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By H. Kulak. Columbia Union College. 2019.

This should hold true even when the 14 Precardiopulmonary Bypass child is born prematurely purchase prednisolone uk. In the past discount prednisolone 10mg amex, deferral of surgery with aggressive medical Routine anesthesia and monitoring procedures are described management led to a high risk of problems with pulmonary in detail in Chapter 3 order prednisolone online from canada, Anesthesia for Congenital Heart hypertension, including pulmonary hypertensive crises in the Surgery, while anesthetic considerations specifc to patients early postoperative period. Maintaining a balanced circulation in these patients in the pre-bypass period may be challenging. Truncal The diagnosis of truncus arteriosus is an indication in itself valve regurgitation will exacerbate this reduction. Ideally, diagnosis should be made end-diastolic and subendocardial pressure will be elevated within hours of birth, if it has not been made prenatally. Ideally, surgery should be undertaken within the frst week of The association of this lesion with DiGeorge syndrome life. If diagnosis is delayed, the child should undergo a brief presents additional management issues. Specifcally, patients period of medical stabilization usually for no longer than 2 or with this syndrome are at risk for hypocalcemia and immune 3 days and then surgery should be undertaken. As a result, some patients with DiGeorge syn- of truncus arteriosus was performed in 1962, as reported by drome will present with a characteristic facies consisting of Behrendt and colleagues in 1974. During this time, valved allografts fell having undergone preoperative intubation and stabilization. Transport to the operating room should be with an frst 6 months of life before referral for surgical correction, FiO2 of 21% and appropriate hypoventilation. Anesthesia can were equally poor because of the morbidity secondary to be maintained with fentanyl and a nondepolarizing muscle pulmonary vascular disease. Pancuronium should be used with caution if the described a series of 100 infants repaired mainly before the heart rate is elevated (>160–170 bpm) and the diastolic blood 574 Comprehensive Surgical Management of Congenital Heart Disease, Second Edition pressure is low <25 mmHg) as a further increase in heart rate drastically reduces run off into the pulmonary bed, elevates will almost certainly compromise diastolic coronary perfu- systolic and diastolic blood pressure and generally reduces sion. Adjustments in minute ventilation The induction of the nonintubated infant must be man- are usually not necessary, despite the fact that the right lung aged carefully. Alternatively ketamine, etomidate, FiO2 may have to be increased slightly (FiO2 30–50%) to or a combination of etomidate and an opioid could be used. Prior to intubation during mask ventilation, 100% oxygen should be Post-Cardiopulmonary Bypass administered. There will be a tendency regurgitation should not compromise separation from bypass to induce hypocarbia due to the increased effcacy of ven- unless the regurgitation is severe. A deep level of anesthesia should be respiratory rate and maintaining tidal volume. It is not nary gas exchange without elevating mean airway pressure unusual to have a tidal volume of 12–15 mL/kg, I:E ratio of to any signifcant degree. Right to left predispose to ischemia should be anticipated and treated shunting across this communication will provide an impor- early. An adequate pulmonary venous saturation be optimized with appropriate depth of anesthesia will help prevent increases in heart rate. This is best by maintaining high systemic oxygen delivery in conjunction accomplished by avoiding unnecessary fuid administration. Cardiac output is optimized by maintaining stroke tricular volume overload and exhausted preload reserve (no volume and heart rate. Increased heart rates will also minimize the hemody- ther elevate ventricular end-diastolic pressure, further com- namic consequences of truncal valve regurgitation. Dopamine 3–5 μg/kg/ eral, dopamine will augment stroke volume and heart rate, min is a better strategy to elevate blood pressure and reduce but atrial pacing may on occasion be necessary. Heart rate can be expected to remain consumption is best achieved by maintaining a deep level constant or fall. If these If surgical exposure permits, the right pulmonary objectives are achieved, an SaO2 > 85–90% is possible even artery can be looped with a vessel loop and occluded. Truncus Arteriosus 575 Technique of Cardiopulmonary Bypass been placed around the right and left pulmonary artery are Bicaval cannulation and continuous cardiopulmonary bypass tightened. Usually there is no ductus present, but if one is at moderate hypothermia can be used in the average-sized present it is doubly suture ligated and divided at the onset of neonate. Deep hypothermia in the neonate provides excel- If deep hypothermia is to be used, the child is cooled to a lent myocardial protection and allows for single-dose car- rectal temperature of less than 18°C using the pH stat strat- dioplegia infusion. Multidose cardioplegia requires direct egy and a fow rate of 150–200 mL/kg/min corresponding to a fow index of more than 2 L/min/m2 in the smaller neonate coronary ostial perfusion and is cumbersome. Some reports have suggested that multidose cardioplegia causes important weighing less than 3 kg. Alternatively, moderate hypothermia myocardial edema in the neonate and therefore should be to 25°C with the pH stat strategy is employed usually when avoided. Hematocrit is maintained rior mediastinum and most importantly ensures that there is above 30%. After at least 5–10 minutes of cooling, the ascending tance in the premature neonate who is at risk of intraventricu- aorta is clamped distally and cardioplegia solution is infused lar hemorrhage. Failure to snare the pulmonary arteries the left side of the truncus leaving the right side intact. Today, would result in runoff through the lungs back to the left heart this technique is only appropriate when a true type I truncus is resulting in inadequate systemic perfusion, as well as the present with a well-developed main pulmonary artery arising potential for left heart distention and pulmonary injury. For all other forms of truncus, often helpful to tighten one of the tourniquets during pre- including the common type 1½, our approach has been one of liminary dissection as this will increase diastolic perfusion transection of the truncus at the level of the pulmonary arter- and improve myocardial perfusion before beginning bypass. First, the distal ascending aorta is usually very much smaller Management of Truncal Valve Regurgitation than the truncal root. If the proximal truncus is tailored down If the truncal valve is severely regurgitant, it is important to uniformly to the size of the distal ascending aorta, this is use- cross-clamp the aorta shortly after commencing cardiopul- ful in limiting the diameter of the sinotubular junction and monary bypass to avoid left heart distention as myocardial probably aids in maintaining truncal valve competence. The remainder distal ascending aorta results in a more symmetrical recon- of the infusion can then be undertaken directly into the coro- struction (Fig. The incision should be suff- distally in the ascending aorta following heparinization. The length of the ventriculotomy is exaggerated in this fgure to allow visualization of intracardiac structures. The top end of the incision should be several millimeters from the truncal valve and the right coronary artery. There is usually considerable disparity in size between the ascending aorta and original truncus necessitating aggressive tailoring of the anasto- mosis to match the two vessels. A separate hood of pericardium is not required in contrast to the situation when a pulmonary or aortic homograft is used. Two atrial and nal diameter of the homograft is generally in the region of one ventricular pacing wires are placed. The homograft is older infant, that is, greater than 3–6 months in whom there is concern that pulmonary resistance is elevated. Exposure of this anastomosis is Weaning from Bypass facilitated by the fact that the truncus has not yet been recon- When the rectal temperature has reached 35°C, the child is stituted (Fig. Following removal of Ascending Aortic Anastomosis the cannulas, protamine is given. Hemostasis is assisted with The proximal truncus is anastomosed to the distal ascend- thrombin-soaked gelfoam.

Notably prednisolone 10mg on line, because various levels of aortic stenosis can coexist in the same patient purchase prednisolone no prescription, multiple angiograms are typically necessary purchase discount prednisolone line. A: In this patient with valvar aortic stenosis, a pigtail catheter is positioned retrograde into the ascending aorta. Contrast injection reveals a doming aortic valve with a narrow effective orifice, seen via the negative contrast washout from anterograde flow of noncontrast blood across the aortic valve (indicated with an asterisk). This aortic valve is bicuspid (best visualized on a lateral projection, which is not shown). The aortic valve annulus can be measured (dotted line) and is used to determine balloon size for balloon aortic valvuloplasty. B: In a patient with subvalvar aortic stenosis, a catheter is positioned retrograde into the left ventricle. With contrast injection, there is a discrete subaortic membrane (marked with an asterisk) visible below the level of the aortic valve (arrow) in the left ventricular outflow tract. C, D: In this patient with Shone complex, injection of contrast through a pigtail catheter positioned in the aortic root reveals supravalvar aortic stenosis with narrowing at the sinotubular junction (arrow; best seen in the anteroposterior projection (C)). There is also a bicuspid aortic valve (indicated with an asterisk) and a mild coarctation (double arrow) best seen on the lateral projection (D). Natural History Valvar Aortic Stenosis Valvar aortic stenosis is a progressive disease (1,9,181,182,183,184). In general, earlier diagnosis and a higher gradient at presentation are risk factors for more rapid progression, the need for intervention, and increased mortality (9,185,186,187), with infantile disease representing the highest risk category (7,188). A recent era analysis of the progression rate of valvar stenosis in children revealed that outside the infant age group, progression is actually quite slow, with an increase in peak systolic velocity of only 0. Estimates of 1-year mortality for nontreated infants diagnosed with aortic stenosis range between 10% and 36% (1,186), while overall mortality for nontreated children with aortic stenosis has been estimated at approximately 1% per year. In the current era, child mortality related to aortic stenosis outside the infant population is quite low (189). Long-term outcomes of valvar aortic stenosis without intervention are influenced by valve morphology and presumably degree of stenosis, with one case series citing mean age of death in patients with unicuspid and bicuspid valves at 52 and 63 years, respectively. Though much less common, sudden cardiac death can also occur in children with aortic stenosis, almost always in the setting of exercise. In one series, aortic stenosis accounted for nearly 10% of pediatric sudden death cases (191). Subvalvar Aortic Stenosis Like valvar aortic stenosis, subvalvar stenosis is generally a progressive disease, although the rate of progression can be highly variable. Some pediatric patients demonstrate rapidly worsening obstruction (192,193) while others exhibit stable, mild stenosis for many years (194). Independent predictors of disease progression include increased gradient at diagnosis, attachment of the subaortic membrane to the mitral valve, aortic valve thickening at diagnosis, and decreased distance between the aortic valve and the subaortic membrane (14,195). In addition to the subaortic obstruction, aortic insufficiency is another important physiologic anomaly associated with subvalvar aortic stenosis. As with the degree of obstruction, the severity of aortic insufficiency also generally worsens with time. Risk factors for progression of aortic insufficiency include increased mean gradient at diagnosis and increased time since diagnosis (14). Supravalvar Aortic Stenosis Like valvar and subvalvar disease, supravalvar stenosis generally worsens with time (66,196). Interestingly, the pulmonary stenosis often frequently found in the same patients generally improves over time (66,196). Medical Management In general, there is a limited role for medical therapy in pediatric patients with left ventricular outflow tract obstruction. Neonates with critical aortic stenosis must be stabilized prior to surgical or catheter-based interventions, and patency of the ductus arteriosus must be maintained with prostaglandin E1, but for these patients and any others with symptomatic aortic stenosis, surgical or percutaneous intervention is needed. One setting in which medical therapy is indicated is hypertension management in patients with a bicuspid aortic valve or aortic stenosis. Hypertension is a significant risk factor for aortic root dilation (197) and further elevates left ventricular afterload above the effects of the stenosis. However, a recent randomized controlled trial failed to show any benefit of losartan compared to atenolol in preventing aortic root dilation among Marfan syndrome patients (198) and the role of angiotensin receptor blockers in the management of aortic root dilation related to bicuspid aortic valve is unclear. Based on the current American Heart Association guidelines for the prevention of infective endocarditis, antibiotic prophylaxis is not indicated for left ventricular outflow tract obstruction, regardless of severity (199). The exceptions to this are patients who have undergone aortic valve replacement or in patients with a prior history of infective endocarditis. While this is a reasonable schedule for adolescents and young adults, the potential for more rapid disease progression in younger children requires more frequent reassessments. Infants with even mild aortic stenosis should be re-evaluated every 4 to 8 weeks until the trajectory of disease has been established. Toddlers and young school-age children should receive echocardiograms yearly, or more frequently if stenosis is severe or progressing. Questions related to sports participation frequently arise when pediatric patients are diagnosed with aortic stenosis. As delineated in the 36th Bethesda Conference recommendations on eligibility for competitive sports (200), asymptomatic patients with mild aortic stenosis (defined as peak-to-peak gradient <30 mm Hg, mean Doppler gradient <25 mm Hg, peak instantaneous Doppler gradient <40 mm Hg) may participate in all sports without restriction. Conversely, all competitive sports should be avoided in patients with severe aortic stenosis (peak-to-peak gradient >50 mm Hg, mean Doppler gradient >40 mm Hg, peak instantaneous Doppler gradient >70 mm Hg). Recommendations are more complex for asymptomatic patients with moderate stenosis (peak-to- peak gradient 30 to 50 mm Hg, mean Doppler gradient 25 to 40 mm Hg, peak instantaneous Doppler gradient 40 to 70 mm Hg). If these patients have no history of tachycardia, they may also participate in sports with moderate static and low dynamic components (including diving, archery, and horseback or motorcycle riding). Concerns regarding potential pregnancy risks may also arise among young female patients with aortic stenosis. Severe aortic stenosis may be poorly tolerated in pregnancy, with hemodynamic changes including increased preload, decreased afterload, and increased heart rate each potentially having negative physiologic consequences. A dilated aortic root also is a risk factor for complications during pregnancy, and a comprehensive echocardiographic P. Any woman with severe stenosis who becomes pregnant should receive counseling on the risks of pregnancy from a cardiologist with expertise in the field, and the pregnancy should be monitored in a tertiary care center with a specialized multidisciplinary care team. Intervention on the aortic valve is recommended for patients with severe aortic stenosis prior to pregnancy. Therapeutic Cardiac Catheterization While cardiac catheterization has largely been replaced by echocardiography for the diagnosis of aortic stenosis, there is still a prominent role for catheterization and balloon aortic valvuloplasty in the treatment of patients with aortic stenosis (Video 44. Balloon aortic valvuloplasty is typically reserved for patients with valvar aortic stenosis, although there is evidence that thin, discrete subaortic membranes may be effectively treated with balloon angioplasty as well (201). For valvar aortic stenosis, percutaneous catheter-based intervention has become the first-line therapy in most patients since its first description in 1984 (202,203). Multiple studies have shown that balloon aortic valvuloplasty has results comparable to surgical valve repair with very low mortality rates beyond the neonatal period (9,204,205,206,207,208,209,210,211,212,213).

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Performance in both moderate and severe stenosis typically improves after intervention (125 order prednisolone amex,126 best order for prednisolone,127) generic prednisolone 10 mg online. Further studies will depend on the severity of the stenosis and the extent of any associated additional cardiac abnormalities. Similar recommendations apply for patients with moderate stenosis and no more than moderate regurgitation. However, exercise testing is useful in this patient population, especially in older patients, for the reasons stated above. These patients may benefit from a formal exercise prescription to help optimize both their dynamic and static exercise performance (Table 10. Patients with severe stenosis should be restricted from exercise until they can undergo repair. Patients with severe stenosis should not engage in competitive sports but they can resume sports 3 to 6 months after successful intervention. Types of activities depend upon residual hemodynamic findings (see above) (82,130). Significant ventricular dilation can lead to arrhythmias as can scarring associated with ventriculotomies. Residual stenosis, regurgitation, and branch pulmonary artery stenosis have all been independently associated with diminished exercise performance, and inefficient ventilation during exercise. The latter is manifested as high ventilatory equivalents for carbon dioxide (minute ventilation is high when compared to carbon dioxide excretion) as well as a steep rise in the slope of minute ventilation relative to carbon dioxide production (131,132,133,134). This heterogeneity in exercise performance reflects both the heterogeneity of the defect itself as well as the broad spectrum of residual disease seen following operative repair. Those patients with significant pulmonary regurgitation accompanied by biventricular systolic dysfunction appear to have the lowest exercise capacity (132). These are often young adults with long-standing residual right-sided abnormalities. Patients with restrictive right ventricular mechanics may not develop significant right ventricular dilation despite severe pulmonary regurgitation and often appear to have more preserved exercise capacity at long-term followup (135,136). Premature atrial and ventricular ectopy is commonly observed on exercise testing and can be seen in as many as 50% of patients. However, fast atrial or ventricular couplets or runs of arrhythmias are not common during exercise testing and are likely a cause for concern. Of note is that in one such study, patients with documented ventricular arrhythmias were excluded from participation (141). All patients should have regular Holter monitoring and exercise testing to evaluate arrhythmias and assess cardiopulmonary capacity during exercise. Leisure Activities and Activities of Daily Living Because of the heterogeneity of this population, recommendations for activities and sports participation will vary widely depending on the state of the individual patient. There are some data that suggest maintenance of an active lifestyle in patients with ToF results in improved long-term aerobic capacity. This may be as a result of improved musculoskeletal conditioning as well as direct cardiac effects (142). Asymptomatic patients with significant pulmonary regurgitation who have at least moderate right ventricular dilation, but with preserved right ventricular function and no arrhythmias at rest or during exercise should follow recommendations as delineated in Table 10. Asymptomatic patients with significant regurgitation, significant right ventricular dilation, and abnormal function may engage in mild dynamic exercise assuming no arrhythmias at rest or during exercise. These patients as well as the symptomatic patients described in the following paragraph may benefit from a formal exercise prescription to better assess their individual limitations and to assure that they are performing activities that are safe and appropriate for their individual capacities. Symptomatic patients with residual right ventricular lesions and/or left ventricular dysfunction, patients with right ventricular to systemic systolic pressures ratios of two-thirds or more, patients with important residual intracardiac shunts, and patients with documented sustained atrial or ventricular arrhythmias that are refractory to treatment should engage in only low-dynamic, low-static activities (Table 10. The recent extraordinary performance of an American freestyle snow boarder is testament of the safety of the pursuit of athletic competition at very high level in repaired patients who do not have significant residual lesions. Ebstein Anomaly There is scant literature regarding exercise performance and the risk associated with exercise in patients with Ebstein anomaly. Heterogeneity in this patient population is great and will vary with the severity of the valvular abnormalities as well as with the presence and degree of atrial right-to-left shunting. Patients repaired at a younger age who have lower cardiothoracic ratios on chest x-ray at the time of intervention appear to have the best outcomes. Preoperative patients frequently have cyanosis at rest that worsens with exercise. Reduced right ventricular and left ventricular stroke volumes may limit cardiac output and therefore exercise performance, even in adult patients who are fully saturated (144). Evaluation Prior to Exercise and Sports Participation Evaluation prior to participation in regular physical activity should be similar to that outlined for patients with ToF. Exercise testing and Holter monitoring are useful to assess exercise-induced arrhythmias and evidence of preexcitation. Exercise testing is also useful to evaluate the presence and degree of desaturation with exercise. Leisure Activities and Activities of Daily Living Asymptomatic, acyanotic patients with no more than mild tricuspid regurgitation, normal left ventricular systolic function, and no resting or exercise-induced arrhythmias may engage in all activities (Table 10. Asymptomatic patients with moderate tricuspid regurgitation and normal arterial saturation with supraventricular arrhythmias that are controlled may participate in low-level dynamic and no more than moderately isometric physical activities (Table 10. Symptomatic patients at rest or during exercise, those with important right atrial or right ventricular dilation, severe regurgitation, left ventricular dysfunction, or chronic atrial or ventricular arrhythmias, should not engage in physical exercise. Competitive Sports Asymptomatic, acyanotic patients with no more than mild tricuspid regurgitation, normal left ventricular systolic function, and no resting or exercise-induced arrhythmias may engage in all competitive sports (82). Asymptomatic patients with no more than moderate tricuspid regurgitation, normal arterial saturation, and no resting or exercise-induced arrhythmias may participate in low-dynamic and low-static competitive sports (Fig. Patients with severe Ebstein anomaly characterized as severe regurgitation and evidence of right ventricular dysfunction (desaturation, exercise-induced arrhythmias, or symptoms during exercise or rest) should not engage in competitive sports. Patients who have had surgical intervention may participate in selected competitive sports 3 months after surgery if they are asymptomatic, have no or mild tricuspid valve regurgitation, and have no resting or exercise-induced arrhythmias. Therefore, almost all patients with this type of procedure are in at least their third or fourth decade of life. Many patients may be more severely limited even in2 performing activities of daily living to varying degrees. The reasons for poor exercise performance are multiple and may include poor systemic right ventricular function, chronotropic impairment, tricuspid valve regurgitation, and ridged atrial baffles that limit augmentation of ventricular preload (145,146,147,148,149). Because of the long-term problems with the atrial switch operations, the current approach has been to perform an arterial switch P. However, as this population has moved into adolescent and young adult ages, there is evidence to suggest that their exercise performance has somewhat declined (153,154,155). Left ventricular function is usually well preserved but there is often a mild degree of chronotropic impairment. This is most likely a result of autonomic denervation from the aortic transection at the time of surgery. In addition, as this population ages, this decline may be related at least in part to lack of physical activity and rising rates of obesity (3,4,157). Symptomatic and asymptomatic occlusion of coronary vessels, myocardial perfusion imaging defects, wall-motion abnormalities on stress echocardiography and diminished coronary reserve have been noted in approximately 10% to 12% of patients following the arterial switch operation (150,152,153,156,158,159).

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Effect of high maternal blood phenylalanine on offspring congenital anomalies and developmental outcome at ages 4 and 6 years: the importance of strict dietary control preconception and throughout pregnancy cheap prednisolone 20mg on-line. Caring for women with childbearing potential taking teratogenic dermatologic drugs buy on line prednisolone. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts discount prednisolone 5mg line. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case-control study. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Assessing evidence of harm: what are the teratogenic effects of lithium carbonate? Folate protection from congenital heart defects linked with canonical Wnt signaling and epigenetics. Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies. When should we prescribe high-dose folic acid to prevent congenital heart defects? Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. First-trimester use of selective serotonin- reuptake inhibitors and the risk of birth defects. First-trimester use of paroxetine and congenital heart defects: a population-based case-control study. Antihypertensive medication use during pregnancy and the risk of cardiovascular malformations. Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants. Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Maternal overweight and obesity and risk of congenital heart defects in offspring. Prepregnancy body mass index and congenital heart defects among offspring: a population-based study. Association between maternal obesity and fetal cardiac malformations in African Americans. Maternal height and prepregnancy body mass index as risk factors for selected congenital anomalies. Association of maternal pre-pregnancy weight with birth defects: evidence from a case-control study in Western Australia. Percentage of gestational diabetes mellitus attributable to overweight and obesity. Modeling the potential public health impact of prepregnancy obesity on adverse fetal and infant outcomes. Maternal exposure to caffeine and risk of congenital anomalies: a systematic review. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 institute of medicine criteria. Maternal alcohol drinking pattern during pregnancy and the risk for an offspring with an isolated congenital heart defect and in particular a ventricular septal defect or an atrial septal defect. Maternal folate-related gene environment interactions and congenital heart defects. Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies. Maternal periconceptional alcohol consumption and risk for conotruncal heart defects. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid. Committee to Study Fetal Alcohol Syndrome: fetal alcohol syndrome— diagnosis, epidemiology, prevention and treatment. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Maternal smoking during pregnancy and the risk of congenital heart defects in offspring: a systematic review and metaanalysis. Risk of congenital heart defects in the offspring of smoking mothers: a population-based study. A maternal dietary pattern characterised by fish and seafood in association with the risk of congenital heart defects in the offspring. High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. High maternal vitamin A intake and risk of anomalies of structures with a cranial neural crest cell contribution. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study. Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry. Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries. Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage. Vitamin supplements and the risk for congenital anomalies other than neural tube defects.