Scientists are discovering increasingly more about kids who were exposed to opioids before birth. This study examined the latest discoveries to provide an updated understanding of what we know about this group.

Key Points

• Recent trends in caring for babies exposed to opioids focus more on non-drug methods and less on giving them medicine after birth for withdrawal symptoms.

• It's hard to separate how opioids affect a baby's brain from other things in their environment like economics, where they live, and their genes.

• Babies who were exposed to opioids before birth are at higher risk for developmental and behavioral concerns and poorer school performance.

• Taking care of these babies and their families should be multi-disciplinary and comprehensive. A non-judgmental focus on strengthening the caregiver–child relationship is important.

Title: Neonatal Opioid Withdrawal Syndrome: An Update on Developmental Outcomes

Published in Clinics in Perinatology, March 2023

Summary in plain English :

After discussing the importance of prenatal opioid exposure, the authors addressed changes in brain development seen in the lab. Studies done with rodents and models of organs show how prenatal opioid exposure can change how the brain develops and how a person behaves. In tests with mice, being exposed to opioids affects how the brain cells grow, how the brain's support cells grow, and how the brain's protective covering forms, as well as memory and behavior. The're not sure if these changes also happen in humans, but studies using brain imaging show differences in brain sizes, small spots of damage in the white matter, changes in the structure of the white matter, changes in how different parts of the brain connect, and more blood flow to the brain in babies and kids who were exposed to opioids before birth.

Cognitive Outcomes

Infants :
In one study, babies with opioid exposure did as well as others on tests at 5 to 8 months. Another study found moms on opioid treatment had babies with normal development scores. But another study showed babies exposed to opioids had lower scores on tests at 6 months. Babies treated for opioid withdrawal or exposed to other drugs did worse on tests too. In a small group, babies treated for withdrawal had lower scores than usual.

Toddlers :
In two studies, babies treated for withdrawal from opioids had lower cognitive scores at 15 to 24 months, but still within the normal range. Another small study showed babies exposed to methadone before birth had lower scores at 18 to 24 months compared to others. But in a recent study, there was no difference in scores between babies treated with morphine or methadone for withdrawal at 18 months. Babies given phenobarbital had lower scores than those who didn't get it. In another study, babies exposed to opioids at birth had lower cognitive scores at 2 years compared to others, with many showing cognitive delay.

Preschool to School Age :
In a study from New Zealand, at 4.5 years old, children exposed to opioids had more problems in areas like language, hearing, thinking, and understanding compared to those who weren't exposed. Their overall IQ scores were lower too. They were three times more likely to have trouble learning or thinking and to have delays in thinking compared to others. In another study, at 4 years old, both groups of children did okay on thinking tests, but those exposed to opioids had more trouble with memory, paying attention, and doing tasks that needed planning.

Speech and Language Outcomes

Infants :
In one study, babies exposed to medication for opioid use disorder (MOUD) or treated for NOWS had similar language scores at 5 to 8 months compared to those not exposed. Another study found that communication scores were normal in babies exposed to MOUD at 3 and 6 months. However, in a different study, babies treated for NOWS had lower language scores compared to typical scores for their age group.

Toddlers :
In studies, babies treated for NOWS had lower language scores at 15 to 24 months but still within normal levels. Another big study showed babies exposed to opioids before birth were more likely to have speech problems than those not exposed. However, a small study found that babies exposed to methadone had similar language scores as others at 18 to 24 months. In a different study, there was no difference in language scores between babies treated with morphine or methadone for NOWS at 18 months, but many had lower scores than usual, indicating a higher risk of language delays. In another study, babies exposed to opioids at birth initially had lower language scores at 2 years, but after considering other factors, the differences disappeared.

Preschool to School Age :
In the New Zealand study, at 4.5 years old, children exposed to opioids had lower scores on language tests compared to the control group. They were also three times more likely to have language delays or problems. Even after considering other factors, like home environment and education, opioid exposure still affected how well they could speak.

Motor Outcomes

In studies from the last 10 years, findings on motor skills in kids with prenatal opioid exposure are mixed. Some studies show these kids have lower motor scores than usual, but still within the normal range. For example, in one study, babies with NOWS had lower motor scores at 1 to 3 months. Another study found that at 6 months, babies exposed to opioids before birth scored lower on motor tests compared to others. However, some studies suggest that the dose of opioids might affect motor scores, with higher doses possibly leading to lower scores. In toddlers, similar findings were seen, with opioid-exposed children having lower motor scores but still falling in the normal range. Only one study looked at motor skills in older children with prenatal opioid exposure, finding they scored lower on motor tests compared to other kids their age.

Behavioral Outcomes

Several studies have shown that children with prenatal opioid exposure are more likely to have behavior problems. One study found that they were more likely to have diagnoses of behavioral or emotional problems compared to children not exposed to opioids before birth. In another study, researchers used a questionnaire to assess behavior in children with prenatal opioid exposure at different ages. They found that these children had higher scores indicating more difficulties, especially with attention, hyperactivity, and peer relationships, and these problems tended to get worse over time compared to children who weren't exposed to opioids before birth. Children with more risk factors in their biology, their mother's social situation, and their upbringing had more behavior problems.

Visual Outcomes

Visual Evoked Potentials :

The Visual Evoked Potentials (VEPs) test checks how well the brain processes visual information by measuring electrical changes. A slower VEP latency suggests slower visual development. In one study, infants exposed to methadone had slower processing times at 6 months compared to others. Another study found that at 4 months, these infants took longer to process visual information, but by 36 months, they caught up, showing that visual development continues into childhood.

Visual Acuity :

There aren't many studies on how well children see if they were exposed to opioids before birth. One study found that at 4.5 years old, children exposed to opioids before birth had lower vision in their left eye compared to others. There was also a hint that their overall vision might be lower too.

Strabismus/Eye Muscle/Binocular Movement :

Many reports on eye muscle and movement problems in children exposed to opioids before birth talk about nystagmus and strabismus. In a big study, babies exposed to opioids who needed medicine for NOWS had the highest rates of strabismus compared to those not needing medicine and babies not exposed to opioids. In another study, babies exposed to opioids had a higher chance of being hospitalized for eye problems and were more likely to have issues with their eye muscles compared to babies exposed to other substances or those not exposed at all. Smoking during pregnancy, which is also linked to strabismus, is an important factor in some studies.

Visual Attention and Smooth Pursuit :

The way our eyes smoothly follow moving objects can be affected by things babies are exposed to before they're born. In one study, researchers found that 4-year-old children exposed to opioids didn't have different numbers of quick eye movements or problems following slow-moving objects compared to others. But when they looked at fast-moving objects, these children's eye movements were slower. However, this difference went away when they considered other factors like how much education their moms had or their birth weight. Another study found that children exposed to opioids had trouble ignoring distractions when doing a special attention test, especially if they were also treated for Neonatal Opioid Withdrawal Syndrome (NOWS) or if their moms used marijuana during pregnancy.

Medical Comorbidities

Babies exposed to opioids before birth often need more medical care and may end up back in the hospital more than other babies, even after they're born. Some studies show they're more likely to go back to the hospital for infections. However, a study from Nordic countries found no difference in antibiotic use or infections between babies exposed to opioids and those who weren't. Two studies found that babies treated for Neonatal Opioid Withdrawal Syndrome (NOWS) were more likely to have torticollis, a condition where the neck muscles cause the head to tilt or turn. Most cases were due to tight muscles and the way babies were positioned.

Recommendations

It's crucial to keep track of how babies with Neonatal Opioid Withdrawal Syndrome are developing to make sure they get the support they need. This means checking in regularly to watch how they're growing, behaving, and learning, and getting them help early if needed. The authors of this study suggest a schedule for visits and what to pay attention to during these visits.

Summary

Exposure to opioids before birth, whether or not it leads to NOWS, is linked to developmental impacts. Yet, it's uncertain if this exposure directly causes these effects or if it's just a correlation, given the many other factors involved like exposure to multiple substances, family challenges, mental health issues, and environmental influences. Nevertheless, children exposed to opioids before birth appear to face greater risks of developmental and behavioral problems and should receive close monitoring.

Many thanks to the authors of this article: Benninger KL, McAllister JM, and Merhar SL

The full report is accessible here: https://doi.org/10.1016/j.clp.2022.10.007