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PubMed2006

Assessment of the potential effect of incremental increases in folic acid intake on neural tube defects in Australia and New Zealand.

OBJECTIVE: To estimate the number of neural tube defects that could be prevented in Australia and New Zealand by increasing levels of folic acid intake. METHODS: Available data on prevalence of neural tube defects in Australia and New Zealand, folic acid supplement use and serum folate were used in a published model to estimate the number of neural tube defects that could be prevented in Australia and New Zealand for increments of folic acid intake from 0.1 mg daily to 1 mg daily. RESULTS: An increase of 0.2 mg folic acid per day was estimated to result in the prevention of 49 (95% CI 27-84) neural tube defects per year in Australia and 11 (95% CI 6-18) in New Zealand. A separate estimation for Indigenous Australians found that 0.2 mg of folic acid daily could prevent 7 (95% CI 4-11) neural tube defects in Indigenous infants per year. CONCLUSIONS: These data should be useful in considering primary preventive strategies for neural tube defects, including the possible introduction of mandatory fortification of food with folic acid. The estimates are imprecise because of limitations in the data used in the model. IMPLICATIONS: More representative and precise data on neural tube defects, serum folate levels and use of folic acid supplements from all Australian States and New Zealand are needed to refine the output from the model and to provide a baseline assessment of folate status against which to measure the effects of any future interventions to prevent neural tube defects.

Australia↗
PubMed2007

Prenatal diagnosis of congenital heart defects - a population based study.

AIM: The aim of this study was to describe the efficiency of routine prenatal ultrasound screening for the detection of cardiac defects in a Swedish region and to study the effect of prenatal diagnosis on the survival and outcome of the child. METHODS: We identified all fetuses and infants with a diagnosed major cardiac defect born in 1999-2003 in a region of Sweden using a register of the regional paediatric cardiac clinic, various health-care registers and registers of prenatally detected malformations. The outcome of newborns with and without a prenatal diagnosis of a cardiac defect was compared. RESULTS: During the study period, 77,241 infants were born in the area. Among 145 major cardiac defects, 21% were detected prenatally. For the two university departments the detection rate was 38%. Of the major cardiac defects diagnosed <23 gestational weeks, 30% were terminated. No significant difference in the outcome was found between children with and without a prenatal diagnosis of a major cardiac defect. CONCLUSIONS: It could not be shown that survival and outcome for children with major cardiac defects was better when the defect was known prenatally than if it was detected postnatally. The size of the study prohibits conclusions on moderate differences.

Case-Control Studies↗
PubMed2006

The occurrence of congenital heart defects in an inbred herd of pigs in Australia.

OBJECTIVE: To report on the first case of congenital heart defects in pigs in Australia. DESIGN: Retrospective analysis of case records from an inbred herd of "Westran" pigs at the University of Sydney, between January 2001 and December 2004. Detailed gross and histological examination of 15 hearts from pigs that had died or were euthanased in 2004. CASE DETAILS: The necropsy records from a population of 471 pigs that had died (106 pigs) or were euthanased for research purposes (365 pigs) were analysed and the incidence of heart defects recorded, together with basic demographic data. No attempts were made to diagnose the condition in live pigs. RESULTS: Congenital heart defects were diagnosed in 6.4% of pigs but this is likely to be an underestimate of the incidence of the deformity. Eighteen pigs died on the farm as a result of the defect, and 12 pigs were diagnosed with the defect as an incidental finding. The most common abnormality seen at necropsy was a sac-like dilatation on the right lateral surface of the right atrium. This was associated with secondary deformity and hypoplasia of the adjacent left ventricle, interventricular region and part of the right ventricle. All hearts showed atrial septal defects of varying size. CONCLUSION: This is the first reported case of congenital heart defects in pigs in Australia, and one of less than five reported cases of atrial septal defects in pigs in the world. The authors conclude that there may be an element of genetic predisposition to the malformation, since it has only been reported in this inbred line of pigs.

Animals↗
PubMed1990

An intragenic revertant of a poliovirus 2C mutant has an uncoating defect.

A revertant was isolated from a temperature-sensitive poliovirus 2C mutant, 2C-31, which is defective in viral RNA synthesis. This revertant, called 2C-31R1, grew well at 39 degrees C and was not defective in RNA synthesis. However, in contrast to its parental mutant, 2C-31R1 was cold sensitive and could hardly grow at all at 32 degrees C. Analysis of a single-cycle growth revealed that 2C-31R1 was defective in virion uncoating at 32 degrees C, and a substantial amount (more than 30%) of input viruses could be recovered as infectious particles from an infected cell lysate up to 6 h postinfection. The uncoating defect and the inability to grow at cold temperatures could be overcome by a brief incubation at the permissive temperature (39 degrees C) before the infection was continued at 32 degrees C. cDNA cloning and mix-and-match recombination experiments indicated that the defect in uncoating was the result of two secondary point mutations, seven nucleotides apart, in the 2C-coding sequence downstream of the inserted linker which is the original mutation in the parental 2C-31 genome. Another revertant, 2C-31R3, isolated from the same 2C-31 stock, was not defective in uncoating and appeared to be a secondary revertant that contained an intragenic suppressor for the uncoating defect. The uncoating defect of 2C-31R1 could be complemented by type 2 poliovirus. These results suggested that protein 2C, in addition to its role in viral RNA synthesis, has a function in determining virion structure.

Base Sequence↗
PubMed1997

Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative interpretation.

OBJECTIVE: To test the hypothesis that liveborn infants conceived by intracytoplasmic sperm injection are at an increased risk of having a major birth defect. DESIGN: Reclassification of the birth defects reported in infants born after intracytoplasmic sperm injection in Belgium and comparison with prevalence estimated in Western Australian population by means of same classification system. SETTING AND SUBJECTS: 420 liveborn infants who were conceived after intracytoplasmic sperm injection in Belgium and 100,454 liveborn infants in Western Australia delivered during the same period. MAIN OUTCOME MEASURES: Estimates of birth prevalence of birth defects and comparisons of odds ratios between cohort conceived after intracytoplasmic sperm injection and Western Australian infants. RESULTS: Infants born after intracytoplasmic sperm injection were twice as likely as Western Australian infants to have a major birth defect (odds ratio 2.03 (95% confidence interval 1.40 to 2.93); P = 0.0002) and nearly 50% more likely to have a minor defect (1.49 (0.48 to 4.66); P = 0.49). Secondary data-led analyses, to be interpreted with caution, found an excess of major cardiovascular defects (odds ratio 3.99), genitourinary defects (1.33), and gastrointestinal defects (1.84), in particular cleft palate (5.11) and diaphragmatic hernia (7.73). CONCLUSIONS: These results do not confirm the apparently reassuring results published by the Belgian researchers of intracytoplasmic sperm injection. Further research is clearly required. Meanwhile, doctors practising intracytoplasmic sperm injection should bear this alternative interpretation in mind when they counsel couples and obtain informed consent for the procedure.

Adolescent↗
PubMed2003

Is there a familial link between Down's syndrome and neural tube defects? Population and familial survey.

OBJECTIVE: To verify whether Down's syndrome and neural tube defects arise more often in the same family than expected by chance. DESIGN: Population and familial survey. SETTING: Network of maternity hospitals in the Latin American collaborative study of congenital malformations (ECLAMC) in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay, and Venezuela between 1982 and 2000. PROBANDS: 2421 cases of neural tube defects, 952 of hydrocephalus, and 3095 of Down's syndrome registered from a total of 1 583 838 live births and stillbirths. MAIN OUTCOME MEASURES: Observed number of cases of Down's syndrome among siblings of probands with a neural tube defect or hydrocephalus and number expected on the basis of maternal age; observed number of cases of neural tube defects or hydrocephalus among siblings of probands with Down's syndrome and number expected according to the prevalence in the same population. RESULTS: Five cases of Down's syndrome occurred among 5404 pregnancies previous to a case of neural tube defect or hydrocephalus, compared with 5.13 expected after adjustment by maternal age. Twelve cases of neural tube defect or hydrocephalus occurred among 8066 pregnancies previous to a case of Down's syndrome, compared with 17.18 expected on the basis of the birth prevalence for neural tube defects plus hydrocephalus in the same population. CONCLUSION: No association occurred between families at risk of neural tube defects and those at risk of Down's syndrome.

Down Syndrome↗
PubMed1980

Pulsed Doppler echocardiography for diagnosis of ventricular septal defects.

In order to assess the performance of pulsed Doppler echocardiography and to examine the factors affecting its reliability for the diagnosis of ventricular septal defects, 51 patients, in whom angiographic studies had recently been performed, were investigated before and after operation by this technique. The diagnosis was correct in all cases with left-to-right shunt, when the defect was located either in the upper muscular or in the infracristal portion of the septum, even when pulmonary hypertension or additional cardiac malformations were present. Pulsed Doppler echocardiography did not differentiate between supracristal ventricular septal defects and obstruction of the right ventricular outflow. Apical muscular defects were never observed in our cases. Defects of the inlet portion were not localised by the method. In cases with bidirectional shunt, pulsed Doppler echocardiography failed to provide any diagnostic clue. When a right-to-left shunt was present, only in one case with membranous pseudoaneurysm could pulsed Doppler echocardiography provide an exact description of the haemodynamics before and after operation. In 12 of 22 patients with tetralogy of Fallot, pulsed Doppler echocardiography showed flow tracings possibly related to the septal defect. The site of defect and the extent and direction of intracardiac shunting seem to be the main factors affecting its diagnostic performance in ventricular septal defects.

Doppler Effect↗
PubMed1980

Classification of ventricular septal defects.

A classification with clinical significance is proposed for ventricular septal defect based on the study of 220 hearts with defects of the ventricular septum. All had atrioventricular and ventriculoarterial concordance with normal relations of cardiac structure. For the purpose of classification, the ventricular septum was considered as possessing muscular and membranous portions, the muscular septum itself being divided into inlet, trabecular, and outlet (or infundibular) components. Defects were observed in the area of the membranous septum, termed perimembranous defects; within the muscular septum, termed muscular defects; or in the area of septum subjacent to the arterial valves, termed subarterial infundibular defects. Perimembranous defects were found extending either into the inlet, trabecular, or infundibular septa. Muscular defects were found in or between the inlet septum, trabecular septum, or infundibular septum. Review of the angiograms showed that the classification was easy to use in the catheterisation laboratory, and our observations suggest that the precision thus obtained has considerable surgical significance.

Heart Septal Defects, Ventricular↗
PubMed1981

Surgical management of coarctation of aorta with ventricular septal defect. Multivariate analysis.

Optimal management of coarctation with ventricular septal defect is difficult. Should one treat the coarctation, the ventricular septal defect, or both? This dilemma was investigated by reviewing 39 successive patients, aged less than 4 months, undergoing coarctation repair without pulmonary artery banding. Twelve hospital deaths occurred. Ventricular septal defect size was graded "blind" according to preoperative angiocardiographic and haemodynamic findings. Of 14 patients classified as having a large ventricular septal defect, necropsy and operative findings in eight showed defects 7 to 12 mm in diameter. Factors associated univariately with significantly increased mortality were young age, raised atrial and ventricular end-diastolic pressures, low weight, high admission blood urea, preoperative ventilation, and a large ventricular septal defect. All but the last two were also closely associated with each other. A jack-knifed discriminant function based upon ventricular septal defect size, blood urea, pulmonary venous oxygen content, and inferior caval oxygen saturation correctly predicted outcome in 78.9% of patients. Combinations of these four giving a probability greater than 0.9 of survival were rare with blood ureas above 8 mmol/litre. Raised blood urea was associated with low descending aortic pressure and subsequent dialysis. Only patients with a large ventricular septal defect stand to benefit from pulmonary artery banding at initial operation. Preoperative treatment to increase renal blood flow (prostaglandins, dopamine) may improve overall survival.

Analysis of Variance↗
PubMed1989

Sinus arrhythmia in children with atrial septal defect: an analysis of heart rate variability before and after surgical repair.

The expression of sinus arrhythmia depends on separation of the systemic and pulmonary venous return to the heart as well as on normal autonomic control mechanisms. Patients with atrial septal defect provide a naturally occurring experiment of communication between the two venous systems. In adults with atrial septal defect sinus arrhythmia is minimal or absent. But children with atrial septal defect retain appreciable sinus arrhythmia, although this is not recognised in published reports. To understand why this is so, continuous electrocardiograms were recorded before and after operation in 10 children (aged 4-16 years, mean 6.3) with atrial septal defects and in 10 normal children (aged 5-7 years, mean 6.1). Mean RR intervals were calculated for periods of one minute, and the standard deviation was used as an index of heart rate variability (that is sinus arrhythmia). Frequency analysis (spectral analysis) was also performed on a continuous beat to beat record of heart rate to describe the frequency components that may reflect autonomic activity. The results confirmed the presence of considerable sinus arrhythmia in children with unoperated atrial septal defect. None the less, the standard deviation of RR intervals in the children with unoperated atrial septal defect was significantly less than that for the normal children, and variation increased after closure of the defect. Power spectral analysis of instantaneous heart rate indicated that the high frequency (0.15-0.45 Hz) vagally mediated component of variability was lower for patients than for controls which may indicate abnormalities of autonomic control of heart rate in these children. The comparative retention of sinus arrhythmia in children with atrial septal defect may relate to the small size of the right atrium or differences in myocardial compliance compared with adults.

Adolescent↗
PubMed1992

Epidemiology of major congenital heart defects in Sweden, 1981-1986.

STUDY OBJECTIVE: The aim was to make an epidemiological study of major congenital heart defects and to make comparisons between groups of heart defects regarding different epidemiological variables. DESIGN: The cases with congenital heart defects were identified from two Swedish registries: the Registry of Congenital Malformations and the Child Cardiology Registry. A classification with nine groups of heart defects is proposed. SETTING: This was a national survey in Sweden during the period 1981-1986. The total number of cases reported during the six years was 1605. Cases that presented a patent ductus arteriosus only and a birthweight below 2500 g were excluded. MEASUREMENTS AND MAIN RESULTS: The prevalence at birth was 2.8 per 1000. When cases with a chromosomal anomaly were excluded, no maternal age effect was observed except a possible under-risk for women above 40 years. The risk for a heart defect seems to increase with increasing parity independent of age. A higher risk was also observed among twin infants compared with singletons although no specificity in cardiac malformation type appeared. Sex ratio, the tendency for having an associated extracardiac malformation, and the proportion of isolated v non-isolated cardiac defects differed between the different groups of heart malformations. CONCLUSIONS: The differences observed between groups of defects indicate different aetiologies and show that this classification may be suitable for further analyses of congenital heart defects.

Chromosome Aberrations↗
PubMedDate not supplied

In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices.

OBJECTIVE: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. METHODS: In 19 fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook) or by closing the skin over the defect. RESULTS: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. CONCLUSIONS: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

Animals↗
PubMed2006

Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation. In 19 of these, a neural tube defect was created, while 4 fetuses served as sham-operated controls. In 7 of the 19 operated fetuses the defect was left uncovered. In the remaining 12 animals the defect was covered either with a collagen biomatrix (4 animals), skin (3 animals), or small intestinal submucosa biomatrix (5 animals). The lambs were sacrificed at 1 week of age and histological examination was performed. RESULTS: All lambs with an uncovered neural tube defect showed histological damage of the spinal cord. In lambs in which the neural tube defect was covered, one half showed a normal architecture of the spinal cord while minor histological damage was present in the other half. Between the three groups in which the defect was covered, the histological outcome was comparable. CONCLUSIONS: Acute covering of an experimental neural tube defect in fetal lambs prevents severe histological damage to the spinal cord independent of the two biomatrices used in this study.

Animals↗
PubMed1989

Acquired obstruction of the ventricular septal defect in tetralogy of Fallot.

The interventricular septal defect in patients with tetralogy of Fallot is, in most cases, a nonrestrictive malalignment type of defect. Rare examples of a restrictive defect have been described. We report a case of tetralogy of Fallot with pulmonic atresia in which the interventricular septal defect was found to be nonrestrictive at birth. The obstruction of the defect developed gradually, until, at the age of 6 years, a gradient of 55 mm Hg across the defect was found at repeat cardiac catheterization. Echocardiography proved that the acquired obstruction was due to excessive tricuspid valve tissue, while Doppler studies suggested a similar gradient between the right ventricle and the ascending aorta. This rare case should alert the clinician to the possibility of an acquired obstruction of the ventricular septal defect, with suprasystemic right ventricular pressure, in cases of tetralogy of Fallot, even if an early study suggested a nonobstructive defect. The diagnosis of this situation is of importance because of the poor prognosis which it carries.

Cardiac Catheterization↗
PubMed2003

Repair of atrial septal defect through a limited right anterolateral thoracotomy in 242 patients: a cosmetic approach?

BACKGROUND: The repair of atrial septal defects (ASD) is often safely performed as a routine procedure in the young and asymptomatic patient. The purpose of this study is to evaluate the feasibility and especially the cosmetic result of this repair performed through a limited right anterolateral thoracotomy (RALT), with the complete cannulation and aortic cross-clamping conducted through the same incision. METHODS: From January 1980 to June 2001 in our hospital, 242 patients (210 female) with atrial septal defects and a mean age of 26.2 +/- 12.0 years underwent operations through a RALT. Repaired defects included 235 ostium secundum defects and 7 sinus venosus defects with partial anomalous pulmonary venous connection (SV). Patients were contacted by phone to evaluate their satisfaction with the thoracic scar. RESULTS: There was neither operative nor early mortality. All of the mentioned defects were successfully corrected. Mean bypass times were 12.37 +/- 4.9 minutes for ASD defects and 47.5 +/- 6.4 minutes for SV defects. The mean stay in the intensive care unit was 1.3 +/- 0.5 days. Most of the patients (86.3%) were fully satisfied with the cosmetic result. CONCLUSIONS: The right anterolateral thoracotomy incision provides a safe and effective approach for the correction of the ASD. This approach can be safely performed without any new instruments and without peripheral incisions, provides good exposure for the surgeon to work comfortably, and achieves a cosmetically superior result in selected cases.

Adolescent↗
PubMed2003

Epidemiological study of congenital heart defects in children and adolescents. Analysis of 4,538 cases.

OBJECTIVE: To analyze the frequency and prevalence of congenital heart defects in a tertiary care center for children with heart diseases. METHODS: We carried out an epidemiological assessment of the first medical visit of 4,538 children in a pediatric hospital from January 1995 to December 1997. All patients with congenital heart defects had their diagnoses confirmed at least on echocardiography. The frequency and prevalence of the anomalies were computed according to the classification of sequential analysis. Age, weight, and sex were compared between the groups of healthy individuals and those with congenital heart defects after distribution according to the age group. RESULTS: Of all the children assessed, 2,017 (44.4%) were diagnosed with congenital heart disease, 201 (4.4%) with acquired heart disease, 52 (1.2%) with arrhythmias, and 2,268 (50%) were healthy children. Congenital heart diseases predominated in neonates and infants, corresponding to 71.5% of the cases. Weight and age were significantly lower in children with congenital heart defects. Ventricular septal defect was the most frequent acyanotic anomaly, and tetralogy of Fallot was the most frequent cyanotic anomaly. CONCLUSION: Children with congenital heart defects are mainly referred during the neonatal period and infancy with impairment in gaining weight. Ventricular septal defect is the most frequent heart defect.

Adolescent↗
PubMed1994

Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects.

Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy.

Alveolar Bone Loss↗
PubMed1995

Treatment of intrabony defects with collagen membrane barriers. Case reports.

Two separate investigations were undertaken to assess the clinical characteristics and the safety, and to determine whether an absorbable type 1 bovine collagen barrier membrane would result in the improvement of clinical parameters during guided tissue regeneration in humans. The collagen membrane barrier was placed over a total of 21 interdental intrabony periodontal defects in 18 patients. The surgical procedures and postsurgical regimen were similar in both components of the investigation. Sulcular incisions were used and the sites were surgically exposed by reflection of full thickness mucoperiosteal flaps. The intrabony defects were debrided and the root surfaces prepared with automatic scalers and curets. Four 1-minute applications of tetracycline HCl 50 mg/ml were applied to the root surface. The collagen membrane barrier was hydrated in sterile saline until pliable, then trimmed so it covered the osseous defect and extended 2 to 3 mm beyond the defect. In both investigations, the collagen barrier membrane was not sutured, but retained by "pouching" or undermining the flap. Healing occurred without complications. There were no untoward or adverse reactions to the material in either phase of the study. In the initial investigation, 13 intrabony defects with probing depths of > or = 5 mm were treated in 9 patients having a mean age of 50.6 years. No controls defects were treated. Soft and hard tissue measurements were taken at the time of initial surgery and at 2, 4, and 6 months. In the second phase, 9 patients were enrolled with a mean age of 49.7 years. They had similar bilateral interdental intrabony defects with probing depths > or = 6 mm. One defect received the collagen membrane barrier, while the other was treated by flap debridement alone. The collagen membrane had undergone modification since the initial investigation, and was more highly cross-linked to retard absorption. After initial therapy, and prior to the surgical procedure, a series of 3 dermal patch tests were used to determine whether the patient would elicit a reaction to the collagen. Venous blood was drawn at baseline, 7 to 10 days, 18 to 21 days and at 8 weeks for analysis by ELISA for comparison of test and control sites relative to baseline. There were no allergic response to the dermal tests, and the ELISA tests indicated no significant differences between test and control sites. An automated probe was used to record soft and hard tissue measurements. These included the probing depths and clinical attachment levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗