Michele G. Sullivan

ORLANDO — All patients hospitalized for stroke should receive at least 24 hours of continuous cardiac rhythm monitoring upon admission to detect silent arrhythmias, Dr. Michael J. Schneck said at the 31st International Stroke Conference.

Dr. Schneck found that 17% of stroke patients developed a change in cardiac rhythm—most often atrial flutter or fibrillation—during the acute poststroke period.

“Of the 30 patients who had atrial fibrillation, only 8 had it detected upon admission,” Dr. Schneck said in an interview. “The other 22 were identified only with telemetry after they converted from normal sinus rhythm.”

Identifying such rhythm conversions can help pinpoint the cause of the stroke and any underlying cardiac disease. It also can help target patients who need anticoagulation therapy, but who might otherwise have been overlooked.

Dr. Schneck and his colleagues at Loyola University, Maywood, Ill., performed a retrospective chart review of 337 stroke patients, of which 289 received continuous cardiac monitoring. The patients' average age was 67 years; 29% had a history of coronary artery disease, and 72% had hypertension.

After initiating telemetry, 80% of the patients had a normal sinus rhythm, and the remaining 20% had atrial fibrillation or flutter, a paced rhythm, junctional rhythms, second-degree heart block, or tachycardic runs.

Within 24 hours, new rhythms developed in 49 patients (17%). About half of these new rhythms developed in patients who had previously normal rhythms.

Most of the new rhythms (in 22 patients) were atrial fibrillation or flutter, a predictive factor for severe stroke and early death in acute ischemic stroke. Of these patients, 9 were discharged on warfarin therapy, and anticoagulation was contraindicated for the other 13 patients.

“Although many of the patients with new onset atrial fibrillation could not be anticoagulated, we still found nine more patients who would otherwise not have been treated with anticoagulation,” Dr. Schneck said at the conference, which was sponsored by the American Stroke Association.

Other new rhythms identified were ectopic atrial rhythm (in six patients), premature ventricular contractions (in five), sinus block with first-degree atrioventricular block (in four), junctional rhythms (in three), ST-segment depression (in two), second-degree atrioventricular block (in two), premature atrial contractions (in one), ventricular tachycardia (in one), and sinus arrhythmia (in one).

“The number of patients with some of these other significant rhythm changes may be small, but some of these rhythm disturbances—such as ventricular tachycardia and heart block—require immediate action,” Dr. Schneck said.

Intracerebral hemorrhage was twice as common in patients who developed a new rhythm than it was in those whose rhythm didn't change (24% vs. 12%).

In a risk factor analysis, only hypercholesterolemia and a previous hemorrhagic stroke were significantly associated with the risk of conversion to an arrhythmia. No other cardiovascular risk factors (prior stroke or coronary artery disease, hypertension, or diabetes) had a significant association, Dr. Schneck said.

This emphasizes the importance of telemetry in this population, he said. “The patient with occult atrial fibrillation may not walk in with a history of myocardial infarction, high cholesterol, or diabetes. Simply based on cardiovascular risk factors, you don't know on admission who is at risk for development of an arrhythmia.”

No one can be sure about the mechanism behind these rhythm changes, Dr. Schneck said. “The stress of the stroke, with its surges of catecholamines, may predispose some to develop an arrhythmia. The other possibility is that the arrhythmia reflects underlying cardiac disease that may then contribute to stroke risk.”

'Simply based on [CV] risk factors, you don't know on admission who is at risk for development of an arrhythmia.' DR. SCHNECK

ORLANDO — All patients hospitalized for stroke should receive at least 24 hours of continuous cardiac rhythm monitoring upon admission to detect silent arrhythmias, Dr. Michael J. Schneck said at the 31st International Stroke Conference.

Dr. Schneck found that 17% of stroke patients developed a change in cardiac rhythm—most often atrial flutter or fibrillation—during the acute poststroke period.

“Of the 30 patients who had atrial fibrillation, only 8 had it detected upon admission,” Dr. Schneck said in an interview. “The other 22 were identified only with telemetry after they converted from normal sinus rhythm.”

Identifying such rhythm conversions can help pinpoint the cause of the stroke and any underlying cardiac disease. It also can help target patients who need anticoagulation therapy, but who might otherwise have been overlooked.

Dr. Schneck and his colleagues at Loyola University, Maywood, Ill., performed a retrospective chart review of 337 stroke patients, of which 289 received continuous cardiac monitoring. The patients' average age was 67 years; 29% had a history of coronary artery disease, and 72% had hypertension.

After initiating telemetry, 80% of the patients had a normal sinus rhythm, and the remaining 20% had atrial fibrillation or flutter, a paced rhythm, junctional rhythms, second-degree heart block, or tachycardic runs.

Within 24 hours, new rhythms developed in 49 patients (17%). About half of these new rhythms developed in patients who had previously normal rhythms.

Most of the new rhythms (in 22 patients) were atrial fibrillation or flutter, a predictive factor for severe stroke and early death in acute ischemic stroke. Of these patients, 9 were discharged on warfarin therapy, and anticoagulation was contraindicated for the other 13 patients.

“Although many of the patients with new onset atrial fibrillation could not be anticoagulated, we still found nine more patients who would otherwise not have been treated with anticoagulation,” Dr. Schneck said at the conference, which was sponsored by the American Stroke Association.

Other new rhythms identified were ectopic atrial rhythm (in six patients), premature ventricular contractions (in five), sinus block with first-degree atrioventricular block (in four), junctional rhythms (in three), ST-segment depression (in two), second-degree atrioventricular block (in two), premature atrial contractions (in one), ventricular tachycardia (in one), and sinus arrhythmia (in one).

“The number of patients with some of these other significant rhythm changes may be small, but some of these rhythm disturbances—such as ventricular tachycardia and heart block—require immediate action,” Dr. Schneck said.

Intracerebral hemorrhage was twice as common in patients who developed a new rhythm than it was in those whose rhythm didn't change (24% vs. 12%).

In a risk factor analysis, only hypercholesterolemia and a previous hemorrhagic stroke were significantly associated with the risk of conversion to an arrhythmia. No other cardiovascular risk factors (prior stroke or coronary artery disease, hypertension, or diabetes) had a significant association, Dr. Schneck said.

This emphasizes the importance of telemetry in this population, he said. “The patient with occult atrial fibrillation may not walk in with a history of myocardial infarction, high cholesterol, or diabetes. Simply based on cardiovascular risk factors, you don't know on admission who is at risk for development of an arrhythmia.”

No one can be sure about the mechanism behind these rhythm changes, Dr. Schneck said. “The stress of the stroke, with its surges of catecholamines, may predispose some to develop an arrhythmia. The other possibility is that the arrhythmia reflects underlying cardiac disease that may then contribute to stroke risk.”

'Simply based on [CV] risk factors, you don't know on admission who is at risk for development of an arrhythmia.' DR. SCHNECK

ORLANDO — All patients hospitalized for stroke should receive at least 24 hours of continuous cardiac rhythm monitoring upon admission to detect silent arrhythmias, Dr. Michael J. Schneck said at the 31st International Stroke Conference.

Dr. Schneck found that 17% of stroke patients developed a change in cardiac rhythm—most often atrial flutter or fibrillation—during the acute poststroke period.

“Of the 30 patients who had atrial fibrillation, only 8 had it detected upon admission,” Dr. Schneck said in an interview. “The other 22 were identified only with telemetry after they converted from normal sinus rhythm.”

Identifying such rhythm conversions can help pinpoint the cause of the stroke and any underlying cardiac disease. It also can help target patients who need anticoagulation therapy, but who might otherwise have been overlooked.

Dr. Schneck and his colleagues at Loyola University, Maywood, Ill., performed a retrospective chart review of 337 stroke patients, of which 289 received continuous cardiac monitoring. The patients' average age was 67 years; 29% had a history of coronary artery disease, and 72% had hypertension.

After initiating telemetry, 80% of the patients had a normal sinus rhythm, and the remaining 20% had atrial fibrillation or flutter, a paced rhythm, junctional rhythms, second-degree heart block, or tachycardic runs.

Within 24 hours, new rhythms developed in 49 patients (17%). About half of these new rhythms developed in patients who had previously normal rhythms.

Most of the new rhythms (in 22 patients) were atrial fibrillation or flutter, a predictive factor for severe stroke and early death in acute ischemic stroke. Of these patients, 9 were discharged on warfarin therapy, and anticoagulation was contraindicated for the other 13 patients.

“Although many of the patients with new onset atrial fibrillation could not be anticoagulated, we still found nine more patients who would otherwise not have been treated with anticoagulation,” Dr. Schneck said at the conference, which was sponsored by the American Stroke Association.

Other new rhythms identified were ectopic atrial rhythm (in six patients), premature ventricular contractions (in five), sinus block with first-degree atrioventricular block (in four), junctional rhythms (in three), ST-segment depression (in two), second-degree atrioventricular block (in two), premature atrial contractions (in one), ventricular tachycardia (in one), and sinus arrhythmia (in one).

“The number of patients with some of these other significant rhythm changes may be small, but some of these rhythm disturbances—such as ventricular tachycardia and heart block—require immediate action,” Dr. Schneck said.

Intracerebral hemorrhage was twice as common in patients who developed a new rhythm than it was in those whose rhythm didn't change (24% vs. 12%).

In a risk factor analysis, only hypercholesterolemia and a previous hemorrhagic stroke were significantly associated with the risk of conversion to an arrhythmia. No other cardiovascular risk factors (prior stroke or coronary artery disease, hypertension, or diabetes) had a significant association, Dr. Schneck said.

This emphasizes the importance of telemetry in this population, he said. “The patient with occult atrial fibrillation may not walk in with a history of myocardial infarction, high cholesterol, or diabetes. Simply based on cardiovascular risk factors, you don't know on admission who is at risk for development of an arrhythmia.”

No one can be sure about the mechanism behind these rhythm changes, Dr. Schneck said. “The stress of the stroke, with its surges of catecholamines, may predispose some to develop an arrhythmia. The other possibility is that the arrhythmia reflects underlying cardiac disease that may then contribute to stroke risk.”

'Simply based on [CV] risk factors, you don't know on admission who is at risk for development of an arrhythmia.' DR. SCHNECK

Rapid glycemic correction before cataract surgery should be avoided in patients with moderate to severe diabetic retinopathy because it might increase the risk of retinopathy or maculopathy progression.

Blood glucose levels that are quickly corrected in the 3 months before surgery might actually contribute to macular damage, wrote Dr. Chikako Suto of the department of ophthalmology at Tokyo Women's Medical University, and associates (Arch. Ophthalmol. 2006; 124:38–45).

“Early [postoperative] worsening might be due to irreversible invasive damage to the macula resulting from vascular hyperpermeability in patients with rapid correction of glycemic control who have maculopathy before surgery. On the basis of these findings, rapid reduction of blood glucose levels should not be advocated” for these patients, they said.

The researchers examined disease progression 1 year after cataract phacoemulsification and lens replacement surgery in 87 patients with type 2 diabetes (mean age 63 years). The same surgeon performed all of the operations.

The patients were divided into three groups. The rapid control group consisted of 27 patients with elevated (9% or higher) glycosylated hemoglobin (HbA_1c) levels, which were reduced by at least 3% at 3 months before surgery. The poor control group consisted of 30 patients with consistently elevated HbA_1c levels that remained high (8.5% or higher) until surgery. The good control group consisted of 30 patients with normalized HbA_1c levels (mean 7%).

Postoperative progression of retinopathy occurred in 30% of the rapid control group, 17% of the poor control group, and 13% of the good control group; there were no significant differences between groups. In a multivariate analysis of risk factors, only the presence of preoperative maculopathy was significantly associated with progression (odds ratio 4).

“[This] indicates that the postoperative rate of retinopathy progression is the same regardless of whether rapid correction is attempted,” the authors wrote.

Postoperative progression of maculopathy occurred in 33% of the rapid control group, 13% of the poor control group, and 3% of the good control group. In the multivariate analysis, rapid preoperative glycemic correction increased the risk of progression by more than 8 times; preexisting maculopathy increased the risk by more than 11 times. “To achieve a good visual outcome, it may be important to perform surgery in cooperation with physicians who are advised to avoid [rapid glycemic correction] in patients with moderate to severe [nonproliferative diabetic retinopathy] or maculopathy,” the researchers concluded.

Rapid glycemic correction before cataract surgery should be avoided in patients with moderate to severe diabetic retinopathy because it might increase the risk of retinopathy or maculopathy progression.

Blood glucose levels that are quickly corrected in the 3 months before surgery might actually contribute to macular damage, wrote Dr. Chikako Suto of the department of ophthalmology at Tokyo Women's Medical University, and associates (Arch. Ophthalmol. 2006; 124:38–45).

“Early [postoperative] worsening might be due to irreversible invasive damage to the macula resulting from vascular hyperpermeability in patients with rapid correction of glycemic control who have maculopathy before surgery. On the basis of these findings, rapid reduction of blood glucose levels should not be advocated” for these patients, they said.

The researchers examined disease progression 1 year after cataract phacoemulsification and lens replacement surgery in 87 patients with type 2 diabetes (mean age 63 years). The same surgeon performed all of the operations.

The patients were divided into three groups. The rapid control group consisted of 27 patients with elevated (9% or higher) glycosylated hemoglobin (HbA_1c) levels, which were reduced by at least 3% at 3 months before surgery. The poor control group consisted of 30 patients with consistently elevated HbA_1c levels that remained high (8.5% or higher) until surgery. The good control group consisted of 30 patients with normalized HbA_1c levels (mean 7%).

Postoperative progression of retinopathy occurred in 30% of the rapid control group, 17% of the poor control group, and 13% of the good control group; there were no significant differences between groups. In a multivariate analysis of risk factors, only the presence of preoperative maculopathy was significantly associated with progression (odds ratio 4).

“[This] indicates that the postoperative rate of retinopathy progression is the same regardless of whether rapid correction is attempted,” the authors wrote.

Postoperative progression of maculopathy occurred in 33% of the rapid control group, 13% of the poor control group, and 3% of the good control group. In the multivariate analysis, rapid preoperative glycemic correction increased the risk of progression by more than 8 times; preexisting maculopathy increased the risk by more than 11 times. “To achieve a good visual outcome, it may be important to perform surgery in cooperation with physicians who are advised to avoid [rapid glycemic correction] in patients with moderate to severe [nonproliferative diabetic retinopathy] or maculopathy,” the researchers concluded.

Rapid glycemic correction before cataract surgery should be avoided in patients with moderate to severe diabetic retinopathy because it might increase the risk of retinopathy or maculopathy progression.

Blood glucose levels that are quickly corrected in the 3 months before surgery might actually contribute to macular damage, wrote Dr. Chikako Suto of the department of ophthalmology at Tokyo Women's Medical University, and associates (Arch. Ophthalmol. 2006; 124:38–45).

“Early [postoperative] worsening might be due to irreversible invasive damage to the macula resulting from vascular hyperpermeability in patients with rapid correction of glycemic control who have maculopathy before surgery. On the basis of these findings, rapid reduction of blood glucose levels should not be advocated” for these patients, they said.

The researchers examined disease progression 1 year after cataract phacoemulsification and lens replacement surgery in 87 patients with type 2 diabetes (mean age 63 years). The same surgeon performed all of the operations.

The patients were divided into three groups. The rapid control group consisted of 27 patients with elevated (9% or higher) glycosylated hemoglobin (HbA_1c) levels, which were reduced by at least 3% at 3 months before surgery. The poor control group consisted of 30 patients with consistently elevated HbA_1c levels that remained high (8.5% or higher) until surgery. The good control group consisted of 30 patients with normalized HbA_1c levels (mean 7%).

Postoperative progression of retinopathy occurred in 30% of the rapid control group, 17% of the poor control group, and 13% of the good control group; there were no significant differences between groups. In a multivariate analysis of risk factors, only the presence of preoperative maculopathy was significantly associated with progression (odds ratio 4).

“[This] indicates that the postoperative rate of retinopathy progression is the same regardless of whether rapid correction is attempted,” the authors wrote.

Postoperative progression of maculopathy occurred in 33% of the rapid control group, 13% of the poor control group, and 3% of the good control group. In the multivariate analysis, rapid preoperative glycemic correction increased the risk of progression by more than 8 times; preexisting maculopathy increased the risk by more than 11 times. “To achieve a good visual outcome, it may be important to perform surgery in cooperation with physicians who are advised to avoid [rapid glycemic correction] in patients with moderate to severe [nonproliferative diabetic retinopathy] or maculopathy,” the researchers concluded.

WASHINGTON – Decreased use of valproate to manage epilepsy during pregnancy in Australia has produced a corresponding drop in fetal malformations associated with the drug, Dr. Frank Vajda said at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

Dr. Vajda, a neurologist at the Victorian Epilepsy Centre in Victoria, Australia, presented the most recent data from the Australian Pregnancy Registry for Women on Antiepileptic Medication. The registry, established in 1999, has enrolled 810 women–77% of all Australian women who had taken antiepilepsy drugs (AEDs) for any reason. The 64-month data contained outcome information on 715 births.

Of the women in the registry, most who were currently taking AEDs (692) were taking the drugs for epilepsy. Other indications were bipolar disorder (11), pain (4), sleep (1), and unspecified (14). The majority of the women (504) were on AED monotherapy.

Most of the births (640) were of live infants without congenital malformations. There were 44 births with fetal malformations: 27 live births with defects, 9 live births with defects that emerged by 1 year, and 8 induced abortions of malformed fetuses. The malformations included spina bifida, anencephaly, holoprosencephaly, Dandy-Walker syndrome, and a variety of cardiac defects.

There were also 23 spontaneous abortions, one induced abortion for maternal indications, and seven stillbirths; no malformations were noted in these fetuses.

The only significant drug/defect associations occurred in women taking high doses of valproate, either as monotherapy or polytherapy.

Women who were taking more than 1,100 mg/day of valproate as monotherapy had a 13-fold increased risk of fetal malformations, compared with women not taking any AEDs. Women taking similar doses of the drug as polytherapy had a sixfold increased risk of fetal malformations.

The rate of malformation among women taking less than 1,100 mg/day was higher than the 2%–3% that occurs in the general population, but the difference was not statistically significant.

Australian physicians appear to be heeding the data linking valproate to birth defects, Dr. Vajda said. The rate of valproate prescribing and dosages prescribed has decreased over the length of the registry, as have the rates of fetal malformation. In 1999, 26% of women on the registry were on the drug. The rate increased to 33% by 2001 and has since dropped to 21%. The average daily dose has decreased from 1,780 mg in 1999 to 936 mg in 2004.

The rate of malformation associated with valproate monotherapy was 16% before 2004, compared with 7% in 2004; the rate associated with polytherapy was 10% before 2004 and 0% in 2004.

However, he noted, the rates of malformation among women on carbamazepine or lamotrigine monotherapy have increased.

For carbamazepine, the pre-2004 rate was 4.8%; it rose to 6.5% in 2004. The rate associated with lamotrigine monotherapy was 4.5% before 2004 and rose to 8.6% in 2004. The average dosages of these drugs increased from 1999–2004 as well.

“These are not regarded as significant as the numbers are,” Dr. Vajda said in an interview. “It's possible that the increases in dosing may play a part, but there is no significant data available as yet.”

The registry does not address the possibility of cognitive problems in children exposed to AEDs in utero, he added.

Valproate is the most frequently prescribed antiepileptic drug in the United States, with 12 million prescriptions written annually for women of childbearing age. About 20% of those prescriptions are for epilepsy, and the rest are for migraine and mood disorders.

WASHINGTON – Decreased use of valproate to manage epilepsy during pregnancy in Australia has produced a corresponding drop in fetal malformations associated with the drug, Dr. Frank Vajda said at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

Dr. Vajda, a neurologist at the Victorian Epilepsy Centre in Victoria, Australia, presented the most recent data from the Australian Pregnancy Registry for Women on Antiepileptic Medication. The registry, established in 1999, has enrolled 810 women–77% of all Australian women who had taken antiepilepsy drugs (AEDs) for any reason. The 64-month data contained outcome information on 715 births.

Of the women in the registry, most who were currently taking AEDs (692) were taking the drugs for epilepsy. Other indications were bipolar disorder (11), pain (4), sleep (1), and unspecified (14). The majority of the women (504) were on AED monotherapy.

Most of the births (640) were of live infants without congenital malformations. There were 44 births with fetal malformations: 27 live births with defects, 9 live births with defects that emerged by 1 year, and 8 induced abortions of malformed fetuses. The malformations included spina bifida, anencephaly, holoprosencephaly, Dandy-Walker syndrome, and a variety of cardiac defects.

There were also 23 spontaneous abortions, one induced abortion for maternal indications, and seven stillbirths; no malformations were noted in these fetuses.

The only significant drug/defect associations occurred in women taking high doses of valproate, either as monotherapy or polytherapy.

Women who were taking more than 1,100 mg/day of valproate as monotherapy had a 13-fold increased risk of fetal malformations, compared with women not taking any AEDs. Women taking similar doses of the drug as polytherapy had a sixfold increased risk of fetal malformations.

The rate of malformation among women taking less than 1,100 mg/day was higher than the 2%–3% that occurs in the general population, but the difference was not statistically significant.

Australian physicians appear to be heeding the data linking valproate to birth defects, Dr. Vajda said. The rate of valproate prescribing and dosages prescribed has decreased over the length of the registry, as have the rates of fetal malformation. In 1999, 26% of women on the registry were on the drug. The rate increased to 33% by 2001 and has since dropped to 21%. The average daily dose has decreased from 1,780 mg in 1999 to 936 mg in 2004.

The rate of malformation associated with valproate monotherapy was 16% before 2004, compared with 7% in 2004; the rate associated with polytherapy was 10% before 2004 and 0% in 2004.

However, he noted, the rates of malformation among women on carbamazepine or lamotrigine monotherapy have increased.

For carbamazepine, the pre-2004 rate was 4.8%; it rose to 6.5% in 2004. The rate associated with lamotrigine monotherapy was 4.5% before 2004 and rose to 8.6% in 2004. The average dosages of these drugs increased from 1999–2004 as well.

“These are not regarded as significant as the numbers are,” Dr. Vajda said in an interview. “It's possible that the increases in dosing may play a part, but there is no significant data available as yet.”

The registry does not address the possibility of cognitive problems in children exposed to AEDs in utero, he added.

Valproate is the most frequently prescribed antiepileptic drug in the United States, with 12 million prescriptions written annually for women of childbearing age. About 20% of those prescriptions are for epilepsy, and the rest are for migraine and mood disorders.

WASHINGTON – Decreased use of valproate to manage epilepsy during pregnancy in Australia has produced a corresponding drop in fetal malformations associated with the drug, Dr. Frank Vajda said at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

Dr. Vajda, a neurologist at the Victorian Epilepsy Centre in Victoria, Australia, presented the most recent data from the Australian Pregnancy Registry for Women on Antiepileptic Medication. The registry, established in 1999, has enrolled 810 women–77% of all Australian women who had taken antiepilepsy drugs (AEDs) for any reason. The 64-month data contained outcome information on 715 births.

Of the women in the registry, most who were currently taking AEDs (692) were taking the drugs for epilepsy. Other indications were bipolar disorder (11), pain (4), sleep (1), and unspecified (14). The majority of the women (504) were on AED monotherapy.

Most of the births (640) were of live infants without congenital malformations. There were 44 births with fetal malformations: 27 live births with defects, 9 live births with defects that emerged by 1 year, and 8 induced abortions of malformed fetuses. The malformations included spina bifida, anencephaly, holoprosencephaly, Dandy-Walker syndrome, and a variety of cardiac defects.

There were also 23 spontaneous abortions, one induced abortion for maternal indications, and seven stillbirths; no malformations were noted in these fetuses.

The only significant drug/defect associations occurred in women taking high doses of valproate, either as monotherapy or polytherapy.

Women who were taking more than 1,100 mg/day of valproate as monotherapy had a 13-fold increased risk of fetal malformations, compared with women not taking any AEDs. Women taking similar doses of the drug as polytherapy had a sixfold increased risk of fetal malformations.

The rate of malformation among women taking less than 1,100 mg/day was higher than the 2%–3% that occurs in the general population, but the difference was not statistically significant.

Australian physicians appear to be heeding the data linking valproate to birth defects, Dr. Vajda said. The rate of valproate prescribing and dosages prescribed has decreased over the length of the registry, as have the rates of fetal malformation. In 1999, 26% of women on the registry were on the drug. The rate increased to 33% by 2001 and has since dropped to 21%. The average daily dose has decreased from 1,780 mg in 1999 to 936 mg in 2004.

The rate of malformation associated with valproate monotherapy was 16% before 2004, compared with 7% in 2004; the rate associated with polytherapy was 10% before 2004 and 0% in 2004.

However, he noted, the rates of malformation among women on carbamazepine or lamotrigine monotherapy have increased.

For carbamazepine, the pre-2004 rate was 4.8%; it rose to 6.5% in 2004. The rate associated with lamotrigine monotherapy was 4.5% before 2004 and rose to 8.6% in 2004. The average dosages of these drugs increased from 1999–2004 as well.

“These are not regarded as significant as the numbers are,” Dr. Vajda said in an interview. “It's possible that the increases in dosing may play a part, but there is no significant data available as yet.”

The registry does not address the possibility of cognitive problems in children exposed to AEDs in utero, he added.

Valproate is the most frequently prescribed antiepileptic drug in the United States, with 12 million prescriptions written annually for women of childbearing age. About 20% of those prescriptions are for epilepsy, and the rest are for migraine and mood disorders.

WASHINGTON – There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine (Lamictal) as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%; among those on polytherapy without valproate it was 2.7%. The rate among women on polytherapy with valproate was 11.8%–significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide.

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%). These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified.

WASHINGTON – There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine (Lamictal) as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%; among those on polytherapy without valproate it was 2.7%. The rate among women on polytherapy with valproate was 11.8%–significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide.

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%). These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified.

WASHINGTON – There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine (Lamictal) as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%; among those on polytherapy without valproate it was 2.7%. The rate among women on polytherapy with valproate was 11.8%–significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide.

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%). These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified.

TORONTO – Fluoxetine combined with cognitive-behavioral therapy was more effective in improving functioning, global health, and quality of life in depressed adolescents than was either treatment alone, Dr. Benedetto Vitiello said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, he noted, although symptoms of depression might have improved, many patients remained functionally impaired after 12 weeks of treatment, even with the most effective therapy. “It's not really surprising that function doesn't improve as quickly as symptoms,” he said in an interview. “You would expect symptoms to improve first, and then to see a gradual improvement in function.”

Dr. Vitiello, chief of the child and adolescent treatment and preventive intervention research branch of the National Institute of Mental Health, presented a secondary analysis of the Treatment for Adolescents with Depression Study (TADS). The TADS trial included 439 patients aged 12–17 years with major depressive disorder. Patients were randomized to either 12 weeks of fluoxetine alone (10–40 mg/day), cognitive-behavioral therapy (CBT) alone, CBT with fluoxetine (10–40 mg/day), or placebo.

The study found that combination therapy reduced the symptoms of depression better than did fluoxetine or CBT alone. But when the main outcome measure was function, rather than symptoms of depression, the results were not as robust, he concluded. “The data seem to show that treatment effects on function lag behind those on symptoms.”

In the analysis, functional outcomes were measured with the Children's Global Assessment Scale (CGAS), the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and the Health of the Nation Outcome Scales for Children and Adolescents (HONOSCA). Baseline scores showed moderate impairment, Dr. Vitiello said. Average scores were 50 (ideal score, 100) on the CGAS, 17 (ideal, 0) on the HONOSCA, and 43 (ideal, 75) on the PQ-LES-Q.

After 12 weeks of treatment, the combination therapy was clearly superior to any of the other arms on the basis of these measurements, he said. Average scores on the CGAS improved to 65 in the combination therapy group, 60 in the fluoxetine-only group, and 57 in the CBT-only and placebo groups.

HONOSCA scores declined (showing improvement) in all arms. However, the only statistically significant decline occurred in the combination therapy group. On the PQ-LES-Q, the most improvement occurred in the combination therapy group, with the average score increasing to 55.

“Combination therapy was consistently superior to the other arms in improving function in all three measures,” Dr. Vitiello said.

Even with these improvements, however, most patients didn't regain normal function. Only 35% of those in the combination therapy group attained a CGAS score higher than 70, representing normal function, although 71% of those in this group were classified as responders when assessing their symptoms of depression.

In the fluoxetine-only group, only 20% of patients attained normalization, although 61% were classified as responders. “It's quite a dramatic difference when you take the level of function as the outcome,” Dr. Vitiello said.

The numbers were significantly lower in the other groups–13% of those in the CBT-only arm and 19% of those in the placebo arm attained normalized function.

“It was quite disappointing that CBT had only a 13% recovery rate,” Dr. Vitiello said.

TORONTO – Fluoxetine combined with cognitive-behavioral therapy was more effective in improving functioning, global health, and quality of life in depressed adolescents than was either treatment alone, Dr. Benedetto Vitiello said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, he noted, although symptoms of depression might have improved, many patients remained functionally impaired after 12 weeks of treatment, even with the most effective therapy. “It's not really surprising that function doesn't improve as quickly as symptoms,” he said in an interview. “You would expect symptoms to improve first, and then to see a gradual improvement in function.”

Dr. Vitiello, chief of the child and adolescent treatment and preventive intervention research branch of the National Institute of Mental Health, presented a secondary analysis of the Treatment for Adolescents with Depression Study (TADS). The TADS trial included 439 patients aged 12–17 years with major depressive disorder. Patients were randomized to either 12 weeks of fluoxetine alone (10–40 mg/day), cognitive-behavioral therapy (CBT) alone, CBT with fluoxetine (10–40 mg/day), or placebo.

The study found that combination therapy reduced the symptoms of depression better than did fluoxetine or CBT alone. But when the main outcome measure was function, rather than symptoms of depression, the results were not as robust, he concluded. “The data seem to show that treatment effects on function lag behind those on symptoms.”

In the analysis, functional outcomes were measured with the Children's Global Assessment Scale (CGAS), the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and the Health of the Nation Outcome Scales for Children and Adolescents (HONOSCA). Baseline scores showed moderate impairment, Dr. Vitiello said. Average scores were 50 (ideal score, 100) on the CGAS, 17 (ideal, 0) on the HONOSCA, and 43 (ideal, 75) on the PQ-LES-Q.

After 12 weeks of treatment, the combination therapy was clearly superior to any of the other arms on the basis of these measurements, he said. Average scores on the CGAS improved to 65 in the combination therapy group, 60 in the fluoxetine-only group, and 57 in the CBT-only and placebo groups.

HONOSCA scores declined (showing improvement) in all arms. However, the only statistically significant decline occurred in the combination therapy group. On the PQ-LES-Q, the most improvement occurred in the combination therapy group, with the average score increasing to 55.

“Combination therapy was consistently superior to the other arms in improving function in all three measures,” Dr. Vitiello said.

Even with these improvements, however, most patients didn't regain normal function. Only 35% of those in the combination therapy group attained a CGAS score higher than 70, representing normal function, although 71% of those in this group were classified as responders when assessing their symptoms of depression.

In the fluoxetine-only group, only 20% of patients attained normalization, although 61% were classified as responders. “It's quite a dramatic difference when you take the level of function as the outcome,” Dr. Vitiello said.

The numbers were significantly lower in the other groups–13% of those in the CBT-only arm and 19% of those in the placebo arm attained normalized function.

“It was quite disappointing that CBT had only a 13% recovery rate,” Dr. Vitiello said.

TORONTO – Fluoxetine combined with cognitive-behavioral therapy was more effective in improving functioning, global health, and quality of life in depressed adolescents than was either treatment alone, Dr. Benedetto Vitiello said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, he noted, although symptoms of depression might have improved, many patients remained functionally impaired after 12 weeks of treatment, even with the most effective therapy. “It's not really surprising that function doesn't improve as quickly as symptoms,” he said in an interview. “You would expect symptoms to improve first, and then to see a gradual improvement in function.”

Dr. Vitiello, chief of the child and adolescent treatment and preventive intervention research branch of the National Institute of Mental Health, presented a secondary analysis of the Treatment for Adolescents with Depression Study (TADS). The TADS trial included 439 patients aged 12–17 years with major depressive disorder. Patients were randomized to either 12 weeks of fluoxetine alone (10–40 mg/day), cognitive-behavioral therapy (CBT) alone, CBT with fluoxetine (10–40 mg/day), or placebo.

The study found that combination therapy reduced the symptoms of depression better than did fluoxetine or CBT alone. But when the main outcome measure was function, rather than symptoms of depression, the results were not as robust, he concluded. “The data seem to show that treatment effects on function lag behind those on symptoms.”

In the analysis, functional outcomes were measured with the Children's Global Assessment Scale (CGAS), the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and the Health of the Nation Outcome Scales for Children and Adolescents (HONOSCA). Baseline scores showed moderate impairment, Dr. Vitiello said. Average scores were 50 (ideal score, 100) on the CGAS, 17 (ideal, 0) on the HONOSCA, and 43 (ideal, 75) on the PQ-LES-Q.

After 12 weeks of treatment, the combination therapy was clearly superior to any of the other arms on the basis of these measurements, he said. Average scores on the CGAS improved to 65 in the combination therapy group, 60 in the fluoxetine-only group, and 57 in the CBT-only and placebo groups.

HONOSCA scores declined (showing improvement) in all arms. However, the only statistically significant decline occurred in the combination therapy group. On the PQ-LES-Q, the most improvement occurred in the combination therapy group, with the average score increasing to 55.

“Combination therapy was consistently superior to the other arms in improving function in all three measures,” Dr. Vitiello said.

Even with these improvements, however, most patients didn't regain normal function. Only 35% of those in the combination therapy group attained a CGAS score higher than 70, representing normal function, although 71% of those in this group were classified as responders when assessing their symptoms of depression.

In the fluoxetine-only group, only 20% of patients attained normalization, although 61% were classified as responders. “It's quite a dramatic difference when you take the level of function as the outcome,” Dr. Vitiello said.

The numbers were significantly lower in the other groups–13% of those in the CBT-only arm and 19% of those in the placebo arm attained normalized function.

“It was quite disappointing that CBT had only a 13% recovery rate,” Dr. Vitiello said.

WASHINGTON — There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%, and the rate among those on polytherapy without valproate was 2.7%.

The rate among women on polytherapy with valproate was 11.8%—significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%).

These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified. The complete interim report of the International Lamotrigine Pregnancy Registry is available by calling the same number.

WASHINGTON — There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%, and the rate among those on polytherapy without valproate was 2.7%.

The rate among women on polytherapy with valproate was 11.8%—significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%).

These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified. The complete interim report of the International Lamotrigine Pregnancy Registry is available by calling the same number.

WASHINGTON — There is no evidence that lamotrigine monotherapy increases the risk of major congenital malformations in infants exposed prenatally to the drug, according to updated data from the International Lamotrigine Pregnancy Registry.

However, when the drug was used as adjunctive therapy along with valproate, the rate of major congenital malformations was significantly higher than the rate for the background population, reported Dr. John A. Messenheimer of GlaxoSmithKline, Research Triangle Park, N.C.

Since its inception in 1992, the lamotrigine registry has recorded 2,000 pregnancies exposed to the drug during the first trimester. The interim report contains data up to September 2005 and was presented as a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

The updated report contained the following outcome data. Most of the women (707) were taking lamotrigine as monotherapy, 256 were on polytherapy with lamotrigine but without valproate, and 119 were on polytherapy with lamotrigine and valproate.

There were 20 major congenital malformations reported. Of those, two were club feet, two were cases of anencephaly, and three were ventricular septal defects. The remaining malformations included midline defects, urogenital defects, cortical dysplasia, hypoplastic left heart syndrome, hypoplasia of the left ventricle, and diaphragmatic hernia with abdominal organ displacement.

The malformation rate among women on lamotrigine monotherapy was 2.8%, and the rate among those on polytherapy without valproate was 2.7%.

The rate among women on polytherapy with valproate was 11.8%—significantly higher than the background population rate of 2%–3%.

There was no significant relationship between lamotrigine dosage and the incidence of malformation, Dr. Messenheimer said. The rate of malformations among women taking more than 400 mg/day was slightly elevated at 4%. But only 100 women were taking such a high dose, and the confidence intervals in the analysis were wide

Published reports have identified a significantly increased risk of major congenital malformations among women taking valproate as monotherapy (10.7%).

These studies prompted the American Epilepsy Society's pregnancy outcomes forum panel to recommend last year that valproate be avoided as a first-line therapy for any indication in women of childbearing age.

However, the lamotrigine registry could not determine whether valproate exposure alone could explain the higher frequency of defects in the lamotrigine/valproate group, said Dr. Messenheimer. The registry determined that because the numbers of antiepileptic drugs used may be inextricably tied to the frequency and severity of seizures, it would be difficult to assess the contribution of each of these factors to the risk of major malformations.

In adults, lamotrigine is approved as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome and for conversion to monotherapy in adults with partial seizures who are receiving treatment. It is also approved for maintenance treatment of bipolar disorder, and it is a pregnancy category C drug.

Physicians are asked to report exposed pregnancies to the international registry by calling 800-336-2176 as soon as the pregnancy is identified. The complete interim report of the International Lamotrigine Pregnancy Registry is available by calling the same number.

Factors such as race, maternal prepregnancy weight, and smoking during pregnancy all exert a significant, long-lasting influence on childhood weight by creating an early tendency for a child to become overweight, which carries forward as the child ages.

Findings from the investigation led by Pamela J. Salsberry, Ph.D., and Patricia B. Reagan, Ph.D., suggest that prepregnancy maternal counseling to lose weight and stop smoking, as well as aggressive action to help even young children lose weight, could help prevent childhood obesity (Pediatrics 2005;116:1329–38).

In addition, certain factors may help “to identify children who are at high risk for the development of overweight at very young ages, thus providing an opportunity to target intensive preventive strategies before the establishment of an unhealthy weight pattern,” wrote Dr. Salsberry and Dr. Reagan of Ohio State University, Columbus.

The investigators examined weight trends in 3,022 children, from age 2 years up to nearly 8 years. They also looked at the influence of conditions that might affect weight, including race, maternal prepregnancy weight, maternal smoking, and breastfeeding. The participants weighed in for the study at the mean ages of 3, 5, and 7 years.

At each of the three weigh-ins, black and Hispanic children were more likely to be overweight than white children, although the percentage of children who were overweight decreased in all race groups as the children aged.

There were no significant differences between boys and girls in their risk of being overweight.

A history of breastfeeding was associated with a significant reduction in the risk of being overweight, especially at the first weigh-in (19% decreased risk).

Children whose mothers were underweight before pregnancy had a decreased risk of becoming overweight, an effect that grew more significant as they aged.

Conversely, children whose mothers were obese before pregnancy were almost three times more likely to become overweight by the last weigh-in than were children of normal-weight mothers.

Children who were overweight at the first weigh-in were more likely to be increasingly overweight later on. Children who were overweight at the second weigh-in were more than 16 times more likely to be overweight at the last weigh-in, compared with those who were not overweight at the second weigh-in.

Factors such as race, maternal prepregnancy weight, and smoking during pregnancy all exert a significant, long-lasting influence on childhood weight by creating an early tendency for a child to become overweight, which carries forward as the child ages.

Findings from the investigation led by Pamela J. Salsberry, Ph.D., and Patricia B. Reagan, Ph.D., suggest that prepregnancy maternal counseling to lose weight and stop smoking, as well as aggressive action to help even young children lose weight, could help prevent childhood obesity (Pediatrics 2005;116:1329–38).

In addition, certain factors may help “to identify children who are at high risk for the development of overweight at very young ages, thus providing an opportunity to target intensive preventive strategies before the establishment of an unhealthy weight pattern,” wrote Dr. Salsberry and Dr. Reagan of Ohio State University, Columbus.

The investigators examined weight trends in 3,022 children, from age 2 years up to nearly 8 years. They also looked at the influence of conditions that might affect weight, including race, maternal prepregnancy weight, maternal smoking, and breastfeeding. The participants weighed in for the study at the mean ages of 3, 5, and 7 years.

At each of the three weigh-ins, black and Hispanic children were more likely to be overweight than white children, although the percentage of children who were overweight decreased in all race groups as the children aged.

There were no significant differences between boys and girls in their risk of being overweight.

A history of breastfeeding was associated with a significant reduction in the risk of being overweight, especially at the first weigh-in (19% decreased risk).

Children whose mothers were underweight before pregnancy had a decreased risk of becoming overweight, an effect that grew more significant as they aged.

Conversely, children whose mothers were obese before pregnancy were almost three times more likely to become overweight by the last weigh-in than were children of normal-weight mothers.

Children who were overweight at the first weigh-in were more likely to be increasingly overweight later on. Children who were overweight at the second weigh-in were more than 16 times more likely to be overweight at the last weigh-in, compared with those who were not overweight at the second weigh-in.

Factors such as race, maternal prepregnancy weight, and smoking during pregnancy all exert a significant, long-lasting influence on childhood weight by creating an early tendency for a child to become overweight, which carries forward as the child ages.

Findings from the investigation led by Pamela J. Salsberry, Ph.D., and Patricia B. Reagan, Ph.D., suggest that prepregnancy maternal counseling to lose weight and stop smoking, as well as aggressive action to help even young children lose weight, could help prevent childhood obesity (Pediatrics 2005;116:1329–38).

In addition, certain factors may help “to identify children who are at high risk for the development of overweight at very young ages, thus providing an opportunity to target intensive preventive strategies before the establishment of an unhealthy weight pattern,” wrote Dr. Salsberry and Dr. Reagan of Ohio State University, Columbus.

The investigators examined weight trends in 3,022 children, from age 2 years up to nearly 8 years. They also looked at the influence of conditions that might affect weight, including race, maternal prepregnancy weight, maternal smoking, and breastfeeding. The participants weighed in for the study at the mean ages of 3, 5, and 7 years.

At each of the three weigh-ins, black and Hispanic children were more likely to be overweight than white children, although the percentage of children who were overweight decreased in all race groups as the children aged.

There were no significant differences between boys and girls in their risk of being overweight.

A history of breastfeeding was associated with a significant reduction in the risk of being overweight, especially at the first weigh-in (19% decreased risk).

Children whose mothers were underweight before pregnancy had a decreased risk of becoming overweight, an effect that grew more significant as they aged.

Conversely, children whose mothers were obese before pregnancy were almost three times more likely to become overweight by the last weigh-in than were children of normal-weight mothers.

Children who were overweight at the first weigh-in were more likely to be increasingly overweight later on. Children who were overweight at the second weigh-in were more than 16 times more likely to be overweight at the last weigh-in, compared with those who were not overweight at the second weigh-in.

A significant annual increase in invasive melanoma, especially in the occurrence of tumors more than 1.5 mm thick in California Hispanics points to a “developing epidemic” of the cancer in that population, Dr. Myles Cockburn and associates have reported.

The results of their epidemiologic study, combined with studies suggesting that Hispanics don't practice skin self-exam or use sunscreen as often as recommended, mean that physicians should stress these prevention measures in Hispanic neighborhoods (Cancer 2006; doi 10.1002/cncr.21654).

“We recommend that efforts are undertaken immediately to target both primary and secondary prevention messages to Hispanic communities,” said Dr. Cockburn of the University of Southern California, Los Angeles, and his coinvestigators. “This effort should include information on sun avoidance, as well as information on self-screening and recommendations on regular skin checks by a qualified professional.”

The researchers used data from the California Cancer Registry to estimate the annual changes in invasive melanoma among Hispanics and non-Hispanic whites from 1988 to 2001.

During the study period, the incidence of the disease rose about 4% per year for white males, 3% per year for white females, 2% per year for Hispanic males, and nonsignificantly for Hispanic females.

However, the researchers said, the overall 2% annual increase for Hispanic males included an annual increase of 7% for the period of 1996–2001.

Even though the annual increase in melanoma was less in Hispanics than in whites, Hispanics had a far greater incidence of thick lesions at presentation. Tumors thicker than 1.5 mm at diagnosis accounted for 24% of lesions in white men but 35% of lesions in Hispanic men.

In addition, 54% of invasive melanomas among white males were thin (less than 0.75 mm), but only 44% of the lesions were thin in Hispanic men. The incidence of thin tumors diagnosed among whites increased by 5% per year during the study period but increased only nonsignificantly among Hispanics. The incidence of thick tumors among white men increased at 12% per year, compared with a 15% annual increase among Hispanic men.

The increase in thick tumors at diagnosis is troubling because thicker lesions have a substantially poorer prognosis than do thin lesions, the authors wrote.

“These trends have important ramifications for melanoma prevention, because primary and secondary melanoma prevention efforts are focused on non-Hispanic populations,” they said.

The study points up the importance of primary prevention counseling among patients with dark skin, many of whom believe their skin color offers some natural protection from the sun's effects, said Marianne Berwick, Ph.D., an epidemiologist with the University of New Mexico, Albuquerque.

“It is obviously important for Hispanic individuals, just as for all individuals, to look for new or changing spots on their skin—all over their skin, not only on places that are highly sun exposed—because melanoma can occur at any place on the body,” she said in an interview.

“We still don't know enough about sun exposure patterns or the utility of sunscreens in preventing melanoma to offer good advice for Hispanic individuals, but again, as with all individuals, it is important to avoid intense intermittent sun exposure and sunburns,” she said.

A significant annual increase in invasive melanoma, especially in the occurrence of tumors more than 1.5 mm thick in California Hispanics points to a “developing epidemic” of the cancer in that population, Dr. Myles Cockburn and associates have reported.

The results of their epidemiologic study, combined with studies suggesting that Hispanics don't practice skin self-exam or use sunscreen as often as recommended, mean that physicians should stress these prevention measures in Hispanic neighborhoods (Cancer 2006; doi 10.1002/cncr.21654).

“We recommend that efforts are undertaken immediately to target both primary and secondary prevention messages to Hispanic communities,” said Dr. Cockburn of the University of Southern California, Los Angeles, and his coinvestigators. “This effort should include information on sun avoidance, as well as information on self-screening and recommendations on regular skin checks by a qualified professional.”

The researchers used data from the California Cancer Registry to estimate the annual changes in invasive melanoma among Hispanics and non-Hispanic whites from 1988 to 2001.

During the study period, the incidence of the disease rose about 4% per year for white males, 3% per year for white females, 2% per year for Hispanic males, and nonsignificantly for Hispanic females.

However, the researchers said, the overall 2% annual increase for Hispanic males included an annual increase of 7% for the period of 1996–2001.

Even though the annual increase in melanoma was less in Hispanics than in whites, Hispanics had a far greater incidence of thick lesions at presentation. Tumors thicker than 1.5 mm at diagnosis accounted for 24% of lesions in white men but 35% of lesions in Hispanic men.

In addition, 54% of invasive melanomas among white males were thin (less than 0.75 mm), but only 44% of the lesions were thin in Hispanic men. The incidence of thin tumors diagnosed among whites increased by 5% per year during the study period but increased only nonsignificantly among Hispanics. The incidence of thick tumors among white men increased at 12% per year, compared with a 15% annual increase among Hispanic men.

The increase in thick tumors at diagnosis is troubling because thicker lesions have a substantially poorer prognosis than do thin lesions, the authors wrote.

“These trends have important ramifications for melanoma prevention, because primary and secondary melanoma prevention efforts are focused on non-Hispanic populations,” they said.

The study points up the importance of primary prevention counseling among patients with dark skin, many of whom believe their skin color offers some natural protection from the sun's effects, said Marianne Berwick, Ph.D., an epidemiologist with the University of New Mexico, Albuquerque.

“It is obviously important for Hispanic individuals, just as for all individuals, to look for new or changing spots on their skin—all over their skin, not only on places that are highly sun exposed—because melanoma can occur at any place on the body,” she said in an interview.

“We still don't know enough about sun exposure patterns or the utility of sunscreens in preventing melanoma to offer good advice for Hispanic individuals, but again, as with all individuals, it is important to avoid intense intermittent sun exposure and sunburns,” she said.

A significant annual increase in invasive melanoma, especially in the occurrence of tumors more than 1.5 mm thick in California Hispanics points to a “developing epidemic” of the cancer in that population, Dr. Myles Cockburn and associates have reported.

The results of their epidemiologic study, combined with studies suggesting that Hispanics don't practice skin self-exam or use sunscreen as often as recommended, mean that physicians should stress these prevention measures in Hispanic neighborhoods (Cancer 2006; doi 10.1002/cncr.21654).

“We recommend that efforts are undertaken immediately to target both primary and secondary prevention messages to Hispanic communities,” said Dr. Cockburn of the University of Southern California, Los Angeles, and his coinvestigators. “This effort should include information on sun avoidance, as well as information on self-screening and recommendations on regular skin checks by a qualified professional.”

The researchers used data from the California Cancer Registry to estimate the annual changes in invasive melanoma among Hispanics and non-Hispanic whites from 1988 to 2001.

During the study period, the incidence of the disease rose about 4% per year for white males, 3% per year for white females, 2% per year for Hispanic males, and nonsignificantly for Hispanic females.

However, the researchers said, the overall 2% annual increase for Hispanic males included an annual increase of 7% for the period of 1996–2001.

Even though the annual increase in melanoma was less in Hispanics than in whites, Hispanics had a far greater incidence of thick lesions at presentation. Tumors thicker than 1.5 mm at diagnosis accounted for 24% of lesions in white men but 35% of lesions in Hispanic men.

In addition, 54% of invasive melanomas among white males were thin (less than 0.75 mm), but only 44% of the lesions were thin in Hispanic men. The incidence of thin tumors diagnosed among whites increased by 5% per year during the study period but increased only nonsignificantly among Hispanics. The incidence of thick tumors among white men increased at 12% per year, compared with a 15% annual increase among Hispanic men.

The increase in thick tumors at diagnosis is troubling because thicker lesions have a substantially poorer prognosis than do thin lesions, the authors wrote.

“These trends have important ramifications for melanoma prevention, because primary and secondary melanoma prevention efforts are focused on non-Hispanic populations,” they said.

The study points up the importance of primary prevention counseling among patients with dark skin, many of whom believe their skin color offers some natural protection from the sun's effects, said Marianne Berwick, Ph.D., an epidemiologist with the University of New Mexico, Albuquerque.

“It is obviously important for Hispanic individuals, just as for all individuals, to look for new or changing spots on their skin—all over their skin, not only on places that are highly sun exposed—because melanoma can occur at any place on the body,” she said in an interview.

“We still don't know enough about sun exposure patterns or the utility of sunscreens in preventing melanoma to offer good advice for Hispanic individuals, but again, as with all individuals, it is important to avoid intense intermittent sun exposure and sunburns,” she said.

Abnormally high testosterone levels may play a part in sudden infant death syndrome, Michael Emery, Ph.D., and colleagues reported.

Their postmortem serum analyses of SIDS infants showed that testosterone levels in some males were comparable to the highest levels reported in living infants (preterm males), and the levels for some SIDS females were more than twice as high as any previously reported levels for any living female infants.

Identifying a link between causality and elevated testosterone will take more study, said Dr. Emery of the University of Miami. But since the hormone decreases ventilation and ventilatory drive during sleep in adults, the researchers postulate a link between hormonal pulses, neuronal excitability, and cardiorespiratory control (J. Pediatr. 2005;147:596–91).

The researchers examined postmortem serum testosterone and estradiol in 127 SIDS infants and 42 control infants who had died unexpectedly, but of known causes. Both male and female controls were significantly older than SIDS infants (males, 155 days vs. 97 days; females, 134 days vs. 86 days).

Testosterone levels were significantly higher in SIDS males, compared with control males (4.8 nmol vs. 2.2 nmol) and in SIDS females, compared with control females (2.4 nmol vs. 1.6 nmol). Estradiol levels did not differ between controls and SIDS infants. Testosterone levels decreased significantly with infant age among male and female SIDS infants but remained steady with age among controls. The difference in testosterone levels between the groups remained significant even when preterm infants (three SIDS and seven controls) were excluded.

Abnormally high testosterone levels may play a part in sudden infant death syndrome, Michael Emery, Ph.D., and colleagues reported.

Their postmortem serum analyses of SIDS infants showed that testosterone levels in some males were comparable to the highest levels reported in living infants (preterm males), and the levels for some SIDS females were more than twice as high as any previously reported levels for any living female infants.

Identifying a link between causality and elevated testosterone will take more study, said Dr. Emery of the University of Miami. But since the hormone decreases ventilation and ventilatory drive during sleep in adults, the researchers postulate a link between hormonal pulses, neuronal excitability, and cardiorespiratory control (J. Pediatr. 2005;147:596–91).

The researchers examined postmortem serum testosterone and estradiol in 127 SIDS infants and 42 control infants who had died unexpectedly, but of known causes. Both male and female controls were significantly older than SIDS infants (males, 155 days vs. 97 days; females, 134 days vs. 86 days).

Testosterone levels were significantly higher in SIDS males, compared with control males (4.8 nmol vs. 2.2 nmol) and in SIDS females, compared with control females (2.4 nmol vs. 1.6 nmol). Estradiol levels did not differ between controls and SIDS infants. Testosterone levels decreased significantly with infant age among male and female SIDS infants but remained steady with age among controls. The difference in testosterone levels between the groups remained significant even when preterm infants (three SIDS and seven controls) were excluded.

Abnormally high testosterone levels may play a part in sudden infant death syndrome, Michael Emery, Ph.D., and colleagues reported.

Their postmortem serum analyses of SIDS infants showed that testosterone levels in some males were comparable to the highest levels reported in living infants (preterm males), and the levels for some SIDS females were more than twice as high as any previously reported levels for any living female infants.

Identifying a link between causality and elevated testosterone will take more study, said Dr. Emery of the University of Miami. But since the hormone decreases ventilation and ventilatory drive during sleep in adults, the researchers postulate a link between hormonal pulses, neuronal excitability, and cardiorespiratory control (J. Pediatr. 2005;147:596–91).

The researchers examined postmortem serum testosterone and estradiol in 127 SIDS infants and 42 control infants who had died unexpectedly, but of known causes. Both male and female controls were significantly older than SIDS infants (males, 155 days vs. 97 days; females, 134 days vs. 86 days).

Testosterone levels were significantly higher in SIDS males, compared with control males (4.8 nmol vs. 2.2 nmol) and in SIDS females, compared with control females (2.4 nmol vs. 1.6 nmol). Estradiol levels did not differ between controls and SIDS infants. Testosterone levels decreased significantly with infant age among male and female SIDS infants but remained steady with age among controls. The difference in testosterone levels between the groups remained significant even when preterm infants (three SIDS and seven controls) were excluded.

Motor symptoms, including stiffness, tremors, and imbalance, are associated with a significantly increased risk of later Parkinson's disease.

“Subjective complaints related to motor function might indicate a very early phase of not-yet-diagnosable Parkinson's disease during which dopamine loss is not sufficient to produce overt typical PD symptoms but may result in subtle signs that are very mild or only intermittently present and therefore not likely to be detected in routine screening examination,” wrote Dr. Lonneke M. L. de Lau and colleagues (Arch. Neurol. 2006;63:doi:10.1001/archneur.63.3.noc50312).

Dr. de Lau of Erasmus Medical Center, Rotterdam, the Netherlands, prospectively followed 6,038 elderly patients (mean age 69 years) who were free of dementia and parkinsonian signs at baseline.

At baseline, 52% of the subjects reported at least one of the five typical features of the disease: stiffness (32%), tremor (11%), slow movement (21%), feeling of imbalance (11%), and falling (15%).

After a mean of 6 years' follow-up, 56 subjects had developed Parkinson's. Of those, 72% had reported at least one motor symptom during the initial assessment, and 41% had reported at least two symptoms.

Complaints of stiffness and tremor at baseline were each associated with more than a twofold increase in the risk of the disease, while a feeling of imbalance was associated with more than a threefold increased risk. Self-reported falling and slow movement were not significantly associated with an increased risk.

If a preclinical screening tool could be developed, the investigators said, it might be able to identify a window of opportunity where neuroprotective medication could someday slow or arrest the progress of the disease, the authors noted.

Motor symptoms, including stiffness, tremors, and imbalance, are associated with a significantly increased risk of later Parkinson's disease.

“Subjective complaints related to motor function might indicate a very early phase of not-yet-diagnosable Parkinson's disease during which dopamine loss is not sufficient to produce overt typical PD symptoms but may result in subtle signs that are very mild or only intermittently present and therefore not likely to be detected in routine screening examination,” wrote Dr. Lonneke M. L. de Lau and colleagues (Arch. Neurol. 2006;63:doi:10.1001/archneur.63.3.noc50312).

Dr. de Lau of Erasmus Medical Center, Rotterdam, the Netherlands, prospectively followed 6,038 elderly patients (mean age 69 years) who were free of dementia and parkinsonian signs at baseline.

At baseline, 52% of the subjects reported at least one of the five typical features of the disease: stiffness (32%), tremor (11%), slow movement (21%), feeling of imbalance (11%), and falling (15%).

After a mean of 6 years' follow-up, 56 subjects had developed Parkinson's. Of those, 72% had reported at least one motor symptom during the initial assessment, and 41% had reported at least two symptoms.

Complaints of stiffness and tremor at baseline were each associated with more than a twofold increase in the risk of the disease, while a feeling of imbalance was associated with more than a threefold increased risk. Self-reported falling and slow movement were not significantly associated with an increased risk.

If a preclinical screening tool could be developed, the investigators said, it might be able to identify a window of opportunity where neuroprotective medication could someday slow or arrest the progress of the disease, the authors noted.

Motor symptoms, including stiffness, tremors, and imbalance, are associated with a significantly increased risk of later Parkinson's disease.

“Subjective complaints related to motor function might indicate a very early phase of not-yet-diagnosable Parkinson's disease during which dopamine loss is not sufficient to produce overt typical PD symptoms but may result in subtle signs that are very mild or only intermittently present and therefore not likely to be detected in routine screening examination,” wrote Dr. Lonneke M. L. de Lau and colleagues (Arch. Neurol. 2006;63:doi:10.1001/archneur.63.3.noc50312).

Dr. de Lau of Erasmus Medical Center, Rotterdam, the Netherlands, prospectively followed 6,038 elderly patients (mean age 69 years) who were free of dementia and parkinsonian signs at baseline.

At baseline, 52% of the subjects reported at least one of the five typical features of the disease: stiffness (32%), tremor (11%), slow movement (21%), feeling of imbalance (11%), and falling (15%).

After a mean of 6 years' follow-up, 56 subjects had developed Parkinson's. Of those, 72% had reported at least one motor symptom during the initial assessment, and 41% had reported at least two symptoms.

Complaints of stiffness and tremor at baseline were each associated with more than a twofold increase in the risk of the disease, while a feeling of imbalance was associated with more than a threefold increased risk. Self-reported falling and slow movement were not significantly associated with an increased risk.

If a preclinical screening tool could be developed, the investigators said, it might be able to identify a window of opportunity where neuroprotective medication could someday slow or arrest the progress of the disease, the authors noted.