11 research outputs found
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Incidencia de nacimientos pretérmino y de término con peso bajo al nacer y existencia de línea Sydney
Identification of a Small Supernumerary Marker Chromosome in a Turner Syndrome Patient with Karyotype mos 46,X,+mar/45,X
Turner Syndrome is characterized by a normal X chromosome and the partial or complete absence of a second sexual chromosome. Small supernumerary marker chromosomes are present in 6.6% of these patients. Because of the wide range of Turner syndrome karyotypes, it is difficult to establish a relationship with the phenotype of the patients. We present the case of a female patient with Turner syndrome, insulin resistance, type 2 diabetes, and intellectual disability. The karyotype revealed the presence of mosaicism with a monosomy X cell line and a second line with a small marker chromosome. FISH of two different tissues was used to identify the marker chromosome with probes for X and Y centromeres. Both tissues presented mosaicism for a two X chromosome signal, differing in the percentage of the monosomy X cell percentage. Comparative genomic hybridization with the CytoScanTMHD assay was performed in genomic DNA from peripheral blood, allowing us to determine the size and breakage points of the small marker chromosome. The patient presents a phenotype that combines classic Turner syndrome features and unlikely ones as intellectual disability. The size, implicated genes, and degree of inactivation of the X chromosome influence the broad spectrum of phenotypes resulting from these chromosomes
Ring chromosome 6 in a child with anterior segment dysgenesis and review of its overlap with other FOXC1 deletion phenotypes
Here, we report a patient with ring chromosome 6 [r(6)], associated with anterior segment dysgenesis (ASD) and other anomalies. The phenotype was due to a 1880 kb microdeletion at 6p25.3 identified by whole-genome array analysis, and was mainly attributable to a FOXC1 haploinsufficiency. Currently 37 patients with r(6) have been reported. We found that facial dysmorphism, ASD, heart anomalies, brain anomalies, and hearing loss are constant features only in severe cases of r(6), mainly related to hemizygosity of FOXC1. Thus, overlaps with other FOXC1 related phenotypes, such as the 6p25 deletion syndrome, Axenfeld-Rieger syndrome type 3, and ASD type 3. Contrarily, those patients whose r(6) does not disrupt FOXC1, have mild or moderate phenotypes and do not exhibit ASD.Fundação para a Ciência e a Tecnologia, Portugal, Research Grant, Grant/Award Number: HMSP‐ICT/0016/2013; CONACYT; Universidad de Guadalajara; PROINPEPinfo:eu-repo/semantics/publishedVersio
Intraoperative Findings Associated to Inpatient Mortality From Patients With Gastroschisis in Western Mexico
GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome
Introduction: GATA2 mutations are associated with several conditions, including Emberger syndrome which is the association of primary lymphedema with hematological anomalies and an increased risk for myelodysplasia and leukemia. Objective: To describe a family with Emberger syndrome with incomplete penetrance. Methods: A DNA sequencing of GATA2 gene was performed in the parents and offspring (5 individuals in total). Results: The family consisted of 5 individuals with a GATA2 null mutation (c.130G>T, p.Glu44*); three of them were affected (2 of which were deceased) while 2 remained unaffected at the age of 40 and 13 years old. The three affected siblings (2 boys and 1 girl) presented with lymphedema of the lower limbs, recurrent warts, epistaxis and recurrent infections. Two died due to hematological abnormalities (AML and pancytopenia). In contrast, the two other family members who carry the same mutation (the mother and one brother) have not presented any symptoms and their blood tests remain normal. Discussion: Incomplete penetrance may indicate that GATA2 haploinsufficiency is not enough to produce the phenotype of Emberger syndrome. Therefore, in cases where incomplete penetrance or high variable expressivity is described, whole exome or genome sequencing would be useful in order to identify specific gene interactions that drastically modify the phenotype. In addition, Skewed gene expression by an epigenetic mechanism of gene regulation should also be considered