A decade-long study demonstrates that a population of invasive sea lamprey (Petromyzon marinus) can be controlled by introducing sterilized males.

The release of sterilized insects to control pest populations has been used successfully during the past 6 decades, but application of the method in vertebrates has largely been overlooked or met with failure. Here, we demonstrate for the first time in fish, that a small population of sea lamprey (Petromyzon marinus; Class Agnatha), arguably one of the most impactful invasive fish in the world, can be controlled by the release of sterilized males. Specifically, the release of high numbers of sterile males (~ 1000's) into a geographically isolated population of adult sea lamprey resulted in the first multiyear delay in pesticide treatment since treatments began during 1966. Estimates of percent reduction in recruitment of age-1 sea lamprey due to sterile male release ranged from 7 to 99.9% with the precision of the estimate being low because of substantial year-to-year variability in larval density and distribution. Additional monitoring that accounts for recruitment variability in time and space would reduce uncertainty in the degree to which sterile male release reduces recruitment rates. The results are relevant to vertebrate pest control programs worldwide, especially as technical opportunities to sterilize vertebrates and manipulate sex ratios expand.

Benchmark dose profiles for bivariate exposures.

While benchmark dose (BMD) methodology is well-established for settings with a single exposure, these methods cannot easily handle multidimensional exposures with nonlinear effects. We propose a framework for BMD analysis to characterize the joint effect of a two-dimensional exposure on a continuous outcome using a generalized additive model while adjusting for potential confounders via propensity scores. This leads to a dose-response surface which can be summarized in two dimensions by a contour plot in which combinations of exposures leading to the same expected effect are identified. In our motivating study of prenatal alcohol exposure, cognitive deficits in children are found to be associated with both the frequency of drinking as well as the amount of alcohol consumed on each drinking day during pregnancy. The general methodological framework is useful for a broad range of settings, including combinations of environmental stressors, such as chemical mixtures, and in explorations of the impact of dose rate rather than simply cumulative exposure on adverse outcomes.

A dose-response analysis of the effects of prenatal alcohol exposure on cognitive development.

BACKGROUND: Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency. METHODS: We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects. RESULTS: The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less. CONCLUSIONS: These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment.

Pathways from prenatal cocaine exposure to adult substance use and behavior.

This is a report from the most recent adult follow-up of the longest running cohort study of prenatal cocaine exposure (PCE), in which women were enrolled prenatally and offspring were assessed in infancy, childhood, adolescence, and young adulthood. In previous studies, PCE was linked to offspring behavior problems such as early substance use and externalizing behavior problems. The current analyses examine pathways from PCE to behavioral outcomes in offspring at the 25-year assessment. Prenatal cocaine exposure was moderate in this cohort; most women decreased or discontinued use after the first trimester. During the first and third trimesters, 38% and 11% used cocaine, respectively. This represents the most common pattern of PCE in non-treatment samples. At this phase, the adult offspring were, on average, 27.3 years old (range = 25-30), had 13.4 years of education, 83% were employed, 55% were Black, and 55% were female. Offspring who were exposed to cocaine during the first trimester were significantly more likely to use marijuana in the past year, report more arrests, and have poorer scores on a decision-making task, controlling for other prenatal substance exposure, demographic, and socioeconomic factors. In mediation analyses, there were indirect pathways from PCE to current marijuana use through early initiation of marijuana use and 21-year marijuana use, and through 15-year status offenses and 21-year marijuana use. There was also an indirect pathway from PCE to lifetime arrests through early initiation of marijuana use and 21-year Conduct Disorder, although the direct pathway from PCE to arrests also remained significant. These findings are consistent with those from previous phases and are an indication that there are detrimental associations with PCE that persist across developmental stages and into adulthood.

Prenatal Substance Use Among Young Pregnant Sexual Minority People.

Purpose: Sexual minority (SM) youth have higher rates of substance use and pregnancy but are absent from the prenatal substance use literature. We modeled the impact of SM identity and syndemic factors on prenatal substance use among 14- to 21-year-olds. Methods: Pregnant people completed an online survey (n = 357). Prenatal substance use was regressed on SM identity, controlling for other syndemic factors (e.g., depressive symptoms, intimate partner violence) and household substance use. Results: Pregnant SM participants (n = 125) were primarily bisexual and were more likely to use tobacco and illicit drugs than heterosexual participants (n = 232). The association between SM identity and prenatal tobacco use was not attenuated by syndemic factors, prenatal cannabis use, or household tobacco use. Conclusion: SM people need increased support for smoking cessation to redress health inequities in tobacco use, prevent prenatal exposures to tobacco, and limit the long-term consequences of tobacco use on health.

Change in marijuana use from adolescence to young adulthood and its relation to gestational alcohol and marijuana exposure.

INTRODUCTION: Many studies have examined changes in marijuana use across adolescence, but few have examined factors associated with transitions from adolescence to young adulthood. We examined prenatal exposures to alcohol and marijuana and adolescent risk and protective factors that best distinguished among abstinence, continuity, or cessation of marijuana use from 16 to 22 years. METHOD: Data were from the Maternal Health Practices and Child Development Project at the prenatal and 16- and 22-year follow-up phases. The offspring were of lower socioeconomic status with an average of 12.8 years of education at 22 years. Participants' frequency and quantity of marijuana use over the past year were used to determine change in use. A discriminant analysis was applied to distinguish among the identified groups. The risk factors considered included prenatal substance exposures and age 16 demographics, behavior, and home environment. RESULT: Four categories of transitions were defined based on marijuana use from 16 to 22 years: non-users (n = 193), stop/decrease (n = 81), continue at same level/increase (n = 125), and initiation after the 16-year phase (n = 122). The factors that best distinguished among these groups were peers' marijuana use, delinquency, caregivers' financial strain, prenatal exposure to alcohol and marijuana, and race. CONCLUSION: Prenatal alcohol and marijuana exposure were significantly related to transitions of marijuana use from adolescence to young adulthood, controlling for peers' use, behavior problems, and home environment. While gestational marijuana exposure was associated with early initiation/increasing use, alcohol exposure was related to later initiation. The findings emphasize the long-term effects of prenatal exposure to alcohol and marijuana.

Factors associated with ever using cannabidiol in a cohort of younger pregnant people.

One in four Americans have used cannabidiol (CBD) products in the past year, and use has become prevalent in many Western countries with recent deregulation from a controlled or illicit substance to an unrestricted product. CBD is also marketed to pregnant people to treat common medical conditions. However, preclinical work has linked cannabidiol exposure to embryotoxicity, as well as neuroendocrine, reproductive, and behavioral effects in offspring. No studies have examined the prevalence or correlates of CBD use among pregnant people. Demographic, medical, and psychosocial correlates of cannabidiol use were examined in the YoungMoms study, a cohort of pregnant people under the age of 22, a population that is at high risk for cannabis use during pregnancy. Few of the participants (n = 186; 75% Black or Biracial) reported use of cannabidiol during pregnancy, but one in five had tried these products. Participants who reported ever using CBD were more likely to report alcohol and other drug use prior to pregnancy, controlling for race.As the use of CBD among people of reproductive age is increasingly prevalent, more research on CBD use in pregnant human populations is needed to investigate the effects of CBD on fetal development and infant outcomes.

Long-term effects of prenatal cannabis exposure: Pathways to adolescent and adult outcomes.

With the increased prevalence, potency, and acceptability of cannabis use during pregnancy, it is important to understand the developmental effects of prenatal cannabis exposure (PCE). This review discusses methodological considerations for studies of PCE, including the assessment of exposures, covariates, and outcomes, and reviews findings from prospective, longitudinal studies of PCE. There is some evidence for associations between PCE and restricted growth at birth, but not for long-term effects on growth. PCE appears to have subtle yet enduring effects on memory and achievement in children and adolescents. Despite differences in sample demographics and measurement, there are remarkably consistent effects of PCE on externalizing behaviors, such as delinquency and substance use, which persist into adulthood. Longitudinal analyses demonstrate the importance of early cannabis initiation for pathways between PCE and adult functioning, including substance use and abuse, memory deficits, and psychotic symptoms. Animal studies demonstrate direct effects on the development of the brain via activation of endogenous endocannabinoid systems. Cannabis-induced activation of the endocannabinoid system causes alterations in the release of neurotransmitters and the modulation of brain plasticity in neural pathways that underlie cognition, motivation, and behavior regulation. Future research should consider cannabis use before pregnancy, the timing and route of exposure, polysubstance exposures, and inter-generational effects.

Environmental Health Information Partnership (EnHIP): Strengthening the Capacity of Minority Serving Institutions.

The U.S. National Library of Medicine's (NLM) Environmental Health Information Partnership (EnHIP) collaborates with Historically Black Colleges and Universities (HBCUs) and other minority-serving academic institutions to enhance their capacity to reduce health disparities through the access, use, and delivery of environmental health information on their campuses and in their communities. The partnership began in 1991 as the Toxicology Information Outreach Panel (TIOP) pilot project, and through successive iterations it is NLM's longest running outreach activity. EnHIP's continued relevance today as an information outreach and training program testifies to the prescience of NLM director, Donald A.B. Lindberg M.D's initial support for the program. Dr. Lindberg's seeing to its continued success to benefit participating institutions and help achieve the societal goals of environmental justice serve as well to benefit NLM by increasing its visibility, and use of its resources in the classroom, for research, and in community outreach. NLM envisions an expanding role for EnHIP in advancing health equity as the impact of environmental exposure, climate change, and increasing zoonotic diseases disproportionately impact their communities.

HIV/AIDS Community Information Outreach Program (ACIOP): A Landmark NIH Conference and an Enduring NLM Role in Meeting the Affected Community's Need for Information Access.

In June 1993, the National Library of Medicine (NLM) joined with the National Institutes of Health's (NIH) Office of AIDS Research (OAR), and the National Institute of Allergy and Infectious Diseases (NIAID) to host a conference at a pivotal time in the HIV/AIDS epidemic to understand better the information needs of five major constituency groups: clinical researchers; clinical providers; news media and the public; patients; and the affected community. NLM's director, Donald A.B. Lindberg M.D., and staff sought to identify new program possibilities benefitting from the input of current and potential users of the Library's information services. Conference recommendations led to a key NLM policy change providing cost-free access to all AIDS data, and the establishment of the HIV/AIDS Community Information Outreach Program (ACIOP), which enabled new partnerships with local community-based organizations serving the affected community. Uniquely funded and long running, more than 300 ACIOP projects have been supported to-date. These projects have improved awareness and use of national HIV/AIDS information resources; enhanced information seeking skills; developed locally generated information resources; and enhanced the capacity of community-based organizations to use new information and computer technologies providing access to essential information resources and services.

Prenatal cocaine exposure, early cannabis use, and risky sexual behavior at age 25.

BACKGROUND: Prior research on prenatal cocaine exposure (PCE) indicates that exposed children experience behavioral dysregulation resulting in risky adolescent behavior including earlier initiation of cannabis use and sexual intercourse. The goal of this study was to examine the long-term effects of PCE on adult sexual behavior. METHODS: This is a prospective cohort study of the association between PCE and risky adult sexual behavior and sexually transmitted infections (STIs) in 202 young adults (mean age = 27, SD = 0.98 years). The sample was 55% female, 46% White, and 54% Black. Data from the prenatal, childhood, and adolescent phases of the study were used to delineate pathways from PCE to adult sexual behavior. RESULTS: The most common risky sexual behavior was having sex while drunk or high (63%). One-third of the sample reported that they "almost always" had sex while drunk or high. We found evidence for an indirect pathway from PCE to adult sex while drunk or high via early cannabis initiation. There were no other effects of PCE on adult risky sexual behavior or on risk for STIs, after controlling for sex assigned at birth, race, age at sexual initiation, and family history of drug and alcohol problems. CONCLUSIONS: Although PCE has been associated with earlier initiation of sex in prior studies, PCE was not directly associated with risky adult sex or history of STI. Exposed individuals were at greater risk of sex under the influence of alcohol or drugs via earlier initiation of cannabis use during adolescence.

Maternal trajectories of cannabis use and young adult cannabis and nicotine dependence.

INTRODUCTION: The goals of this study were to model maternal patterns of cannabis use from one year pre-pregnancy to 16 years postpartum and to determine if different patterns of maternal cannabis use predicted offspring substance use at age 22. METHODS: Women were recruited from a prenatal clinic between 1982 and 1984. Maternal cannabis use was assessed by trained interviewers twice during pregnancy, at delivery, 8 and 18 months, 3, 6, 10, 14, and 16 years postpartum. At age 22, substance use and dependence were measured in offspring. Growth mixture models of maternal cannabis use were calculated and adult offspring substance use outcomes were regressed onto maternal cannabis trajectory classes (n = 551). RESULTS: There were five distinct patterns of maternal cannabis use. Offspring of mothers who were chronic cannabis users were more likely to use cannabis (p < 0.001) and develop CUD (p < 0.05) than offspring whose mothers did not use cannabis. Offspring of chronic cannabis users were also more likely to be nicotine dependent by age 22 than offspring whose mothers did not use cannabis (p < 0.01) and than offspring whose mothers were decreasingly likely to use over time (p < 0.01). CONCLUSIONS: Integrated variable- and person-centered analyses revealed long-term and meaningful patterns of cannabis use and desistance. Chronic maternal cannabis use is a risk factor for regular and dependent cannabis use and for dependent tobacco use among young adult offspring. These findings have implications for maternal-child health given the increasing prevalence of cannabis use among women.

A hierarchical meta-analysis for settings involving multiple outcomes across multiple cohorts.

Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. Iongitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose-response coefficients for each outcome and then pooling these correlated dose-response coefficients to obtain an estimated "global" effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose-response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.

Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta-analysis of data from six prospective longitudinal U.S. cohorts.

BACKGROUND: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. METHODS: Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. RESULTS: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting. CONCLUSIONS: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared.

A longitudinal study of the impact of marijuana on adult memory function: Prenatal, adolescent, and young adult exposures.

More Americans are using marijuana than in previous decades but there are concerns over its long-term impact on cognitive functioning, especially memory. The literature on marijuana use and cognitive functioning is mixed, with some studies showing recovery of functioning upon abstinence from the drug and others showing long-term effects that persist. The latter seems especially true for individuals who initiate marijuana at a younger age and engage in more chronic patterns of use. The goal of the current study is to use prospectively collected data on young adults from a prenatal cohort to determine if there is an effect of early and/or current marijuana use on young adult memory, controlling for prenatal exposure to marijuana use, childhood memory deficits, and other significant covariates of memory functioning. At the 22-year follow-up phase of the Maternal Health Practices and Child Development (MHPCD) study, 524 young adults (58% Black, 42% White, 52% female) completed the Wechsler Memory Scale-III. Multiple regression analyses and structural equation modeling were used to determine the effect of marijuana exposure during gestation, early adolescence, and young adulthood on young adult memory function. Results indicated that initiating marijuana use before age 15 placed young adults at greater risk of memory deficits, even after controlling for childhood memory and current marijuana use. First trimester marijuana exposure also indirectly predicted young adult memory function via childhood memory deficits and early initiation of marijuana. These findings highlight the risk of prenatal marijuana exposure and early initiation of marijuana for long-term memory function in adulthood.

Prenatal exposure to tobacco and cannabis, early cannabis initiation, and daily dual use of combustible cigarettes and cannabis during young adulthood.

INTRODUCTION: Daily combustible cigarette use is common among cannabis users, and dual use of cigarettes and cannabis is associated with detrimental outcomes. This study addresses gaps in the literature by examining data from the prenatal and adolescent phases of a prospective, longitudinal study to predict adult daily dual use. METHODS: Young adult offspring (M age = 22.8 years, 53% female) from a prenatal cohort reported on combustible cigarette and cannabis use (N = 500, 58% Black, 42% White). Pathways to daily dual use were modeled using variables from the gestational and adolescent phases of the study including prenatal tobacco, alcohol, and cannabis exposures; ages at initiation of cigarettes and cannabis; and adolescent learning/memory, impulsivity, and behavior problems. RESULTS: Prenatal cannabis and tobacco use were not directly linked to adult daily dual use of cannabis and tobacco. However, structural equation modeling revealed three significant indirect pathways from prenatal cigarette and cannabis exposures to adult daily dual use of cigarettes and cannabis via early cigarette initiation, early cannabis initiation, and adolescent behavior problems. CONCLUSIONS: This study identified pathways from prenatal cannabis and tobacco exposure to adult daily dual use, in addition to clarifying adolescent outcomes that may be part of the pathways. In a climate of growing acceptance of cannabis use and increasing legalization of recreational use, these findings serve as a warning that early exposure to cannabis may have an important role in shaping long-term dual use of tobacco and cannabis.

Environmental Health Information Partnership (EnHIP): Strengthening the capacity of minority serving institutions.

The U.S. National Library of Medicine's (NLM) Environmental Health Information Partnership (EnHIP) collaborates with Historically Black Colleges and Universities (HBCUs) and other minority-serving academic institutions to enhance their capacity to reduce health disparities through the access, use, and delivery of environmental health information on their campuses and in their communities. The partnership began in 1991 as the Toxicology Information Outreach Panel (TIOP) pilot project, and through successive iterations it is NLM's longest running outreach activity. EnHIP's continued relevance today as an information outreach and training program testifies to the prescience of NLM director, Donald A.B. Lindberg M.D's initial support for the program. Dr. Lindberg's seeing to its continued success to benefit participating institutions and help achieve the societal goals of environmental justice serve as well to benefit NLM by increasing its visibility, and use of its resources in the classroom, for research, and in community outreach. NLM envisions an expanding role for EnHIP in advancing health equity as the impact of environmental exposure, climate change, and increasing zoonotic diseases disproportionately impact their communities.

HIV/AIDS community information outreach program (ACIOP): A landmark NIH conference and an enduring NLM role in meeting the affected community's need for information access.

In June 1993, the National Library of Medicine (NLM) joined with the National Institutes of Health's (NIH) Office of AIDS Research (OAR), and the National Institute of Allergy and Infectious Diseases (NIAID) to host a conference at a pivotal time in the HIV/AIDS epidemic to understand better the information needs of five major constituency groups: clinical researchers; clinical providers; news media and the public; patients; and the affected community. NLM's director, Donald A.B. Lindberg M.D., and staff sought to identify new program possibilities benefitting from the input of current and potential users of the Library's information services. Conference recommendations led to a key NLM policy change providing cost-free access to all AIDS data, and the establishment of the HIV/AIDS community information outreach program (ACIOP), which enabled new partnerships with local community-based organizations serving the affected community. Uniquely funded and long running, more than 300 ACIOP projects have been supported to-date. These projects have improved awareness and use of national HIV/AIDS information resources; enhanced information seeking skills; developed locally generated information resources; and enhanced the capacity of community-based organizations to use new information and computer technologies providing access to essential information resources and services.

Life-course impact of child maltreatment on midlife health-related quality of life in women: longitudinal mediation analysis for potential pathways.

PURPOSE: We examined (1) if child maltreatment (CM) is associated with lower health-related quality of life (HRQoL) and fewer quality-adjusted life years (QALY) over a 9-year follow-up of midlife women and (2) if adulthood psychosocial mediators could explain these associations. METHODS: Women (n = 342) completed the Childhood Trauma Questionnaire. Longitudinal HRQoL and QALY outcomes measured at five study visits include 36-item Short-Form Health Survey mental component score and physical component score and the Short Form-6 Dimension health index. Aims 1 and 2 were investigated by generalized estimating equations and sequential structural nested mean models, respectively. RESULTS: Twenty percent reported 2+ CM types. Compared with women without CM, women who experienced 2+ CM types reported 5- and 4-points lower scores in mental component score and physical component score, respectively, and 28 fewer healthy days per year in QALY. Low optimism, sleep problems, and low social support each explained greater than 10% of the relationship between 2+ CM and HRQoL and QALY over time. CONCLUSIONS: CM is a life-course social determinant of HRQoL and QALY throughout midlife, particularly in women who experienced 2+ CM types. Several mediators are modifiable and could be targets of interventions to mitigate the negative impact of CM on midlife HRQoL and QALY in women.

Trends in long-stay admissions to a UK paediatric intensive care unit.

OBJECTIVE: Prolonged admission to a paediatric intensive care unit (PICU) consumes significant healthcare resource. An increase in the number of long-stay admissions and bed utilisation has been reported elsewhere in the world but not in the UK. If an increasing trend of long-stay admissions is evident, this may have significant implications for provision of paediatric intensive care in the future. DESIGN/SETTING/PATIENTS: We retrospectively analysed prospectively collected data from Birmingham Children's Hospital, UK, over a 20-year period from 1998 to 2017. PICU admissions, bed-days, length of stay and mortality trends were analysed and reported over four different epochs (1998-2002, 2003-2007, 2008-2012 and 2013-2017) for long-stay admissions (PICU length of stay ≥28 days) and others. Differences in patient demographics, diagnostic categorisation and hospital utilisation were also analysed. RESULTS: In total, 24 203 admissions accounted for 131 553 bed-days over the 20-year period. 705 (2.9%) long-stay admissions accounted for 42 312 (32%) bed-days. Proportion of long-stay admissions and corresponding bed-days increased from 1.6% and 20.5% in 1998-2002 to 4.5% and 42.6%, respectively, in 2013-2017 (p<0.001). Long-stay patients had a significantly higher number of hospital admissions (median: 4 vs 2, p<0.001) per patient and overall hospital length of stay (median: 98 vs 15, p<0.001) bed-days compared with other patients. Long-stay admissions were associated with significantly higher crude mortality (23% vs 6%, p<0.001) compared with other admissions. CONCLUSIONS: A significant increase in the proportion of prolonged PICU admissions with disproportionately high resource utilisation and mortality is evident over two decades.