Children exposed to opioids before birth may face developmental challenges that extend well beyond infancy.
While the effects of prenatal opioid exposure (POE) on pregnancy, birth and early childhood outcomes have been studied extensively, considerably less is known about what happens once those children reach school age.
And this brings us to … ?
A new systematic review published in Addiction examined evidence from the past decade on health, developmental, behavioral and educational outcomes among children ages 5 to 18 with POE.
Researchers found the most consistent associations in three areas: vision, hyperactivity and attention, and cognitive functioning.
What do we already know about prenatal opioid exposure?
Opioid exposure during pregnancy can occur through illicit opioid use or medication for opioid use disorder (MOUD), including methadone and buprenorphine.
Previous research has linked POE with several adverse pregnancy and early childhood outcomes, including increased risks of preterm birth and low birthweight—as well as differences in cognitive, psychomotor, behavioral and attention during the early years.
What else?
While a 2020 systematic review examining longer-term outcomes found associations between POE and poorer vision, educational attainment and other outcomes, much of the available research involved small samples.
- To note: 32 of 43 included studies in that review had fewer than 100 participants per group.
Since then, the evidence base has expanded considerably, prompting researchers to take another look specifically at school-aged children.
Got it. Now let’s talk about the study.
Researchers searched PubMed, Web of Science, Scopus and CINAHL for studies published between January 2015 and February 2025 and conducted an updated search in October 2025. Grey literature was also searched through Google.
Studies could include exposure to illicit opioids, methadone or buprenorphine, as well as neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS), which were frequently used as proxies for prenatal opioid exposure.
Because the studies differed substantially in how opioid exposure and outcomes were measured, the researchers conducted a narrative synthesis rather than a meta-analysis.
And who was included in the research?
The initial search identified 11,965 records.
Ultimately, 32 papers comprising 16 studies underwent full review and risk-of-bias assessment. Five papers considered to have a very high risk of bias were excluded, leaving 27 papers in the final analysis.
Collectively, those papers included:
- 31,104 children with prenatal opioid exposure
- 5,430,272 controls
- Data from 10 countries
The research included prospective birth cohorts, retrospective administrative data studies, studies combining the two approaches and one cross-sectional study.
Notably: 20 of the 27 papers were published after May 2019 and therefore weren't included in the previous systematic review. And despite the enormous overall control population, many individual POE cohorts remained relatively small.
So what did the researchers find?
All four papers examining visual outcomes reported poorer results among children with POE. Reported problems included reduced visual acuity, strabismus, nystagmus and reduced accommodation amplitude.
Worth noting: One study identified strabismus in 30.2% of exposed children compared with 4.8% of controls. Nystagmus occurred in 15.9% to 20% of exposed children compared with 0% to 1.6% of controls.
Go on …
Researchers also found evidence of impaired visual-motor integration, with one study suggesting that deficits became more pronounced with age.
Interestingly, children exposed to methadone had poorer outcomes than those exposed to buprenorphine across several visual domains.
Was vision the only concern?
No. Attention, hyperactivity and cognitive development also raised concerns.
Every study examining hyperactivity and inattention found greater difficulties among children with POE. Exposed children were also more likely to receive an attention deficit hyperactivity disorder (ADHD) diagnosis in studies using diagnostic data—including one analysis reporting a 43% higher hazard of ADHD.
However: ADHD is highly heritable. Plus, opioid use and ADHD can occur within the same families.
- As such, the authors cautioned against attributing the entire association to prenatal exposure.
What else was analyzed?
Cognitive and educational outcomes showed a similar pattern.
Seven of 10 studies assessing cognitive development reported poorer outcomes, including differences in verbal IQ, memory, developmental delay, intellectual disability and educational performance.
One study found that, by ages 12 to 13, 37.7% of opioid-exposed children failed to meet national educational standards compared with 18.4% of controls.
Language differences also appeared more clearly later in childhood, suggesting some difficulties may become more apparent as academic demands increase.
Any limitations to keep in mind?
Several. While the review demonstrates associations, it does not establish that prenatal opioid exposure caused the observed outcomes.
With this in mind: Seventeen of the original 32 papers had a high or very high risk of bias, and five of the very-high-risk studies were excluded.
Exposure definitions also varied considerably:
- Only one study examined different opioid doses, and none adequately investigated timing, duration, frequency or route of exposure
- Potential confounders, including tobacco, alcohol and other drug exposures, weren't always sufficiently controlled
Evidence was also limited for physical health, motor skills, brain structure and function, internalizing symptoms, dental health and social outcomes.
And remarkably little is known about adolescence. No included study focused exclusively on adolescents, and only three reported results for children older than 13.
So what do researchers think should change?
The authors argue that POE shouldn't be treated primarily as a neonatal issue. Instead, longer-term developmental surveillance may be warranted as children progress through school.
Greater awareness of visual and neurodevelopmental difficulties could help clinicians identify problems earlier, while schools may play an important role in recognizing emerging attention and learning difficulties.
Importantly: The findings shouldn't be interpreted as a reason for pregnant patients to discontinue prescribed MOUD—the authors emphasized continued treatment engagement and stabilization with medication for opioid use disorder as part of appropriate antenatal care.
Anything else?
The consistency of the visual findings makes ophthalmic follow-up particularly noteworthy.
Previous systematic research has already identified increased ophthalmic morbidity among children exposed to opioid maintenance treatment in utero. The current review extends that concern into the school years, when visual deficits can overlap with educational and neurodevelopmental difficulties.
That distinction matters clinically. A child struggling to read, sustain attention or perform in the classroom may have multiple contributing factors, and unrecognized reduced acuity, strabismus, nystagmus or other visual dysfunction could add to that burden.
Greater clinician awareness of visual difficulties among children with known POE may therefore support earlier identification and intervention.