Long-term Child Health Outcomes Research Articles

Considerations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings.

Anti-obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long-term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end-points, secondary end-points, eligibility criteria, trial run-in and follow-up phases, use of active comparators and guidelines for down-titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end-points, emphasis was placed on moving away from BMI z-score as a primary outcome, incorporating multiple alternative BMI-related outcomes and measuring adiposity/body fat as a prominent secondary end-point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run-in phases was discussed. It was also underscored that designing trials with extended follow-up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo-controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down-titration to avoid excessive weight reduction when applicable.

Is the impact of the South African child support grant on childhood stunting robust? An instrumental variable evaluation

The Child Support Grant (CSG) is part of the South African Social Assistance Programme, which costs the country approximately 1.3% of GDP annually. Given the scale of this programme, it is important to assess whether it has had an impact on the long-term health outcomes of children. Extant literature on the impact of CSG on a child’s long run nutritional status as measured by the height-for-age relies on the optimistic assumption that estimation controls for all relevant variables (i.e. the ignorability assumption). Further existing analysis are based on older datasets (i.e. older waves of the National Income Dynamic Study (NIDS)). We examine the robustness of the results to bias due to unobserved variables, using more recent data (the 2014/2015 and 2017 NIDS). Using the possession of the necessary government-issued documentation to access the grant as an instrumental variable (IV) we find that existing results are robust to the IV framework. Further, acknowledging the limitation of the instrumental variable, we show that the result is robust to violation of various assumptions underlying the IV approach. We argue that while the CSG remains a crucial contributor to early childhood development in South Africa, there is a need to critically examine its impact on nutritional status given the importance of this variable for intergenerational transmission of poverty.

Factors predicting depressive symptoms in parents of children with autism spectrum disorder in eastern China

BackgroundParents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms.MethodsA multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD.ResultsA total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026–7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234–8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108–5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093–1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201–0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221–0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950–0.996) were less likely to have depressive symptoms.ConclusionsDepressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

Long-term outcomes for children conceived by assisted reproductive technology

Worldwide, more than 10 million children have been born after Assisted Reproduction Technology (ART) and comprised up to 7.9% of children born in Europe and up to 5.1 % of children born in the US in 2018 (1, 2). The short-term outcome for children born after ART is well-known from numerous publications, with higher rates of preterm birth and low birth weight in children born after fresh embryo transfer and higher rates of large for gestational age and high birth weight in children born after frozen embryo transfer compared to children born after spontaneous conception (3, 4). Higher rates of birth defects in children born after ART have also been shown consistently over time (5). Studies on long-term health outcomes after ART are scarcer but suggest an increased risk of altered blood pressure and cardiovascular function in children born after ART. In this review we summarize long-term health outcomes in children born after ART and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to sub fertility or to the ART treatments per se. Finally, we speculate where the future will bring us with regards to ART treatment strategies and safety of the mother and child.

Maternal Multiple Sclerosis and Health Outcomes Among the Children: A Systematic Review.

To summarize the available literature and provide an overview of in utero exposure to maternal multiple sclerosis (MS) and the influence on offspring health outcomes. We conducted a systematic review by searching Embase, Medline and PubMed.gov databases, and we used covidence.org to conduct a thorough sorting of the articles into three groups; 1) women with MS and the influence on birth outcomes; 2) women with MS treated with disease-modifying therapy (DMT) during pregnancy and the influence on birth outcomes; and 3) women with MS and the influence on long-term health outcomes in the children. In total, 22 cohort studies were identified. Ten studies reported on MS without DMT and compared with a control group without MS, and nine studies on women with MS and DMT prior to or during pregnancy met the criteria. We found only four studies reporting on long-term child health outcomes. One study had results belonging to more than one group. The studies pointed towards an increased risk of preterm birth and small for gestational age among women with MS. In terms of women with MS treated with DMT prior to or during pregnancy, no clear conclusions could be reached. The few studies on long-term child outcomes all had different outcomes within the areas of neurodevelopment and psychiatric impairment. In this systematic review, we have highlighted the research gaps on the impact of maternal MS on offspring health.

Assisted reproductive technology and association with childhood cancer subtypes.

To investigate the association between assisted reproductive technology (ART) use and childhood cancer subtype. We deployed a cross-sectional survey of 1701 parents of children with cancer about their ART use, demographics, and gestational and perinatal factors. Multivariable logistic regression modeled the association between ART use, birthweight and multiple gestation status with childhood cancer, by subtype. ART use was highest among children with osteosarcoma relative to children with other cancer types, and this association was statistically significant in multivariable models (OR=4.4; 95% CI=1.7-11.3; p=0.0020). ART use was also elevated among children with hepatoblastoma, but this relationship appeared to be due to the strong associations between ART use and lower birthweight in our sample. No specific ART modality appeared to drive these associations. In univariate models, multiple gestation was associated with a 2.7-fold increased odds of hepatoblastoma (OR=2.71; 95% CI=1.14-6.42; p=0.02) and a 1.6-fold increased odds of neuroblastoma (OR=1.62; 95% CI=1.03-2.54; p=0.03), but these associations were not retained in multivariable models. Associations between ART use and hepatoblastoma risk may be attributable to birthweight, a known hepatoblastoma risk factor. ART use may also be associated with osteosarcoma, independent of birthweight, an association not previously observed in studies limited to cancers diagnosed before adolescence. Evaluating long-term health outcomes in children conceived by ART, throughout adolescence and potentially into adulthood, appears warranted.

The Effects of a Prenatal Mindfulness Intervention on Infant Autonomic and Behavioral Reactivity and Regulation.

ABSTRACTObjectiveMaternal health and wellness during pregnancy are associated with long-term health outcomes in children. The current study examined whether infants of women who participated in a mindfulness-based intervention during pregnancy that reduced levels of stress and depression, increased physical activity, and improved glucose tolerance differed on biobehavioral markers of psychopathological and physical health risk compared with infants of women who did not.MethodsParticipants were 135 mother-infant dyads drawn from a racially and ethnically diverse, low-income sample experiencing high stress. The women participated in an intervention trial during pregnancy that involved assignment to either mindfulness-based intervention or treatment-as-usual (TAU). Infants of women from both groups were assessed at 6 months of age on sympathetic (preejection period), parasympathetic (respiratory sinus arrhythmia), and observed behavioral (negativity and object engagement) reactivity and regulation during the still face paradigm. Linear mixed-effects and generalized linear mixed-effects models were used to examine treatment group differences in infant outcomes.ResultsRelative to those in the intervention group, infants in the TAU group showed a delay in sympathetic activation and subsequent recovery across the still face paradigm. In addition, infants in the intervention group engaged in higher proportions of self-regulatory behavior during the paradigm, compared with the TAU group. No significant effect of intervention was found for parasympathetic response or for behavioral negativity during the still face paradigm.ConclusionsFindings provide evidence that maternal participation in a short-term, group mindfulness-based intervention during pregnancy is associated with the early development of salutary profiles of biobehavioral reactivity and regulation in their infants. Because these systems are relevant for psychopathology and physical health, prenatal behavioral interventions may benefit two generations.

Comprehensive Nutrition Interventions in First Nation-Operated Schools in Canada.

Comprehensive school-based nutrition interventions offer a promising strategy to support healthy eating for First Nations children. A targeted strategic review was performed to identify nutrition interventions in 514 First Nation-operated schools across Canada through their websites. Directed content analysis was used to describe if interventions used 1 or more of the 4 components of the Comprehensive School Health (CSH) framework. Sixty schools had interventions. Nearly all (n = 56, 93%) schools offered breakfast, snack, and (or) lunch programs (social and physical environment). About one-third provided opportunities for students to learn about traditional healthy Indigenous foods and food procurement methods (n = 18, 30%) (teaching and learning) or facilitated connections between the school and students' families or the community (n = 16, 27%) (partnerships and services). Few schools (n = 10, 17%) had a nutrition policy outlining permitted foods (school policy). Less than 1% (n = 3) of interventions included all 4 CSH components. Results suggest that most First Nation-operated schools provide children with food, but few have nutrition interventions that include multiple CSH components. First Nation-operated schools may require additional financial and (or) logistical support to implement comprehensive school-based nutrition interventions, which have greater potential to support long-term health outcomes for children than single approaches.

Mediating effects of early health on the relationship between early poverty and long-term health outcomes of children: a birth cohort study

ObjectiveThis study analyses the mediating effects of early health prior to age 3 on the association between early poverty and the health outcomes of children at age 12.DesignPopulation-based longitudinal birth...

Optimal gestational weight gain

Optimal gestational weight gain

Impact of maternal medication for opioid use disorder on neurodevelopmental outcomes of infants treated for neonatal opioid withdrawal syndrome.

Increasing rates of maternal opioid use disorder has led to greater number of opioid exposed newborns (OENs). Maternal enrollment in medication for opioid use disorder (MOUD) program improves short term neonatal outcomes. This study aimed at assessing neurobehavioral outcomes for OENs. Retrospective observational cohort study of OENs between Jul 2006 and Dec 2018. Two study groups were identified as initiation of medication for opioid use disorder (MOUD) prior to diagnoses of pregnancy or after. Primary outcome variables were enrollment in and duration of EI services. Secondary outcome variable was diagnoses of a behavioral and/or developmental disorder (BDD) during the study period. Of 242 infants, 113 were enrolled in EI and BDD diagnoses data was available for all infants [age range 6 to 12 years], 82% infants had exposure to maternal MOUD, while 18% were exposed to either maternal prescription non-MOUD opioids or illicit opioids. Maternal MOUD initiation prior to pregnancy was associated with improved short term outcomes for OENs. Almost a third of infants were diagnosed with a BDD with no differences between the two study groups. Early initiation of maternal MOUD improved short term outcomes and discharge disposition for OENs. Prolonged in-utero exposure to opioids presents a potential for negative impact on neurodevelopmental and behavioral outcomes. These risks must be considered to increase access and adherence to EI services, as well as to focus on non-opioid based maternal MOUD. Longitudinal studies assessing the safety of MOUD on short and long-term child health outcomes are needed.

Outcomes following admission to paediatric intensive care: A systematic review.

To describe the long-term health outcomes of children admitted to a paediatric intensive care unit. A systematic review of the literature was performed. Studies of children under 18 years of age admitted to a paediatric intensive care unit were included. Studies focussed on neonatal admissions and investigating specific paediatric intensive care unit interventions or admission diagnoses were excluded. A table was created summarising the study characteristics and main findings. Risk of bias was assessed using the Newcastle Ottawa Quality Assessment Scale for observational studies. Primary outcome was short-, medium- and long-term mortality. Secondary outcomes included measures of neurodevelopment, cognition, physical, behavioural and psychosocial function as well as quality of life. One hundred and eleven studies were included, most were conducted in high-income countries and focussed on short-term outcomes. Mortality during admission ranged from 1.3 to 50%. Mortality in high-income countries reduced over time but this trend was not evident for lower income countries. Higher income countries had lower standardised mortality rates than lower income countries. Children had an ongoing increased risk of death for up to 10 years following intensive care admission as well as increased physical and psychosocial morbidity compared to healthy controls, with associated poorer quality of life. There is limited high-level evidence for the long-term health outcomes of children after intensive care admission, with the burden of related morbidity remaining greater in poorly resourced regions. Further research is recommended to identify risk factors and modifiable factors for poor outcomes, which could be targeted in practice improvement initiatives.

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries.

The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

ObjectiveThe aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD...

Impact of Interdisciplinary Team Care for Children With 22q11.2 Deletion Syndrome.

To evaluate disease-specific guideline adherence among children with 22q11.2 deletion syndrome receiving multidisciplinary team care through a 22q specialty clinic compared to children not receiving team care. Retrospective chart review; quality improvement project. Tertiary care pediatric hospital. One hundred eighty-nine patients with 22q11.2 deletion syndrome were categorized into those receiving team care and those not receiving team care. Guideline adherence was compared between the 2 groups. Percent adherence across 8 disease-specific guidelines. A Welch t test revealed mean adherence among patients receiving team care was significantly higher (83% vs 42%, P < .001) compared those not receiving team care. Among team patients with a single 22q Center visit, a paired samples t test showed that mean adherence increased from 63% before the clinic encounter to 86% six months after the encounter (P < .001). Some guidelines were more likely to be associated with provider nonadherence, whereas others were more likely to be associated with patient nonadherence. Multidisciplinary team care is associated with significantly higher guideline adherence in children with 22q11DS. Additional research is needed to investigate the effect of team care on long-term health outcomes in children with 22q11DS.

In utero exposure to thiopurines/anti-TNF agents and long-term health outcomes during childhood and adolescence in Denmark.

Data on long-term health outcomes of children exposed in utero to thiopurines and anti-TNF medications are lacking. To examine the association between in utero exposure to thiopurines and anti-TNF medications and child health outcomes of site-specific groups of infections, using a composite endpoint including psychiatric diagnoses/autism spectrum disorder (ASD)/attention deficit hyperactivity disorder (ADHD), and malignancies during childhood/adolescence. A nationwide cohort study based on Danish health registries included 1311009 live born children during 1995 through 2015. Outcomes were based on hospital diagnoses (in-patients/out-patients/emergency department contacts). In total, 1048 children were exposed in utero to thiopurines and 1309961 were unexposed. The adjusted hazard ratios (HRs) for site-specific groups of infections in the first 3years of life were close to unity. The adjusted HR of psychiatric diagnoses/ASD/ADHD was 1.11 (95% CI 0.81-1.52). The HR of malignancies was not calculated (only two events among the exposed). In total, 493 children were exposed in utero to anti-TNF medications and 728055 were unexposed. Within the first year of life, the adjusted HR of respiratory, urological/gynaecological infections and other infections were 1.34 (95% CI 1.03-1.74), 2.36 (95% CI 1.15-4.81) and 1.61 (95% CI 1.21-2.13), respectively. We found no increased risk of other adverse outcomes. After in utero exposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. After in utero exposure to anti-TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.

Water, Sanitation, and Hygiene: Linkages with Stunting in Rural Ethiopia.

Stunting is a global burden affecting nearly 160 million children younger than five years of age. Whilst the linkages between nutrition and stunting are well recognized, there is a need to explore environmental factors such as water and sanitation, which may influence feeding practices and result in potential infection pathways. This paper explores the linkages between stunting and water, sanitation and hygiene (WASH) factors in Ethiopia, which is a relatively understudied context. The research draws upon baseline data for children under the age of five from 3200 households across four regions in Ethiopia as part of a wider study and integrated program led by the United Nations Children’s Fund (UNICEF). Using World Health Organization (WHO) z-scoring, the average stunting rate in the sample is 47.5%. This paper also takes into account demographic and social behavioural factors such as the age, gender of children, and gender of the primary caregiver, in addition to handwashing behaviour and drinking water facilities. The evidence recommends efforts to improve handwashing behaviour for mothers and children with a focus on access to clean water. Higher stunting rates with an increase in the age of children highlight the need for continued interventions, as efforts to improve nutrition and WASH behaviours are most effective early on in promoting long-term health outcomes for children.

Maternal Hemoglobin Concentrations Across Pregnancy and Maternal and Child Health: A Systematic Review and Meta-analysis (P11-033-19)

ObjectivesMaternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin thresholds that predict health risk or protection for mother and child. Our objective was to conduct a systematic review and meta-analysis to examine the associations of maternal hemoglobin concentrations with a range of maternal and infant health outcomes, accounting for timing of measurement (preconception, first, second and third trimesters), etiology of anemia and cut-off category. MethodsOur search strategy identified 7,677 articles. Screening and article selection was conducted using Covidence systematic review software to organize search results from PubMed and Cochrane Review. The systematic review included 272 studies and the meta-analysis included 102 studies. ResultsLow maternal hemoglobin (< 110 g/L) was associated with poor birth outcomes (low birth weight, OR (95%CI): 1.43 (1.31-1.55); preterm birth, 1.35 (1.25-1.46); small-for-gestational age, 1.08 (1.00-1.18); stillbirth, 1.43 (1.05-1.95); perinatal mortality, 1.73 (1.32-2.26); and neonatal mortality, 1.49 (1.19-1.87); and adverse maternal outcomes (post-partum hemorrhage, 2.17 (1.51-3.10); preeclampsia, 1.84 (1.31-2.59); and blood-transfusion, 6.57 (3.59-12.00). High maternal hemoglobin (> 130 g/L) was associated with increased odds of small-for-gestational age, 1.22 (1.08-1.37); stillbirth, 1.88 (1.21-2.91); preeclampsia, 1.48 (1.10-2.01); and gestational diabetes, 2.02 (1.63-2.50). Relationships varied by timing of measurement and cut-off category; limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. ConclusionsCurrent data are insufficient for determining if revisions to current hemoglobin cut-offs are required. Pooled high-quality individual-level data analyses as well as prospective cohort studies that measure hemoglobin throughout pregnancy would be valuable to inform the re-evaluation of hemoglobin cut-offs. Funding SourcesThis work was commissioned and financially supported by the Evidence and Programme Guidance Unit, Department of Nutrition for Health and Development of the World Health Organization (WHO), Geneva, Switzerland.

Maternal hemoglobin concentrations across pregnancy and maternal and child health: a systematic review and meta-analysis.

Maternal anemia is a well‐recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta‐analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta‐analysis included 95 studies. Low maternal Hb (<110 g/L) was associated with poor birth outcomes (low birth weight, preterm birth, small‐for‐gestational‐age (SGA), stillbirth, and perinatal and neonatal mortality) and adverse maternal outcomes (postpartum hemorrhage, preeclampsia, and blood transfusion). High maternal Hb (>130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long‐term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high‐quality individual‐level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.

2324. Long-Term Health Outcomes of Children Evaluated for Unexplained Fevers in a Pediatric Infectious Diseases Clinic

BackgroundUnexplained fever is a common reason for outpatient referral to pediatric infectious diseases (PID) subspecialists. A previous study at our center concluded that most children referred to PID for prolonged or recurrent unexplained fever have self-limited illnesses and receive no specific diagnosis. Studies looking at long-term outcomes of such patients have not been published.MethodsThe study cohort consisted of 156 patients seen in the PID clinic for unexplained fever from 2008 through 2012 who were not given a definitive diagnosis or were thought to have sequential self-limited illnesses, plus 20 patients seen during that time who were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. A scripted telephone interview with consenting parents or guardians who could be reached was conducted in 2018.ResultsAttempts were made to contact all 176 families; to date, 100 interviews have been completed. Thirteen of the children initially had prolonged, 45 recurrent, and 25 periodic fever; 17 had PFAPA. The mean follow-up period was 8 years. Only 2 patients developed new diagnoses in the interval since their initial PID visit. One who was thought to have PFAPA developed genital ulcers and was diagnosed with Behcet’s disease 4 years after the PID visit. Another who was thought to have self-limited, prolonged fever was eventually diagnosed with juvenile idiopathic arthritis. None of the remaining 98 children developed serious diagnoses. However, 14 of these children reportedly have continued fevers; 9 of the children suffer from anxiety, and 4 of the remaining 5 report good general health.ConclusionMost children seen in PID clinic for unexplained fever who were not given a specific diagnosis remained well after their initial visit. Two were diagnosed with autoinflammatory diseases after the appearance of telltale signs and symptoms, and none were diagnosed with immunodeficiency or cancer. The children who reportedly continue having fevers but are otherwise healthy warrant further study, with particular attention to their families’ health and illness beliefs.Disclosures All authors: No reported disclosures.