Socioeconomic inequalities in risk of congenital anomaly

AIMS—To investigate socioeconomic inequalities in the risk of congenital anomalies, focusing on risk of specific anomaly subgroups.METHODS—A total of 858 cases of congenital anomaly and 1764 non-malformed control births were collected between 1986 and 1993 from four UK congenital malformation registers, for the purposes of a European multicentre case control study on congenital anomaly risk near hazardous waste landfill sites. As a measure of socioeconomic status, cases and controls were given a value for the area level Carstairs deprivation index, by linking the postcode of residence at birth to census enumeration districts (areas of approximately 150households).RESULTS—Risk of non-chromosomal anomalies increased with increasing socioeconomic deprivation. The risk in the most deprived quintile of the deprivation index was 40% higher than in the most affluent quintile. Some malformation subgroups also showed increasing risk with increasing deprivation: all cardiac defects, malformations of the cardiac septa, malformations of the digestive system, and multiple malformations. No evidence for socioeconomic variation was found for other non-chromosomal malformation groups, including neural tube defects and oral clefts. A decreasing risk with increasing deprivation found for all chromosomal malformations and Down''s syndrome in unadjusted analyses, occurred mainly as a result of differences in the maternal age distribution between social classes.CONCLUSION—Our data, although based on limited numbers of cases and geographical coverage, suggest that more deprived populations have a higher risk of congenital anomalies of non-chromosomal origin and some specific anomalies. Larger studies are needed to confirm these findings and to explore their aetiological implications.     

Postmortem Findings and Clinicopathological Correlation in Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a severe life-threatening disease, with an incidence of 3 per 10,000 births, that can occur as an isolated defect or in combination with other congenital anomalies. We reviewed the clinical and autopsy reports of 39 subjects with CDH that were autopsied between 1988 and 2001 to determine whether autopsy had an additional value in the detection of malformations in patients with CDH. We compared the clinical data (including echographic results in some patients) concerning congenital anomalies with the autopsy results. Before autopsy, 6 structural cardiac defects, 3 anomalies of the urogenital system, and 3 anomalies of the digestive tract were observed in 10 patients (clinical and echographic results). However, with postmortem examination, only 4 structural cardiac defects were confirmed, 2 cases showed another cardiac anomaly, and 7 new cardiac defects were found. In the urogenital system, 1 anomaly was confirmed, 1 was not confirmed, and 1 showed another malformation. In addition, in 7 patients new urogenital malformations were found after autopsy. In the digestive tract, all 3 malformations were confirmed, but we found 3 new malformations after postmortem examination. All clinically established dysmorphic features and anomalies of the skeletal system and central nervous system were confirmed by autopsy, and no additional malformations were found. We concluded that postmortem examination has an important additional role in the detection of structural cardiac defects and malformations of the urogenital system and digestive tract in children with CDH.Marieke F. van Dooren and Natascha N.T. Goemaere both contributed equally to this article.     

Prevalence of hypospadias and other genital anomalies among singleton births, 1988-1997, in Scotland

BACKGROUND: Considerable debate exists on the epidemiology of genital anomalies. METHODS: All genital anomalies, excluding undescended testes, were identified from neonatal returns, stillbirth and infant death survey records, and returns relating to hospital admissions and linked to form infant profiles on a cohort of singleton births between 1988 and 1997 with follow up for a minimum of three years. FINDINGS: The mean genital anomaly prevalence rate in Scotland was calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9 per 1000 births in 1996. However, there was no evidence of a clear trend to an increasing prevalence of hypospadias, which constituted 73% of the anomalies studied. Logistic regression analysis of the data also showed this rate to be independently associated with being relatively small for gestational age (odds ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05). Infants born in deprived areas, as judged by the Carstairs deprivation score, were least likely to have a genital anomaly (OR 0.73, p < 0.01). INTERPRETATION: A new linked register of congenital genital anomalies in Scotland suggests that over a decade, the birth prevalence of genital anomalies has changed little. The associations between genital anomalies, maternal age, and socioeconomic deprivation require further study.     

Anorectal malformation with malrotation of gut.

Infants with anorectal anomaly have a high risk of having other congenital anomalies, but associated gastrointestinal tract anomalies are quite rare. Malrotation of gut is rarely associated with anorectal anomaly. We report two such cases of anorectal malformation with malrotation of gut. The high index of suspicion, diagnostic difficulty and surgical management with avoidance of appendicectomy in these neonates is discussed.     

Prevalence of congenital anomalies in five British regions, 1991-99

AIMS: To describe trends in total and live birth prevalence, regional differences in prevalence, and outcome of pregnancy of selected congenital anomalies. METHODS: Population based registry study of 839,521 births to mothers resident in five geographical areas of Britain during 1991-99. Main outcome measures were: total and live birth prevalence; pregnancy outcome; proportion of stillbirths due to congenital anomalies; and secular trends. RESULTS: The sample consisted of 10,844 congenital anomalies, giving a total prevalence of 129 per 10,000 registered births (95% CI 127 to 132). Live birth prevalence was 82.2 per 10,000 births (95% CI 80.3 to 84.2) and declined significantly with time. The proportion of all stillbirths with a congenital anomaly was 10.5% (453 stillbirths). The proportion of pregnancies resulting in a termination increased from 27% (289 cases) in 1991 to 34.7% (384 cases) in 1999, whereas the proportion of live births declined from 68.2% (730 cases) to 58.5% (648 cases). Although similar rates of congenital anomaly groups were notified to the registers, variation in rates by register was present. There was a secular decline in the total prevalence of non-chromosomal and an increase in chromosomal anomalies. CONCLUSIONS: Regional variation exists in the prevalence of specific congenital anomalies. For some anomalies this can be partially explained by ascertainment variation. For others (neural tube defects, diaphragmatic hernia, gastroschisis), higher prevalence rates in the northern regions (Glasgow and Northern) were true differences. Live birth prevalence declined over the study due to an increase in terminations of pregnancy.     

Aberrant right subclavian artery with left aortic arch: Associated cardiac anomalies

Summary Anomalous origin of the right subclavian artery (ARSA) from the aorta distal to the normally positioned left subclavian artery is a relatively frequent congenital anomaly in subjects with left aortic arch. The purpose of this study was to determine the relative frequency of associated cardiovascular anomalies in individuals with this anomaly. From the records of approximately 11,000 pathologic specimens in the Registry of Cardiovascular Disease of United Hospital (St. Paul, MN, USA), we found 128 (1.2%) with ARSA.Of the 128 ARSA, 117 (2.9%) occurred among 4102 instances of congenital heart disease.The 117 cases with congenital heart disease and ARSA were conotruncal anomalies in 38%, septal defects in 28%, obstructive anomalies of the left side of the heart in 21%, right heart anomalies in 5%, and miscellaneous conditions in the other 8%. Down syndrome existed in 14 (12%) of the 117 specimens with ARSA and some congenital cardiac anomaly; nine of the latter had an atrioventricular canal (AVC) malformation.     

Incidence of acute rheumatic fever in New Zealand children and youth

Aim: To estimate acute rheumatic fever (ARF) incidence rates for New Zealand children and youth by ethnicity, socioeconomic deprivation and region. Methods: National hospital admissions with a principal diagnosis of ARF (ICD9_AM 390‐392; ICD10‐AM I00‐I02) were obtained from routine statistics and stratified by age, ethnicity, socioeconomic deprivation index (NZDep2006) and District Health Board (DHB). Results: The mean incidence rate for ARF in 2000–2009 peaked at 9 to 12 years of age. Incidence rates for children 5 to 14 years of age for Māori were 40.2 (95% confidence interval 36.8, 43.8), Pacific 81.2 (73.4, 89.6), non‐Māori/Pacific 2.1 (1.6, 2.6) and all children 17.2 (16.1, 18.3) per 100 000. Māori and Pacific incidence rates increased by 79% and 73% in 1993–2009, while non‐Māori/Pacific rates declined by 71%. Overall rates increased by 59%. In 2000–2009, Māori and Pacific children comprised 30% of children 5–14 years of age but accounted for 95% of new cases. Almost 90% of index cases of ARF were in the highest five deciles of socioeconomic deprivation and 70% were in the most deprived quintile. A child living in the most deprived decile has about one in 150 risk of being admitted to the hospital for ARF by 15 years of age. Ten DHBs containing 76% of the population 5 to 14 years of age accounted for 94% of index cases of ARF. Conclusions: ARF with its attendant rheumatic heart disease is an increasing public health issue for disadvantaged North Island communities with high concentrations of Māori and/or Pacific families.     

Biliary dysgenesis and congenital cardiovascular malformation association

In a population-based unselected registry material involving 1038 unidentified multiple congenital abnormalities there were 20 cases with a combination of biliary dysgenesis and congenital cardiovascular malformations. One subgroup contained 7 cases where the above combination was associated with other major congenital abnormalities. Another subgroup contained 13 cases with this combination of congenital anomalies. The family study detected two sib-occurrences. One of them was a typical manifestation of Alagille syndrome. There are probably some other characteristic combinations of these two types of congenital anomaly, e.g. ventricular septal defect and extrahepatic biliary taresia. This group of congenital anomaly combination of heterogeneous origin has been named biliary dysgenesis-congenital cardiovascular malformation association.     

Associations of anorectal malformations and related syndromes

Anorectal malformations (ARMs) represent a complex group of congenital anomalies resulting from abnormal development of the hindgut, allantois and Mullerian duct resulting in complete or partial urorectal septal malformations. There is a wide variety of phenotypic expression, ranging from mild anorectal to very complex severe ARM with >75 % having other associated malformations. 50 % of cases are syndromic although many may have other associated anomalies. This suggests a genetic link but the genetics of ARM are highly complex with a number of candidate genes being identified. Many can be classified as “field defects” as a result of a complex set of genetic interactions. Patients with associated malformations can be classified into those with multiple congenital anomalies (non-syndromic), those with chromosomal abnormalities and those with non-chromosomal syndromic associations, also, those with non-chromosomal syndromes and the influence of environmental factors (e.g. drugs in pregnancy). Although much is not known about the aetiology of ARM, the weight of evidence points to genetic factors as major causes for the condition. In this review, we look at the chromosomal and genetic associations and their underlying signalling pathways, to obtain a better understanding of the pathogenetic mechanisms involved in developing ARM. The spectrum of ARM phenotypic expression probably results from involvement and crosstalk between a number of critical signalling systems involved in development of this region. As a result, it may be expressed as a “field developmental defect” with many associated abnormalities. The role of environmental factors in the development of ARM is probably less.     

Morfologia kliniczna wad spływów żył płucnych i systemowych

Abnormal pulmonary and systemic venous return is a heterogeneous group of congenital heart defects. Part of them are incidental findings, even in adulthood, and they have little haemodynamic significance. The other ones are isolated anomalies or they associate different cardiac malformations. In those cases they need to be treated in newborns or infants. Normal venous development is a process of progressive appearance of paired venous structures, development of anastomoses between them and selective regression of certain segments. Initially, three major veins drain into each horn of sinus venosus: vitelline vein, common cardinal vein and umbilical vein. Their transformations lead to formation of caval veins, coronary sinus and part of the atrial wall. A left-sided superior vena cava draining into the coronary sinus is the most common systemic venous anomaly. Nevertheless, the most common venous malformation involving the inferior vena cava is absence of its suprahepatic segment, with azygos vein continuation. The development of the pulmonary venous system is of significance, considering the co-existence of anomalies of pulmonary and systemic venous drainage. Anomalous pulmonary venous connection take various forms. In morphological point of view partial and total anomalous pulmonary venous return are known. Each of them is classified as a supracardiac, cardiac, infradiaphragmatic or infracardiac and mixed type. The knowledge of embryology and anatomy is helpful in understanding of genesis and haemodynamics of above malformations, as well as in therapy decisions.     

A genetic model for cloacal exstrophy, the extreme cloacal malformation

Cloacal exstrophy (CE) or vesicointestinal fissure is an uncommon but well known anomaly that represents the extreme cloacal malformation. It is most often seen as an isolated anomaly, or as part of the OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects). Limb anomalies are also seen with CE. Unlike the OEIS complex, limb anomalies occur as independent malformations. Here, we present two cases of CE with limb anomalies that are consistent with the phenotype seen in Disorganization (Ds), an unusual human malformation syndrome. From reviewing the mouse model, it may be that the Ds gene is a candidate for isolated CE as well.     

Ipsilateral hemangioma and aortic arch anomalies in posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and cardiac defects and eye abnormalities (PHACE) anomaly: report and review

Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and cardiac defects and eye abnormalities (PHACE) is a rare congenital anomaly with a broad spectrum of clinical manifestations with a striking female predominance. We describe an infant with PHACE anomaly and aortic coarctation who underwent cardiac catheterization to clearly define the complex anatomy of the aortic lesion before surgical repair. Review of the literature documents a highly significant association between ipsilateral hemangiomas and cerebrovascular and aortic arch anomalies. We conclude that cardiac catheterization is required to define the complex anatomy of aortic lesions and should be performed in all patients with PHACE and evident aortic involvement to plan appropriate and safe surgical repair.     

Congenital malformations in the newborn--a prospective study

In a prospective study of 4098 births the incidence of congenital malformations was 1.464 per 100 births. Major malformations were seen in 1.1% births and minor malformations in 0.4% births. Patterns of congenital anomalies included multiple anomalies (37.68%), CNS malformations (13.33%), alimentary tract anomalies (6.66%), cardiovascular malformations (8.99%), genitourinary malformation (6.66%), limb anomalies (13.33%), and anomalies of skin and appendages (13.33%). Factors like maternal age, hormone testing and drug ingestion during pregnancy, radiation exposure and maternal infections were identified as possible risk factors for congenital malformations in the newborn.     

Adrenal Fusion

Fusion of the adrenal glands is a rare congenital anomaly. The six cases described here were encountered in 3537 pediatric-perinatal autopsy cases. A fused adrenal was always associated with multiple congenital anomalies, including major central nervous system malformations in four cases, renal agenesis in three cases, anomalies of internal genitalia in three cases, and complex cardiac anomalies in two cases. The fused adrenal had either a horseshoe or butterfly shape. Neither adrenal hypoplasia nor hyperplasia appeared to be present, and the histologic appearance of the fused adrenal was normal in all cases. Received July 10, 1997; accepted December 22, 1997.     

Urethral duplication in association with anorectal malformation.

Urethral duplication is an uncommon congenital anomaly, not often reported, which may be partial or complete. Anorectal malformations are not as uncommon and they may be associated with a host of associated anomalies. However, the association of urethral duplication with anorectal malformation is rare; this report describes two such cases. In one case the intervening septum could be incised endoscopically and in the other case the duplicated urethra was excised.     

Cardiovascular anomalies with imperforate anus.

In 68 patients with anorectal malformations cardiovascular anomalies (CVA) were seen in 15 and genitourinary (GU) anomalies in 30. CVA were more frequent (33%) whenever there was a GU anomaly. Ventricular septal defect was the most frequent lesion. All but 1 CVA occurred with type III anorectal malformation. The complexity of the cardiac lesion did not parallel that of the GU anomaly.     

Polydactyly and genes

Pediatricians deal with cases with the congenital malformations and malformation syndromes interest many of them. A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations: how it is studied and what is known. Genetic and chromosomal defects are often associated with congenital malformations. Polydactyly is one of the commonly seen malformations and genetic defects of many malformation syndromes associated with polydactyly are known. The role of genetic defect in polydactyly syndromes and the correlation between genotypes and phenotypes is discussed in this review article.     

Congenital Cystic Adenomatoid Malformation Type 4 and Aneurysm of the Vein of Galen: A Rare Coincidence or Possibly Related Association

As far as the prognosis is concerned, it is important to diagnose the exact type of congenital cystic adenomatoid malformation (CCAM) in order to exclude associated anomalies, as well as the risk of development of malignancies in later life. The frequency of associated malformations of CCAM type 4 is unknown. We report a 4-month-old boy with CCAM type 4 and aneurysmal malformation of the vein of Galen (AVG). Although AVG is the most frequent arteriovenous malformation during childhood, this is the first case report, to our knowledge, of CCAM type 4 in association with an anomaly. In addition, we speculate that the relation between CCAM type 4 and AVG appears to be more likely a possibly related association rather than a rare coincidence, as both malformations develop at the same stages of embryonic life, and pathogenetically, apoptosis play a significant role in both entities. However, further studies are needed to validate this speculation placing emphasis on the association of the two anomalies, otherwise a rare coincidence cannot be excluded.     

Ischio-spinal dysostosis: a previously unrecognised combination of malformations

BACKGROUND: Ischial hypoplasia is an extremely rare malformation, both as an isolated anomaly and as a syndromic constituent. OBJECTIVE: To elucidate the clinical and radiological characteristics in five patients with the combination of ischial hypoplasia and spinal malformations. MATERIALS AND METHODS: The clinical records and radiographs of two females and three males, ranging in age from 3 months to 38 years, were evaluated. RESULTS: Ossification defects of the ischial rami were symmetrical and total in four patients, whereas the right ischial ramus was partly ossified in the other patient. All patients possessed multiple segmental defects of the spine, with rib anomalies of varying severity. One patient characteristically showed multiple rib gaps, resulting in respiratory distress. Severe anomalies of the cervical spine were evident in two patients. Four patients exhibited lumbosacral hypoplasia, which ultimately led to cauda equina syndrome in three older patients. One patient had mild facial dysmorphism and another had a diversity of anomalies, including ichthyosiform skin changes. Four patients were sporadic cases, whereas the other patient was born to consanguineous parents. CONCLUSIONS: The combination of anomalies in these patients constitutes a recognisable pattern of malformations but may represent a heterogeneous group of disorders.     

Unusual hand malformations with cardiac defects—A variant of heart-hand syndrome IV

Reported below is the association of unusual hand malformations and congenital cardiac anomalies, possibly a variant of Heart-Hand syndrome IV in a 10 year old male. In addition to these malformations, he also had genitourinary defects. The differential diagnosis of polydactyly with cardiac defects is discussed along with a review of relevant literature.