Child-resistant (CR) packaging is required for nearly all medications in the United States and is designed to prevent, or at least delay, access to medications by young children.¹ Nonetheless, during the early 2000s, emergency department (ED) visits and hospitalizations for unsupervised medication exposures among young children increased approximately 30%; poison center calls for unsupervised exposures also increased.^{2, 3} In response, efforts to reduce pediatric medication exposures through packaging and labeling improvements and updated safe storage educational messages were initiated,^4-6 and estimated ED visits among children aged ≤5 years declined from a peak of 76,000 visits in 2010 to 59,000 in 2013.³

Throughout the 2010s, prevention efforts continued and expanded to target additional medications and additional caregivers (e.g., grandparents).⁷ Further reducing ED visits for unintentional medication overdoses among young children is a Healthy People 2030 goal for the nation.⁸ Nationally-representative surveillance data were used to assess overall and medication-specific trends in ED visits for unsupervised medication exposures from 2009 to 2020 to help target interventions.

Over the 12-year period from 2009-2020, based on 14,716 surveillance cases, there were an estimated 677,968 (95% CI, 550,089-805,846) ED visits for unsupervised medication exposures among children aged ≤5 years in the United States. From 2009-2012 to 2017-2020, the estimated number of annual ED visits for unsupervised medication exposures declined 38.6% (95% CI, −49.5% - −27.7%), from 70,119 estimated visits annually (95% CI, 56,118-84,120) to 43,070 visits annually (95% CI, 34,521-51,620) (Table 1). Patient and case characteristics were similar in 2009-2012 and 2017-2020. In both periods, over two-thirds of estimated visits were made by children aged 1 or 2 years (70.3% and 67.4%, respectively), approximately one-half of visits were made by boys (51.5% and 54.8%, respectively), and nine-tenths involved accessing a single medication (90.4% and 87.7%, respectively). For both periods, at least one-tenth of visits resulted in hospitalization (11.7% and 13.2%, respectively).

In 2009-2012 and 2017-2020, nearly one-half of ED visits for unsupervised medication exposures involved oral prescription solid medications (49.4% and 48.1%, respectively) (Table 2). The estimated number of visits involving prescription solids declined by 40.3% (95% CI, −50.4% - −30.2%), from 34,656 visits annually in 2009-2012 to 20,697 visits annually in 2017-2020. Oral OTC solid medications were implicated in nearly one-quarter (23.1%) of ED visits for unsupervised medication exposures in 2009-2012, but nearly one-third (30.8%) in 2017-2020. The estimated number of exposure visits involving OTC solids was 16,218 visits annually in 2009-2012 and 13,283 visits annually in 2017-2020, a nominal decline of 18.1% (95% CI, −36.4% - 0.2%).

In 2009-2012 and 2017-2020, oral OTC liquid medications were implicated in fewer ED visits for unsupervised medication exposures (12.6% and 10.1%, respectively) than oral solid medications. The estimated number of visits involving OTC liquid exposures declined 50.9% (95% CI, −63.4% - −38.5%), from 8,863 visits annually in 2009-2012 to 4,348 visits annually in 2017-2020. Oral prescription liquid medications were implicated in significantly fewer ED visits for unsupervised exposures than OTC liquids in both 2009-2012 and 2017-2020 (2.1% and 1.1%, respectively). In 2017-2020, 62.1% (95% CI, 54.6%-69.6%) of ED visits for OTC liquid medication exposures involved children aged ≤2 years, while 78.9% (95% CI, 75.7%-82.0%) of visits for prescription solid medication exposures involved this age group.

Trends in the estimated numbers of ED visits for unsupervised medication exposures from 2009-2012 to 2017-2020 varied by medication (Table 3). Estimated numbers of visits for prescription solid exposures declined for nearly all medication classes. The largest significant declines in estimated numbers of annual ED visits for prescription solid exposures were for benzodiazepines (−2,636 visits; −72.0%), opioids (−2,596 visits; −53.6%), antidepressants (−1,354 visits; −35.6%), and skeletal muscle relaxants (−1,106 visits; −72.0%). Declines in ED visits for medication exposures were smaller and not statistically significant for classes commonly used to treat attention-deficit hyperactivity disorder (ADHD), such as amphetamine-related stimulants (−22.1%; 95% CI, −52.1% - 7.9%) and centrally-acting antiadrenergics (−9.1%; 95% CI, −38.1% - 19.8%). In 2017-2020, the most commonly implicated prescription solid medications were antidepressants (5.7%), opioids (5.2%), and amphetamine-related stimulants (3.7%).

Estimated numbers of ED visits for unsupervised OTC solid medication exposures declined for some medications and increased for others from 2009-2012 to 2017-2020. The largest declines in estimated numbers of annual visits for OTC solid exposures were for vitamins/minerals (−1,038 visits; −36.3%), acetaminophen- or aspirin-containing analgesic combination products (−726 visits; −58.9%), and single-ingredient aspirin (−453 visits; −44.8%). For OTC solid cough and cold medications (CCMs), the estimated number of annual visits for unsupervised exposures in 2017-2020 was too low to be considered statistically stable, suggesting a substantial decline. The estimated number of annual visits increased significantly for exposures involving herbals/alternative remedies (+1,028 visits; +65.6%). Most of the increase in exposure visits involving OTC solid herbals/alternative remedies was attributed to increased melatonin exposures (+1,440 visits; +421.1%; 95% CI, 68.3%-774.0%), of which 56.5% involved children aged 3-5 years in 2017-2020. In 2017-2020, the three OTC solid products implicated in the highest numbers of annual ED visits for unsupervised medication exposures were acetaminophen (2,533; 95% CI, 1,588-3,479), melatonin (1,782; 95% CI, 1,152-2,412), and ibuprofen (1,737; 95% CI, 1,078-2,396).

The most commonly implicated oral OTC liquid medications in ED visits for unsupervised exposures were the same in 2009-2012 and 2017-2020 (acetaminophen, diphenhydramine, ibuprofen, and CCMs). The largest declines in estimated numbers of annual ED visits for OTC liquid exposures were for CCMs (−1,954 visits; −71.6%) and acetaminophen (−1,418 visits; −53.4%). For exposure visits involving OTC CCMs, 54.4% (95% CI, 38.8%-70.1%) involved pediatric products in 2009-2012; in 2017-2020, the estimated number of visits involving pediatric products was too low to be considered statistically stable. In 2017-2020 the most commonly implicated OTC liquid medications were acetaminophen (2.9%) and diphenhydramine (2.8%).

In 2017-2020, at least one of these four OTC liquid products (acetaminophen, diphenhydramine, ibuprofen, or CCMs) was implicated in 9.2% (95% CI, 7.8%-10.6%) of ED visits for unsupervised medication exposures overall; most of these visits involved pediatric products (85.2%; 95% CI, 79.6%-90.8%). The OTC solid dosage forms of these four medications were implicated in 12.7% (95% CI, 10.4%-15.1%) of all unsupervised medication exposure visits, and unspecified oral dosage forms of these four medications were implicated in 1.4% (95% CI, 0.7%-2.1%) of visits.

Estimated numbers of annual ED visits involving prescription non-oral medications were similar in 2009-2012 (1,216 visits) and 2017-2020 (926 visits); however, ED visits for unsupervised epinephrine needlestick injuries increased nominally (49.8%; 95% CI, −13.2%-112.8%). In 2017-2020, 78.7% (95% CI, 66.3%-91.1%) of ED visits for unsupervised exposures involving prescription non-oral medications were for unintended epinephrine needlesticks and 87.5% (95% CI, 74.5%-100.0%) of these visits were made by children aged ≥3 years.

From 2009-2020, the estimated number of ED visits for unsupervised medication exposures among children aged ≤5 years decreased, with an annual percentage change (APC) of −6.0%, from 66,416 (95% CI, 50,119-82,713) in 2009 to 36,564 (95% CI, 27,520-45,609) in 2020 (Table 4; Appendix Figure 1). During this time, there were similar decreases in ED visits for other types of common unintentional injuries among children aged ≤5 years, including falls (APC −5.4%), injuries from being struck by/against objects (APC −6.2%), foreign body exposures (APC −3.3%), and fire/burn-related injuries (APC −5.3%). The estimated number of ED visits for unsupervised medication exposures resulting in hospitalization also declined across the 12-year study period (APC −4.5%), from 6,909 (95% CI, 4,131-9,686) in 2009 to 5,813 (95% CI, 3,392-8,235) in 2020; however, the estimated number of emergent hospitalizations did not change significantly for other common unintentional injuries among young children except for struck-by/against object injuries (APC −3.0%) (Table 4; Appendix Figure 2).

The estimated number of ED visits for unsupervised medication exposures among children aged ≤5 years declined significantly from 66,416 in 2009 to 36,564 in 2020 (the lowest annual estimate since surveillance was initiated in 2004),³ with a corresponding significant decline in emergent hospitalizations. Patient and case characteristics were similar throughout 2009-2020, but trends in estimated numbers of visits varied by medication.

The decline in ED visits for medication exposures among young children from 2009-2020 is consistent with reported declines in calls to US poison centers for medication exposures among young children over the same period.^{19, 20} However, a decline from 2009-2020 in estimated ED visits for other common unintentional injuries among children aged ≤5 years suggests that a secular trend of declining numbers of ED visits among this age group could be a contributing factor to the decline in ED visits for unsupervised medication exposures. On the other hand, the number of hospitalizations did not decline significantly for other unintentional injuries (except for injuries from being struck by/against objects), suggesting that declines in ED visits for other injuries may reflect a shift in treatment of less severe cases to other settings (e.g., urgent care centers, telehealth visits), while both ED visits and hospitalizations declined for unsupervised medication exposures, suggesting a decline in incidence of unsupervised medication exposures. In addition, trends in ED visits for unsupervised exposures differed by medication, suggesting that the decline in ED visits was not solely related to a secular trend of fewer unintentional injury ED visits among young children.

Following reports of increases in unsupervised medication exposures in the early 2000s, renewed prevention efforts were initiated through the CDC Prevention of Overdoses and Treatment Errors in Children Taskforce (PROTECT) Initiative and partner organizations.²¹ In the 2010s, voluntary addition of flow restrictors on OTC pediatric liquid products containing acetaminophen, including CCMs, withdrawal of infant CCM products, and labeling warning against CCM use in children aged <4 years coincided with reductions in ED visits and poison center calls for pediatric exposures, including those involving potentially toxic doses.^22-24 In this study, from 2009-2012 to 2017-2020, ED visits for OTC liquid medication exposures declined significantly, except for exposures involving diphenhydramine. Notably, flow restrictors have not been broadly implemented for liquid diphenhydramine (or CCMs not containing acetaminophen), but studies have suggested that their use on these products would help further reduce pediatric ingestions,²⁵ and draft FDA Guidance identifies diphenhydramine and several CCM ingredients in recommendations for flow restrictors.²⁶

Other public health interventions may have also impacted trends in pediatric medication exposures. Some of the largest declines in visits for prescription solid exposures involved medication classes for which there have been interventions to reduce overdose among adults and adolescents (e.g., opioids, benzodiazepines) by reducing the amount of these products available through judicious prescribing, use of alternate therapies, take-back programs, and education.²⁷ Studies from the 2000s found increases in pediatric prescription opioid exposures corresponding to increases in opioid prescribing.²⁸ Similarly, recent declines in ED visits for pediatric opioid and benzodiazepine exposures correspond to decreases in prescribing, including coprescribing.^{29, 30}

While flow restrictors have the potential to prevent or limit unsupervised exposures involving most liquid medications, identifying interventions to address prescription solid medication exposures is more challenging since these medications are often taken out of CR packaging by adults (e.g., transferred to pill organizers or other easy-open containers) before being accessed by young children.^{31, 32} Indeed, nearly 80% of ED visits for unsupervised exposures involving prescription solids involved children aged ≤2 years who are unlikely able to open CR packaging.

While it is recommended to always keep medications in their original CR containers, eliciting behavior change is complex, and engineering or packaging solutions may have the greatest impact. Many of the most frequently implicated prescription solids can be harmful to children in low doses, and CR unit-dose packaging has been suggested to protect each dose until taken.^{7, 33-35} Development of adult-friendly, child-deterrent pill organizers may also provide safer options for those who use these devices to aid medication adherence.^{7, 36} Nonetheless, even with better engineering or packaging solutions, it is essential to keep all medications out of young children’s sight and reach.⁵

Trends in medication use or availability of some products may have affected unsupervised pediatric exposure trends. Notably, ED visits for OTC solid melatonin exposures increased >400% and ED visits for epinephrine needlestick injuries increased nominally during the study period. Indeed, studies have found a rise in melatonin use³⁷ and allergy prevalence among children during this period.³⁸ Additionally, although we were not always able to determine the exact formulation of melatonin implicated in ED visits, its common availability in gummy formulations may be enticing to young children. While over two-thirds of ED visits for medication exposures overall involved children aged ≤2 years, these melatonin and epinephrine exposures most commonly involved children aged 3-5 years. To help prevent these exposures, it may help to teach young children that they should never access medications on their own, in addition to reminding caregivers about safe storage.

Significant declines in ED visits and hospitalizations for unsupervised medication exposures among young children from 2009-2020 coincided with renewed prevention efforts. Targeted approaches may be needed to achieve continued declines and reach the Healthy People 2030 goal of further reducing unintentional medication overdoses among young children.⁸