System Congenital Malformations Research Articles

Epidemiological trends of isolated and non-isolated central nervous system congenital malformations in live births in a middle-income setting

ObjectivesThis study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015.MethodsPopulation-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004–2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00–Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00–Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained.Results7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC −1.66; 95%CI −3.09 to −0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth.ConclusionsDuring a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

Anencephaly, Bifid Tongue, and Cleft Palate in a Pomeranian Dog: GFAP and NeuN Immunoreactivities.

Anencephaly is a congenital disease manifesting with the absence of the brain due to the failure of the cranial part of the neural tube to close during the embryonic stage. The disease may be accompanied by other anomalies and usually results in premature death. A stillborn puppy of a 2-year-old female Pomeranian dog is examined in this case. The lack of brain tissue and accompanying abnormal skull formation was noted macroscopically. The eyes were protruding out of their normal position (exophthalmos), and a bifid tongue together with a secondary cleft palate was present. On serial sections stained with Haematoxylin-Eosin, only the medulla spinalis among the central nervous system structures could be inspected microscopically. Immunohistochemistry staining revealed GFAP immunoreactivity in the astrocytic glial cells. NeuN immunoreactivity was detected in the neurons in the medulla spinalis and spinal ganglions. Incomplete retinal layers were observed on the eye sections stained with Haematoxylin-Eosin and NeuN. The case was concluded to be coherent with skull and nervous system congenital malformations rarely observed in dogs. To the best of our knowledge, this represents the first description of a dog with anencephaly, bifid tongue and cleft palate.

Next Generation Sequencing after Invasive Prenatal Testing in Fetuses with Congenital Malformations: Prenatal or Neonatal Investigation.

Congenital malformations diagnosed by ultrasound screening complicate 3–5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the ‘Prenatal assessment of genomes and exomes’ (PAGE) study and ‘Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study’ performed at Columbia University in the US. These were large and prospective studies but relatively ‘unselected’ congenital malformations, with little Clinical Genetics input to the pre-test selection process. This review focuses on the incremental yield of next generation sequencing in single system congenital malformations, using evidence from the PAGE, Columbia and subsequent cohorts, with particularly high yields in those fetuses with cardiac and neurological anomalies, large nuchal translucency and non-immune fetal hydrops (of unknown aetiology). The total additional yield gained by exome sequencing in congenital heart disease was 12.7%, for neurological malformations 13.8%, 13.1% in increased nuchal translucency and 29% in non-immune fetal hydrops. This demonstrates significant incremental yield with exome sequencing in single-system anomalies and supports next generation sequencing as a secondary genetic test in routine clinical care of fetuses with congenital abnormalities.

Comparative Study between the Role of Two dimensional and Three dimensional Ultrasound in Assessment of Fetal Central Nervous System Congenital Anomalies

ABSTRACT Objective: This study aimed to evaluate the role of three dimensional (3D) ultrasound compared with two dimensional (2D) ultrasound in diagnosis of fetal central nervous system congenital malformations. Patients and Methods: this Prospective study was performed on total 100 patients with gestational age from 18 weeks to 24 weeks who underwent 2D ultrasound then examined by 3D ultrasound at Obstetrics and Gynecology Department, Bab el-Sheria, Al-azhar University Hospital. Results: Statistical analysis revealed that the most common neurological malformations detected were Holoprosencephaly and Anencephaly which had significant high agreement between 2D and 3D regarding their diagnosis. There was significant agreement between 2D and 3D regarding the congenital fetal spinal and cranial malformations. The 2D and 3D ultrasound provided equal diagnostic information in microcephaly while 3D US provided more diagnostic information than 2D US for Choroid plexus cyst, agenesis of the corpus callosum and spina bifida. Our study revealed that the 3D US was superior to 2D US in identifying small cranial malformations as choroid plexus cyst and the spine e.g Spina bifida. Conclusion: In comparison with 2D US, 3D US improves the diagnostic capability by illustrating more diagnostic details in evaluation of malformations of the fetus, especially in visualization of fetal malformations of the small cranial anomalies and spina bifida . In addition to 2D US, 3D US is a valuable adjunct in prenatal detection of anomalies.

OC14.02: Association between maternal systemic lupus erythematous and congenital malformations of the circulatory system

OC14.02: Association between maternal systemic lupus erythematous and congenital malformations of the circulatory system

POLLUTION OF THE ENVIRONMENT WITH PERSISTENT TOXIC SUBSTANCES AND PREVENTION OF THEIR HARMFUL IMPACT ON THE HEALTH OF THE INDIGENOUS POPULATION RESIDING IN THE ARCTIC ZONE OF THE RUSSIAN FEDERATION

The article presents results of cohort epidemiological studies conducted in the period from 2001 to 2010 among the indigenous population residing in Chukotka (ChAO) and Nenets (NAO) autonomous districts. The aim was to document temporal changes in blood concentrations of persistent contaminants that caused the serious health concern from the first Arctic Monitoring and Assessment Program (AMAP) survey in 2001 “Persistent toxic substances, food security and indigenous peoples of the Russian North”. In monitored indigenous cohorts there have been measured blood concentrations of persistent contaminants including polychlorinated biphenyls (28/31; 52; 99; 101; 105; 118; 128; 138; 153; 156; 170; 180; 183 and 187); hexachlorocyclohexane (α, β, γ - isomers of HCH); oxychlordane (trans chlordane, cis-chlordane); DDT (2,4 DDE; 4,4 DDE; 2,4 DDD; 4,4 DDD; 2,4 DDT; 4,4 DDT); hexachlorobenzene (HCB); heptachlor; dieldrin; mirex; toxaphene (Par 26, the Par 50, the Par 62); PBDEs (28; 47; 100; 99; 153; 154; 183); metals (Cd, Pb, Hg). During 2003-2004 there was implemented a set of measures for the disposal and detoxification of local sources of persistent pollutants and reduction of the risk of associated health effects that had been recommended by the international AMAP expert panel. As a result of 2010 study a significant reduction in the average serum concentrations of DDT and DDE 4.4, as well as blood concentrations of lead was found to occur, they were observed only in men living in NAO. Changes in concentrations of a number of other persistent toxic substances (PTS) although show a tendency to decrease, but these changes failed to reach the level of statistical significance. The mean annual incidence rates of diseases associated with harmful impact of PTS, in particular, cancer, endocrine system diseases, congenital malformations, and immunodeficiency, unlike most of the other classes of diseases in the population showed a clear trend towards to the increase in the period of observation. Conclusion. The results obtained did not allow to confirm the sufficient effectiveness of implemented measures for the rehabilitation of residential areas both in Chukotka and NAO. The period of re-measuring blood concentrations of PTS was assumed not be appropriate due to longer half-life of many PTS studied. The health importance of long-range transboundary transport of PTS is likely to be also underestimated especially due to the observed high contamination of migrating of commercial species of wild birds, fish and marine animals that make up a significant part of the traditional diet of indigenous peoples of the North. There is need for the improvement of national biomonitoring as well as information systems for appropriate assessment, prediction and management of health risks associated with long-range biotransportation of PTS into the arctic food chains.

Nephroprotective therapy with angiotensin converting enzyme inhibitors effect evaluation on the course of chronic kidney disease in children with urinary system congenital malformations

The aim : to evaluate the effect of angiotensin-converting enzyme inhibitor (ACEI) therapy on the course of chronic kidney disease (CKD) in children with urinary system congenital malformations. Patients and methods . 119 patients with urinary system congenital malformations aged 3 to 18 years were examined. A control group of 10 clinically healthy children. There were 3 groups: I - 55 children with congenital vesicoureteral reflex, II - 34 children with congenital hydronephrosis, III - 30 children with other forms of urinary systems dysembryogenesis. ACEI therapy Enap (KRKA, Slovenia), held for 6 months (children up to 14 years at a dose of 0.2 mg/kg/24 h in 1 reception, adolescents 5-10 mg/24 h in 1 reception). Results . were evaluated according to clinical data, according to the daily monitoring of blood pressure (BP), renal function, renin concentration, plasma aldosterone. Renin and aldosterone production was determined in blood plasma (lying down) by enzyme immunoassay. Results . During ACEI treatment in all children there was stabilization of BP, renal function improvement. Patients with hypertension showed a significant decrease in the concentration of renin. ACEI therapy leads to normalization of aldosterone concentration in patients with hypertension and without hypertension. Conclusion. The analysis of the course of CKD in patients with US CM on the background of ACEI therapy demonstrates the main aspects of the anti-fibrotic action of the pharmacological blockade of the renin-aldosterone ACEI system.

Invited Commentary: Male Reproductive System Congenital Malformations and the Risk of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a prevalent developmental disorder. Studies indicate that while ASD etiology has a genetic component, the risk is polygenic, with gene-environment interactions being likely. The prenatal period is a critical exposure window for nongenetic risk factors. Previous studies have found positive associations between congenital malformations (all types) and ASD; a few also found specific associations between genitourinary system malformations and ASD; and one study found an association between hypospadias and ASD. In the accompanying article, Rotem et al. (Am J Epidemiol. 2018;187(4):656-663) describe how they conducted a comprehensive analysis focusing on the shared risk of ASD with hypospadias or cryptorchidism, using existing data from a large Israeli health services system, which afforded several advantages because of the large sample size and low attrition of the patient population. The authors conducted a careful analysis, including sensitivity analyses, to account for risk factor and case misclassifications that might have occurred had they relied solely on preexisting diagnostic codes to define exposures and outcome. They observed positive associations between both hypospadias and cryptorchidism and ASD that were independent of numerous sociodemographic and pregnancy health factors. This study advances our understanding of ASD etiology and illustrates how existing data might be used to assess some ASD risk factors.

Long-term outcome in children with prenatally diagnosed central nervous system congenital malformations

Long-term outcome in children with prenatally diagnosed central nervous system congenital malformations

A Study on Incidence of Various Systemic Congenital Malformations at Birth in a Tertiary Care Hospital of North Western Rajasthan

ABSTRACT Aims To study the overall incidence, proportion, and type of congenital malformations in newborns and immediate outcome of anomalous neonates. Materials and methods The present study was an observational study. It was carried out between January 2012 to July 2013 among patients admitted to the Department of Gynecology and Obstetrics, PBM Hospital, Bikaner. Results We found that the maximum number of mothers was in the age group of 21 to 25 years (44.9%). Central nervous system (CNS) was the most common anomaly (53.3%), followed by gastrointestinal (GIT) anomaly (13.2%). All three anomalies of respiratory system were diaphragmatic hernia. There were totally 35.7% mothers who had consanguinity. Accuracy of ultrasonography was 71.4%. Out of 167 deliveries, 85 babies were live birth, 79 were still birth, and 3 abortions, in that 92 (55.1%) cases were males while 71 (42.5%) babies were females, and 4 (2.4%) ambiguous genitalia. Maximum number of babies (40.1%) had their birth weight between1.5 and 2.50 kg, while 30.6% babies had their birth weight < 1.5 kg, and 29.3% had their birth weight > 2.5 kg. Conclusion The overall incidence of congenital malformation in our study was 1.23%. The most common anomaly was of CNS (53.3%), followed by GIT (13.2%); multiple system (10.2%); musculoskeletal (9%); urogenital (4.8%); respiratory (4.8%); and central venous system (1.25%). Consanguinity (35.3%) was a common associated factor in this study. Clinical significance These patients need good counseling, balanced diet with folic acid supplementation, treatment of precipitating factors, regular follow-up in subsequent pregnancies, early screening for congenital malformations, and early termination if an anomaly is present. How to cite this article Verma SV, Sehra RN. A Study on Incidence of Various Systemic Congenital Malformations at Birth in a Tertiary Care Hospital of North Western Rajasthan. J South Asian Feder Obst Gynae 2016;8(4):309-313.

URINARY SYSTEM PATHOLOGY IN CHILDREN POPULATION OF KHARKIV REGION: MORBIDITY AND SOME RISK FACTORS

Urinary system pathology in children now is one of the most important problems of medical science.
 The aim of this study – to analyze the morbidity and reveal the risk factors for development of urinary system diseases in children of Kharkiv region.
 Materials and methods. The material of the study was the information (gender, age, weight and body length at birth, gestational age, clinical diagnosis), obtained during hospitalization of 663 patients aged from 3 months to 17 years in the nephrological center of Kharkiv regional children clinical hospital during the period from 2012 to 2013 years.
 Results. The authors found that in children population of Kharkiv region among all diseases of urinary system a significant number of cases occur in congenital malformations, dismetabolic nephropathy, urolithiasis.
 Conclusions. Regional risk factors for development of urinary system pathology in children are female and living in the village. Decreased weight and body length at birth are risk factors for development in children urinary system congenital malformations.

Importance of GLUT1 in differential diagnosis of vascular anomalies

Vascular anomalies (VAs) include a group of distinct lesions, such as vascular system congenital malformations, as well as benign and malignant vascular tumors. These lesions may present similar clinical and histopathological features, leading to mistaken diagnoses and incorrect treatment choices. It is important that professionals responsible for monitoring the development of VAs conduct precise investigations and use the appropriate terminology. The human glucose transporter protein isoform 1 (GLUT1) has been proposed as a tool to aid in differential diagnosis between different VAs, given that it is a sensitive and specific marker for identification of infantile hemangiomas (HIs) in any organ. This article presents a review of the literature on this protein as an effective tool for identification and possible differential diagnosis between several VAs.

Prevalence and Factors Associated at Presence of Central Nervous System Congenital Malformations

Introduction: Congenital malformations are currently an important cause of morbidity and mortality in many countries, though in most cases their etiology is unknown. The central nervous system (CNS) is involved in many of these defects. Original Research Article Porto et al.; BJMMR, 6(10): 956-964, 2015; Article no.BJMMR.2015.272 957 Objective: To study the factors associated with CNS congenital malformations and their prevalence in infants born at a high risk maternity hospital in Northeastern Brazil. Materials and Methods: A case-control study performed from January 2010 to December 2011, with data from The Latin American Collaborative Study of Congenital Malformations. Results: Among the 8.405 registered births, 187 were malformed newborns (2.2%). Nervous system malformations were diagnosed in 61 patients (32.6% (CI = 95% 27.5 to 38.0)), the most frequent being neural tube defects and congenital hydrocephaly. Previous history of miscarriage and/or stillbirth (p = 0.008), family history of malformations (p < 0.001) and parental consanguinity (p = 0.028) are associated with CNS malformation. Environmental factors such as maternal chronic diseases, smoking, exposure to teratogenic drugs and alcohol presented no statistically significant differences. Conclusions: The genetic component was an important contributing factor to the etiology of the malformations studied.

Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond–Blackfan anemia

Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The main features of the disease are normochromic and macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. The patients also present with growth retardation and craniofacial, upper limb, heart and urinary system congenital malformations in ~30-50 % of cases. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients. Here, we report a novel large deletion in RPL15, a gene not previously implicated to be causative in DBA. Like RPL26, RPL15 presents the distinctive feature of being required both for 60S subunit formation and for efficient cleavage of the internal transcribed spacer 1. In addition, we detected five deletions in RP genes in which mutations have been previously shown to cause DBA: one each in RPS19, RPS24, and RPS26, and two in RPS17. Pre-ribosomal RNA processing was affected in cells established from the patients bearing these deletions, suggesting a possible molecular basis for their pathological effect. These data identify RPL15 as a new gene involved in DBA and further support the presence of large deletions in RP genes in DBA patients.

Congenital non-central nervous system malformations in cerebral palsy: a distinct subset?

The aim of this article was to identify and contrast the subset of children with cerebral palsy (CP) and non-central nervous system (CNS) congenital malformations with children with CP but no coexisting non-CNS congenital malformations. A population-based regional comprehensive CP registry was used to identify children with CP who had non-CNS congenital malformations (n = 34; 19 males, 15 females; 22 classified as Gross Motor Function Classification System [GMFCS] levels I-III, 12 as GMFCS level IV or V). Their clinical features were then compared with other children with CP without non-CNS congenital malformations (n = 207; 115 males, 92 females; 138 classified as GMFCS levels I-III, 69 as GMFCS level IV or V). Children with CP and non-CNS congenital malformations did not differ from those without in terms of neurological subtype distribution or functional severity, as measured by the GMFCS. Also, there was no association with previous maternal infections (i.e. toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus 2 [TORCH]), maternal fever, use of illicit substances, asphyxia, neonatal encephalopathy, intraventricular haemorrhage, or septicaemia. The incidence of comorbidities such as convulsions, communication difficulties, gavage feeding, cortical blindness, and auditory impairment was not higher in this subgroup. The incidence of congenital non-CNS malformations among children with CP is appreciable. Children with these non-CNS malformations do not appear to differ from other children with CP regarding neurological subtype, functional severity, and comorbidities, or maternal or obstetrical factors. Thus, the specific presence of a non-CNS congenital malformation does not appear to assist the practitioner in the management or understanding of a child's CP.

The Smith-Lemli-Opitz syndrome with a G303R/R352W mutation: in an extremely irritable child responsive to cholesterol supplementation

Smith-Lemli-Opitz syndrome(SLOS) is a hereditary disorder of cholesterol biosynthesis. It is characterized by growth deficiency, mental retardation and multiple congenital anomalies, including a typical facial appearance, cleft palate, syndactyly, and a variety of central nervous system and/or major congenital malformations. There are very few reports of the Smith-Lemli-Opitz syndrome in Korean children. Here, we report on a girl with a G303R/R352W mutation. The patient was extremely irritable; assessment of the severity of the irritability included severity scoring and the amount of sleep. Cholesterol supplementation was started with egg yolks, and the irritability improved.

Central nervous system congenital malformations in a developing country: issues and challenges against their prevention

Little efforts are geared towards prevention of CNS anomalies in the developing countries. A 1-year prospective cross-sectional analysis of the cases of CNS congenital anomalies seen in a Nigerian neurosurgical unit. This included both the children's and parents' sociodemographics, the profiles of the CNS anomalies, and the maternal obstetric health behaviors toward primary and/or secondary prevention of the anomalies. Statistical analysis was done with the Pearson's chi-square (or Fishers' exact) test. Level of significance set at P < 0.05. There were 54 cases of cranial and spinal gross CNS anomalies, including 32 neural tube defects; two thirds of the parents were low-income earners, and half had only basic education. Thirty percent of the pregnancies were unbooked; the mean gestational age (GA) at booking and commencement of obstetric micronutrient supplementation was 4.6 months. No case had periconceptional folic acid supplementation. Obstetric ultrasonography was performed late in pregnancy (mean GA 6 months), made positive diagnosis of CNS anomaly in only 14%, and was performed mainly in unsupervised private clinic settings in 98%. Little or no attention is currently paid to the prevention of CNS congenital anomalies in much of the low- and middle-income countries of the world. There is a great need to regulate the practice of obstetric ultrasonography in Nigeria. There is even a much greater, more fiercely urgent need to ensure periconceptional folic acid supplementation for all women of childbearing age through appropriate food fortification in these societies.

Anomalous bilateral lateral rectus muscles and anterior polar cataract with dysmorphic features

Congenital anomalies, such as absence, hypoplasia, bifurcation, or reduplication of various extraocular muscles, including lateral rectus muscles have been reported previously. We report a 5-year-old girl who had posteriorly malinserted lateral rectus at 15 mm from the limbus in the right eye with multiple associated ocular and systemic congenital malformations.

Congenital malformations in paediatric and neurosurgical practices: problems and pattern (A preliminary report)

Aim: To determine the pattern and identify problems and outcome of management of congenital anomalies in Ilorin, Nigeria. Methodology: We retrospectively studied all children presenting over a 5-year period (1998 to 2002) with congenital anomalies to the Paediatric Surgery and Neurosurgery units of the University Teaching Hospital, Ilorin, Nigeria. Clinical data abstracted and analyzed include age, type of congenital anomaly, management, complications and outcome. Results: There were 803 children with various systemic congenital malformations. Of these, 588 (73.2%) were operated, constituting 54.4% of the total operations performed on children (1080) during the study period. Malformations of the gastrointestinal tract (536) including hernias (317), anorectal malformations (61), Hirschsprung\'s disease(45), and omphalocoeles(19), were the most frequent. Next in frequency were malformations of the central nervous system (114), the commonest being spinal dysraphism (50) and hydrocephalus (44). Less common malformations included urogenital (105) and biliary (3) anomalies as well as lesions of the neck (35), skin (8) and soft tissues(2). The overall mortality rate of 3.4% (20/586) was predominantly due to the deaths of infants with oesophageal atresia, gastroschisis, and ruptured myelomeningocoele. Conclusion: The commonest systemic congenital malformations encountered by the paediatric and neurosurgical units in this center are in order of decreasing frequency gastrointestinal, central nervous and genitourinary. Keywords : congenital malformation, pattern, management, outcome Sahel Medical Journal Vol. 8(1) 2005: 4-8

Congenital ptosis and associated congenital malformations

We report a case of unilateral congenital ptosis which is associated with ocular and systemic congenital malformations including mild microphthalmia, microcornea, cataract, iris and chorioretinal coloboma, ectopic kidney, and ventricular septal defect. An inciting factor, acting during the second month of gestation, may affect the development of the eye, heart, and abdomen and may lead to congenital malformations. Although congenital ptosis rarely presents with ocular and systemic congenital malformations, ophthalmologists should be alert for the possibility of coexisting structural defects. Congenital ptosis is a muscular dystrophy demonstrated by various degrees of muscular degeneration and it may rarely be associated with ocular and systemic congenital malformation. Here, we report a case of congenital ptosis associated with more than one ocular and systemic malformation.