Deputy Director, Medical University of South Carolina College of Medicine
Although a few patients have been described who lived into adulthood arteries where you can take a pulse procardia 30mg sale, most patients die in infancy or childhood cardiovascular training definition buy 30mg procardia visa. The typical pathologic finding is the markedly dilated right ventricle arteries that supply blood to cardiac muscle buy cheap procardia 30mg on-line, which is described as parchment-like cardiovascular system elderly buy procardia discount. Histologically, the endocardium is thickened, and there are few if any true myocardial cells in the right ventricular free wall. Indeed, the right atrial wall may be thicker than the right ventricular anterior wall. The tricuspid valve arises normally from a dilated valve annulus and may be dysplastic but is not displaced into the right ventricular cavity as is typical for Ebstein anomaly. Various surgical procedures have been performed, including atrial septal defect closure, Potts anastomosis, and Glenn anastomosis. However, procedures that create total cavopulmonary anastomosis and right ventricular exclusion, with or without resection of the dilated right ventricular anterior wall, have resulted in survival into later years (6365). Although this lesion is extremely rare, at least one patient has undergone successful heart transplantation (66) and it has been considered in others (67). This form of treatment seems to be an option for long-term survival in symptomatic patients with findings of Uhl anomaly. Die Krankheiten des Herzens: Systematisch Bearbeitet und Durcheigne Beobachtungen Erlautert. Natural history of the ventricular septal defect in tricuspid atresia and its surgical implications. The electrocardiogram in tricuspid atresia and pulmonary atresia with intact ventricular septum. The surgical treatment of malformations of the heart in which there is pulmonary stenosis or pulmonary atresia. Shunt between superior vena cava and distal right pulmonary artery: Report of clinical application in thirty-eight cases. Increasing the accuracy of lung perfusion scintigraphy in children with bidirectional Glenn circulation. In vitro flow experiments for determination of optimal geometry of total cavopulmonary connection for surgical repair of children with functional single ventricle. Effect of ventricular volume before unloading in a systemic ventricle supporting the Fontan circulation. Impact of age at Fonran completion on postoperative hemodynamics and long-term aerobic exercise capacity in patients with dominant left ventricle. Chronologie changes in P-wave characteristics after the Fontan procedure: the effect of surgical modification. Occurrence and management of atrial arrhythmia after long-term Fontan circulation. Baffle fenestration with subsequent transcatheter closure: modification of the Fontan operation for patients at increased risk. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome. Protein-losing enteropathy after Fontan operation for tricuspid atresia (imperforate tricuspid valve). Protein-losing enteropathy following the Fontan operation: resolution with prednisone therapy. A previously undescribed congenital malformation of the hearr: almost total absence of the myocardium of the right ventricle. Usefulness of corricosteroid therapy for protein-losing enteropathy after Fontan operation. Reversal of protein-losing enteropathy with heparin therapy in three patients with univentricular hearrs and Fontan palliation. Exercise tolerance and cardiorespiratory response to exercise after the Fontan operation for tricuspid atresia or functional single ventricle. Severe tricuspid stenosis presenting as tricuspid atresia: echocardiographic diagnosis and surgical management. Congenital tricuspid stenosis: the diagnostic value of cineangiography and hepatic pulse tracing. Transient tricuspid insufficiency of the newborn: a form of myocardial dysfunction in stressed newborns. He accurately described the characteristic anatomic and the hemodynamic abnormalities of Ebstein anomaly. Adherence of the septal and inferior leaflets to the underlying myocardium (failure of delamination) 2. Downward (apical) displacement of the functional annulus (septal> inferior> anterior) 3. The point of maximal displacement is at the commissure between the inferior and septal leaflets (11). This is our preferred approach, which is to describe the exact anatomy of each of the involved structures of the heart as visualized at operation. The life story of Wilhelm Ebstein (1836-1912) and his almost overlooked description of a congenital heart disease. Mayo Clin Proc 1979;54:197-204, used with permission of the Mayo Foundation for Medical Education and Research. This may warrant genetic testing and family evaluation in this subset of patients. In addition, when functioning at lower pulmonary pressures after a double-switch procedure, the regurgitation is reduced markedly; that is, it tends to be a high-pressure regurgitant valve rather than a low-pressure regurgitant valve (25).
When this occurs in the absence of other anomalies it may go unrecognized or may cause vertebrobasilar insufficiency with so-called congenital subclavian steal coronary artery ultrasound order 30mg procardia mastercard. This may be recognized with angiography by delayed filling of the subclavian artery after aortic root injection heart disease nausea purchase procardia 30mg with amex. Symptomatic patients are treated by implantation of the subclavian artery into the ipsilateral carotid artery or the aorta cardiovascular system worksheet pdf buy procardia 30 mg lowest price. When the fourth arch is absent or atretic ipsilateral to the definitive aortic arch cardiovascular disease statistics buy procardia line, there are also three possibilities, which are elaborated upon below: (a) interrupted aortic arch, in which the sixth arch replaces the fourth, (b) persistent fifth aortic arch with atresia of the distal fourth, and (c) cervical aortic arch, in which the third arch replaces the fourth, analogous to cervical origin of the subclavian artery on the side opposite the arch. Of note is the fact that all of these have been seen in association with 22qll deletion, and collectively are more common than cases with normal origin of the subclavian arteries and well developed fourth arches (22,24). There are four major types of right arch: (a) with mirror-image branching and right descending aorta, (b) with retroesophagealleft subclavian artery, (c) with retroesophageal diverticulum of Kommercll, and (d) with left descending aorta. The incidence of right aortic arch among patients with tetralogy of Fallot has been reported to be anywhere from 13% to 34% (53); however studies vary as to the source of the material (chest roentgenogram, angiography, surgery, or postmortem examination) and frequently do not distinguish between specific types of right arch. A relatively rare but important subset of right aortic arch is that with coarctation of the aorta. Of interest is the high incidence of aberrant left subclavian artery-65% compared with only 25% of all right arches (16), and the similarly high incidence of vascular rings-70%. Left Aortic Arch with Cervical Origin of the Right Subclavian Artery this rare anomaly was first reported by Kutsche and Van Mierop (52) in association with type B interrupted aortic arch. It was subsequently found in patients with tetralogy of Fallot, with or without pulmonary atresia, and has only been seen in patients with 22qll deletion (25). Normally, the right innominate artery bifurcates into a common carotid and subclavian artery near its origin from the aorta. However, in this anomaly, the innominate trifurcates in the neck, giving rise to external and internal carotids and the subclavian artery, which then travels caudally back to the thorax before heading out to the arm. Right Aortic Arch with Mirror-Image Branching Embryology the presumptive embryology has been elegantly described by Kutsche and Van Mierop (52). There appears to be a predilection for unilateral or bilateral absence or atresia of the embryonic fourth arch. When this occurs on the side opposite the definitive arch, there are three main variations in the fate of the subclavian artery: (a) origin from the descending aorta, that is, from the dorsal aorta distal to the seventh intersegmental artery-retroesophageal subclavian artery or circumflex aortic arch as described above (b) origin from the sixth arch-isolated subclavian artery, also described above, and (c) origin from the third arch, which, being more cephalad than Mirror-image right arch has the first branch as a left innominate artery which, in turn, divides into left carotid and left subclavian arteries, the second as the right carotid, and the third as a right subclavian. However, frequently that is the end of the symmetry, since the ductus arteriosus (or ligamentum arteriosum) is usually the left-sided one, arising from the base of the innominate artery rather than from the aortic arch. Therefore, typical mirror-image right aortic arch with left ductus or ligamentum does not form a vascular ring. This arch anomaly is almost always associated with congenital intracardiac disease. The most common association is with tetralogy of Fallot (48% in a series of 74 postmortem cases [57]), but truncus arteriosus communis, other conotruncal anomalies including transposition of the great arteries, double-outlet right ventricle, right ventricular aorta with pulmonary atresia, and anatomically corrected malposition were also seen. A rare variation of mirror-image right aortic arch has a left ductus or ligamentum arising from a retroesophageal dimple pointing toward the left from the right-sided descending aorta. This is different from right arch with diverticulum of Kommerell in that no arch vessel arises from the dimple. Unlike other patients with mirror-image right aortic arch, the few reported cases with retroesophageal ductus dimple appear not to have associated congenital heart disease (58). In one case, this compression was exaggerated by a unique ligamentum arteriosum passing beneath the right bronchus in a patient with discontinuous branch pulmonary arteries with a thrombosed left pulmonary artery arising exclusively from a left ductus off the left innominate artery (59). However, with disappearance of the left dorsal aorta distal to the left seventh intersegmental artery, the sixth arch usually connects to the proximal or subclavian artery side of the disruption. Thus, in the definitive arch the left ductus arises from the underside of the left innominate artery and passes to the left pulmonary artery appearing as a congenital modified left Blalock-Thomas-Taussig shunt. Other cases, particularly when associated with tetralogy of Failor, may have dissolution of both ductus. Finally, in those with retroesophageal ductus dimple the left sixth arch connects left pulmonary artery with the distal left dorsal aorta. Diagnosis and Management Since this type of right arch usually produces no retroesophageal compression or vascular ring, there are, with rare exceptions, no symptoms produced by the arch itself. Therefore, the diagnosis is usually made during imaging of the associated congenital intracardiac disease. The distinctive branching pattern can be used for echocardiographic and angiographic diagnosis, while the appearance of a right-sided indentation of trachea and esophagus on plain radiograph and barium esophagography, respectively, but without posterior impression on the esophagram, permits the diagnosis to be made with those modalities. The presence of a left innominate artery in a patient with symptoms suggestive of a vascular ring and in the absence of cyanotic congenital heart disease should suggest the differential diagnosis of the rare right arch, retroesophageal ductus or the more common right arch, or left descending aorta or double aortic arch with atretic left arch distal to the subclavian artery (discussed below) (differentiated by presence of a left upper descending aorta). No treatment of right aortic arch per se is required; however, it may be helpful for surgeons to know the sidedness of the aortic arch in certain circumstances. For systemic-topulmonary shunts, the classical Blalock-Thomas-Taussig (subclavian artery to pulmonary artery, direct end-to-side) anastomosis or the modified form (polytetrafluoroethylene [Gore- Tex] tube graft interposition side-to-side anastomosis of subclavian artery to pulmonary artery) is best carried out using the side with an innominate artery. With the classical form, the more nearly horizontal takeoff of the subclavian artery makes kinking of the vessel less likely when the cut end is brought down to the level of the pulmonary artery than with the subclavian artery arising directly from the arch. Even with Gore-Tex tube graft interposition, the innominate is a more favorable site of origin since the overall diameter of the innominate is greater, making the proximal anastomosis easier. Furthermore, the angle of takeoff is less acute, making kinking of the vessel of origin less likely even if there is some downward traction after completion of the anastomosis. Another situation in which knowledge of the side of the aortic arch may be useful is in the repair of esophageal atresia and tracheoesophageal fistula where it may be desirable to avoid having the arch obscure the view of the fistula.
The American Heart Association 2011 Scientific Statement on Indications for Cardiac Catheterization and Intervention in Pediatric Cardiac Disease (115) provides guidelines for the management of infants and children with congenital aortic valve stenosis arteries in the brain buy procardia 30 mg lowest price. Given the absence of clinical trial data capillaries exchange food oxygen and purchase discount procardia on line, these recommendations are based on nonrandomized studies and expert opinion rather than data from randomized prospective clinical trials coronary artery 3 vessel disease buy on line procardia. For infants with isolated critical ductal-dependent valvular aortic stenosis arteries 90 blocked cheap procardia 30mg otc, or any infant or child with isolated aortic stenosis with left ventricular systolic dysfunction, balloon valvuloplasty is indicated regardless of the measured pressure gradient. Most infants and children with aortic stenosis are asymptomatic, however, and the guidelines recommend that the catheter gradient should be measured. If the catheter-measured peak-to-peak gradient is ~50 mm Hg, then balloon valvuloplasty is indicated. Valvuloplasty is not recommended for asymptomatic patients with peak-to-peak gradient <40 mm Hg unless cardiac output is impaired, in which case, the gradient underestimates the true severity of the obstruction. For patients under deep sedation or general anesthesia, the measured gradients are likely to be lower, and the guidelines state that it is reasonable to consider balloon valvuloplasty in asymptomatic patients if the mean Doppler gradient when not sedated is >50 mm Hg, even if the measured catheterization-derived peak-to-peak gradient is <50 mm Hg. However, given the relatively slow rate of progression of stenosis outside of infancy (86), caution should be exercised in borderline cases due to the risk of introducing significant aortic regurgitation that might progress and necessitate valve replacement sooner than might have occurred without intervention. According to the American College of Cardiology/American Heart Association 2006 Guidelines for the Management of Valvular Heart Disease (8), for adolescents and young adults with peak Doppler gradients <50 mm Hg or mean gradients <30 mm Hg, follow-up is recommended every 2 years. For those with peak Doppler gradients >50 mm Hg or mean gradients >30 mm Hg, follow-up should be yearly. These guidelines seem reasonable for most children as well, although infants and young children should be followed more closely as progression of aortic valve dysfunction may be more rapid. If the clinical findings and the echo-Doppler evaluation are disparate, then cardiac catheterization may be indicated for complete hemodynamic assessment including direct measurement of the peak-to-peak gradient. The 36th Bethesda Conference Task Force recommendations for competitive athletics (116) defines patients to have mild aortic stenosis if the catheter-derived peak-to-peak gradient is <30 mm Hg, the mean Doppler gradient is <25 mm Hg, or the peak instantaneous Doppler gradient is <40 mm Hg. Such patients are permitted to participate in all competitive sports if they are asymptomatic and have normal exercise tolerance. In addition, if such patients also have no history of supraventricular tachycardia or ventricular tachyarrhythmia at rest or with exercise, then they may participate in sports with moderate static component and low dynamic component (such as diving, archery, equestrian, and motorcycling). Patients with severe aortic stenosis (peak-to-peak gradient >50 mm Hg, mean Doppler gradient >40 mm Hg, or peak Doppler gradient >70 mm Hg) should not participate in any competitive sports. For aortic valve stenosis patients who also have significant aortic regurgitation, these recommendations must be considered in concert with the Task Force recommendations for aortic regurgitation. Even in the absence of stenosis or significant regurgitation, patients with bicuspid aortic valve are at risk of progressive aortic root dilation and aortic dissection; the mortality risk is as high in younger patients as in those over 40 years old (117). Because of the high prevalence of bicuspid aortic valve, it is a more common etiology of aortic dissection than Marfan syndrome (118). However, approximately half of young adults with a bicuspid aortic valve have significant aortic root dilation (30). Most patients with aortic dissection have hypertension (120,121), and this helps to explain the strong association of aortic dissection with bicuspid aortic valve and aortic coarctation (10). Aggressive and meticulous management of hypertension is therefore the mainstay of medical treatment. The angiotensin receptor blocker losartan is an antihypertensive medication that also inhibits transforming growth factor-beta signaling, and is now frequently used in this setting. Increased transforming growth factor-beta signaling has been implicated as an important factor in aortic root dilation in Marfan syndrome, Loeys-Dietz syndrome, and some patients with familial thoracic aneurysm and dissection (122), but this mechanism has not been demonstrated in patients with bicuspid aortic valve-associated aortic dilation. Nevertheless, the potential association in some patients may justify the use of losartan as the antihypertensive medication of choice in this setting. Because aortic root dilation is a precursor of aortic dissection, careful surveillance with serial noninvasive imaging examinations is warranted to detect progressive aortic root dilation so that prophylactic surgery can be performed preemptively before aortic dissection occurs. Prophylactic surgery is sometimes recommended in asymptomatic adolescents or young adults if the aortic diameter reaches 4. Pregnancy can be managed conservatively in women with mild aortic stenosis and normal left ventricular function (8). In women with moderate to severe aortic stenosis, pregnancy should be deferred until the stenosis is successfully treated by valvuloplasty or valve replacement. Women with moderate to severe aortic stenosis who become pregnant should be followed closely. If symptoms develop or left ventricular dysfunction develops, consideration should be given to either balloon valvuloplasty or surgery (8). If significant aortic root dilation is present, there is risk of aortic dissection, particularly in the third trimester, and the aortic root size should be followed closely along with careful attention to blood pressure control. Infective endocarditis prophylaxis precautions are no longer recommended for patients with congenital aortic valve stenosis (125). However, those with prosthetic valves or surgically repaired valves with prosthetic material remain candidates for premedication with antibiotics in the event of a procedure expected to induce bacteremia. In some centers, the Ross procedure (127) is the preferred procedure, particularly in infants and small children. The need for anticoagulation is avoided, and importantly the autograft (neoaortic valve) has growth potential. The major disadvantage of the Ross procedure is that pulmonary homograft dysfunction is universal, frequently relatively early in children. Given current technology, children who undergo a Ross procedure can expect several additional procedures over their lifetime for recurrent pulmonary homograft dysfunction. In addition, progressive neoaortic valve dysfunction, with or without dilation of the neoaortic root, is not uncommon over time. However, modifications of the Ross operation have reduced the incidence of these complications, and in many cases, the function of the autograft valve remains excellent for many years (128-130). Percutaneous aortic valve implantation is a promising new technique that has been developed as an alternative to surgical valve replacement in adult patients with severe aortic stenosis who are deemed inoperable (131). Currently, this procedure is not an option for children and adolescents with congenital aortic stenosis, but results in inoperable elderly patients and in patients with high surgical risk have shown significant improvement in survival compared to medical treatment (132) and similar rates of survival at 1 year compared to surgical replacement (133).
Order 30mg procardia with visa. Cardio-Barre Fusion for Fast Fat Burning ♥ Total Body Workout Ballet Inspired 30 mins Dance Fit.
Anatomical and Functional Mitral Valve Abnormalities in the Pediatric Population Andrew S cardiovascular system glossary order procardia 30mg mastercard. As well heart disease in young adults cheapest generic procardia uk, we exclude hearts with hypoplastic left heart syndrome coronary heart disease quality of life buy cheap procardia 30 mg on-line, as these patients follow a different clinical pathway blood vessels in neck 30mg procardia free shipping. Three-dimensional echocardiography provides novel anatomical and functional information above and beyond 2-D echocardiography and is emphasized throughout this chapter. Sox 9 is activated when endocardial cells undergo mesenchymal transformation and Sox-9-deficient mesenchymal cells fail to express ErbB3, which is required for proliferation of the cells within the endocardial cushions. The mesenchymal cells migrate into the cushions and differentiate into the fibrous tissue of the valves. The atrioventricular canal is occupied by the inferior and superior endocardial cushions that fuse during the 6th week, producing separate right and left atrioventricular junctions. The mural leaflet or posterior leaflet is formed by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface (3). This is an important component, since changes in the mitral annulus during the cardiac cycle are heterogeneous, such that the outlet maintains maximum dimension during contraction to prevent any impediment to flow (10,11). Threedimensional imaging has demonstrated that it is saddle shaped (9), with two high and two low points. The two low points are along the commissure lines of the anterior and posterior leaflets. The lower right hand image shows the reconstructed image of the valve and the two planes (red and green) can be seen. During mid ventricular systole there is a dominant inward motion of the annulus in an anterior-posterior direction. This helps maintain an oval shape just when the orifice area is at its greatest, with the added advantage of helping to keep the leaflets together. During ventricular contraction, the annulus descends with a gradual increase in annular area, height, and bending angle. This reaches its maximum at end systole and during the period of isovolumic relaxation. The anterior leaflet has been arbitrarily divided into three components, Al to A3, which is a useful description for both the echo cardiographer and the surgeon. The mural or posterior leaflet is anchored along the parietal part of the left atrioventricular junction. As with its anterior counterpart, this is divided into three components, Pl to P3. The posterior or mural leaflet frequently has a series of scallops, which are supported by chordal structures. This technique emphasizes that the leaflets are not flat, but consist of a series of undulations, which are in part related to the chordal attachments (13). There are several chordal support mechanisms that can be appreciated in pathologic specimens (19), as well as by real-time 3-D echocardiography. The strut chordae insert into the undersurface of the anterior leaflet and in part result in the appearance of a series of peaks and valleys in the anterior leaflet when seen in real time from the left atrial view. These chordae run onto the belly of the leaflet, whereas the rough zone chordae insert into the tip of the anterior leaflet. The image on the left demonstrates the anterior papillary muscles with mitral chordal insertion. We therefore describe the types of pathology and their echocardiographic appearances together. The angle between the papillary muscle tips and the mitral annulus is about 70 to 80 degrees, as determined by 3-D echocardiography. The papillary muscle morphology is also variable, in particular with regard to the number of heads. Indeed if they are removed during valve replacement, then this results in left ventricular dysfunction (22). These features are readily appreciated by 3-D echocardiography, both from a left atrial and left ventricular view. This is of particular value for imaging the chordal apparatus, as they are imaged in the axial plane that provides optimal resolution. The left ventricular view is of particular importance for imaging the commissures, because they are imaged more reliably from below than from the left atrial view. This is due to the fact that the normal mitral leaflets billow toward the left atrium, just as a parachute does when seen from the sky. The area of this jet correlates well with absolute volume regurgitation, providing a semiquantitative assessment of the degree of regurgitation. As well, it provides an accurate road map to the location of the regurgitation, providing vital information for the surgeon when contemplating repair. The upper left hand image shows the 2-D appearance of the anterior papillary muscle and leaflet. The restrictive functional orifice is clearly seen in the lower right hand panel (black arrow). Note that the relationship of this to the valve can be appreciated from this image. The mitral orifice and the thickened leaflets can be seen, as well as the tethering of the mural leaflet (black arrow). Unfortunately, in the majority of children, it is not possible to calculate a pressure halftime that can provide an absolute valve area in adults. The leaflet is invariably tethered by shortened chordae, preventing normal coaptation with the anterior leaflet. The regurgitant jet invariably extends along the total length of the valve orifice and may respond to surgical repair by leaflet extension. Three-dimensional echocardiography provides optimal imaging of this entity, as well as an accurate assessment of the severity of regurgitation.
Fever and Flu Fever and hyperthermia are established teratogens in animal models (186-188) arteries and veins buy discount procardia on line. However cardiovascular medical definition discount 30mg procardia otc, the extent of cardiac teratogenicity of fever and flu-like illnesses in humans is unclear cardiovascular system role in homeostasis buy procardia 30 mg. The evaluation is made challenging also because reports of febrile illness in pregnancy are difficult to validate coronary heart artery procardia 30mg generic, and because the association could be confounded by the underlying infection or use of medications. The balance of the evidence to date suggests that first-trimester febrile or flu-like illnesses are associated with a moderately increased risk for congenital heart defects in the aggregate (relative risks of approximately 1. In addition to magnitude of risk, these medications are also concerning because of the severity of the heart defects they typically cause, including complex conotruncal anomalies, and the frequent presence of extracardiac defects (197-199). From a prevention perspective, retinoic acid and its congeners, which include isotretinoin and etretinate, are also concerning because they may be used by young women for the treatment of acne and other skin conditions (200). Strict regulatory guidelines have been issued in some but not all countries, and exposures continue to occur (141,200,201). Lithium Lithium is used for manic-depressive disorders, and has been in clinical practice for decades in many countries. Because lithium was found early on to be teratogenic in experimental animals, several studies were initiated to assess the risk for congenital malformations in humans. An early report from the Danish Lithium Babies Registry, a voluntary reporting system (223), described 188 babies born of exposed pregnancies, of which six (5%) had a congenital heart defect, including two cases (1. The final report, 3 years later (224), described 225 exposed pregnancies, of which 25 had birth defects (11 %), including 18 with congenital heart defects (8%) and six with Ebstein anomaly (2. However, such estimates, as noted also in first reports, are unrealistic because of the reporting biases that can affect voluntary registries. In fact, later studies suggested that whereas an excess risk for congenital heart defects probably exists, it is much lower than initially thought (222,225,226). More specifically, a cohort study from Sweden, using a series of data linkages, identified 59 pregnancies exposed to lithium alone and of these seven had birth defects, and four (6. Another cohort study, from the United States, evaluated 148 pregnancies of women with first trimester use of lithium, identified through a teratogen information system (225). Overall birth defect rates in the two groups were similar (four cases in the exposed cohort, three in the reference group). However, one of three affected pregnancies in the exposed cohort had Ebstein anomaly. In addition to these two cohort studies, several case-control studies with data on birth defects, some specifically on Ebstein anomaly, are available and have been reviewed in detail (222). Briefly, these studies reported very few exposed pregnancies and the associated odds ratios did not indicate an increased risk for congenital heart defects. Based on the cohort studies, it appears that the risk associated with first trimester use of lithium is probably increased moderately for birth defects overall, perhaps two- to threefold. The specific risk for congenital heart defects seems to be in the same range or somewhat higher, increased from two- to sevenfold. The risk for Ebstein anomaly in particular is very likely increased but the magnitude is unclear. These findings can help clinicians assess the use of lithium during pregnancy in an appropriate context of risks and benefits Epilepsy and Antiepileptic Drugs Most women with epilepsy have uneventful pregnancies and give birth to healthy newborns. Pooling data from different studies is challenging and sometime suspect, because of the heterogeneity in methods and study quality. A more recent approach is the use of networks of pregnancy registries sharing common methods and data (204,205). Medications associated with teratogenic risk include phenytoin, hydantoin, and valproic acid, and among newer agents, carbamazepine and lamotrigine (211-216). For carbamazepine, one study in India suggested an increased risk for congenital heart defects (217), but this was not confirmed in a large cohort study in the United Kingdom (218). For phenobarbital, several studies reported the occurrence of congenital heart defects in exposed pregnancies (203,212,217,219), but the small number of cases and the variability among studies make it difficult to establish conclusively the presence and magnitude of cardiac risk (202). In the United States, seizure medications are prescribed for an estimated 1 million women (19 per 1,000 population) (141) potentially affecting an estimated 30,000 to 75,000 pregnancies every year (141,204). Women with manic-depressive conditions may benefit from targeted preconceptional counseling and prenatal care, also because they could be at risk for adverse pregnancy outcomes independent of lithium exposure (222,225-227). Whether or not this can be extrapolated to women is unknown, but suggests nevertheless that women who need to use lithium in pregnancy should adhere to basic preconceptional care recommendations, including taking folic acid from before conception. For congenital heart defects, results are often inconsistent and vary across different types and classes of antidepressants. The more recent study (230) generated a summary relative risk estimate for heart defects of 1. Studies on paroxetine are also inconsistent regarding the specificity of the association; for example, one study reported an increased risk for right-sided obstructive heart defects (233), another for atrial septal defects but no other heart defect (234), and another still for minor defects such as ventricular septal defects and bicuspid aortic valve (235). Although the magnitude of putative risks seems small, the high prevalence of use of these medications in women of childbearing age makes them potentially important. In counseling women, the appropriate balance of risk and benefits needs to be reached, taking into account not only the potential risks for some heart defects, but also the serious consequences of untreated or undertreated depression during pregnancy. The mild-to-moderate risk associated with antihypertensives could have different causes, including the underlying maternal hypertension. Hypertension commonly occurs in women with obesity and diabetes, which are risk factors for congenital heart defects, and these factors have not been consistently accounted for in all studies. Women with hypertension should be appropriately counseled, ideally before conception, so they can start pregnancy on a safer medication that appropriately controls hypertension. Other Medications Trimethoprim-sulfonamide and sulfasalazine have been associated with a mild-to-moderate increase in risk for congenital heart defects (246,247). In one study, the use of folic acid supplements decreased the excess risk associated with these compounds (247). Both positive and negative findings have been reported for heart defects in aggregate, as well as for specific phenotypes such as septal defects, left- or right-sided obstructive defects, and some conotruncal defects (16,248-255).
