Lung T1 MRI assessments in children with mild cystic fibrosis lung disease.

RATIONALE: Lung T1 MRI is a potential method to assess cystic fibrosis (CF) lung disease that is safe, quick, and widely available, but there are no data in children with mild CF lung disease. OBJECTIVE: Assess the ability of lung T1 MRI to detect abnormalities in children with mild CF lung disease. METHODS: We performed T1 MRI, multiple breath washout (MBW), chest computed tomography (CT), and spirometry in a cohort of 45 children with mild CF lung disease (6-11 years of age). MAIN RESULTS: Despite mean normal ppFEV1 values, the majority of children with CF in this study exhibited mild lung disease evident in lung clearance index (LCI) measured by MBW, chest CT Brody scores, and percent normal lung perfusion (%NLP) measured by T1 MRI. The %NLP correlated with chest CT Brody scores, as did LCI, but %NLP and LCI did not correlate with each other. Analysis of the Brody subscores showed that %NLP and LCI largely correlated with different Brody subscores. CONCLUSIONS: T1 MRI can detect mild CF lung disease in children and correlates with chest CT findings. The %NLP from T1 MRI and LCI correlate with different chest CT Brody subscores, suggesting they provide complementary information about CF lung disease.

Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease.

BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. CONCLUSIONS: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD. CLINICAL TRIAL REGISTRATION: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).

Ultra-processed foods in a rural Ecuadorian community: associations with child anthropometry and bone maturation.

Frequent ultra-processed food (UPF) consumption is consistently associated with poor health outcomes. Little is known about UPF intake during early childhood and its effects on growth. We assessed UPF in relation to child anthropometry, bone maturation, and their nutrition profiles in a rural Ecuadorian community. Covariate-adjusted regression models estimated relationships between UPF intake from a 24-hour Food Frequency Questionnaire and three outcomes: linear growth, weight status and bone maturation. Nutrient Profiling Models (NPM) evaluated a convenience sample of UPF (n 28) consumed by children in the community. In this cohort (n 125; mean age = 33·92 (sd 1·75) months), 92·8 % consumed some form of UPF the previous day. On average, children consuming UPF four to twelve times per day (highest tertile) had lower height-for-age z-scores than those with none or a single instance of UPF intake (lowest tertile) (ß = -0·43 [se 0·18]; P = 0·02). Adjusted stunting odds were significantly higher in the highest tertile relative to the lowest tertile (OR: 3·07, 95 % CI 1·11, 9·09). Children in the highest tertile had significantly higher bone age z-scores (BAZ) on average compared with the lowest tertile (ß = 0·58 [se 0·25]; P = 0·03). Intake of savoury UPF was negatively associated with weight-for-height z-scores (ß = -0·30 [se 0·14]; P = 0·04) but positively associated with BAZ (ß = 0·77 [se 0·23]; P < 0·001). NPM indicated the availability of unhealthy UPF to children, with excessive amounts of saturated fats, free sugars and sodium. Findings suggest that frequent UPF intake during early childhood may be linked to stunted growth (after controlling for bone age and additional covariates), despite paradoxical associations with bone maturation.

Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study.

BACKGROUND: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD. METHODS: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event. RESULTS: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×103/microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6-11.8) vs NL (5.3, 4.2-7, p < 0.0001). Over 6.3 years follow-up (1.3-10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events. CONCLUSIONS: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease.

Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children.

OBJECTIVES: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. METHODS: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. RESULTS: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. CONCLUSIONS: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.

Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: study protocol for a randomized controlled trial.

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/.

Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis.

Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (rs =  - 0.28, P = 0.0071) and positive correlation with aspartate aminotransferase-to-platelet ratio index (rs = 0.38, P = 0.0002), Fibrosis-4 index (rs = 0.36, P = 0.0007), gamma-glutamyltransferase (GGT; rs = 0.35, P = 0.0017), GGT-to-platelet ratio (rs = 0.35, P = 0.003), and US spleen size z-score (rs = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF.

Fetal brain ultrasound measures and maternal nutrition: A feasibility study in Ecuador.

OBJECTIVE: Nutrition during pregnancy is an important modifiable determinant of fetal growth and development. This pilot study aimed to characterize the association between fetal anthropometry, fetal brain development, and maternal diet among women in Ecuador using portable ultrasound in resource-limited clinics, including measurements of brain structures not typically imaged in this setting. METHODS: Pregnant women (n = 47) from four resource-limited health centers were surveyed on demographic, socioeconomic, morbidity, and dietary information. Maternal height, weight, and blood pressure were taken. A sonographer took 15 images per participant, including those standardly assessed during the fetal survey and additional brain structures identified as potentially responsive to maternal nutrition, but not part of the standard fetal survey. RESULTS: Mean percentiles for all standard fetal survey measurements generated from WHO Fetal Growth Curves fell below 50%, and negative mean Z scores were found for biparietal diameter (-0.95 ± 1.11) and femur length (-0.22 ± 1.10). Generalized linear modeling adjusting for gestational age and other covariates showed frequency of seafood consumption was positively associated with fetal biparietal diameter Z score (P = 0.005), beans and legumes positively associated with femur length (P = 0.006), and a negative association was found for soda consumption and fetal head circumference (P = 0.013). CONCLUSIONS: This pilot study demonstrated the feasibility of capturing images of nutrition-relevant fetal brain structures not part of the standard fetal survey in resource-limited settings using portable ultrasound. Our study revealed associations between anthropometry, brain structure size, and maternal diet demonstrating potential for prenatal nutrition research using ultrasound in the field.

US Evaluation of Bone Age in Rural Ecuadorian Children: Association with Anthropometry and Nutrition.

Background Stunted growth and development is a serious global public health problem. A limited number of field measures exist that can be used to evaluate stunting and its underlying biologic mechanisms. Purpose To assess bone age using tablet-based US in young children living in a rural community in Ecuador, where stunting is prevalent, and to evaluate the associations between bone age, anthropometry, and diet. Materials and Methods From June through August 2017, tablet-based US was used to assess bone age in young children within their homes in rural Cotopaxi, Ecuador. Bone age z scores (BAZs) were assigned using the standards of Greulich and Pyle. Anthropometric data were collected using international protocols; z scores were generated from World Health Organization Child Growth Standards. Groups were compared using the Student t test. Univariate analyses and generalized linear regression modeling were applied to test the association between bone age and anthropometry, adjusting for covariates including age, sex, dietary intake, and morbidities. Results A total of 128 children (mean age, 33.9 months ± 1.8 [standard deviation]; 59 girls, 69 boys) were evaluated. Mean BAZ was -1.20 ± 1.16. Mean BAZ was lower in children with stunted growth (-1.42 ± 1.18) than in children without stunted growth (-0.98 ± 1.10, P = .04). In adjusted analysis, BAZ was associated with the following variables: height-for-age z score (ß coefficient, 0.26; 95% confidence interval [CI]: 0.05, 0.46; P = .01), female sex (ß coefficient, 0.51; 95% CI: 0.15, 0.88; P = .006), number of times eggs were consumed in the previous 24 hours (ß coefficient, 0.22; 95% CI: 0.05, 0.38; P = .009), number of times savory or salty snacks were consumed in the previous 24 hours (ß coefficient, 0.42; 95% CI: 0.15, 0.68; P = .002), and ownership of pig livestock, which was a binary variable (ß coefficient, -0.46; 95% CI: -0.82, -0.09; P = .01). Conclusion Bone age determined using tablet-based US was lower in children who had stunted growth and was associated with diet in a cohort of children living in rural Ecuador. © RSNA, 2020 See also the editorial by Dillman and Ayyala in this issue.

Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study.

OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

Severe bilateral adrenal hemorrhages in a newborn complicated by persistent adrenal insufficiency.

Bilateral adrenal hemorrhages rarely occur during the neonatal period and are often associated with traumatic vaginal deliveries. However, the adrenal gland has highly regenerative capabilities and adrenal insufficiency typically resolves over time. We evaluated a newborn female after experiencing fetal macrosomia and a traumatic vaginal delivery. She developed acidosis and acute renal injury. Large adrenal hemorrhages were noted bilaterally on ultrasound, and she was diagnosed with adrenal insufficiency based on characteristic electrolyte changes and a low cortisol (4.2 µg/dL). On follow-up testing, this patient was unable to be weaned off of hydrocortisone or fludrocortisone despite resolution of hemorrhages on ultrasound. Providers should consider bilateral adrenal hemorrhage when evaluating critically ill neonates after a traumatic delivery. In extreme cases, this may be a persistent process. LEARNING POINTS: Risk factors for adrenal hemorrhage include fetal macrosomia, traumatic vaginal delivery and critical acidemia.Signs of adrenal hemorrhage include jaundice, flank mass, skin discoloration or scrotal hematoma.Adrenal insufficiency often is a transient process when related to adrenal hemorrhage.Severe adrenal hemorrhages can occur in the absence of symptoms.Though rare, persistent adrenal insufficiency may occur in extremely severe cases of bilateral adrenal hemorrhage.Consider adrenal hemorrhage when evaluating a neonate for shock in the absence of an infectious etiology.

Ultrasound Shear Wave Elastography: A Novel Method to Evaluate Bladder Pressure.

PURPOSE: Children with bladder dysfunction resulting in increased storage pressure are at risk for renal deterioration. The current gold standard for evaluation of bladder pressure is urodynamics, an invasive test requiring catheterization. We evaluated ultrasound shear wave elastography as a novel means of assessing bladder biomechanical properties associated with increased bladder pressure. MATERIALS AND METHODS: Concurrent shear wave elastography and urodynamics were performed. Ultrasound shear wave elastography images were obtained of the anterior and posterior wall when empty and at 25%, 50%, 75% and 100% expected bladder capacity, and end fill volume. Regions of interest were confirmed by a pediatric radiologist. Bladder cohorts were defined as compliant (capacity detrusor pressure less than 25 cm H2O) and noncompliant (25 cm H2O or greater). Pearson correlation coefficients and a mixed effects model evaluated the relationship between shear wave speed and detrusor pressure, compliance and normalized compliance. An unpaired t-test was used for between cohort analyses. RESULTS: In all 23 subjects mean shear wave speed of the anterior and posterior bladder walls significantly correlated with detrusor pressure throughout filling. When comparing compliant and noncompliant bladders, mean shear wave speed and detrusor shear wave speed of the anterior wall significantly increased with filling of noncompliant bladders. Shear wave speed remained at baseline levels in compliant bladders. Mean shear wave speed of the anterior wall was significantly correlated with compliance and normalized compliance. CONCLUSIONS: Ultrasound shear wave elastography bladder measurements correlate well with bladder storage pressure, and shear wave speed measurements differ between compliant and noncompliant bladders. This is the first known study to demonstrate that shear wave elastography is promising as a bedside modality for the assessment of bladder dysfunction in children.

Imaging of pediatric head and neck masses.

Medical imaging is an important tool in the evaluation and classification of pediatric head and neck masses. Such lesions may include congenital, inflammatory, infectious, vascular, or neoplastic processes. Ultrasound is often the first line modality in the workup of a neck mass in a child, followed by MRI or CT depending on the scenario. This information must be interpreted in the context of the patient's clinical history, physical examination, and demographics. The medical imaging workup of a neck mass in a child must be focused to yield the maximum information possible while minimizing the risks of radiation and sedation.

Computer-aided classification of breast masses: performance and interobserver variability of expert radiologists versus residents.

PURPOSE: To evaluate the interobserver variability in descriptions of breast masses by dedicated breast imagers and radiology residents and determine how any differences in lesion description affect the performance of a computer-aided diagnosis (CAD) computer classification system. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study, and the requirement to obtain informed consent was waived. Images of 50 breast lesions were individually interpreted by seven dedicated breast imagers and 10 radiology residents, yielding 850 lesion interpretations. Lesions were described with use of 11 descriptors from the Breast Imaging Reporting and Data System, and interobserver variability was calculated with the Cohen κ statistic. Those 11 features were selected, along with patient age, and merged together by a linear discriminant analysis (LDA) classification model trained by using 1005 previously existing cases. Variability in the recommendations of the computer model for different observers was also calculated with the Cohen κ statistic. RESULTS: A significant difference was observed for six lesion features, and radiology residents had greater interobserver variability in their selection of five of the six features than did dedicated breast imagers. The LDA model accurately classified lesions for both sets of observers (area under the receiver operating characteristic curve = 0.94 for residents and 0.96 for dedicated imagers). Sensitivity was maintained at 100% for residents and improved from 98% to 100% for dedicated breast imagers. For residents, the computer model could potentially improve the specificity from 20% to 40% (P < .01) and the κ value from 0.09 to 0.53 (P < .001). For dedicated breast imagers, the computer model could increase the specificity from 34% to 43% (P = .16) and the κ value from 0.21 to 0.61 (P < .001). CONCLUSION: Among findings showing a significant difference, there was greater interobserver variability in lesion descriptions among residents; however, an LDA model using data from either dedicated breast imagers or residents yielded a consistently high performance in the differentiation of benign from malignant breast lesions, demonstrating potential for improving specificity and decreasing interobserver variability in biopsy recommendations.