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PloS One 2022Meconium-related ileus in very low birth weight infants can lead to increased morbidity or mortality and prolonged hospitalization without prompt diagnosis and...
BACKGROUND
Meconium-related ileus in very low birth weight infants can lead to increased morbidity or mortality and prolonged hospitalization without prompt diagnosis and treatment. This study primarily aimed to identify the incidence of and factors associated with meconium-related ileus and secondarily sought to investigate clinical and growth outcomes after water-soluble contrast media (Gastrografin) enema.
METHODS
We retrospectively reviewed medical records of very low birth weight infants born between February 2009 and March 2019 in the neonatal intensive care unit of a single medical center. Perinatal factors, clinical outcomes, and growth outcomes were compared between the group with meconium-related ileus that received Gastrografin enema and the control group.
RESULTS
Twenty-four (6.9%) patients were diagnosed with meconium-related ileus among 347 very low birth weight infants. All achieved successful evacuation of meconium with an average of 2.8 (range: 1-8) Gastrografin enema attempts without procedure-related complications. Initiation of Gastrografin enema was performed at mean 7.0 days (range: 2-16) after birth. Incidences of moderate to severe bronchopulmonary dysplasia were higher and the duration of mechanical ventilation and need for oxygen were longer in the meconium-related ileus group (P = 0.039, 0.046, 0.048, respectively). Meconium-related ileus infants took more time to start enteral feeding and the nothing per oral time was longer (P = 0.001 and 0.018, respectively). However, time to achieve full enteral feeding and Z-scores for weight and height at 37 weeks and at 6 months corrected age did not differ between the two groups.
CONCLUSIONS
Gastrografin enema in very low birth weight infants with meconium-related ileus was an effective and safe medical management. Following Gastrografin enema, very low birth weight infants with meconium-related ileus achieved similar subsequent feeding progress and similar growth levels as the control groups without meconium-related ileus.
Topics: Diatrizoate Meglumine; Enema; Humans; Ileus; Infant, Newborn; Infant, Very Low Birth Weight; Intestinal Obstruction; Meconium; Retrospective Studies
PubMed: 35951504
DOI: 10.1371/journal.pone.0272915 -
Indian Journal of Gastroenterology :... Jun 2022To describe the demography and spectrum of pancreatic, hepatobiliary, and gastrointestinal (GI) manifestations in children with cystic fibrosis (CF) from the Indian...
OBJECTIVES
To describe the demography and spectrum of pancreatic, hepatobiliary, and gastrointestinal (GI) manifestations in children with cystic fibrosis (CF) from the Indian subcontinent.
METHODS
In this retrospective study, relevant information from the database of all children with CF below 18 years of age was collected and analyzed.
RESULTS
Among the total 109 children, 58 (53%) were from the southern states of India. The most common manifestation was pancreatic insufficiency (PI) in 85 (83%) children. Those with PI presented at an earlier age (1.8 vs. 6.9 years). Cirrhosis with portal hypertension was documented in only one patient and meconium ileus in three (2.8%). There was significant malnutrition in the PI cohort with a mean weight-for-age Z-score of - 3.17 ± 1.79 at diagnosis. Twenty-one (19%) patients had died during the follow-up and 18 (90%) of them had PI. There was no difference in the prevalence of selected pulmonary manifestations in the PI and pancreatic sufficient (PS) groups. Among children with PI, 78 were screened for ΔF508 mutation, 16 (21%) were homozygous, and 17 (22%) were heterozygous. In the PS group, only 2 (14%) were heterozygous for ΔF508 mutation. The median duration of follow-up of the patients was 1.8 (1.5) years.
CONCLUSION
PI is the most common GI manifestation of children with CF and is associated with severe malnutrition and poor outcome. Timely identification and management of the comorbidities involving the digestive system are essential for better growth and quality of life in these children.
Topics: Child; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Humans; Malnutrition; Mutation; Quality of Life; Retrospective Studies; Tertiary Care Centers
PubMed: 35761057
DOI: 10.1007/s12664-021-01225-0 -
Journal of Indian Association of... 2022Gastrointestinal (GI) malformations have varied short-term and long-term outcomes reported across various neonatal units in India.
BACKGROUND
Gastrointestinal (GI) malformations have varied short-term and long-term outcomes reported across various neonatal units in India.
METHODS
This descriptive study was done to study the clinical profile, outcomes and predictors of mortality in neonates operated for congenital GI malformations in a tertiary neonatal care unit in South India between years 2011 and 2020. Details were collected by retrospective review of the case sheets.
RESULTS
Total of 68 neonates were included with esophageal atresia (EA) in 10, infantile hypertrophic pyloric stenosis (IHPS) in 9, duodenal atresia (DA) in 10, ileal atresia in 8, jejunal atresia in 5, anorectal malformations (ARM) in 11, meconium ileus/peritonitis in 9, malrotation in 2, and Hirschsprung's disease (HD) in 4. Antenatal diagnosis was highest in DA (80%). Associated anomalies were maximum in EA (50%), the most common being vertebral, anal atresia, cardiac defects, tracheoesophageal fistula, renal and radial abnormalities, and limb abnormalities association (VACTERL). Overall mortality was 15%. IHPS, DA, Malrotation, HD and ARM had 100 % survival while ileal atresia had the least survival (38%). Gestational age <32 weeks (odds ratio [OR] 12.77 [1.96, 82.89]) and outborn babies (OR 5.55 [1.01, 30.33]) were significant predictors of mortality in babies operated for small intestinal anomalies. None of the surviving infants were moderately or severely underweight at follow-up.
CONCLUSION
Overall survival of surgically correctable GI anomalies is good. Among the predictors for mortality, modifiable factors such as in-utero referral of antenatally diagnosed congenital anomalies need attention. One-fifth had associated anomalies highlighting the need to actively look for the same. Although these neonates are vulnerable for growth failure, they had optimal growth on follow-up possibly due to standardized total parenteral nutritional policy during neonatal intensive care unit stay.
PubMed: 35733590
DOI: 10.4103/jiaps.JIAPS_10_21 -
Molecular Pharmacology Jun 2022Loss of prosecretory Cl channel CFTR activity is considered as the key cause of gastrointestinal disorders in cystic fibrosis including constipation and meconium ileus....
Loss of prosecretory Cl channel CFTR activity is considered as the key cause of gastrointestinal disorders in cystic fibrosis including constipation and meconium ileus. Clc-2 is proposed as an alternative Cl channel in intestinal epithelia that can compensate for CFTR loss-of-function. Lubiprostone is an FDA-approved drug with Clc-2 activation as its presumed mechanism of action. However, relative contribution of Clc-2 in intestinal Cl secretion and the mechanism of action of lubiprostone remain controversial due to lack of selective Clc-2 inhibitors. Using recently identified selective Clc-2 inhibitor AK-42, we characterized the roles of Clc-2 in Cl secretion in human intestinal epithelial T84 cells. Clc-2 inhibitor AK-42 had minimal (15%) inhibitory effect on secretory short-circuit current (I) induced by cAMP agonists, where subsequently applied CFTR inhibitor (CFTR-172) caused 2-3 fold greater inhibition. Similarly, AK-42 inhibited lubiprostone-induced secretory I by 20%, whereas CFTR-172 caused 2-3 fold greater inhibition. In addition to increasing CFTR and Clc-2-mediated apical Cl conductance, lubiprostone increased basolateral membrane K conductance, which was completely reversed by cAMP-activated K channel inhibitor BaCl All components of lubiprostone-induced secretion (Clc-2, CFTR and K channels) were inhibited by ~65% with the extracellular Ca-sensing receptor (CaSR) activator cinacalcet that stimulates cAMP hydrolysis. Lastly, EP4 prostaglandin receptor inhibitor GW627368 pretreatment inhibited lubiprostone-induced secretion by 40% without any effect on forskolin response. Our findings suggest that Clc-2 has minor role in cAMP-induced intestinal Cl secretion; and lubiprostone is not a selective Clc-2 activator, but general activator of cAMP-gated ion channels in human intestinal epithelial cells. Cl- channel Clc-2 activation is the proposed mechanism of action of the FDA-approved constipation drug lubiprostone. Using first-in-class selective Clc-2 inhibitor AK-42, we showed that Clc-2 has minor contribution in intestinal Cl- secretion induced by lubiprostone and cAMP agonists. We also found that lubiprostone is a general activator of cAMP-gated ion channels in human intestinal epithelial cells (via EP4 receptors). Our findings clarify the roles of Clc-2 in intestinal Cl- secretion and elucidate the mechanism of action of approved-drug lubiprostone.
PubMed: 35680165
DOI: 10.1124/molpharm.122.000542 -
Cureus Apr 2022Background and objective Intestinal perforations and necrotizing enterocolitis (NEC) requiring the formation of temporary intestinal stoma are prevalent conditions...
Background and objective Intestinal perforations and necrotizing enterocolitis (NEC) requiring the formation of temporary intestinal stoma are prevalent conditions worldwide. This prospective study aimed to address the following research question: does sutureless enterostomy lead to fewer complications compared to conventional enterostomy in critically sick surgical neonates who need a stoma? Methods We conducted a randomized control trial (TCTR20211011004) from October 2020 to October 2021. A total of 120 patients were randomized to the following two study groups: Group A: conventional sutured enterostomy; Group B: sutureless enterostomy, with 60 patients in each group. The operative time, complications, and mortality were compared between the two groups using the chi-squared test. Results The groups were comparable with respect to the mean age at presentation, gestational age, weight, and sex ratio. In Group A, the main operative diagnoses were NEC in 22 patients, pneumoperitoneum in 25, complicated meconium ileus in nine, bowel atresia in three, and midgut volvulus in one; while in Group B, 25 patients had NEC, 20 had pneumoperitoneum, eight had meconium ileus, two had bowel atresia, and five had midgut volvulus. The mean operative time (93.5 ± 28.71 minutes) was significantly longer in the conventional group compared to the sutureless group (52.08 ± 18.53 minutes). Oral feed was started significantly earlier in the sutureless stoma group. Mortality was 43.3% in Group A and 46.6% in Group B. Complication rate was significantly higher in sutured stoma group. Conclusion The management of critically sick neonates, especially those with NEC and intestinal perforation, still presents a surgical dilemma. Based on our findings, the sutureless enterostomy may reduce operative time and complications in critically sick neonates.
PubMed: 35573560
DOI: 10.7759/cureus.24057 -
International Journal of Pediatrics &... Mar 2022Meconium ileus (MI) is one of the most common causes of intestinal obstruction in newborns. It is the earliest clinical manifestation of cystic fibrosis (CF). MI is...
INTRODUCTION
Meconium ileus (MI) is one of the most common causes of intestinal obstruction in newborns. It is the earliest clinical manifestation of cystic fibrosis (CF). MI is suspected if a baby fails to pass meconium shortly after birth and develops symptoms of bowel obstruction, such as distention of the abdomen or vomiting. MI can lead to bowel perforation, a twisting of the bowel, or inflammation and infection of the abdominal cavity.
OBJECTIVES
To find the incidence and prevalence of meconium ileus in cystic fibrosis patients and to report on the most common gene mutation of MI in CF patients.
METHODOLOGY
Retrospective review of the medical documentations of all MI patients during the period of 1989-2018.
RESULTS
A total of 40 CF confirmed patients were presented with MI. Twenty-nine patients (71%) are alive and 11 patients (29%) died or lost to follow-up. The following CFTR mutations were found: Eight patients (20%) with c.2988+1G>A; Intron 18. Seven patients (17.5%) with c.1418delG; Exon 11. Five patients (12.5%) with c.579+1G>T; Intron 5. Four patients (10%) with c.1911delG; Exon 14. Four patients (10%) with c.1521_1523delCTT; Exon 11. Four patients (10%) with c.416A>T; Exon 13. Three patients (7.5%) with c.2421A>G; Exon 14. Two patients (5%) with c.3908A>C; Exon 21. One patient (2.5%) with c.3889dupT; Exon 24. One patient (2.5%) with c.1657C>T; Exon 12. One patient (2.5%) with c.2547C>A; Exon 14a. Eighteen patients (45%) were presented with vomiting, 38 patients (95%) had postnatal radiological findings, 7 patients (17.5%) had electrolytes imbalance. Five patients (12.5%) had cholestasis and 4 patients (10%) developed chronic liver disease. Thirty-five patients (79.5%) underwent surgical repair and 9 patients (20.5%) were treated medically. Mean age of operation was 2.25 (2) days. Of 9 patients, 6 (66.6%) were treated with gastrograffin enema, 2 patients (22.2%) with oral N-acetylcysteine and 1 patient (11.1%) with saline rectal wash. Thirteen patients (31.5%) required TPN. Five patients had recurrent operation.
CONCLUSION
CF and meconium ileus are commonly present in CF patients in Saudi Arabia. Prognosis is similar to other CFs without MI, if treated early. Thirty percent of our CF/MI patients have intronic mutations.
PubMed: 35573065
DOI: 10.1016/j.ijpam.2021.03.008 -
BMC Pediatrics May 2022This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases,... (Review)
Review
BACKGROUND
This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases, mainly affecting the lungs and the liver. The combination of both diseases together is rare and may lead to a fulminant disease with limited life span. To the best of our knowledge, no case has been reported of a patient born with both diseases.
CASE PRESENTATION
After an uneventful pregnancy, a male baby was born with meconium ileus. The suspected diagnosis of CF was confirmed based on the sweat test and genetic analysis. The child developed persisting cholestasis, too severe to be likely caused by CF alone and indicating an associated problem. The diagnosis of A1ATD was established based on clinical suspicion (persisting cholestasis), decreased serum alpha-1 antitrypsin and genetic analysis. Supportive therapy was started, however the boy evolved to rapidly progressive liver disease leading to liver failure which necessitated an infant liver transplantation.
CONCLUSIONS
This case illustrates the complexity of care in case of two severe inherited diseases as well as post solid organ transplant care.
Topics: Child; Cholestasis; Cystic Fibrosis; Humans; Infant; Liver Transplantation; Male; alpha 1-Antitrypsin Deficiency
PubMed: 35505316
DOI: 10.1186/s12887-022-03290-6 -
Cureus Mar 2022Background Anatomical abnormalities leading to bowel movement failure are the major cause of intestinal obstruction. This study was done to assess the diagnostic...
Background Anatomical abnormalities leading to bowel movement failure are the major cause of intestinal obstruction. This study was done to assess the diagnostic efficacy of contrast enema in neonates with lower intestinal obstruction. Methodology This prospective study was conducted in The Children's Hospital and University of Child Health Sciences, Lahore from February 2021 to July 2021. Patients presenting with constipation, abdominal distension, vomiting, and unable to pass meconium, evaluated clinically and by X-rays, were included in the study. Patients with lower intestinal obstruction (i.e., meconium ileus, Hirschsprung's disease, ileal atresia, meconium plug syndrome, and small left colon) were given contrast enema (gastrografin) after hydration. The radiologist was blinded by the clinical diagnosis or reference standard diagnosis, which was labeled prior to image interpretation. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for major contrast enema diagnosis. Results During this period, a total of 34 patients were included in the study. The mean age of presentation was 72.0 ± 24 hours. There were 21 (61.8%) boys and 13 (38.2%) girls, representing a male to female ratio of 1.7:1. In four cases, our diagnosis on the basis of contrast enema was proven wrong. Sensitivity, specificity, PPV, and NPV of Hirschsprung's disease were found to be 93.3%, 50%, 87.5%, and 66.7%, while these were 84.6%, 66.7%, 91.7%, and 50.0%, respectively, for meconium ileus. Conclusion The diagnostic efficacy of contrast enema was found to be good in neonates with lower intestinal obstruction. The spectrum of intestinal obstruction among neonates shows diversity while contrast enema seems to play a major role in the identification and remodeling of the diagnostic plan in a major proportion of cases.
PubMed: 35495017
DOI: 10.7759/cureus.23458 -
Journal of Cystic Fibrosis : Official... Jul 2022We report elexacaftor-tezacaftor-ivacaftor (ETI) treatment of a F508del carrier who was pregnant with a F508del homozygous fetus. At 23-weeks gestation meconium ileus...
We report elexacaftor-tezacaftor-ivacaftor (ETI) treatment of a F508del carrier who was pregnant with a F508del homozygous fetus. At 23-weeks gestation meconium ileus (MI) was evident on ultrasound including dilated, hyperechoic bowel, which persisted on subsequent imaging. Through shared decision-making, the mother began ETI at 32 weeks with intent to treat fetal MI. The ultrasound findings persisted at treatment day 13, but bowel dilation had resolved by imaging on treatment day 27. A female infant was delivered vaginally at 36 weeks with no complications. The mother continued ETI while breastfeeding. Stool elastase at age 2 weeks was 240 mcg/g. Sweat chloride measurement was 64 and 62 mEq/L. Maternal and infant liver function testing have been normal. Maternal ETI treatment likely led to resolution of the MI and there is evidence supporting continued infant benefit through breastmilk. Logistical and ethical considerations regarding treatment of a carrier mother for infant benefit are discussed.
Topics: Aminophenols; Benzodioxoles; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Fetus; Humans; Infant, Newborn; Meconium Ileus; Mothers; Mutation; Pregnancy
PubMed: 35422395
DOI: 10.1016/j.jcf.2022.04.005 -
Journal of Pediatric Surgery Nov 2022Patients with Hirschsprung disease (HD) mostly undergo surgery around the age of three to six months. While awaiting surgery, therapy to treat the obstruction such as...
BACKGROUND
Patients with Hirschsprung disease (HD) mostly undergo surgery around the age of three to six months. While awaiting surgery, therapy to treat the obstruction such as transanal irrigation (TAI) or laxatives is applied. The aim of this study was to gain insight in the prevalence and severity of complications occurring while awaiting surgery and to identify patient characteristics associated with the development of these complications.
METHODS
This study retrospectively analyzed data of patients with HD operated in our center between 2000 and 2021. Complications emerging while awaiting surgery were graded using Clavien-Dindo (CD). Patient characteristics as predictor of a complication were tested using logistic regression analysis.
RESULTS
Twenty-two of 132 (17%) included patients (preoperative treatment: 94% TAI; 2% laxatives; 2% other therapy) developed 45 complications while awaiting surgery, including predominantly major complications (91%). Bowel perforation occurred most frequently (n = 9, 7%) wherefrom six caused by TAI (5%), including three patients with total colon aganglionosis (TCA) (2%) counting one life-threatening and one lethal perforation. The other perforations were caused by meconium ileus (n = 2) and Hirschsprung associated enterocolitis (HAEC) (n = 1). Other frequent complications were: sepsis (5%), ileus (4%) and persistent obstruction (4%). Predictive factor for developing complication was TCA (OR 9.905, CI 2.994-32.772, p < 0.001).
CONCLUSION
We found a complication rate of 17% in patients while awaiting surgery, reporting bowel perforation most frequently. We found this complication in patients with TCA being highly dangerous causing one life-threatening and one lethal perforation. Therefore, we advise in patients with (suspected) TCA to limit the time awaiting surgery.
LEVEL OF EVIDENCE
level III.
Topics: Enterocolitis; Hirschsprung Disease; Humans; Infant; Intestinal Perforation; Laxatives; Postoperative Complications; Retrospective Studies; Risk Factors
PubMed: 35354528
DOI: 10.1016/j.jpedsurg.2022.02.022