Systematic estimates of the global, regional and national under-5 mortality burden attributable to birth defects in 2000-2019: a summary of findings from the 2020 WHO estimates.

OBJECTIVES: To examine the potential for bias in the estimate of under-5 mortality due to birth defects recently produced by the WHO and the Maternal and Child Epidemiology Estimation research group. DESIGN: Systematic analysis. METHODS: We examined the estimated number of under-5 deaths due to birth defects, the birth defect specific under-5 mortality rate, and the per cent of under-5 mortality due to birth defects, by geographic region, national income and under-5 mortality rate for three age groups from 2000 to 2019. RESULTS: The under-5 deaths per 1000 live births from birth defects fell from 3.4 (95% uncertainty interval (UI) 3.1-3.8) in 2000 to 2.9 (UI 2.6-3.3) in 2019. The per cent of all under-5 mortality attributable to birth defects increased from 4.6% (UI 4.1%-5.1%) in 2000 to 7.6% (UI 6.9%-8.6%) in 2019. There is significant variability in mortality due to birth defects by national income level. In 2019, the under-5 mortality rate due to birth defects was less in high-income countries than in low-income and middle-income countries, 1.3 (UI 1.2-1.3) and 3.0 (UI 2.8-3.4) per 1000 live births, respectively. These mortality rates correspond to 27.7% (UI 26.6%-28.8%) of all under-5 mortality in high-income countries being due to birth defects, and 7.4% (UI 6.7%-8.2%) in low-income and middle-income countries. CONCLUSIONS: While the under-5 mortality due to birth defects is declining, the per cent of under-5 mortality attributable to birth defects has increased, with significant variability across regions globally. The estimates in low-income and middle-income countries are likely underestimated due to the nature of the WHO estimates, which are based in part on verbal autopsy studies and should be taken as a minimum estimate. Given these limitations, comprehensive and systematic estimates of the mortality burden due to birth defects are needed to estimate the actual burden.

Incidence and predictors of mortality among neonates referred to comprehensive and specialized hospitals in Amhara regional state, North Ethiopia: a prospective follow-up study.

BACKGROUND: Neonatal mortality is a major global public health problem. Ethiopia is among seven countries that comprise 50 % of global neonatal mortality. Evidence on neonatal mortality in referred neonates is essential for intervention however, there is no enough information in the study area. Neonates who required referral frequently became unstable and were at a high risk of death. Therefore, this study aimed to assess the incidence and predictors of mortality among referred neonates. METHOD: A prospective follow-up study was conducted among 436 referred neonates at comprehensive specialized hospitals in the Amhara regional state, North Ethiopia 2020. All neonates admitted to the selected hospitals that fulfilled the inclusion criteria were included. Face-to-face interviews, observations, and document reviews were used to collect data using a semi-structured questionnaire and checklists. Epi-data™ version 4.2 software for data entry and STATA™ 14 version for data cleaning and analysis were used. Variables with a p-value < 0.25 in the bi-variable logistic regression model were selected for multivariable analysis. Multivariable analyses with a 95% confidence level were performed. Variables with P < 0.05 were considered statistically significant. RESULT: Over all incidence of death in this study was 30.6% with 95% confidence interval of (26.34-35.16) per 2 months observation. About 23 (17.83%) deaths were due to sepsis, 32 (24.80%) premature, 40 (31%) perinatal asphyxia, 3(2.33%) congenital malformation and 31(24.03%) deaths were due to other causes. Home delivery [AOR = 2.5, 95% CI (1.63-4.1)], admission weight < 1500 g [AOR =3.2, 95% CI (1.68-6.09)], travel distance ≥120 min [AOR = 3.8, 95% CI (1.65-9.14)], hypothermia [AOR = 2.7, 95% CI (1.44-5.13)], hypoglycemia [AOR = 1.8, 95% CI (1.11-3.00)], oxygen saturation < 90% [AOR = 1.9, 95% (1.34-3.53)] at admission time and neonate age ≤ 1 day at admission [AOR = 3.4, 95% CI (1.23-9.84) were predictors of neonatal death. CONCLUSION: The incidence of death was high in this study. The acute complications arising during the transfer of referral neonates lead to an increased risk of deterioration of the newborn's health and outcome. Preventing and managing complications during the transportation process is recommended to increase the survival of neonates.

Decreasing death rates and causes of death in Icelandic children-A longitudinal analysis.

BACKGROUND: Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century. METHODS: The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear. FINDINGS: Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant. INTERPRETATION: Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide.

The Unrecognized Mortality Burden of Genetic Disorders in Infancy.

Objectives. To determine how deaths of infants with genetic diagnoses are described in national mortality statistics. Methods. We present a retrospective cohort study of mortality data, obtained from the National Death Index (NDI), and clinical data for 517 infants born from 2011 to 2017 who died before 1 year of age in the United States. Results. Although 115 of 517 deceased infants (22%) had a confirmed diagnosis of a genetic disorder, only 61 of 115 deaths (53%) were attributed to International Classification of Diseases, 10th Revision codes representing congenital anomalies or genetic disorders (Q00-Q99) as the underlying cause of death because of inconsistencies in death reporting. Infants with genetic diagnoses whose underlying causes of death were coded as Q00-Q99 were more likely to have chromosomal disorders than monogenic conditions (43/61 [70%] vs 18/61 [30%]; P < .001), which reflects the need for improved accounting for monogenic disorders in mortality statistics. Conclusions. Genetic disorders, although a leading cause of infant mortality, are not accurately captured by vital statistics. Public Health Implications. Expanded access to genetic testing and further clarity in death reporting are needed to describe properly the contribution of genetic disorders to infant mortality.

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study.

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 middle-income 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 low-income 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 low-income, 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. FUNDING: Wellcome Trust.

Laryngeal cleft: A literature review.

INTRODUCTION: Laryngeal cleft is a congenital condition in which an opening in the posterior laryngotracheal wall allows food and liquid to pass from the esophageal lumen to the airway and causes aspiration. The severity of a laryngeal cleft is measured using the Benjamin-Inglis system, and can be managed conservatively or with a variety of surgical options With increased awareness, higher suspicion among primary physicians, advanced technology and improved intensive neonatal care services, more babies with laryngeal clefts survive in the modern era. Therefore, the focus has shifted from infant survival to treatment of laryngeal clefts and the challenging, complex medical conditions they create. OBJECTIVE: To understand current laryngeal cleft management and post-operative outcomes. METHODS: Literature review of laryngeal cleft studies from 2010 to 2021. RESULTS: A total of 1033 patients were included. Based on 415 cases for whom sufficient classification data were available, the predominate symptom for patients with type I, III, and IV clefts is swallowing dysfunction, while the predominant symptoms for patients with type II clefts are stridor and aspiration. A wide variety of comorbidities involving several major organs has been reported with laryngeal clefts, which tend to impact clinical outcomes negatively. Approximately 19% of type I clefts have been treated conservatively successfully, but the majority was treated surgically. Most studies that used injection laryngoplasty for type I clefts reported highly successful repairs without complications or delays in additional procedures. Ninety-eight percent all type II clefts were treated with endoscopic repair; 87% of patients with type III clefts received endoscopic repair; and 66% of patients with type IV clefts underwent open surgery. Approximately 62% of resolved cases were reported within 12 months, while 50.87% of failed cases were reported within 6 weeks. CONCLUSIONS: There are multiple treatment approaches, each of which may be applicable depending on factors such as laryngeal cleft type, severity of presentation, and comorbidities. Conservative approaches appear to be most useful for type I clefts or in patients with mild symptoms, while surgical management can be considered for any type of laryngeal cleft. The benefit of injection laryngoplasty, endoscopic repair and open surgery can also vary, but injection laryngoplasty and endoscopic repair are used most commonly. Open surgery should be to be considered if patients present with severe cleft types or if it is unsafe to perform other surgical techniques. Familiarity with this literature review should help clinicians understand clinical characteristics, direct medical management, and guide successful resolution of laryngeal clefts.

County Poverty, Urban-Rural Classification, and the Causes of Term Infant Death : United States, 2012-2015.

OBJECTIVE: Higher mortality among full-term infants (term infant deaths) contributes to disparities in infant mortality between the United States and other developed countries. We examined differences in the causes of term infant deaths across county poverty levels and urban-rural classification to understand underlying mechanisms through which these factors may act. METHODS: We linked period birth/infant death files for 2012-2015 with US Census poverty estimates and county urban-rural classifications. We grouped the causes of term infant deaths as sudden unexpected death in infancy (SUDI), congenital malformations, perinatal conditions, and all other causes. We computed the distribution and relative risk of overall and cause-specific term infant mortality rates (term IMRs) per 1000 live births and 95% CIs for county-level factors. RESULTS: The increase in term IMR across county poverty and urban-rural classification was mostly driven by an increase in the rate of SUDI. The relative risk of term infant deaths as a result of SUDI was 1.6 (95% CI, 1.5-1.8) times higher in medium-poverty counties and 2.3 (95% CI, 1.2-2.5) times higher in high-poverty counties than in low-poverty counties. Cause-specific IMRs of congenital malformations, perinatal conditions, and death from other causes did not differ by county poverty level. We found similar trends across county urban-rural classification. Sudden infant death syndrome was the main cause of SUDI across both county poverty levels and urban-rural classifications, followed by unknown causes and accidental suffocation and strangulation in bed. CONCLUSIONS: Interventions aimed at reducing SUDI, particularly in high-poverty and rural areas, could have a major effect on reducing term IMR disparities between the United States and other developed countries.

European trends in mortality in children with congenital anomalies: 2000-2015.

OBJECTIVE: To investigate if the survival of children with congenital anomalies has improved from 2000 to 2015 and whether there is heterogeneity in the improvements across Europe. DESIGN: Population-based study of routine collected data from the WHO database on mortality and causes. SETTING: Data on 31 European countries from 2000 to 2015. MAIN OUTCOME MEASURES: All-cause and congenital anomaly mortality rates for infants and children up to age 9 in countries and regions of Europe. RESULTS: The relative odds of all-cause mortality in 2015 compared with 2000 was 0.54 (95% CI: 0.50-0.59) for under 1, 0.48 (95% CI: 0.44-0.53) for ages 1-4, and 0.53 (95% CI: 0.49-0.56) for ages 5-9 with the relative odds of mortality from congenital anomalies being 0.49 (95% CI: 0.44-0.55), 0.51 (95% CI: 0.44-0.60), and 0.65 (95% CI: 0.53-0.80), respectively. The proportion of deaths from congenital anomalies remained relatively constant over time (26, 16, and 9% for under 1, ages 1-4, and ages 5-9, respectively) and was similar in all regions of Europe. For mortality from all causes and from congenital anomalies heterogeneity between countries and regions of Europe was high, with the countries in Eastern Europe having higher rates, but also experiencing greater relative reductions in mortality from 2000 to 2015. CONCLUSION: There was a large geo-spatial disparity in all cause and congenital anomaly mortality for infants and children up to 9. However, all regions saw a significant decrease in all cause and congenital anomaly mortality rates, with the proportions of deaths from congenital anomalies remaining constant over this time.

Caso Clínico: Meningohidroencefalocele Gigante / Case Report: Giant Meningohydroencephalocele

INTRODUCCIÓN: Los encefaloceles son una anomalía congénita rara, que afecta a 1 de cada 5 000 nacidos vivos. Un meningohidroencefalocele es la herniación de meninges, ventrículos y parte del encéfalo a través de un defecto congénito en el cráneo. El pronóstico de los recién nacidos con encefalocele depende de varios factores. La corta edad y las anomalías congénitas asociadas en estos pacientes plantean desafíos en el diagnóstico y manejo. CASO CLÍNICO: Recién nacido masculino, nacido a las 37 semanas de gestación, por cesárea de emergencia por parto en fase latente, presentado una masa de gran tamaño, sobre la región parieto-occipital, de bordes lobulados, irregulares, cubierta en parte por cuero cabelludo, y en otras zonas de un tono rojo violáceo. El neonato fue poco reactivo, con tono disminuido, llanto ausente. EVOLUCIÓN: Tras valoración del caso por especialistas, debido al importante defecto de la calota craneal y las anomalías estructurales cerebrales, el paciente no fue candidato para tratamiento quirúrgico. Neonato fue dado de alta con expectativa de vida reducida, para recibir cuidados en el hogar. CONCLUSIÓN: El meningohidroencefalocele gigante es un defecto del tubo neural poco frecuente. El manejo de las encefaloceles puede ser complicado y debe ser individualizado y dependerá de las estructuras anatómicas comprometidas. Si bien en este caso el pronóstico fue malo, siempre es necesario el trabajo multidisciplinario para un adecuado manejo.

BACKGROUND: Encephaloceles are a rare congenital anomaly, affecting 1 in 5 000 live births.A meningohydroencephalocele is the herniation of the meninges, ventricles, and part of the brain through a congenital defect in the skull. The prognosis of newborns depends on several factors. The young age and the associated congenital anomalies in these patients contribute to the diagnostic and treatment challenge. CASE REPORT: Male newborn, born at 37 weeks of gestation, by emergency C-section due to latent labor, presenting a large mass over the parieto-occipital region, with lobed, irregular edges, partially covered by the scalp, and in other areas a purplish red tone. The newborn was no very reactive, had decreased tone, absent crying. EVOLUTION: After specialist's evaluation, due to the significant defect in the cranial shell and the structural brain abnormalities, the patient was not a candidate for surgical treatment. The newborn was discharged with a reduced life expectancy, to receive care at home. CONCLUSION: giant meningohydroencephalocele is a rare neural tube defect. The management of encephaloceles can be complicated and must be individualized, and will depend on the anatomical structures involved. Although in this case the prognosis was bad, multidisciplinary work is always necessary for proper management.

Role of prenatal imaging in the diagnosis and management of fetal facio-cervical masses.

Congenital facio-cervical masses can be a developmental anomaly of cystic, solid, or vascular origin, and have an inseparable relationship with adverse prognosis. This retrospective cross-sectional study aimed at determining on the prenatal diagnosis of congenital facio-cervical masses, its management and outcome in a large tertiary referral center. We collected information on prenatal clinical data, pregnancy outcomes, survival information, and final diagnosis. Out of 130 cases of facio-cervical masses, a total of 119 cases of lymphatic malformations (LMs), 2 cases of teratoma, 2 cases of thyroglossal duct cyst, 4 cases of hemangioma, 1 case of congenital epulis, and 2 cases of dermoid cyst were reviewed. The accuracy of prenatal ultrasound was 93.85% (122/130). Observations of diameters using prenatal ultrasound revealed that the bigger the initial diameter is, the bigger the relative change during pregnancy. Magnetic resonance imaging (MRI) revealed that 2 cases of masses were associated with airway compression. In conclusion, ultrasound has a high overall diagnostic accuracy of fetal face and neck deformities. Prenatal US can enhance the management of ambulatory monitoring and classification. Furthermore, MRI provided a detailed assessment of fetal congenital malformations, as well as visualization of the trachea, presenting a multi-dimensional anatomical relationship.

Influence of indications on perinatal outcomes after radio frequency ablation in complicated monochorionic pregnancies: a retrospective cohort study.

BACKGROUND: Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation. METHODS: This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student's t-test and Mann-Whitney U test, respectively, and for categorical variables, Chi-square and Fisher's exact tests were used. P < 0.05 indicated a significant difference. RESULTS: We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin-twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate was significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks. CONCLUSIONS: The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.

Perinatal mortality and morbidity, timing and route of delivery in monoamniotic twin pregnancies: a retrospective cohort study.

PURPOSE: Monoamniotic twin pregnancies are at high risk of perinatal complications and fetal loss. The objective of this study is to describe the management and outcomes of monoamniotic twin pregnancies in a French university obstetrics department. METHODS: Retrospective review of all consecutive monoamniotic twin pregnancies managed between 1992 and 2018 in a level-3 university hospital maternity unit. Antenatal variables, gestational age and other neonatal characteristics at delivery, mode of delivery, and its reason were recorded, together with outcomes, including a composite adverse neonatal outcome. RESULTS: Overall, 46 monoamniotic twin pregnancies (92 fetuses) were identified during the study period. Among them, 27 fetal losses and 2 early neonatal deaths were reported. Congenital abnormalities accounted for 33.3% of the 27 fetal losses, and unexpected fetal deaths for 29.6%. Among the 37 women who gave birth to 65 live infants at 23 or more weeks of gestation, 17 had cesarean and 19 vaginal deliveries. Overall and composite adverse neonatal outcomes did not differ significantly for the 33 children born vaginally and the 31 by cesarean deliveries. The prospective risk of intrauterine death in all 92 fetuses reached its nadir of 1.8% at 336/7 weeks. CONCLUSION: This series confirms the still high risk of fetal and neonatal death of these twins and shows that congenital abnormalities but also unexpected fetal deaths account for the majority of pre- and postnatal mortality. Our data suggest that vaginal delivery of monoamniotic twins is safe and that delivery for uncomplicated monoamniotic twins should be considered around 33 weeks of gestation, but not later than 35 weeks.

Social and financial barriers may contribute to a "hidden mortality" in Uganda for children with congenital anomalies.

BACKGROUND: The true incidence of congenital anomalies in sub-Saharan Africa is unknown. Owing to complex challenges associated with congenital anomalies, many affected babies may never present to a health facility, resulting in an underestimation of disease burden. METHODS: Interviews were conducted with Ugandans between September 2018 and May 2019. Responses from community members versus families of children with congenital anomalies were compared. RESULTS: A total of 198 Ugandans were interviewed (91 family members, 80 community members). All participants (N = 198) believed that seeking surgical care would lead to poverty, 43% (n = 84) assumed fathers would abandon the child, and 26% (n = 45) thought a child with a congenital anomaly in their community had been left to die. Causes of anomalies were believed to be contraceptive methods (48%, n = 95), witchcraft (17%, n = 34), or drugs (10%, n = 19). Of family members, 25 (28%) were advised to allow the child to die. Families with affected children were more likely to have a lower income (P < .001), believe anomalies could be treated (P = .007), but thought that allowing the child to die was best for the family (32% vs 9%; P < .0001). Monthly household income <50,000 Uganda shillings ($13 United States dollars) was a significant predictor of the father leaving the family (P = .024), being advised to not pursue medical care (P = .046), and believing that God should decide the child's fate (P = .047). CONCLUSION: Families face significant financial and social pressures when deciding to seek surgical care for a child with a congenital anomaly. Many children with anomalies may die and never reach a health facility to be counted, thus contributing to a hidden mortality.

Lethal Cenani Lenz syndrome in two consecutive pregnancies: Further extension of phenotype from Maldives.

Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development. Mutations in the APC gene have also been occasionally associated with CLS. The phenotypic spectrum ranges from mild to very severe perinatal lethal type depending on the type of variant. We report a pathogenic variant, c.2710 del T (p.Trp904GlyfsTer5) in theLRP4 gene, in a fetus with lethal Cenani Lenz syndrome with antenatal presentation of tetraphocomelia and symmetrical involvement of hands and feet.

Diagnostic and perinatal outcomes in consanguineous couples with a structural fetal anomaly: A cohort study.

INTRODUCTION: Consanguineous unions occur when a couple are related outside marriage and is associated with adverse genetic and perinatal outcomes for affected offspring. The objectives of this study were to evaluate: (i) background characteristics, (ii) uptake of prenatal and postnatal investigation and (iii) diagnostic outcomes of UK consanguineous couples presenting with a fetal structural anomaly. MATERIAL AND METHODS: This was a retrospective and partly prospective cohort study comparing consanguineous (n = 62) and non-consanguineous (n = 218) pregnancies with current or previous fetal structural anomalies reviewed in a UK prenatal genetic clinic from 2008 to 2019. Outcomes were compared using odds ratios (OR). RESULTS: Most consanguineous couples were of Pakistani ethnicity (odds ratio [OR] 29, 95% confidence interval [95% CI] 13-62) and required use of an interpreter [OR 9, 95% CI 4-20). In the consanguineous group, the uptake of prenatal invasive testing was lower (OR 0.4, 95% CI 0.2-0.7) and the number declining follow up was greater (OR 10, 95% CI 3-34) than in the non-consanguineous group. This likely explained the lower proportion of consanguineous couples where a final definitive unifying diagnosis to explain the fetal structural anomalies was reached (OR 0.3, 95% CI 0.2-0.6). When a diagnosis was obtained in this group, it was always postnatal and most often using genomic sequencing technologies (OR 6, 95% CI 1-27). The risk of perinatal death was greater (OR 3, 95% CI 1-6) in the consanguineous group, as was the risk of fetal structural anomaly recurrence in a subsequent pregnancy (OR 4, 95% CI 1-13). There was no difference in the uptake of perinatal autopsy or termination of pregnancy between groups. CONCLUSIONS: Consanguineous couples are a vulnerable group in the prenatal setting. Although adverse perinatal outcomes in this group are more common secondary to congenital anomalies, despite the evolution of genomic sequencing technologies, due to a lower uptake of prenatal testing it is less likely that a unifying diagnosis is obtained and recurrence can occur. There is a need for proactive genetic counseling and education from the multidisciplinary team, addressing language barriers as well as religious and cultural beliefs in an attempt to optimize reproductive options.

Prevalence of fetal and neonatal mortality due to congenital anomalies in the state of Maranhão, Brazil, from 2001-2016

Introduction: The infant mortality rate (IMR) is an important health indicator directly associated with living conditions, prenatal care coverage, social development conditions, and parental education, among others. Worldwide, the infant mortality rate was 29/1000 live births in 2017. Therefore, this study aimed to evaluate the fetal and infant mortality rates due to congenital anomalies (CA) in Maranhão from 2001 to 2016. Methods: Data were obtained from the SINASC, and SIM databases. We used simple linear regression, Poisson distribution, and ANOVA (Bonferroni's post hoc test). We analyzed the public data (2001­2016) of 1934858 births and determined the fetal, neonatal, perinatal, and post-neonatal mortality rates associated with CA by mesoregions. Results: The IMR in Maranhão was 17.01/1000 live births (95%CI, 13.30-20.72) and CA was the cause of death in 13.3% of these deaths. Mortality due to CA (per 1000 live births) was 0.76 (95%CI, 0.74­0.85) for fetal mortality rate and 2.27 (95%CI, 1.45-3.10) for infant mortality rate. Geographic and temporal variations were observed with a slight increase in recent years for deaths attributable to CA, and in the northern part of Maranhão. Conclusions: Mortality rates due to CA in Maranhão increased over the period 2001­2016 possibly as a result of improved maternal-infant health conditions eliminating other causes of death. Therefore, efforts to improve early diagnosis and better treatment of congenital anomalies should be considered to reduce its impact on child mortality. (AU)

Postmortem Computed Tomography Angiography of Newborns.

We propose an original method of postmortem computed tomography angiography of the body of a deceased newborn. The work is based on the analysis of the results of comprehensive postmortem computed tomography and pathological examination of 30 newborns, who died from congenital malformations. The key to a full-fledged postmortem radiation study using intravascular contrasting of deceased newborns and infants is the presence of vascular catheters established during life, as well as conducting it no earlier than 12 h and no later than 48 h after death. As a contrast agent, we recommend to use an iodine-containing water-soluble radiopaque drug containing at least 250 mg of iodine per 1 ml. The volume of contrast agent is calculated based on body weight, taking into account the general edema syndrome. The introduction of a contrast agent is carried out through vascular catheters in 3 stages in various positions of the body. The analysis of tomograms and 3D-reconstruction of blood vessels using their pseudocoloring allows accurate assessment of the topography of blood vessels with the possibility of separate study of the arterial and venous vessels, and to identify both congenital abnormalities of the heart and blood vessels, and their acquired pathology. CT angiography in some cases is superior to traditional autopsy in the diagnosis of blood vessel pathology. Postmortem CT angiography should be considered as an important stage of postmortem radiology in the structure of comprehensive pathological analysis of newborns and infants.

Mortalidad infantil en la Cuenca Matanza Riachuelo. Comparación con la Ciudad de Buenos Aires, la provincia de Buenos Aires y la Argentina (de 2010 a 2017)Infant mortality in the Matanza-Riachuelo / River Basin. Comparison with the Autonomous City of Buenos Aires, the province of Buenos Aires, and Argentina (2010-2017)

Introducción. La tasa de mortalidad infantil (TMI) es un indicador de salud y de condiciones socioeconómicas, ambientales y sanitarias. Basurales a cielo abierto y desechos cloacales e industriales hacen de la Cuenca Matanza Riachuelo (CMR) la más contaminada de Argentina.Objetivo. Analizar la mortalidad infantil (MI) en la CMR en comparación con Argentina, provincia de Buenos Aires (PBA) y Ciudad Autónoma de Buenos Aires (CABA), y la evolución entre los años 2010 y 2017.Población y métodos. Estudio descriptivo a partir de datos del Ministerio de Salud de la Nación.Resultados. En 2017, la TMI en la CMR fue del 9,4 ‰; en Argentina, del 9,3 ‰; en PBA, del 9,4 ‰, y, en CABA, del 6,9 ‰. Entre 2010 y 2017, se observó una disminución de la TMI en la CMR del 20,6 %, similar a PBA y Argentina. En CABA, no hubo descenso.En las 4 jurisdicciones, las afecciones perinatales representaron la primera causa de muerte, seguidas por las malformaciones congénitas y las enfermedades respiratorias. Solo para enfermedad respiratoria, en la CMR, el riesgo fue 4 veces mayor que en CABA (riesgo relativo: 3,9; intervalo de confianza del 95 %: 1,4-10,7).Conclusión. La estructura de causas, la evolución y el riesgo de MI en la CMR, Argentina y PBA fueron similares entre 2010 y 2017. CABA presentó una TMI menor que CMR, pero no mostró descensos. El riesgo de MI en la CMR fue mayor que en CABA a expensas del mayor riesgo por enfermedad respiratori

Introduction. Infant mortality rate (IMR) is an indicator of health and socioeconomic, environmental, and health care conditions. Open dumps and sewage and industrial waste make the Matanza-Riachuelo River Basin the most polluted in Argentina.Objective. To analyze infant mortality (IM) in the Matanza-Riachuelo River Basin compared to Argentina, the province of Buenos Aires (PBA), and the Autonomous City of Buenos Aires (CABA), and its evolution between 2010 and 2017.Population and methods. Descriptive study based on data from Argentina's Ministry of Health.Results. In 2017, the IMR was 9.4 ‰ in the Matanza-Riachuelo River Basin; 9.3 ‰ in Argentina; 9.4 ‰ in PBA; and 6.9 ‰ in CABA. Between 2010 and 2017, the IMR in the Matanza-Riachuelo River Basin decreased by 20.6 %, similar to PBA and Argentina. No reduction was observed in CABA.In the 4 jurisdictions, perinatal conditions were the leading cause of death, followed by congenital malformations and respiratory diseases. For respiratory diseases only, the risk in the Matanza-Riachuelo River Basin was 4 times higher than in CABA (relative risk: 3.9; 95 % confidence interval: 1.4-10.7).Conclusion. The structure of causes, evolution, and risk of IM in the Matanza-Riachuelo River Basin, Argentina, and PBA was similar between 2010 and 2017. IMR was lower in CABA than in the Matanza-Riachuelo River Basin, but no reduction was observed in the former. The risk of IM was higher in the Matanza-Riachuelo River Basin than in CABA, at the expense of the increased risk of respiratory disease

Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies.

BACKGROUND: Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival. METHODS AND FINDINGS: Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24-1.46), OR = 1.50 (95% CI 1.38-1.62), OR = 1.62 (95% CI 1.28-2.05), OR = 1.57 (95% CI 1.37-1.81), OR = 1.24 (95% CI 1.02-1.5), and OR = 1.99 (95% CI 1.67-2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95-1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88-1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals. CONCLUSIONS: This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675).