Cognitive function following diabetic ketoacidosis in young children with type 1 diabetes.

2023

e412

05/2023

2398-9238

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.

METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 22 children and mild in 24 children. Neurocognitive function was assessed once 2-6 months after the DKA episode. A comparison group of 27 children with T1D, but no DKA exposure, was also assessed. Patient groups were matched for age and T1D duration at the time of neurocognitive testing.

RESULTS: Children who experienced DKA, regardless of its severity, exhibited significantly lower IQ scores than children who did not experience DKA, F(2, 70) = 6.26, p = .003, partial η  = .15. This effect persisted after accounting for socioeconomic status and ethnicity.

CONCLUSIONS: A single DKA episode is associated with lower IQ scores soon after exposure to DKA in young children.

10.1002/edm2.412

Endocrinol Diabetes Metab

36788736

Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

2023

04/2023

1097-6760

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes.

METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes.

RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes.

CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

10.1016/j.annemergmed.2023.01.001

Ann Emerg Med

37024382

Relationships among biochemical measures in children with diabetic ketoacidosis.

2023

313-318

03/2023

2191-0251

OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.

METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.

RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19).

CONCLUSIONS: Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

10.1515/jpem-2022-0570

J Pediatr Endocrinol Metab

36637392

Cognitive function following diabetic ketoacidosis in young children with type 1 diabetes.

2023

e412

02/2023

2398-9238

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.

METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 22 children and mild in 24 children. Neurocognitive function was assessed once 2-6 months after the DKA episode. A comparison group of 27 children with T1D, but no DKA exposure, was also assessed. Patient groups were matched for age and T1D duration at the time of neurocognitive testing.

RESULTS: Children who experienced DKA, regardless of its severity, exhibited significantly lower IQ scores than children who did not experience DKA, F(2, 70) = 6.26, p = .003, partial η  = .15. This effect persisted after accounting for socioeconomic status and ethnicity.

CONCLUSIONS: A single DKA episode is associated with lower IQ scores soon after exposure to DKA in young children.

10.1002/edm2.412

Endocrinol Diabetes Metab

36788736

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

2022

100-104

11/2022

1097-6833

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

10.1016/j.jpeds.2022.07.033

J Pediatr

35944716

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

2022

e2223253

07/2022

2574-3805

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children.

Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs.

Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls.

Exposure: SARS-CoV-2 detected via nucleic acid testing.

Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey.

Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]).

Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

10.1001/jamanetworkopen.2022.23253

JAMA Netw Open

35867061

Clinical Characteristics of Children with Cerebral Injury Preceding Treatment of Diabetic Ketoacidosis.

2022

08/2022

1097-6833

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

10.1016/j.jpeds.2022.07.033

J Pediatr

35944716

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

2022

e2142322

2022 01 04

2574-3805

<p><strong>Importance: </strong>Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.</p>

<p><strong>Objective: </strong>To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).</p>

<p><strong>Design, Setting, and Participants: </strong>This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021.</p>

<p><strong>Exposures: </strong>Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing.</p>

<p><strong>Main Outcomes and Measures: </strong>Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death.</p>

<p><strong>Results: </strong>Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (&gt;99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to &lt;10 years vs &lt;1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to &lt;18 years vs &lt;1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%).</p>

<p><strong>Conclusions and Relevance: </strong>In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.</p>

10.1001/jamanetworkopen.2021.42322

JAMA Netw Open

35015063

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis.

2021

2021 Jun 29

1935-5548

<p><strong>OBJECTIVE: </strong>Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>The current analysis involved moderate or severe DKA episodes ( = 714) in children age &lt;18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration).</p>

<p><strong>RESULTS: </strong>The rate of change of pH did not differ by treatment arm, but Pco increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%).</p>

<p><strong>CONCLUSIONS: </strong>In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.</p>

10.2337/dc20-3113

Diabetes Care

34187840

Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes.

2020

e2025481

2020 Dec 01

2574-3805

<p><strong>Importance: </strong>Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear.</p>

<p><strong>Objective: </strong>To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA.</p>

<p><strong>Design, Setting, and Participants: </strong>This cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L.</p>

<p><strong>Exposures: </strong>DKA requiring intravenous insulin therapy.</p>

<p><strong>Main Outcomes and Measures: </strong>AKI occurrence and stage were assessed using serum creatinine measurements using Kidney Disease: Improving Global Outcomes criteria. DKA episodes with and without AKI were compared using univariable and multivariable methods, exploring associated factors.</p>

<p><strong>Results: </strong>Among 1359 DKA episodes (mean [SD] patient age, 11.6 [4.1] years; 727 [53.5%] girls; 651 patients [47.9%] with new-onset diabetes), AKI occurred in 584 episodes (43%; 95% CI, 40%-46%). A total of 252 AKI events (43%; 95% CI, 39%-47%) were stage 2 or 3. Multivariable analyses identified older age (adjusted odds ratio [AOR] per 1 year, 1.05; 95% CI, 1.00-1.09; P = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P &lt; .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P &lt; .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P &lt; .001) as variables associated with AKI. Children with AKI, compared with those without, had lower scores on tests of short-term memory during DKA (mean [SD] digit span recall: 6.8 [2.4] vs 7.6 [2.2]; P = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2]; P = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status.</p>

<p><strong>Conclusions and Relevance: </strong>These findings suggest that AKI may occur more frequently in children with greater acidosis and circulatory volume depletion during DKA and may be part of a pattern of multiple organ injury involving the kidneys and brain.</p>

10.1001/jamanetworkopen.2020.25481

JAMA Netw Open

33275152