Pediatric Melatonin Ingestions — United States, 2012–2021

Karima Lelak, MD; Varun Vohra, PharmD; Mark I. Neuman, MD; Michael S. Toce, MD; Usha Sethuraman, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(22):725-729. 

In This Article

Abstract and Introduction

Introduction

Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle.[1] It is used therapeutically for insomnia in adults and for primary sleep disorders in children.[2] Melatonin is regulated by the Food and Drug Administration (FDA) as a dietary supplement. Various synthetic melatonin preparations are widely available over the counter (OTC) in the United States with sales increasing from $285 million in 2016 to $821 million in 2020.[3] Children are at increased risk for melatonin exposure because of the supplement's widespread use and growing popularity as a sleep aid. In 2020, melatonin became the most frequently ingested substance among children reported to national poison control centers;[4] however, more research is needed to describe the toxicity and outcomes associated with melatonin ingestions in children. This study assessed isolated melatonin ingestions among the pediatric population (defined here as children, adolescents, and young adults aged ≤19 years) during January 1, 2012–December 31, 2021, using the American Association of Poison Control Centers' National Poison Data System (NPDS). During the 10-year study period, 260,435 pediatric melatonin ingestions were reported to NPDS, and the annual number of ingestions increased 530%. In addition, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers in 2021 compared with 0.6% in 2012. Pediatric hospitalizations and more serious outcomes due to melatonin ingestions increased during the study period, primarily related to an increase in unintentional ingestions among children aged ≤5 years. Five children required mechanical ventilation, and two died. Consumers and health care professionals should be encouraged to report any melatonin product–related adverse events to MedWatch, the FDA's medical product safety reporting program. Public health initiatives should focus on raising awareness of increasing numbers of melatonin ingestions among children and on the development of preventive measures to eliminate this risk.

This was a cross-sectional study of pediatric melatonin ingestions reported to U.S. poison control centers. All closed cases of single substance melatonin ingestions (generic code 0201106) involving children, adolescents, and young adults aged ≤19 years during January 1, 2012–December 31, 2021, were included.[5] A closed case is one for which the regional poison control center determined that either no further follow-up or recommendations were required or no further information on the case was available.[5] Aggregate national data were abstracted from NPDS.[5] Noningestion routes of exposure, information requests, exposures with unknown age, and nonhuman exposures were excluded. Abstracted data included age group (≤5, 6–12, and 13–19 years), sex, ingestion reason (unintentional versus intentional), exposure and management site, disposition, and medical outcome. Those managed on-site included children treated at home or any other non–health care site. Standard descriptive statistics were used to describe and compare variables of interest. Rates (exposures per 100,000 population aged ≤19 years) were calculated using population estimates from the U.S. Census Bureau.[6] More serious outcomes were defined as a moderate or major effect or death, as defined by the NPDS Coding Manual.[5] Moderate effects include symptoms following an exposure that are more pronounced or systemic in nature and warrant a treatment intervention but are not life-threatening. Major effects involve symptoms considered life-threatening or that result in substantial residual disability. This study was determined to be nonhuman research and was exempt from human subject review by the Institutional Review Board of Central Michigan University.*

During 2012–2021, a total of 260,435 pediatric melatonin ingestions were reported to poison control centers, representing 2.25% of all pediatric ingestions reported during the same period. The majority of ingestions were unintentional (94.3%), involved males aged ≤5 years, occurred in the home (99.0%), and were managed on-site (88.3%) (Table). Most children (82.8%) were asymptomatic. Among those with reported symptoms, most involved the gastrointestinal, cardiovascular, or central nervous systems. Among 27,795 patients who received care at a health care facility, 19,892 (71.6%) were discharged, 4,097 (14.7%) were hospitalized, and 287 (1.0%) required intensive care. Among all melatonin ingestions, 4,555 (1.6%) resulted in more serious outcomes. Five children required mechanical ventilation, and two died. Both deaths occurred in children aged <2 years (3 months and 13 months) and occurred in the home. One ingestion involved intentional medication misuse; the reason for the other is unknown.

The number of pediatric melatonin ingestions increased 530% from 8,337 in 2012 to 52,563 in 2021, with the largest yearly increase (37.9%) occurring from 2019 to 2020. In 2021, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions compared with 0.6% in 2012. The annual rate of ingestions per 100,000 U.S. population increased during the 10-year study period (Figure 1). This resulted largely from an increase in unintentional ingestions among children aged ≤5 years. There was also an increase in the number of ingestions requiring hospitalization and in those resulting in more serious outcomes (Figure 2). Most hospitalized patients were teenagers with intentional ingestions, whereas the largest increase in hospitalization occurred among children aged ≤5 years with unintentional ingestions.

Figure 1.

Rate* of pediatric melatonin ingestions reported to poison control centers, by year§ — United States, 2012–2021
*Ingestions per 100,000 population, based on U.S. Census Bureau Annual Estimate.
Aged ≤19 years.
§Linear trend, p<0.001.

Figure 2.

Number of pediatric* melatonin ingestions reported to poison control centers, by outcome and year — United States, 2012–2021
*Aged ≤19 years.
More serious outcomes include moderate or major effect or death, as defined by the National Poison Data System Coding Manual. Disposition (including hospitalization) and medical outcome (including more serious outcomes) are not mutually exclusive because persons with more serious outcomes are likely to be hospitalized.

*45 C.F.R. part 46; 21 C.F.R. part 56.

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