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

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

Predictors of Invasive Herpes Simplex Virus Infection in Young Infants.

2021

2021 Aug 26

1098-4275

<p><strong>OBJECTIVES: </strong>To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.</p>

<p><strong>METHODS: </strong>In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.</p>

<p><strong>RESULTS: </strong>Of all infants included , 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] &lt;14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with &gt;28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43).</p>

<p><strong>CONCLUSIONS: </strong>A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.</p>

10.1542/peds.2021-050052

Pediatrics

34446535

Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.

2021

2021 Aug 09

1098-4275

<p><strong>OBJECTIVES: </strong>Diabetic ketoacidosis (DKA) is typically characterized by low or low-normal serum sodium concentrations, which rise as hyperglycemia resolves. In retrospective studies, researchers found associations between declines in sodium concentrations during DKA and cerebral injury. We prospectively investigated determinants of sodium concentration changes and associations with mental status alterations during DKA.</p>

<p><strong>METHODS: </strong>Using data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial, we compared children who had declines in glucose-corrected sodium concentrations with those who had rising or stable concentrations. Children were randomly assigned to 1 of 4 intravenous fluid protocols that differed in infusion rate and sodium content. Data from the first 4, 8, and 12 hours of treatment were analyzed for 1251, 1086, and 877 episodes, respectively.</p>

<p><strong>RESULTS: </strong>In multivariable analyses, declines in glucose-corrected sodium concentrations were associated with higher sodium and chloride concentrations at presentation and with previously diagnosed diabetes. Treatment with 0.45% (vs 0.9%) sodium chloride fluids was also associated with declines in sodium concentration; however, higher rates of fluid infusion were associated with declines in sodium concentration only at 12 hours. Frequencies of abnormal Glasgow Coma Scale scores and clinical diagnoses of cerebral injury were similar in patients with and without declines in glucose-corrected sodium concentrations.</p>

<p><strong>CONCLUSIONS: </strong>Changes in glucose-corrected sodium concentrations during DKA treatment are influenced by the balance of free-water loss versus sodium loss at presentation and the sodium content of intravenous fluids. Declines in glucose-corrected sodium concentrations are not associated with mental status changes during treatment.</p>

10.1542/peds.2021-050243

Pediatrics

34373322

Electrocardiogram as a Lyme Disease Screening Test.

2021

2021 Jul 12

1097-6833

<p><strong>OBJECTIVE: </strong>To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease.</p>

<p><strong>STUDY DESIGN: </strong>We performed an eight-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease with the presence of an erythema migrans lesion or a positive two-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and AV block or any ECG evidence of carditis.</p>

<p><strong>RESULTS: </strong>Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis of which 24 had atrioventricular (AV) block (20 first degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (odds ratio 4.7, 95% confidence interval 1.8-12.1) and any ECG evidence of carditis (odds ratio 2.3, 95% confidence interval 1.2-4.3) were both associated with diagnosis of Lyme disease.</p>

<p><strong>CONCLUSIONS: </strong>ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.</p>

10.1016/j.jpeds.2021.07.010

J Pediatr

34265339

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

Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis.

2021

306-309

2021 Apr 01

1532-0987

<p><b>BACKGROUND: </b>The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease.</p><p><b>METHODS: </b>We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis.</p><p><b>RESULTS: </b>Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%).</p><p><b>CONCLUSIONS: </b>The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.</p>

10.1097/INF.0000000000003003

Pediatr Infect Dis J

33710975

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

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.

2020

2020 Sep 22

1935-5548

<p><strong>OBJECTIVE: </strong>This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled.</p>

<p><strong>RESULTS: </strong>Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, &lt; 0.001), item-color recall (β = -0.08, = 0.010), and forward digit span (β = -0.06, = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, &lt; 0.01) and higher HbA was associated with lower item-color recall (β = -0.10, = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.</p>

<p><strong>CONCLUSIONS: </strong>A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.</p>

10.2337/dc20-0187

Diabetes Care

32962981

Hypertension During Diabetic Ketoacidosis in Children.

2020

2020 May 06

1097-6833

<p><strong>OBJECTIVES: </strong>To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension.</p>

<p><strong>STUDY DESIGN: </strong>This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension.</p>

<p><strong>RESULTS: </strong>Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower PCO), and stage 2 or 3 Acute Kidney Injury (AKI). More severe acidosis and lower Glasgow Coma Scale (GCS) scores were associated with hypertension occurring at any time during DKA treatment.</p>

<p><strong>CONCLUSIONS: </strong>Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower PCO and lower GCS scores during DKA treatment, suggesting that hypertension might be centrally mediated.</p>

10.1016/j.jpeds.2020.04.066

J. Pediatr.

32387716