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Insights on the Complexity of the Prenatal Opioid Epidemic

After returning to work from my third maternity leave, one thought still plagues my mind. Is my child going to be okay?

I am an incoming faculty member at Northern Kentucky University in the Department of Psychological Science, with a PhD in neuroscience. I study how the prenatal environment (the period before birth) influences the brain. I am dedicated to understanding how early life experiences set the stage for how we think and act later in life.

In this blog, I share my journey researching prenatal exposure to opioids and illustrate the complexity of this problem. Opioids are a class of pain-relieving drugs, such as fentanyl or heroin, and prescription varieties such as OxyContin®, Vicodin®, morphine, and more. I hope that my journey will help inform how we approach research on prenatal drug exposure.

Parents all want one thing: an instruction manual

I was once asked: what is the one thing that causes problems for kids? It’s a burning question for all parents, and we want a simple answer. We want a precise list of “what” to avoid during pregnancy to protect our baby, and later during their childhood and adolescence to guarantee their wellbeing — an instruction manual. If we had a manual to follow, we could have reassurance that our child is going to be okay.

I am currently focused on understanding the consequences of prenatal opioid exposure. I intended to understand one thing. It sounded simple at first, if a mother takes this one drug while pregnant, then XYZ happens to the baby. I was ready to get my straightforward answers to help kids one day, but as I immersed myself in this work, it was not so simple.

A complex leap from animals to humans

Up until this point my research had been with animal models. Animal research improves the depth of our understanding, but it always seemed there was a disconnect between studying a mouse in a laboratory and what human beings go through. Therefore, I joined a group of neonatologists (i.e. Drs. Jae Kim, Jennifer McAllister, Scott Wexelblatt, and Stephanie Merhar) at Cincinnati Children’s Hospital who work with infants exposed prenatally to opioids. I listened to their stories, eager to incorporate their experiences into my work.

The neonatologists immediately asked if my animal models could include several other exposures. Prevalent exposures in the pregnant opioid-using population, such as stress and nicotine use, are known to have a detrimental impact on child development, while others such as hepatitis C infection are poorly understood in how they impact the child. Animal researchers are taught to isolate just one “thing”, and study it, but this problem is more complex. Neonatologists have a murky crisis on their hands and want evidence to guide them in treating children exposed to opioids prenatally.

Photo by Dan Gleiter on Pennlive

The multifactorial problem

What started as a journey to understand one thing became a much larger mission.

To help children exposed to opioids prenatally, we need to consider more than just the exposure to this one type of drug. Beyond the immediate concern of neonatal opioid withdrawal syndrome (that is when the baby is born suffering the symptoms of opioid withdrawal), children exposed prenatally to opioids are more likely to display behavioral problems. Their learning and memory may be impaired, or they may have difficulties in controlling their impulses, attention, or emotions. They also have an increased risk of neurodevelopmental disorder diagnoses, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. I began to wonder: is there more behind this association than just the opioid exposure?

Mothers who use opioids are more likely to use multiple substances, such as nicotine, cocaine, methamphetamine, and benzodiazepines. Prenatal exposure to an opioid along with multiple other substances exacerbates neonatal opioid withdrawal syndrome, with emerging evidence suggesting it may further increase the risk for neurodevelopmental disorders. Opioid and nicotine use have an especially tight overlap. Nicotine exposure itself is associated with childhood impulsive behavior and self-control deficits, which may exacerbate issues associated with prenatal opioid exposure.

Another factor to consider is infection risk, which is more common in pregnant women who use opioids, via both intravenous (i.e. injected into the vein) drug use and drug-induced suppression of the immune system. For instance, up to 40% of pregnant women using opioids are hepatitis C positive. Opioids can cross the placenta (the structure that nourishes the unborn baby and removes waste) and reach the fetal brain, where they can cause inflammation. Inflammation is the body’s natural defense mechanism but when it reaches the brain, it can be associated with behavioral problems. Exposure to multiple substances along with infection could induce a chronic inflammatory state. While prenatal exposure to opioids, hepatitis C, or nicotine alone has not been reported to cause structural damage to the infant brain, the exposure to all three factors together could in some cases result in mild brain injury.

Beyond multiple substance use and infection, mothers who use opioid drugs are also more likely to face undernutrition, psychiatric illness, decreased prenatal care, and many other extreme stressors. Overall, opioid exposure is a red flag to a potential myriad of other adversities that the mother and child are facing.

Adaptability against adversity

Infants with prenatal substance exposure are more likely to encounter childhood adversity, such as abuse, neglect, or household dysfunction. The combination of prenatal substance exposure and childhood adversity further increases the risk of behavioral disorder diagnoses in adolescence and adulthood. However, this risk is not a guaranteed outcome. While adversity represents an environmental challenge, adaptability is the capacity to successfully adjust to those challenges.

In fact, the immature brain is highly flexible and adaptable, offering a unique window of opportunity to intervene and make adjustments from infancy to adolescence. Beyond the exposure is adaptation to adversity, which varies from child to child.

Initially, I wanted to study one exposure and ‘fix’ the outcome. Now, I am tempted to track down how these complex exposures may lead to a range of different outcomes.

In animals and humans, can we predict risk based on exposure combinations, to develop preventative strategies tailored to the individual?

All I know is that I have an entire career ahead of me to get answers.

Photo by Antonius Ferret on Pexels


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