Davis, the interim chair of the NUFSM Department of Pediatrics and interim chair of the Department of Medicine at Lurie Children’s Hospital, interim president and Chief Research Officer of the Stanley Manne Children’s Research Institute, Deputy Director of DevSci, and a collaborator on B4. Davis was one of the first researchers to raise concerns, back in 2012, about rapidly rising rates in the United States of infants born with symptoms of withdrawal from maternal opioid use.
DevSci and Lurie Children’s are uniquely situated to conduct this research with robust scientific and community partnerships and to address the challenges to this endeavor regionally and nationally. “The partnership with Washington University will also be critical to the success of this study, given their complementary areas of expertise,” says Davis.
The B4 consortium is proud to be one of a dozen sites selected nationally to tackle these crucial issues and lay the groundwork for a much-needed national study that will follow at-risk mothers, their infants and families from birth through early adolescence to generate practices and policies that can improve the health and provide supports for families affected by opioid use.
B4 is funded by the National Institute of Drug Abuse R34DA050266