Paving a brighter future for drug-exposed newborns

In the past few decades, opioids regained considerable public attention due to the ongoing epidemic sweeping across the US. With a high rate of overdose deaths, the topic continues to attract international concern and scrutiny.

“The reasons for opioid use are complicated, political and social,” says Associate Professor Kelly Clemens from UNSW Sydney’s School of Psychology.

Australia is experiencing its own crisis—benzodiazepines and opioids remain the largest contributors to drug-induced deaths.

Trends now indicate that women of a reproductive age are also using opioids more.

“There has been a 400 per cent increase in opioid use by women across the past 10 years,” A/Prof. Clemens says. “And this is a problem as everything that goes into the mum goes through to the baby.”

A/Prof. Clemens is a behavioural neuroscientist. Her research extends to real-life cases in Sydney’s hospitals, where newborns are born with a deeper struggle of addiction, sometimes unbeknownst to medical staff.

Having exposure to opioids in the womb means babies start facing withdrawal symptoms just moments after birth. But A/Prof. Clemens has found a simple dietary supplement could have a dramatic impact on the future lives of these infants. Just a seemingly small improvement early on could lead to a whole different future.

“Opioid use changes how the brain of the baby grows across pregnancy,”—A/Prof. Kelly Clemens

Challenges & opportunities

Opioids are a class of drugs that includes prescription-only medicines such as oxycodone, fentanyl and tramadol. These are typically used for pain relief. But they are addictive. And in high doses, fatal.

The withdrawal symptoms in newborns can range from irritability and feeding difficulties to seizures and respiratory distress.

“When a baby is born with an opioid addiction and goes through withdrawal, they can be quite sick, which in turn requires replacements like methadone or morphine,” A/Prof. Clemens says. “So these kids can be exposed to drugs for quite some time both before and after birth.”

A/Prof. Clemens says half of the children affected are typically diagnosed with a mental health disorder such as attention deficit disorder and other conduct disorders by the age of five.

The effects can linger beyond infancy, shaping early childhood and beyond.

“At school, they do poorly, performing worse across NAPLAN,” A/Prof. Clemens says. “Long-term, they are at high risk of drug addiction themselves, or death by suicide.”

A/Prof. Clemens has been studying how in-utero exposure to these drugs affect the brain and behaviour of offspring. She found that opioids interact closely with our immune system—with neuroinflammation changing how the brain works and recovers.

“That also means they might have less resistance to viruses and bacteria,” A/Prof. Clemens says.

She says considering the microbiome of the gut is key—this is where we host trillions of bacteria. A healthy gut is important for digesting our food and vitamins, as well as combating the ‘bad’ microbes.

A/Prof. Clemens says the poorer brain outcome of kids born with an opioid exposure may be linked to gut health.

“The gut becomes leaky, letting toxins and bad metabolites leak into the blood,” she says. “Opioids also make the blood brain barrier leakier—so toxins reach the brain, and this might contribute to neuroinflammation.”

“I really want to find out what is happening so I can figure out a treatment,”— A/Prof. Kelly Clemens

Future focused

A/Prof. Clemens’s findings suggest that early intervention is crucial in moderating the effects. Specifically, through targeting gut health.

Sodium butyrate is a compound produced naturally in the human body by digesting fibre. It has shown promise in animal studies for its ability to reverse some of the neurological effects of prenatal opioid exposure.

“It works by modifying gene expression and promoting healthy brain function, potentially offering a new avenue for treatment in affected infants,” A/Prof. Clemens says.

Sodium butyrate is also a common dietary supplement.

“The more I looked into it, the better it was.”

She used animal models to test her theory.

“When we gave sodium butyrate to our rats, it improved brain development and growth,” she says. “It decreased indicators of inflammation. It improved the gut health of our pups by promoting good bacteria in their gut. And, it made them smarter.”

She says the pups exposed to opioids during pregnancy had significantly better long-term outcomes from taking sodium butyrate than the pups that didn’t.

In partnering with several local Sydney hospitals, affected infants can be monitored closely to understand the effectiveness of sodium butyrate in improving their developmental outcomes.

Senior Neonatologist Professor Ju Lee Oei is a clinical partner on the project, based at The Royal Hospital for Women. She says while her focus on clinical medicine uncovers the unmet need, the science is what helps to resolve the need.

“Our collaboration is built on a shared vision, to understand the mechanisms underlying the poor outcomes of children with prenatal drug exposure and to develop interventions to predict and prevent this harm,” Prof. Oei says.

A/Prof. Clemens says, “with early detection and care, these children can receive the support they need to thrive despite the challenges they face from the very beginning of their lives.”