A Finnish nationwide register-based study shows a further 50% decline in already low child mortality.

AIM: Child mortality declined significantly in Finland in 1969-2004. We investigated whether the already low mortality rate could still decline from 2005 to 2020. METHODS: This was a nationwide register-based study. The subjects were children under 16 years of age who had resided in Finland between 2005 and 2020. The study population was identified from Finland's Population Information System of the Digital and Population Data Services Agency. Causes of death were obtained from Statistics Finland. Changes in annual overall and cause-specific mortality rates were evaluated. RESULTS: 3685 children (55% boys) under 16 years of age died in Finland in 2005-2020 from 325 causes. Overall annual child mortality declined by 50% (95% confidence interval 37 to 64%) during the study period, from 0.31/1000 in 2005 to 0.16/1000 in 2020. The mortality rate in children under one year of age declined from 3.1/1000 in 2005 to 1.8/1000 in 2020. The deaths from sudden infant death syndrome fell by 84%, congenital malformations by 62%, infectious diseases by 60%, external causes by 52%, and perinatal disorders by 41%. CONCLUSION: Finland's low child mortality further declined over the past two decades. Contributing factors likely include achievements in paediatric research, public health, and clinical practice.

Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study.

BACKGROUND: Partial or complete thymectomy is routinely performed in paediatric open-heart surgeries when treating congenital heart defects. Whether or not thymectomised children require systematic immunological monitoring later in life is unknown. The objective of this study was to investigate the effects of preoperatively and postoperatively used antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability in paediatric patients with early thymectomy to better recognise the patients who could benefit from immunological follow-up in the future. METHODS: We conducted a retrospective cohort study, including 98 children and adolescents aged 1-15 years, who had undergone an open-heart surgery and thymectomy in infancy and who had previously answered a survey regarding different immune-mediated symptoms and diagnoses. We performed a comprehensive chart review of preoperative and postoperative factors from 1 year preceding and 1 year following the open-heart surgery and compared the participants who had self-reported symptoms of immunological vulnerability to those who had not. RESULTS: The median age at primary open-heart surgery and thymectomy was 19.5 days in the overall study population (60% men, n=56) and thymectomies mainly partial (80%, n=78). Broad-spectrum antibiotics were more frequently used preoperatively in participants with self-reported immunological vulnerability (OR=3.05; 95% CI 1.01 to 9.23). This group also had greater overall use of antibiotics postoperatively (OR=3.21; 95% CI 1.33 to 7.76). These findings were more pronounced in the subgroup of neonatally operated children. There was no statistically significant difference in the duration of intensive care unit stay, hospitalisation time, prevalence of severe infections, surgical complications or glucocorticoid use between the main study groups. CONCLUSION: Antimicrobial agents were more frequently used both preoperatively and postoperatively in thymectomised children with self-reported immunological vulnerability after thymectomy. Substantial use of antimicrobial agents early in life should be considered a potential risk factor for increased immunological vulnerability when evaluating the significance of immune-mediated symptom occurrence in thymectomised paediatric patients.

Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery.

AIM: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. METHODS: The subjects were patients aged 1-15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population-based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. RESULTS: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0-13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1-5.6), asthma (aOR 2.5, 95% CI 1.5-4.1) and wheezing (aOR 2.1, 95% CI 1.5-2.9). CONCLUSION: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open-heart surgery than population-based controls, underlining the importance of immunological follow-ups.

Risk of immune-related diseases in childhood after intrapartum antibiotic exposure.

BACKGROUND: Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. OBJECTIVE: This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. STUDY DESIGN: We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. RESULTS: The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). CONCLUSION: Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children: A Randomized Clinical Trial.

Importance: New approaches for the prevention of acute otitis media (AOM), the most common reason for antibiotic use in children, are needed. Objective: To assess the efficacy of the Streptococcus salivarius K12 oral probiotics in the primary prevention of AOM. Design, Setting, and Participants: This double-blind, randomized placebo-controlled clinical trial was conducted from August 1, 2020, to May 31, 2021, at 50 day care centers in the Oulu region of Finland. A total of 827 children aged 1 to 6 years attending day care were included. The exclusion criteria consisted of ongoing antimicrobial prophylaxis or immunodeficiency. The follow-up time was 6 months and was completed on May 31, 2021. Data were analyzed from October 24, 2022, to September 16, 2023, based on intention to treat. Intervention: Eligible participants were randomly allocated to receive 1 daily dose of a S salivarius K12 product or placebo every evening for 6 months. A daily dose was defined as 1 sachet of soluble oral powder for children younger than 3 years or 1 chewable tablet for children 3 years or older containing 1 × 109 colony-forming units of S salivarius K12. Main Outcomes and Measures: The primary outcome was the proportion of children with at least 1 episode of AOM requiring antimicrobial therapy within 6 months of randomization. All physician visits and purchases of antimicrobial drugs were retrieved from the electronic national medical record and prescription register. The primary outcome was met if the legal guardian had purchased an antimicrobial prescription for AOM. Results: A total of 827 children with a mean (SD) age of 4.1 (1.6) years (433 boys [52.4%]) were randomized to S salivarius K12 oral products (n = 413) or placebo (n = 414). Thirty-four children (8.2%) in the S salivarius group and 24 children (5.8%) in the placebo group experienced at least 1 episode of AOM requiring antimicrobial therapy during the 6-month follow-up period (relative risk, 1.42 [95% CI, 0.86-2.34]; proportion difference, -2.44% [95% CI, -5.94% to 1.09%]; P = .17). Time to first AOM episode did not differ between the groups (174 [95% CI, 171-177] days in the S salivarius group vs 176 [95% CI, 173-179] days in the placebo group; P = .18). Conclusions and Relevance: In this randomized placebo-controlled clinical trial, the daily use of the S salivarius K12 products for 6 months did not reduce the occurrence of AOM. New approaches for primary prevention of AOM among children are needed. Trial Registration: ClinicalTrialsRegister.eu Identifier: 2020-001076-14.

Clinical Outcomes of Acutely Ill Children According to Cycle Threshold Values of Respiratory Viruses Detected by Multiplex PCR Testing.

In this cohort study of 800 children attending a pediatric emergency department at Oulu University Hospital, Finland with fever or respiratory symptoms, the cycle threshold values of point-of-care multiplex polymerase chain reaction testing for respiratory viruses were not associated with hospitalization, respiratory support, or need for intensive care.

Nasopharyngeal detection of atypical bacteria by multiplex polymerase chain reaction panel in acutely ill children was associated with an increased risk of pneumonia.

AIM: We aimed to assess whether detection of respiratory bacteria by multiplex polymerase chain reaction (PCR) testing associates with clinical outcomes in acutely ill children. METHODS: This cross-sectional study enrolled children under the age of 18 with a suspected respiratory infection treated in a paediatric emergency department of Oulu University Hospital, Finland from January 2015 through December 2015. Nasopharyngeal samples were routinely analysed for 16 respiratory viruses and later, after storage, analysed with a multiplex PCR panel for seven respiratory bacteria. RESULTS: At least one bacterial pathogen was detected in 600 out of the 1195 children (50%). The mean age was 3.3 (SD 3.7) years and 54% were boys. Atypical bacteria were associated with a risk of pneumonia (adjusted odds ratio [aOR] 14.1, 95% CI 3.98-50.1). Co-detection of rhinovirus with Streptococcus pneumoniae was not associated with risk of pneumonia (aOR 2.39, 95% CI 0.78-7.30). Detection of Streptococcus pneumoniae, Haemophilus influenzae or both was not associated with the risk of hospital admission or prescription of antibiotics. CONCLUSION: Nasopharyngeal detection of atypical bacteria in acutely ill children was associated with a markedly increased risk of pneumonia. The clinical utility of wide testing for other respiratory bacteria needs further evaluation.

Duration of clinical symptoms in children with acute respiratory infection.

AIM: To investigate duration of clinical symptoms associated with various respiratory viruses and with the co-detection of respiratory viral and bacterial pathogens. METHODS: This prospective cohort study included 737 acutely ill children treated in a paediatric emergency department prior to the COVID-19 pandemic. Nasal swab samples were analysed with multiplex PCR panels for 16 viral and 7 bacterial respiratory pathogens. Parents filled in a questionnaire about the symptoms at the time of the visit and 14 days afterwards. RESULTS: Persistent symptoms 2 weeks after the onset of acute illness were common: 32% of the patients with a coronavirus 229 E, NL63 or OC43 finding, 31% of those with human metapneumovirus and 25% of those with rhinovirus reported ongoing symptoms. At least one symptom lasting more than 4 weeks was observed in 3-4% of the children. Children with viral and bacterial co-detection had a longer duration of fever than those with only viral detection (3.3 days [SD 2.8] vs. 1.6 days [SD 2.4], p < 0.001). CONCLUSION: Symptoms lasting for more than 2 to 4 weeks appear to be relatively frequent in all respiratory viral infections in children. Viral and bacterial co-detection may increase the duration of illness.

Absence from day care or school and parental absence from work during children's respiratory infections.

AIM: To investigate the social burden of nasopharyngeal detection of various respiratory viruses and the co-detection of viral and bacterial pathogens. METHODS: This prospective cohort study included 737 children with a suspected respiratory tract infection or fever in a paediatric emergency department during one epidemiological year (2014-2015) in Finland. Nasopharyngeal swab samples were analysed with multiplex polymerase chain reaction for 16 viruses and 7 respiratory bacteria. Parents filled out a questionnaire regarding child's and parents' absence from day care, school, or work at the time of the visit and 14 days afterward. RESULTS: The length of the children's absence from day care or school, or parental absence from work, did not significantly differ between the detected viral pathogens. Co-detection of any respiratory virus and Streptococcus pneumoniae or Haemophilus influenzae in the nasopharynx were associated with a 2.5-day (95% CI of the difference: 0.71 to 4.3) and 3.0-day (95% CI: 0.35 to 5.7) longer parental absence from work, respectively, compared with the detection of viruses alone when adjusted for age. CONCLUSION: Nasopharyngeal detection of S. pneumoniae or H. influenzae was associated with an increase in the length of parental absence from work when compared with the detection of virus alone.

Effect of Topical Antibiotics on Duration of Acute Infective Conjunctivitis in Children: A Randomized Clinical Trial and a Systematic Review and Meta-analysis.

Importance: Although topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain. Objective: To assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis. Design, Setting, and Participants: A randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis. Interventions: Participants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention. Main Outcomes and Measures: The primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6. Results: The randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, -1.9 days; 95% CI, -3.7 to -0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of children who had symptoms of conjunctivitis on days 3 to 6 compared with placebo eye drops (odds ratio, 0.59; 95% CI, 0.39 to 0.91). Conclusions and Relevance: In this randomized clinical trial and systematic review and meta-analysis, topical antibiotics were associated with significantly shorter durations of conjunctival symptoms in children with acute infective conjunctivitis. Trial Registration: ClinicalTrialsRegister.eu Identifier: 2013-005623-16.

Effect of Point-of-Care Testing for Respiratory Pathogens on Antibiotic Use in Children: A Randomized Clinical Trial.

Importance: Limited data are available on the clinical impact of multiplex polymerase chain reaction (PCR) point-of-care testing for respiratory pathogens in acutely ill children. Objective: To evaluate the effect of multiplex PCR point-of-care testing for respiratory pathogens on antibiotic use in acutely ill children. Design, Setting, and Participants: This unblinded, randomized clinical trial was conducted from May 6, 2019, through March 12, 2020. The participants were followed up until hospitalization or discharge from the emergency department (ED) for primary outcome. The study was conducted at the pediatric ED of Oulu University Hospital, Finland. Eligible study participants were children aged 0 to 17 years with fever and/or any respiratory signs or symptoms. Children with underlying medical conditions were included. The statistical analyses were performed between August 11, 2020, and September 14, 2021. Interventions: The participants were randomly assigned in a 2:1 ratio either to undergo multiplex PCR point-of-care testing (18 respiratory viruses and 3 bacteria with results ready within 70 minutes) upon arrival at the ED or to receive routine care. Main Outcomes and Measures: The primary outcome was the proportion of children receiving antibiotic therapy. The secondary outcomes were the numbers of diagnostic tests and radiographic imaging procedures performed and costs. Results: A total of 1417 children were assessed for eligibility. After exclusions, 1243 children (692 boys [56%]) were randomly allocated to either the intervention (829 children) or control (414 children) group. The mean (SD) age of the participants was 3.0 (3.6) years in the intervention group (median [IQR], 1.7 [0.4-4.1] years) and 3.0 (3.5) years (median [IQR], 1.9 [0.4-4.1] years) in the control group. Multiplex PCR point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (226 children [27.3%] in the intervention group vs 118 children [28.5%] in the control group; risk ratio, 0.96; 95% CI, 0.79-1.16). Targeted antibiotic therapy was started in 12 children (1.4%) tested with point-of-care multiplex PCR and 2 children (0.5%) in the control group (risk ratio, 3.0; 95% CI, 0.76-11.9). The numbers of diagnostic tests did not differ between the groups, nor did the costs. Conclusions and Relevance: In this randomized clinical trial, point-of-care testing for respiratory pathogens did not reduce the use of antibiotics at the pediatric ED. Testing for respiratory pathogens appears to have a limited impact on clinical decision-making for acutely ill children. Trial Registration: ClinicalTrials.gov Identifier: NCT03932942.

The incidence, hospitalisations and deaths in acutely ill children with dysnatraemias.

AIM: The aim was to evaluate the incidence, hospitalisations and deaths in acutely ill children with dysnatraemias. METHODS: This was a register-based cohort study of 46 518 acutely ill children aged <16 years who visited a paediatric emergency department. Risk factors were assessed using two nested case-control studies. RESULTS: Moderate to severe hypernatraemia occurred in 92 children (0.20%; 95% confidence interval [CI]: 0.16%-0.24%) and moderate to severe hyponatraemia in 131 children (0.28%; 95% CI: 0.24%-0.33%). Underlying medical conditions increased the risk of both moderate to severe hypernatraemia (odds ratio [OR]: 17; 95% 5.5-51) and moderate to severe hyponatraemia (OR: 3.5; 95% CI: 2.0-5.9). The use of a feeding tube (OR: 14; 95% CI: 3.2-66) and intellectual disability (OR: 7.3; 95% CI: 3.0-18) was associated with moderate to severe hypernatraemia. The risk of death was associated with moderate to severe hypernatraemia (OR: 19; 95% CI: 2.0-2564) and moderate to severe hyponatraemia (OR: 33; 95% CI: 3.7-4311). CONCLUSIONS: Severe dysnatraemias were more prevalent in acutely ill children with underlying medical conditions and were markedly associated with the risk for death.

Severe hospital-acquired hyponatremia in acutely ill children receiving moderately hypotonic fluids.

BACKGROUND: Hypotonic fluids have been associated with hospital-acquired hyponatremia. The incidence of life-threatening severe hyponatremia associated with hypotonic fluids has not been evaluated. METHODS: This was a population-based cohort study of 46,518 acutely ill children 15 years of age or under who visited the pediatric emergency department (ED) at Oulu University Hospital, Finland, between 2007 and 2017. We retrieved all electrolyte measurements from the comprehensive electronic laboratory system and reviewed medical records for all patients with severe hyponatremia. RESULTS: The overall occurrence of severe hyponatremia (serum sodium < 125 mmol/L) was found in 27 out of 46,518 acutely ill children (0.06%, 95% confidence interval 0.04-0.08%). After admission, severe hyponatremia developed in seven of 6,984 children receiving moderately hypotonic fluid therapy (0.1%, 95% confidence interval 0.04-0.2%), usually within 8 h of admission. All children who developed severe hyponatremia during hospitalization were severely ill. CONCLUSION: In this register-based cohort study of children presenting to the ED, severe hyponatremia developed in one of 998 acutely ill children receiving moderately hypotonic fluid therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Multi-inflammatory syndrome and Kawasaki disease in children during the COVID-19 pandemic: A nationwide register-based study and time series analysis.

AIM: We investigated whether the ongoing COVID-19 pandemic was associated with the occurrence of Kawasaki disease or with multi-inflammatory syndrome in children (MIS-C). METHODS: This national Finnish register-based study was based on laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, MIS-C and Kawasaki disease cases. We performed a time series analysis on the occurrence of Kawasaki disease in 2016-2020. RESULTS: In 2020, there were 5170 laboratory-confirmed COVID-19 cases in children under 18 years of age and five fulfilled the MIS-C case definition. The occurrence of MIS-C was 0.97 per 1000 (95% confidence interval: 0.31-2.26) laboratory-confirmed SARS-CoV-2 infections in children. Our time series analysis showed that Kawasaki disease cases decreased during the COVID-19 pandemic. The seasonally adjusted incidence rate ratio was 0.49 (95% confidence interval: 0.32-0.74) when it was compared to pre-pandemic levels. This coincided with a reduced occurrence of respiratory infections, due to social distancing in the population. CONCLUSION: This nationwide register-based study found that MIS-C was a rare complication of the SARS-CoV-2 infection. The occurrence of Kawasaki disease and respiratory infections decreased during the pandemic. This suggests that transmissible microbes may play an important role in Kawasaki disease and social distancing may have a protective effect.

Etiology of Infectious Diseases in Acutely Ill Children at a Pediatric Hospital in Finland.

This is a brief report of the etiology of infectious diseases in a pediatric emergency department. Our cohort study of 4647 children demonstrated rhinovirus as the most common etiology in a pediatric emergency department (23%) and intensive care (48%). The population-based incidence of rhinovirus-related visits was 1796/100,000/yr in children <5 years. The most common bacterial pathogen was Escherichia coli (5%).

Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction.

BACKGROUND: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency. OBJECTIVE: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1. METHODS: Exome sequencing, genotyping and haplotype analysis, B- and T-cell phenotyping, in vitro lymphocyte stimulation assays, analyses of mitochondrial function, immunofluorescence staining for cytoskeletal proteins and mitochondria, and CRISPR-Cas9 DIAPH1 knockout in heathy donor PBMCs were used. RESULTS: Genetic analyses found all Finnish patients homozygous for a rare DIAPH1 splice-variant (NM_005219:c.684+1G>A) enriched in the Finnish population, and Omani patients homozygous for a previously described pathogenic DIAPH1 frameshift-variant (NM_005219:c.2769delT;p.F923fs). In addition to microcephaly, epilepsy, and cortical blindness characteristic to SCBMS, the patients presented with infection susceptibility due to defective lymphocyte maturation and 3 patients developed B-cell lymphoma. Patients' immunophenotype was characterized by poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells. CRISPR-Cas9 knockout of DIAPH1 in PBMCs from healthy donors replicated the T-cell activation defect. Patient-derived peripheral blood T cells exhibited impaired adhesion and inefficient microtubule-organizing center repositioning to the immunologic synapse. The clinical symptoms and laboratory tests also suggested mitochondrial dysfunction. Experiments with immortalized, patient-derived fibroblasts indicated that DIAPH1 affects the amount of complex IV of the mitochondrial respiratory chain. CONCLUSIONS: Our data demonstrate that individuals with SCBMS can have combined immune deficiency and implicate defective cytoskeletal organization and mitochondrial dysfunction in SCBMS pathogenesis.

Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial.

Importance: The use of isotonic fluid therapy is currently recommended in children, but there is limited evidence of optimal fluid therapy in acutely ill children. Objective: To evaluate the risk for electrolyte disorders, including hyponatremia, hypernatremia, and hypokalemia, and the risk of fluid retention in acutely ill children receiving commercially available plasmalike isotonic fluid therapy. Design, Setting, and Participants: This unblinded, randomized clinical pragmatic trial was conducted at the pediatric emergency department of Oulu University Hospital, Finland, from October 3, 2016, through April 15, 2019. Eligible study subjects (N = 614) were between 6 months and 12 years of age, required hospitalization due to an acute illness, and needed intravenous fluid therapy. Exclusion criteria included a plasma sodium concentration of less than 130 mmol/L or greater than 150 mmol/L on admission; a plasma potassium concentration of less than 3.0 mmol/L on admission; clinical need of fluid therapy with 10% glucose solution; a history of diabetes, diabetic ketoacidosis, or diabetes insipidus; a need for renal replacement therapy; severe liver disease; pediatric cancer requiring protocol-determined chemotherapy hydration; and inborn errors of metabolism. All outcomes and samples size were prespecified except those clearly marked as exploratory post hoc analyses. All analyses were intention to treat. Interventions: Acutely ill children were randomized to receive commercially available plasmalike isotonic fluid therapy (140 mmol/L of sodium and 5 mmol/L potassium in 5% dextrose) or moderately hypotonic fluid therapy (80 mmol/L sodium and 20 mmol/L potassium in 5% dextrose). Main Outcomes and Measures: The primary outcome was the proportion of children with any clinically significant electrolyte disorder, defined as hypokalemia less than 3.5 mmol/L, hypernatremia greater than 148 mmol/L, or hyponatremia less than 132 mmol/L during hospitalization due to acute illness. The main secondary outcomes were the proportion of children with severe hypokalemia and weight change. Results: There were 614 total study subjects (mean [SD] age, 4.0 [3.1] years; 315 children were boys [51%] and all 614 were Finnish speaking [100%]). Clinically significant electrolyte disorder was more common in children receiving plasmalike isotonic fluid therapy (61 of 308 patients [20%]) compared with those receiving moderately hypotonic fluid therapy (9 of 306 patients [2.9%]; 95% CI of the difference, 12%-22%; P < .001). The risk of developing electrolyte disorder was 6.7-fold greater in children receiving isotonic fluid therapy. Hypokalemia developed in 57 patients (19%) and hypernatremia developed in 4 patients (1.3%) receiving plasmalike isotonic fluid therapy. Weight change was greater in children receiving isotonic, plasmalike fluid therapy compared with those receiving mildly hypotonic fluids (mean weight gain, 279 vs 195 g; 95% CI, 16-154 g; P = .02). Conclusions and Relevance: In this randomized clinical trial, commercially available plasmalike isotonic fluid therapy markedly increased the risk for clinically significant electrolyte disorders, mostly due to hypokalemia, in acutely ill children compared with previously widely used moderately hypotonic fluid therapy containing 20 mmol/L of potassium. Trial Registration: ClinicalTrials.gov identifier: NCT02926989.