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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., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

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) ( β = -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 ( β = 0·58 [se 0·25]; P = 0·03). Intake of savoury UPF was negatively associated with weight-for-height z-scores ( β = -0·30 [se 0·14]; P = 0·04) but positively associated with BAZ ( β = 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.

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)., Competing Interests: Declaration of Competing Interest The authors disclosure the following Sarah Jane Schwarzenberg serves as a: consultant for AbbVie, Michael R Narkewicz serves as a consultant for Vertex, and has received research grants from Gilead, AbbVie and has a family member with stock in Merck. Jean Molleston has research funding from Abbvie, Albireo, Gillead, Shire. Daniel H. Leung has served as a consultant for Merck, Gilead and Vertex and has received research grants from Gilead, Abbvie and Mirum. A. Jay Freeman has done consulting work for AbbVie and Takeda and has received research support from Allergan and Travere Therapeutics. Wikrom Karnsakul has received grants from Albireo Pharma, Gilead, and Travere Therapeutics. Alexander J Towbin received author royalites from Elsevier, served as a consultant to Applied Radiology and received grant funding from the Cystic Fibrosis Foundation. Simon Ling has received research grants from Abbvie and Gilead. The remaining authors disclose no conflicts., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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 331×10 3 /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., (Copyright © 2022. Published by Elsevier B.V.)

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., Competing Interests: S.J.S. serves as a consultant for Nestle, UpToDate, and AbbVie. A.J.F. has grant/research support through Travere Therapeutics and Allergan; serves as an advisor for Abbvie and Takeda. W.K. has received research grants from Gilead Sciences and Albireo Pharma; serves as an advisor for Mirum and Travere Therapeutics. D.H.L. has grant/research support from Abbvie, Gilead, and Mirum; serves as a consultant for Gilead, Vertex, and Merck. S.C.L. receives research funding from Abbvie and Gilead and serves as a consultant for Abbvie JPM has research funding from Gillead, Abbvie, Albireo, Mirum. K.F.M. is a consultant for Albireo and Gilead. M.R.N. serves as a consultant for Vertex, has received research grants from Gilead, AbbVie, and has a family member with stock in Merck. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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/., (© 2022. The Author(s).)