Genetic epidemiology of cardiovascular malformations

Pediatric heart disease includes an array of structural and functional abnormalities ranging from cardiovascular malformations (CVMs; also known as congenital heart defects, CHDs) to cardiomyopathy, tissue dysplasia, and disorders of rhythm. This review focuses on CVMs, an extremely important group of birth defects, because of their frequent occurrence (birth prevalence slightly less that one out of a hundred), contribution to morbidity and mortality (one-third of infant deaths due to congenital anomalies), association with additional anomalies (one-fourth), and frequent presentation in malformation syndromes. As such, they represent a familiar public health concern. There has been tremendous progress in the medical and surgical treatment of CVMs. Current research pursues genetic epidemiology (the interplay of genetic and environmental factors), molecular determinants, and prevention by folic acid-containing multivitamins.     

Prevalence and Pattern of Congenital Heart Disease among Neonates in Gorgan,Northern Iran (2007-2008)

Objective

Congenital heart disease (CHD) is the most common congenital anomaly in newborns. The aim of this longitudinal, hospital-based study was to evaluate the prevalence and pattern of CHD among Iranian newborns in Gorgan, Northern Iran.

Methods

11739 live births in Dezyani hospital in Gorgan were screened for CHD, 2007 through 2008. Clinical examination, echocardiography, color Doppler and cardio catheterization were used as diagnostic tools. Clinical and demographic factors, namely sex, type of CHD and associated anomalies of diagnosed cases were recorded in a pre-designed questionnaire for analysis.

Findings

The overall prevalence rate of CHD was 8.6 per 1000 live births. This was 9.96 per 1000 male births and 7.34 per 1000 female births. It was 4.5 and 13.19 per 1000 in 2007 and 2008, respectively. ASD was the commonest lesion (2.64 per 1000), followed by VSD+ASD (1.28 per 1000) and PDA (1.28 per 1000). The rate of ASD in male and female was 3.02 and 2.26 per 1000 respectively. Parents of 40 (39.6%) babies were related. 39 (38.6%) couples were first cousins.

Conclusion

This study showed that the prevalence of CHD among live births in Gorgan is lower than reported in the studies for Middle East and European countries.     

Renal dysplasia: An autopsy study of associated congential malformations

A retrospective analysis of infant autopsies in the last 14 years was done with the aim of determining the frequency of associated malformations. Renal dysplasia comprised 36 of 594 autopsies done and was the commonest congenital urologic malformation (6.06% of all infant autopsies). Histologically all cases were characterised by hallmarks of disordered metanephric differentiation and organisation. Extrarenal malformations were seen in all (100%) of the cases of which other urologic anomalies were the commonest (28) followed by those of musculoskeletal (18), gastrointestinal (13), cardiovascular (10) and central nervous system (6). Syndromic association was seen in 5 (14%) cases. There were twenty two percent still births and 47% infants died perinatally. A thorough search for systemic malformations is mandatory in all cases of renal dysplasia as these may influence the survival significantly. Cystic renal dysplasia should be differentiated from other causes of cystic renal diseases.     

Gastrointestinal malformations in Funen county, Denmark--epidemiology, associated malformations, surgery and mortality.

AIM: To report the epidemiology, associated malformations, morbidity and mortality for the first 5 years of life for infants with gastrointestinal malformations (GIM). METHODS: Population-based study using data from a registry of congenital malformations (Eurocat) and follow-up data from hospital records. The study included livebirths, fetal deaths with a gestational age of 20 weeks and older and induced abortions after prenatal diagnosis of malformations born during the period 1980 - 1993. RESULTS: A total of 109 infants/fetuses with 118 GIM were included in the study giving a prevalence of 15.3 (12.6 - 18.5) cases per 10 000 births. Anal atresia was present in seven of the 9 cases with more than one GIM. There were 38 cases (35 %) with associated malformations and/or karyotype anomalies. Thirty-two of the 90 live-born infants died during the first 5 years of life with the majority of deaths during the first week of life. Mortality was significantly increased for infants with associated malformations or karyotype anomalies compared to infants with isolated GIM (p < 0.01). An uneventful surgical course was reported for 74 % of the 58 survivors. CONCLUSIONS: The prognosis for infants with GIM is highly dependent on the presence of associated malformations or karyotype anomalies. Surgery for GIM can be performed with low mortality. Morbidity is high for a small group of infants, but the majority of survivors have an uncomplicated surgical course.     

Gastrointestinal malformations, associated congenital abnormalities, and intrauterine growth

BACKGROUND: In contrast with other malformations, congenital anomalies of the gastrointestinal tract have been scarcely investigated. METHODS: The prevalence of gastrointestinal malformations with special reference to associated disorders and intrauterine growth was retrospectively analyzed in the newborn infants admitted to the Neonatal Intensive Care Unit of the Department of Pediatrics, University of Pécs, Hungary, in the 14-year period between 1987 and 2000. RESULTS: Of 4,241 neonates with gastrointestinal malformations, 241 (5.68%) had a total of 304 malformations (excluding Hirschsprung disease). In 133 patients, the gastrointestinal anomalies were observed as one of multiple malformations; a specific syndrome or association was diagnosed in 36 cases. Skeletal disorders were the most frequently associated anomalies. Intrauterine growth retardation was found in a large number of patients with both isolated and multiple gastrointestinal malformations (38.9% and 30.8%, respectively). CONCLUSIONS: Gastrointestinal malformations often are complicated by skeletal anomalies and intrauterine growth retardation. The association among these disorders requires further investigation. However, from a practical point of view, this association should be considered in treating affected patients.     

Window rectostomy: an alternative method of fecal diversion for high anorectal malformations in males without a urinary fistula

This report analyzes our initial experience with window rectostomy (WR) as a new method of fecal diversion for high anorectal malformations (ARM) in 27 males without a urinary fistula between May 1994 and May 1998; total correction was achieved in two stages. In the first stage, during the neonatal period, the dilated rectum was exteriorized as a WR through the left lower abdomen. In the second, after 3–5 months an abdominoperineal pull-through (APPT) procedure was performed in which the window rectostomy was mobilized and taken down to form a new anus. The results were compared with cases of high ARM with urinary fistula that were managed in three stages, i.e., proximal sigmoid colostomy, APPT, and colostomy closure. All 27 cases showed satisfactory results without any mortality or major pelvic infection. The main advantages of WR are that it provides more functioning bowel length after diversion and avoids a colostomy-closure operation and repeated hospitalizations, thus reducing the total cost of treatment. Accepted: 6 October 1999     

先天性脊柱畸形合并泌尿生殖系统畸形发病情况及相关因素分析

目的 了解先天性脊柱畸形患儿中泌尿生殖系统畸形的发生率并探讨其与多种因素之间的联系.方法 选取2003年3月至2008年11月入院治疗的425例先天性脊柱畸形患儿,术前均行腹部B超了解泌尿生殖系统畸形情况、行脊柱CT了解脊柱畸形及脊柱内神经畸形、行心电图除外心脏异常,出现阳性结果行MRI及超声心动网以确诊.结果 先天性脊柱畸形患儿中泌尿生殖系统的发生率为11.8%(50/425),其发病与胎次、母亲年龄、出生地差异、脊柱畸形的分类、侧弯部位、侧弯方向以及是否合并心血管畸形、椎管内神经系统畸形均无统计学关系.泌尿生殖系统畸形的患儿出生时父亲年龄较无泌尿生殖畸形的患儿父亲年龄大(P=0.018),合并泌尿生殖系统畸形的患儿较易合并肋骨畸形(P=0.011).结论 先天性脊柱畸形患儿合并泌尿生殖系统畸形的发生率较高,需引起临床高度重视,从而给予适当处理.     

Thalassemia in Iran: epidemiology, prevention, and management

PURPOSE: To determine the prevalence and geographic distribution of thalassemia and to evaluate the success of the thalassemia prevention and treatment programs in Iran. METHODS: Data were obtained from the National Thalassemia Registry of Iran, Iranian Blood Transfusion Organization, genetic laboratories involved in prenatal diagnosis, related pharmaceutical companies, and centers performing bone marrow transplantation for thalassemic patients. RESULTS: A total of 13,879 living patients have been registered, mostly from the northern and southern parts of Iran with the median age of 15 years. Twenty-three percent of patients were older than 20 years. The number of newly diagnosed cases has been decreased considerably after the start of the prevention program. Since the introduction of prenatal diagnosis, 2819 couples (2549 fetuses) have been tested, with only 6 false results. Elective abortion was not performed in 10 affected fetuses. Most common mutations detected were IVS II-1 and IVS I-5. In 2003, approximately 25% of the national blood products and 6 million vials of desferal were used for thalassemic patients. Overall, 340 patients have received allogeneic bone marrow transplantation, of those 46 patients deceased. Bloodborne infections have also been decreased significantly owing to the national screening of blood products for bloodborne viral infections. DISCUSSION: Owing to the national prevention program and provided special care, the age distribution of thalassemic patients in Iran is getting adapted to a full prevention and treatment program and life expectancy of these patients has been increased considerably. This shift in the age distribution of thalassemia, a traditionally considered pediatric disease, will face us with new challenges and the health care system should be prepared for this new face of thalassemia.     

The epidemiology and factors associated with nocturnal enuresis and its severity in primary school children in Taiwan

PURPOSE: To investigate the prevalence of nocturnal enuresis among children in elementary school in Taiwan and to evaluate its associated factors and severity. MATERIALS AND METHODS: A randomly selected cross-sectional study was conducted from elementary schools in Changhua county, Taiwan in 2003. In all, 9228 questionnaires were sent to 46 schools in 26 districts. RESULTS: A total of 92.1% (8496/9228) of questionnaires were completed. The overall prevalence of nocturnal enuresis was 6.8%. The ratio of male to female was about 1.5 (8.0% vs. 5.5%). The prevalence of enuresis according to age group declined from 12.5% at 6 years to 2.0% at 12 years. The prevalence of enuresis in the urban area did not show significant difference from that of rural area (6.2% vs. 6.9%). Of the factors associated with enuresis, gender, age, urinary frequency or urgency, heredity, drinking habit before sleep and difficulty in waking showed significant difference after multiple logistic regression analysis. After multivariate analysis, difficulty in waking and time of wetting were the only factors significantly associated with the severity of enuresis. CONCLUSION: Our investigation showed the prevalence of enuresis is similar to those reports from the north of Taiwan and most of other western countries, but higher than that of China and Hong-Kong. Difficulty in waking and time of wetting were the only factors significantly associated with the severity of enuresis.     

Congenital bronchopulmonary foregut malformations: concepts and controversies

This article addresses the scope, etiology, important associations and imaging features of congenital bronchopulmonary foregut malformations. Etiologic concepts, including airway obstruction and vascular anomalies, are highlighted. Technical imaging advances, especially CT and MR, have greatly enhanced our diagnostic abilities in evaluating these lesions; however, thorough and careful assessment of all aspects of the malformation is still necessary. Several specific lesions are discussed in more detail, particularly regarding controversial issues in classification, understanding, imaging and management.     

小儿胃肠功能障碍与胃肠保护

胃肠功能障碍是指胃肠道消化、吸收功能因各种原因受损,表现为胃肠道内细菌异常定植、细菌/内毒素移位、胃肠黏膜屏障损害、免疫紊乱.儿童和新生儿期胃肠功能障碍/衰竭是继发于危重疾病的严重综合征之一,经常是多器官功能障碍综合征的一部分.儿童发育期与成年期肠道在结构和功能上均有明显差别,容易遭受外来感染的打击.胃肠功能障碍的治疗关键是维护肠黏膜屏障,重建肠道的连续性,调整内稳态、循环与氧供,同时积极治疗原发病.     

Herbicides and congenital malformations: A review for the paediatrician

The herbicides 2,4,5-T and 2,4-D are relatively non-toxic to primates, in acute exposure. Dioxins, which have occurred as impurities in these two herbicides, manifest universal biological toxicity. The best understood dioxin TCDD, has, in susceptible strains of mice, a very low teratogenic minimal effective dose of 1–10 μg/kg. This fact has engendered an era of uncertainty about the potential teratogenic effects of herbicides, in the context of potential human exposure. This paper reviews current knowledge concerning herbicide teratogenesis following maternal exposure. Because of species specificity of teratogenic agents, it is not possible to extrapolate from effects in lower animals to potential effects in humans. It remains a fact however that all proven human teratogens have parallel animal models. Following maternal exposure to herbicides and to dioxins, it has not been possible to produce teratogenic effects in primates, although fertility may be affected. Epidemiological reports from Hungary, Italy (the ICMESA accident), New Zealand, the United States, Europe and Australia have not revealed any positive evidence to indicate that a human herbicide teratogenic syndrome exists.     

Lymphatic malformations: Diagnosis and management

Lymphatic malformations are benign vascular lesions that arise from embryological disturbances in the development of the lymphatic system. They encompass a wide spectrum of related abnormalities, including cystic lymphatic lesions, angiokeratoma, lymphatic malformations that occur in bones (Gorham–Stout Syndrome), lymphatic and chylous leak conditions, and lymphedema. This article will focus only on lymphatic malformation mass lesions, whereas other related disease entities will be covered elsewhere in this journal issue. Lymphatic malformations occur frequently in lymphatic-rich areas such as the head and neck region, but they can also be found on any anatomical site in the body. In general, lymphatic malformations are categorized into macrocystic, microcystic, or combined depending on the size of the cysts contained within the lesion. Lymphatic malformations can cause both deformation of the anatomical site involved and functional deficits. The goal of this article is to discuss the etiology, epidemiology, treatment modalities, and comorbidities associated with lymphatic malformations.     

Congenital malformations and perinatal morbidity associated with intestinal neuronal dysplasia

A close relation between different forms of dysganglionosis such as intestinal neuronal dysplasia (IND) type B and aganglionosis has been established. No systematic analysis of other malformations and diseases accompanying IND has been made as yet. Congenital malformations and perinatal morbidity were analyzed in 109 patients with IND seen at the Department of Pediatric Surgery in Mainz from 1977 to 1996. IND was associated with Hirschsprung's disease in 47 cases; 22 children with IND had other abdominal malformations, including anal atresia, rectal stenosis, sigmoidal stenosis, ileal atresia, pyloric stenosis, and esophageal atresia. A cystic bowel duplication, a choledochal cyst, and a persisting urachus were also found. Extra-abdominal malformations such as Down's syndrome, congenital diaphragmatic hernia, aortic stenosis, and malformations of vertebral bodies were seen. Twin siblings of children with IND were either healthy (n=3) or died in utero (n=1). Seventeen children with IND developed severe intra-abdominal complications during the perinatal period such as necrotizing enterocolitis (NEC), meconium ileus, or bowel perforations. NEC was frequently associated with preterm birth. Bowel perforations were seen in mature and preterm newborns with IND. Taken together, IND is found in a variety of obstructive bowel diseases. This may support the hypothesis that IND is a secondary phenomenon or that congenital atresias and stenoses of the digestive tract have a pathogenesis similar to that of intestinal innervation disturbances. IND may also be a part of complex malformation patterns since it occurs with a number of extraintestinal and non-obstructive intestinal malformations.     

Parenting children with anorectal malformations: implications and experiences

Parents play a crucial role in the life of a child suffering from an anorectal malformation (ARM), since their guidance contributes to the degree to which the child learns to cope with his or her disability. We investigated whether they experience stress in parenting such a child and also attempted to identify somatic or behavioral characteristics in the child that influence the stress of parenting. The parents of 109 children (69 males, 40 females; median age 5.9 years, range 1–18 years) with an ARM (58 low, 10 intermediate, 41 high) were studied. The Nijmegen Questionnaire on Child-rearing Situations (NQCS) was used to investigate the existing parenting situation. Behavioral characteristics of the children were studied by means of the Child Behaviour Checklist (CBCL) and the Teacher Report Form (TRF). In a semi-structured interview, we investigated how parents experienced the implications of the disability in everyday life with their child. Our study showed that as far as the perception of parenting stress is concerned, parents of children with an ARM do not differ from those with healthy primary-school children. Within the group of parents with ARM-afflicted children, the parents of older, incontinent children experienced relatively more stress, especially when the child concerned was male. With regard to the children's behavior, the parents and teachers under investigation did not report a higher than normal incidence of deviant behavior. However, when individual parents observed difficult behavior in their child, they found it harder to deal with than the incontinence for feces. Regarding the implications of the disorder for their everyday lives, parents were concerned and indicated a need for specific counselling. We conclude that having a child with a somatic affliction, in this case an ARM, does not automatically imply that the parents experience child-rearing problems. However, certain groups of parents are more at risk, i.e., parents with older, incontinent sons and parents with children exhibiting behavioral problems. In addition, our study shows that parents do have difficulties in coping with the implications of the disorder and express a need for support. We feel that patient care can be improved if aid is tailored to these specific problems. Accepted: 12 September 1997     

59例儿童脑动静脉畸形诊治体会

目的报道59例儿童脑动静脉畸形诊治体会。方法回顾分析长征医院1990～2000年收治59例18岁以下脑AVM患儿诊治结果，其中单纯手术治疗10例；栓塞后再手术7例；栓塞后伽玛刀治疗18例；手术后伽马刀治疗3例；单纯栓塞治疗5例；直接伽玛刀治疗13例；未治3例。结果48例（48／59）患儿临床表现为出血，47例（47／56）治疗后没有产生任何新的神经功能缺损，6例（6／56）治疗后出现轻度神经功能缺损或神经功能缺损加重，2例（2／56）患儿遗留严重的神经后遗症，死亡1例。未治3例，死亡1例。结论儿童脑AVM具有出血率高及出血凶猛的特点，应争取积极治疗，合理正确使用显微手术、放疗、血管内栓塞等治疗手段．临床效果满意。     

The role of colostomy in the management of anorectal malformations

The role of the colostomy in the definitive correction of anorectal malformations is controversial with regard no only to indications for its use, but also to location and type. We reviewed the records of 272 patients with 307 colostomies and analyzed the frequency of complications related to these controversial points. There were 250 completely divided and 57 loop colostomies, constructed in either the sigmoid or transverse colon. Twenty-five colostomies were associated with complications that included retraction, stenosis, dehiscence, prolapse, infection, bowel obstruction, sepsis, and death. Twelve additional colostomies were placed in positions that impeded the definitive correction of the malformation: 9 sigmoidostomies were too distal and 3 were located in the right-upper abdominal quadrant and did not permit pull-through without tension. Colostomy prolapse and pull-through infection were statistically less likely with a completely diverting colostomy. Thirty-five patients with rectovestibular malformations were encountered in this series. Ten were referred from other institutions after attempted repair without a colostomy and all 10 had complications of infection, dehiscence, retraction, and reopening of the fistula. In contrast, there were no complications in the remaining 25, in whom the repair was preceded by a colostomy, nor after re-repair of the other 10. These findings support the need for a colostomy prior to the repair of this malformation. We recommend a carefully constructed, high, completely diverting sigmoid colostomy prior to the initial definitive repair of anorectal malformations. A right transverse colostomy is preferable preceding redo operations.     

Perinatal mortality in Vellore Part II: lethal malformations

One hundred and thirtyone lethal congenital malformations (LM) comprised 0·6 per cent of 21,585 total births during 1979–1983; and caused 13 per cent of stillbirths, 18 per cent of early neonatal deaths (END) and 15 per cent of perinatal deaths. Seventyone per cent of 117 infants weighed below 2500 gm and 46 per cent were preterm. There were five times as many preterm in the birth weight category 1501–2500 gm as that in above 2500 gm category (p<·001). Ten per cent weighed below 1000gm/ and eleven per cent between 1001 to 1500 gm. Fiftythree CNS LM (40·4%) and, 40 MS LM (30·5%) together, comprised 70·9 per cent of all LM, CNS LM was present in 43 of 64 stillbirths and MS LM in 29 of 67 END. Twentyseven, that is, half the CNS LM were anencephalies; 22 in stillbirths. The highest proportion of LM among END was 24·4 per cent noted in 1981, and the lowest 15·85 per cent in 1979 (p<·01). Among stillbirths the proportion was lower; 11·6 per cent in 1981 and 13·7 per cent in 1982. Only one of 27 anencephalies was suspected prenatally and confirmed by ultrasound. Surgical correction of LM was not feasible in 67 neonates with forty dying within two hours of birth.