Cancer and congenital abnormalities in Asian children: a population-based study from the West Midlands

Cancer and associated congenital abnormalities were investigated in Muslim and non-Muslim Asian children from the West Midlands. Cancer incidence rates were calculated for Indian (non-Muslim), Pakistani/Bangladeshi (Muslim) and white children diagnosed from 1978 to 1992. Incidence was significantly higher in the Pakistanis, with an age-standardised rate (ASR) of 163 cases per million per year, compared with 115 for Indian and 125 for white children. Among Asian cancer patients, congenital malformations were significantly more common in Muslim (21%) compared with non-Muslim (7%). In Muslims the malformation excess was caused by autosomal recessive and dominant disorders (in 8% and 5% of cases respectively). Cancer malformation/predisposition syndromes were found in 10% of Muslims, compared with 2% of non-Muslims. In 33% of the Muslims with malformations, childhood cancer and a malformation were also present in a close relative. None of the non-Muslims with malformations had a relative with childhood cancer. The cancer excess in Muslims may be partly related to inherited genes causing both malformations and cancer. The prevalence of autosomal recessive disorders may be related to consanguinity, which is common in the Pakistani Muslim population. The high incidence of autosomal dominant disorders may be related to older paternal age at conception, giving rise to spontaneous mutations.     

Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects?

Down syndrome is commonly associated with significant congenital heart disease with the potential for early development of pulmonary hypertension. As such, children with Down syndrome may be at increased risk for both perioperative and long-term mortality. The purpose of this study, using data collected from a population-based outcomes study, is to analyze the potential role that Down syndrome plays in the outcome of surgically "corrected" congenital heart disease. Data were collected from a registry of all Oregon residents who, in the period 1958 to the present, had a reparative operation for one of 14 congenital cardiac malformations when younger than 18 years (N = 3965 patients). Down syndrome was present in 289 (7%) of the total registry patients. In evaluating the cardiac mortality associated with Down syndrome for each of the repaired cardiac malformations, only complete atrioventricular septal defect was associated with significantly higher perioperative (13% vs 5%) as well as higher overall late cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The survival outcomes for each of the other cardiac malformations were similar for children with and without Down syndrome.     

Associations between congenital malformations and childhood cancer. A register-based case-control study

This report describes a population-based case-control study that aimed to assess and quantify the risk of children with congenital malformations developing cancer. Three sources of data were used: the Victorian Cancer Register, the Victorian Perinatal Data Register (VPDR) and the Victorian Congenital Malformations/Birth Defects Register. Cases included all Victorian children born between 1984 and 1993 who developed cancer. Four controls per case, matched on birth date, were randomly selected from the VPDR. Record linkage between registers provided malformation data. A matched case-control analysis was undertaken. Of the 632 cancer cases, 570 (90.2%) were linked to the VPDR. The congenital malformation prevalence in children with cancer was 9.6% compared with 2.5% in the controls [odds ratio (OR) 4.5, 95% CI 3.1-6.7]. A strong association was found with chromosomal defects (OR=16.7, 95% CI 6.1-45.3), in particular Down's syndrome (OR=27.1, 95% CI 6.0-122). Most other birth defect groups were also associated with increased cancer risk. The increased risk of leukaemia in children with Down's syndrome was confirmed, and children with central nervous system (CNS) defects were found to be at increased risk of CNS tumours. The report confirms that children with congenital malformations have increased risks of various malignancies. These findings may provide clues to the underlying aetiology of childhood cancer, as congenital malformations are felt to be a marker of exposures or processes which may increase cancer risk. The usefulness of record linkage between accurate population-based registers in the epidemiological study of disease has also been reinforced.     

Transforming growth factor-beta isoforms expressions in pulmonary adenocarcinomas as prognostic markers: an immunohistological study of one hundred and twenty patients

Congenital eye malformations were studied in a small geographical area in 212,479 consecutive births. For each of the 145 new cases studied during the period 1979 to 1994, more than 50 factors were compared in probands and in controls. The prevalence rate of congenital eye malformations was 6.8 per 10,000 for microphthalmia 1.7, anophthalmia 0.23, cataract 2.7 and coloboma 1.4 respectively. Sex ratio was 0.82. Prenatal diagnosis was performed in 18 cases and 7 cases were induced abortions. The more common types of associated malformations in the 81 affected cases (53.8%) with at least one anomaly other than an eye malformation were clubfeet, microcephaly, hydrocephaly, cleft lip/palate and facial dysmorphia. At birth infants with eye malformations and other malformations were smaller, weighted less and their head circumference was lower than in controls. Placental weight was also lower than in controls. Pregnancies with eye malformations were more often complicated by threatened abortion, oligoamnios and polyhydramnios. Mothers of children with congenital eye malformations took more often drugs during pregnancy than mothers of controls. Fathers of children with congenital eye malformations were more often exposed to occupational hazards than fathers of controls. There was a significant association between eye malformations and consanguinity of parents. The recurrence risk for first degree relatives of probands was 8.9%. First degree relatives of probands had more than three times the prevalence of non-eye malformations than controls. These results are of relevance to genetic counseling.     

Children conceived by in vitro fertilisation after fresh embryo transfer

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.     

Risk factors in congenital anal atresias

Congenital anal atresias were studied in a small geographical area in 225,752 consecutive births. For each of the 108 new cases studied during the period 1979 to 1995, more than 50 factors were compared in probands and in controls. The prevalence rate of congenital anal atresias was 4.8 per 10,000 births. Sex ratio was 0.96. Prenatal diagnosis was performed in 14 cases and 11 cases were induced abortions. The more common types of associated malformations in the 45 non syndromic affected cases with at least one major anomaly other than anal atresia were renal agenesia, genital anomalies and ventricular septal defect. At births infants with anal atresia and other malformations were smaller, weighted less and their head circumference was lower than in controls. Placental weight was also lower than in controls. Pregnancies with anal atresia were more often complicated by threatened abortion, oligoamnios and polyhydramnios. Mothers of children with congenital anal atresia took more often drugs during pregnancy than mothers of controls. Fathers of children with anal atresia were more often exposed to occupational hazards than fathers of controls. There was a significant association between anal atresia and consanguinity of parents (p < 0.05). The recurrence risk for first degree relatives of probands was 3.7%. First degree relatives of probands had more than twice the prevalence of non-anal atresia malformations than controls.     

A modulatory effect of extracellular Ca2+ on type 1alpha metabotropic glutamate receptor-mediated signalling

DiGeorge syndrome or anomaly consists of a developmental field defect which is characterized by congenital absence or hypoplasia of the thymus and parathyroids, as well as facial dysmorphism and congenital heart defects. Other congenital malformations may coexist, in particular, thyroid abnormalities. A case of congenital hypothyroidism and DiGeorge syndrome is reviewed. Necropsy, clinical, and experimental studies also show that thyroid abnormalities may be a feature of DiGeorge syndrome. Although this could be purely coincidental, our case suggests that thyroid gland dysgenesis may be more common than previously thought. Thus, children with the DiGeorge syndrome may be at higher risk for hypothyroidism. Because of this potential association, patients who are considered to have this anomaly should have early newborn thyroid screening.     

Congenital heart disease in patients with Turner's syndrome. Italian Study Group for Turner Syndrome (ISGTS)

OBJECTIVE: There is a high prevalence of congenital heart defects in patients with Turner's syndrome. Few studies have reported echocardiographic data in unselected patients according to the different chromosomal patterns. The aim of our study was to evaluate a large series of patients with Turner's syndrome, comparing these data with those of the general population. METHODS: Five hundred ninety-four patients with Turner's syndrome, aged 1 month to 24 years, in the Italian Study Group for Turner Syndrome underwent full cardiologic evaluation. Karyotype distribution was: 45,X (54%), X-mosaicism (13%), and X-structural abnormalities (33%). RESULTS: The prevalence of cardiac malformations was 23%. Bicuspid aortic valve (12.5%), aortic coarctation (6.9%), and aortic valve disease (3.2%) were the most prevalent malformations. In comparison with the general population, partial anomalous pulmonary venous drainage had the highest relative risk. A correlation was found between type of congenital heart defect and karyotype. The patients with 45,X karyotype had the greatest prevalence of partial anomalous pulmonary venous drainage and aortic coarctation, whereas bicuspid aortic valve and aortic valve disease were more common in the patients with X-structural abnormalities. The patients with severe dysmorphic signs showed a significantly higher relative risk of cardiac malformations. CONCLUSION: X-linked factors may be involved in determining cardiac defects in Turner's syndrome.     

A methodology for sampling and accessing homeless individuals in Melbourne, 1995-96

BACKGROUND: After resection of advanced abdominal neuroblastoma, children may have persistent postoperative diarrhea. Until recently, the magnitude of this problem had not been appreciated. METHODS: To assess the incidence, severity, and management of chronic postoperative diarrhea in these patients, we reviewed the case notes of all children with stage III or IV abdominal and pelvic neuroblastoma who underwent tumor resection in our hospital between January 1985 and September 1996. We classified the severity of diarrhea as follows: mild, less than 3 loose stools per day; moderate, 3 to 5 loose stools per day; and severe, more than 5 loose stools per day and/or urgency, incontinence, or nocturnal diarrhea. RESULTS: Seventy-seven children underwent resection during this period, and 23 (30%) had postoperative diarrhea, classified as mild in 11 patients, moderate in 7, and severe in 5. Dissection around the superior mesenteric and celiac arteries was associated with a significantly higher incidence of diarrhea. Fifteen children (65%) received treatment with loperamide, which reduced but did not abolish symptoms. Twelve children subsequently died of progressive neuroblastoma. Of the 11 surviving children (mean duration of follow-up, 8.4 years), 8 have persistent loose stools. CONCLUSIONS: Diarrhea, probably resulting from disruption of the autonomic nerve supply to the gut during clearance of tumor from the major vessels of the retroperitoneum, is common after resection of advanced abdominal neuroblastoma. Many children require long-term treatment to slow intestinal peristalsis, and a few have severe and unremitting diarrhea. More effective medical management of this complication is needed.     

Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors: enalapril, enalaprilat, and lisinopril

Three-dimensional magnetic resonance angiography (MRA) is a noninvasive technique that images the intracranial arterial vasculature without contrast agents. The suitability of MRA was evaluated for routine use and all children were prospectively studied with conventional MR imaging and time off flight MRA (FISP3D). All MR studies were performed on a 1.5 T-MRA system using a circularly polarized head coil. The study comprised 140 children, ages 3 weeks to 18 years, with different neuropediatric diseases. Major cervical and intracranial arteries were visualized in all age groups. Smaller branches of the supratentorial arteries were identified inconstantly and the number of arteries visualized increased up to the age of 6 years. Sixty-seven children (47%) had normal intracranial vasculature. MRA demonstrated anatomic variations in 21 patients (15%). Twenty-two of 32 children with congenital malformations demonstrated abnormalities of the intracranial vasculature. The diagnostic value of MRA was confirmed in 11 of 12 patients after neonatal stroke and in 3 of 10 children after stroke at older ages. Seven of 18 children with acute hemorrhage demonstrated arteriovenous malformations or an aneurysm on MRA. The correlation with digital subtraction angiographic findings was established in 13 patients. In 9 of 13 children with brain tumor, MRA proved to be diagnostically valuable. MRA proved to be of particular value in the evaluation of the carotid artery following extracorporeal membrane oxygenation therapy. MRA can be used in children of all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malignant adenomyoepithelioma of the breast with mixed osteogenic, spindle cell, and carcinomatous differentiation

Antenatal echocardiographic diagnosis of congenital heart disease in 699 women living in the department of the C?te d'Or between 1988 and 1996 revealed 39 cardiac abnormalities which were later confirmed by anatomical examination or echocardiography. During the same period, 157 cardiac malformations which could have been detected in the antenatal period were diagnosed after birth. The detection rate of congenital heart disease was 19.8% over the whole study period, and 33.3% in the last three years. The malformations which were most easily diagnosed were hypoplastic left ventricle, single ventricle, atriventricular canal and severe obstruction of the ventricular outflow tracts. Twenty-one abortions (53.8%) were undertaken because of the severity of the cardiac lesion or of a genetic abnormality. Seventeen children were live born (43.5%) but, globally, they had severe malformations and the mortality rate was 84.5% whereas in the children diagnosed post-partum, the lesions were generally less severe and the mortality was 19.7%. The detection rate of congenital heart disease depends on the screening of first intention. Thus, 90% of the lesions diagnosed in this series were referred because of a foetal heart abnormality and, in this indication, echographic expertise was by far the most accurate with 33% of confirmation. As other workers have reported, teaching programmes and regional collaboration between physicians implicated in antenatal care are essential.     

Extracranial neuroblastomas and neurological complications

Between October 1989 and March 1997, 25 pediatric inpatients were treated for primary extracranial neuroblastoma (NB; n=20) or ganglioneuroblastoma (GNB; n=5) at the University of Istanbul, Institute of Pediatric Oncology, and these children were the subjects of this retrospective study. Seventeen (68%) of these patients experienced 19 neurological complications during the course of their disease. Fourteen had nervous system metastases or invasion. Nonmetastatic complications, including CNS infections (n=3) and new onset of seizures (n=2) secondary to metabolic encephalopathy were seen in 5 cases. By the time of the final analysis of the results, 8 of the 17 patients with neurological complications had died, 7 had either been lost to follow-up (n=4) or were in the terminal stage of their disease (n=3), and 2 were in remission. Both of the patients who were in remission had dumbbell neuroblastoma (DNB), and 1 of them, with congenital DNB, also had neurological sequelae, characterized by paraplegia and neurogenic bladder. Neurological complications occurred in 68% of NB and GNB cases. Metastatic complications were more common than nonmetastatic complications and had a poor prognosis. Neurological complications were the primary cause of mortality in this study, mortality being related to neurological complications in 63% of cases, and the final outcome was worse than expected. However, regardless of any differences in social, economic and geographic factors and different treatment protocols for NB in different pediatric oncology institutions, neurological complication rates in pediatric NB are similar in all.     

Visual impairment in Swedish children. III. Diagnoses

PURPOSE: To gain an overview of the spectrum of diagnoses among Swedish visually impaired children. METHODS: An epidemiological study of all known visually impaired children was made by review of medical records. RESULTS AND CONCLUSION: In all we found 2373 children, 0-19 years of age, with an age-specific prevalence of 10.9/10,000. The two largest diagnostic groups included neuro-ophthalmological and retinal diseases. The most frequent disorders were cerebral visual impairment, non-hereditary optic atrophy, retinal dystrophy (when regarded as a general entity), congenital hypoplasia of the optic nerve and congenital cataract. Nystagmus secondary to brain disorder, albinism, congenital nystagmus, retinopathy of prematurity and high myopia were also found in a considerable number of patients. The leading diagnoses in children with WHO-defined childhood blindness were non-hereditary optic atrophy, cerebral visual impairment and retinopathy of prematurity. A large proportion of the children, especially in the groups with neuro-ophthalmological disorders and malformations of the posterior segment had additional impairments, emphasizing the importance of a multi-disciplinary approach when assessing multi-handicapped children.     

Blindness in children with neuroblastoma

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor among pediatric patients, and orbital metastatic disease is not uncommon in these children. Physical signs as a consequence of orbital metastases, such as proptosis and periorbital ecchymosis, frequently are encountered. However, subsequent blindness is rare. METHODS: A retrospective study was conducted to determine the incidence, related physical findings, treatment, and outcome of children who developed visual loss during treatment for neuroblastoma. Medical records for a 24-year period (1971-1994) were reviewed to identify these patients. The charts, diagnostic imaging studies, and autopsy material of these patients were reviewed. RESULTS: Of the 450 patients treated for neuroblastoma at the study institution during this period, 47 presented with abnormalities in physical examination of the eye. Eight of these 47 patients and 7 others developed visual loss in at least 1 eye during the first week after diagnosis (n = 5), during primary therapy (n = 6), at recurrence (n 2), or after completion of therapy (n = 2). In ten patients the visual loss was a direct consequence of the primary disease process, whereas a direct relationship between loss of vision and neuroblastoma could not be identified in the remaining five patients. Proptosis and periorbital ecchymosis were the most common associated physical findings. Although ten patients received steroids and eight received radiation, visual loss could not be prevented or reversed in these patients. CONCLUSIONS: Early initiation of effective, multiagent chemotherapy remains the primary approach for the treatment of neuroblastoma and its ophthalmologic complications. Radiation therapy and steroids may have benefit but failed to show good effect in this series. The prevention and treatment of blindness is probably most relevant in infants and children age < 2 years because they have the best chance for cure.     

Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection

The aim of this study was to describe the obstetric and perinatal outcome for births following intracytoplasmic sperm injection (ICSI). Of 210 infants born, 140 were singletons and 70 were twins. There were no triplets or higher births. The multiple birth frequency was 20%. Overall, 17% of deliveries were preterm, although for singleton pregnancies the incidence was reduced to 9%. The median birth weight of all live born infants was 3168 g and singletons 3470 g. Of all infants, 17% had a low birth weight (<2500 g) and 2% had a very low birth weight (<1500 g). Two major malformations occurred in two singleton children and four minor malformations occurred in four children. This was within the range of expected values in Sweden. Karyotyping was performed in 58 pregnancies. All of them were normal. The perinatal mortality was 0.5%. In conclusion, in this observational study from Sweden of the first infants born after ICSI in our programme, the incidence of multiple births, preterm births, low birth weight babies and congenital malformations was low compared with other series of in-vitro fertilization pregnancies not associated with ICSI.     

A second-generation study of 427 probands with congenital heart defects and their 837 children

OBJECTIVES: This study attempted to answer the question, Do mothers with congenital cardiovascular defects have more affected children than fathers with cardiac anomalies? BACKGROUND: In the 1950s to 1960s, concern was expressed about the safety of pregnancy in women with cardiac anomalies and the possibility of inheritance. METHODS: In a prospective study over 25 years, 236 women with cardiac defects were followed through pregnancy, and their 418 offspring were examined during their 1st 3 years. A high incidence of congenital cardiac malformations was noted. Then, a retrospective study of 191 men from the same clinic group and their total family (419 children) was performed to compare the incidence of affected children between the maternal study and this subsequent paternal study. RESULTS: Of 837 live children of these 427 probands, 14.1% (118) had a congenital heart defect (13.4% in the maternal study, 14.8% in the paternal study). There was no correlation with the surgical status of the proband. Concordance was somewhat greater among the children of affected mothers compared with those of affected fathers. Included in these studies were 31 high risk probands, 10 with genetic syndromes and 21 who had an affected sibling. Respectively, 53% and 41% of their children had cardiac anomalies, with a concordance > 50%; three fourths of these children had moderate to severe anomalies. CONCLUSIONS: The incidence of congenital heart defects in the children was not statistically different between the maternal and paternal studies. With removal of the high risk probands from the total study group, the risk of one affected parent having a child with a cardiac anomaly was 10.7%. Of the entire 837 children, only 7.5% had moderate or severe defects.     

Neuroimaging in children with congenital disorders of the peripheral visual system

The study investigates the neurological substrate in children with congenital disorders of the peripheral visual system (CDPVS), i.e. disorders of the anterior visual pathways and the globe. The design is retrospective; brain MRI and/or CT scans were traced and reviewed for 79 of 254 children with CDPVS on our database. The neuroradiological findings were considered in the context of degree of visual impairment (profound [PVI] and severe [SVI]), developmental outcome (setback and non-setback), and mode of imaging (MRI and CT). Scans were abnormal in 40 of 79 (51%) children; 23 of 40 (58%) had more than one lesion; and in some children lesions not previously reported were found. The number of abnormalities per child was significantly higher in the PVI than the SVI group (P<0.05); the level of significance varied according to the method of scanning (MRI, P<0.001; CT, ns). Seven children were known to have had developmental setback; significantly more brain abnormalities per child were found in the group with setbacks than in the group without (P<0.001). Eighty-six percent (24 of 28) of MRI compared with 38% (22 of 58) of CT scans were abnormal. MRI detected more lesions per child than CT (P< 0.001). Thus, a significant amount of brain pathology occurs in children with CDPVS. The number of lesions varies directly with degree of visual impairment and both correlate with developmental outcome. As brain pathology will be only one of many factors influencing developmental progress in visually impaired children, prospective multifactorial studies of the CDPVS population, which include MRI studies of the neurological substrate, will be required to clarify the latter.     

A comparative evaluation of two day hospitals. Goal attainment scaling of behavior therapy vs. milieu therapy

A retrospective anatomical, family, and epidemiological study was made of 143 patients (81 female and 62 male) with diaphragmatic hernia who were born in the south-west of England between 1943 and 1974. Thirty-nine cases were stillborn. Seventy-five per cent of patients had a left-sided diaphragmatic defect, 22% had a right-sided defect, and 3% had a bilateral defect. Fifty per cent of the patients had other congenital malformations, most frequently of the nervous system. No maternal age or birth order effect was noted. Cases of diaphragmatic hernia without other malformations had in general a normal fetal growth rate. Eight per cent of the cases were illegitimate. There were two pairs of twins discordant for diaphragmatic hernia, one pair being dizygotic and the other monozygotic. In no case of diaphragmatic hernia was there a relative affected with a diaphragmatic hernia. The most common type of diaphragmatic defect was a posterolateral hernia (92%), followed in frequency by an eventration of the diaphragm (5%), the least common defect being a retrocostosternal hernia (2%). Diaphragmatic hernia appears to be aetiologically as well as anatomically heterogeneous. In this series there were two cases of trisomy 18, one case of trisomy 21, one case trisomic for a small part of chromosome 20, and two cases with the Pierre Robin syndrome. It seems likely that diaphragmatic hernia is a non-specific consequence of several teratological processes.