Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis.

As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including elexacaftor/tezacaftor/ivacaftor (ETI) have become widely used in eligible patients with cystic fibrosis (CF), the use of these medications in pregnant people has become a critical area of investigation. Since these medications appear generally safe to both mother and fetus when taken by pregnant people with CF, interest has pivoted to the use of ETI in CF carrier mothers to decrease morbidity and mortality from meconium ileus (MI) in fetuses with cystic fibrosis. Here we discuss three infants at our institution with ultrasound findings of MI who were exposed to prenatal ETI through CF carrier mothers for the purposes of treating MI and lowering risk of intestinal complications from this severe manifestation of CF.

Prediction of Intestinal Perforation by Daily Radiographic Findings in Very Low Birth Weight Infants With Meconium Ileus.

Background: This study aimed to develop a prediction model for intestinal perforation from meconium ileus (MI) based on findings from plain X-ray images.

Methods: Very low birth weight (VLBW) infants with MI hospitalized in two tertiary centers between 2011 and 2022 were included in this study. We retrospectively reviewed clinical parameters and assessed plain X-ray images from 0 to 5 days of age.

Four-year evaluation of neonatal cystic fibrosis screening in Southern Belgium.

Unlabelled: Newborn screening for cystic fibrosis (CF-NBS) using an IRT-DNA algorithm with a 12 CFTR-variant panel and an IRT/IRT failsafe was officially implemented in the French-speaking Community of Belgium in January 2020. This screening protocol was evaluated after 4 years according to the criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening. Immunoreactive trypsinogen concentration (IRT) was measured on dried blood spots collected between the second and the fourth day of life.

Complicated meconium ileus in a male neonate with cystic fibrosis: Case report.

In about 10%-15% of instances, meconium ileus (MI) is the first sign of cystic fibrosis (CF). If a newborn exhibits signs of intestinal obstruction and does not pass meconium within a short period of time after birth, MI is suspected. The cystic fibrosis transmembrane conductance regulator gene (CFTR), which is found on chromosome 7q31, is mutated in CF patients.

[Neonatal screening for cystic fibrosis in the Liège region : first evaluation after 4 years].

Since January 2020, neonatal screening for cystic fibrosis (CF-NBS) has been implemented in the Wallonia-Brussels Federation. It's based on the immunoreactive trypsin (IRT1) assay between day 2 and day 4, associated with a 12 CFTR pathogenic variants analysis and with an IRT control on day 21. The aim of this study is to evaluate the performance of our CF-NBS in Liège according to the quality criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening.

Meconium Ileal Obstruction and Functional Immaturity: Review.

Introduction: Ileal obstruction caused by thick meconium associated with functional immaturity (IOMFI) is an uncommon disease associated with prematurity. IOMFI is not well known, and late or wrong diagnosis is a problem. In this research, we review the clinical characteristics and therapeutic methods of IOMFI.

Disparities in outcomes by race and ethnicity in the Canadian cystic fibrosis population.

Background: Cystic Fibrosis has historically been described as a disease that affects people of European ancestry. Consequently, much of what we know about CF is based on evidence generated from data collected in white individuals. This may lead to systematic bias in how non-white people with CF are diagnosed and treated.

Direct healthcare costs in the first 2 years of life: A comparison of screened and clinically diagnosed children with cystic fibrosis - The Irish comparative outcomes study of CF (ICOS).

Background: In July 2011, Cystic Fibrosis (CF) was added to the Newborn Bloodspot Screening Programme in Ireland. The Irish Comparative Outcomes Study (ICOS) is a historical cohort study established to compare outcomes between clinically-detected and screen-detected children with CF. Here we present the results of economic analysis comparing direct healthcare costs in the first 2 years of life of children born between mid-2008 and mid-2016, in the pre-CF transmembrane conductance regulator modulator era.

Investigations, management and outcome of neonates presenting with distal intestinal obstruction: challenging the need for contrast enemas.

Purpose: To characterise the investigations, management and ultimate diagnosis of neonates with distal intestinal obstruction.

Methods: Retrospective review of term (> 37 weeks) neonates with admission diagnosis of distal intestinal obstruction over 10 years (2012-2022). Patient pathways were identified and associations between presentations, response to treatments and outcome investigated.

Ileocecal valve-preservation ileocecostomy (IVPI) in infants with extremely short distal ileum after primary stoma.

Purpose: Preserving the ileocecal valve (ICV) has shown significant benefits. We present our experience with 18 infants who underwent ileocecal valve-preservation ileocecostomy (IVPI) with an extremely short distal ileum after primary ileostomy.

Methods: A retrospective analysis was conducted on IVPI cases between 2014 and 2020.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs.

Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines.

Introduction: Meconium ileus (MI) is a life-threatening obstruction of the intestines affecting ∼15% of newborns with cystic fibrosis (CF). Current medical treatments for MI often fail, requiring surgical intervention. MI typically occurs in newborns with pancreatic insufficiency from CF.

In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor/lumacaftor (VX-770/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF.

Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy.

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction.

Sonographic findings of transient marked proximal bowel dilatation in a growth-restricted fetus at 35 weeks' gestation.

Etiologies underlying the relatively infrequent third-trimester sonographic depiction of dilated fetal bowel include (functional or mechanical) bowel obstruction, intestinal atresia, volvulus, annular pancreas, intestinal malrotation, intussusception, gastrointestinal duplications, cystic fibrosis-associated meconium ileus, congenital chloride diarrhea, microvillus inclusion disease, intestinal neuronal dysplasia, and meconium plug syndrome. Fetal bowel obstruction may be associated with aneuploidy (mostly Trisomy 21 in association with esophageal or duodenal atresia), and rarely select microduplications or deletions. We present unusual sonographic findings associated with transient marked proximal fetal bowel dilatation in association with concurrent development of oligohydramnios, in a growth-restricted fetus at 35 weeks' gestation.

Cerebral near-infrared spectroscopy for early recognition of impending cardiac tamponade in a preterm neonate.

Cardiac tamponade is a rare but life-threatening complication of umbilical venous catheter (UVC) placement in neonates. Mortality rates are high; therefore, early diagnosis is important. We present a case of a preterm infant with a UVC in situ who underwent a laparotomy on the first day of life for pneumoperitoneum secondary to meconium ileus.

The evolutionary divergence of receptor guanylyl cyclase C has implications for preclinical models for receptor-directed therapeutics.

Mutations in receptor guanylyl cyclase C (GC-C) cause severe gastrointestinal disease, including meconium ileus, early onset acute diarrhea, and pediatric inflammatory bowel disease that continues into adulthood. Agonists of GC-C are US Food and Drug Administration-approved drugs for the treatment of constipation and irritable bowel syndrome. Therapeutic strategies targeting GC-C are tested in preclinical mouse models, assuming that murine GC-C mimics human GC-C in its biochemical properties and downstream signaling events.

Selective isoxazolopyrimidine PAT1 (SLC26A6) inhibitors for therapy of intestinal disorders.

A loss of prosecretory Cl channel CFTR activity in the intestine is considered as the key cause of gastrointestinal problems in cystic fibrosis (CF): meconium ileus, distal intestinal obstruction syndrome (DIOS) and constipation. Since CFTR modulators have minimal effects on gastrointestinal symptoms, there is an unmet need for novel treatments for CF-associated gastrointestinal disorders. Meconium ileus and DIOS mainly affect the ileum (distal small intestine).