Obstetrics

RENO, NEV. — A retrospective study examining 473 pregnancies complicated by preeclampsia has uncovered a number of significant racial and ethnic differences in the expression of the disorder.

African American women with preeclampsia tend to have more severe hypertension and more often require antihypertensive medication than the population at large, according to a poster presentation by Amy Goodwin, M.D., of Case Western Reserve University, Cleveland, and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

While 37% of the full sample had severe hypertension at diagnosis, 45% of African American women had severe hypertension. African American women were also significantly more likely to require antihypertensive medication intrapartum (12% vs. 8.8%), post partum (18% vs. 13%), and at discharge (35% vs. 27%).

Non-Hispanic Caucasian women more frequently manifest severe hypertension with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. While 24% of the full sample exhibited HELLP, the rate among Caucasian women was 30%.

Hispanic women tend to present with preeclampsia later in gestation and with less severe disease than the rest of the population. They presented at a mean of 36 weeks of gestation vs. 34.4 weeks for the rest of the population, and a smaller proportion of them exhibited severe hypertension at diagnosis (27% vs. 37%).

The study found no significant differences by race or ethnicity in a number of other factors including proteinuria, eclampsia, intrauterine fetal distress, intrauterine growth retardation, abruption, and recurrent preeclampsia.

RENO, NEV. — A retrospective study examining 473 pregnancies complicated by preeclampsia has uncovered a number of significant racial and ethnic differences in the expression of the disorder.

African American women with preeclampsia tend to have more severe hypertension and more often require antihypertensive medication than the population at large, according to a poster presentation by Amy Goodwin, M.D., of Case Western Reserve University, Cleveland, and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

While 37% of the full sample had severe hypertension at diagnosis, 45% of African American women had severe hypertension. African American women were also significantly more likely to require antihypertensive medication intrapartum (12% vs. 8.8%), post partum (18% vs. 13%), and at discharge (35% vs. 27%).

Non-Hispanic Caucasian women more frequently manifest severe hypertension with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. While 24% of the full sample exhibited HELLP, the rate among Caucasian women was 30%.

Hispanic women tend to present with preeclampsia later in gestation and with less severe disease than the rest of the population. They presented at a mean of 36 weeks of gestation vs. 34.4 weeks for the rest of the population, and a smaller proportion of them exhibited severe hypertension at diagnosis (27% vs. 37%).

The study found no significant differences by race or ethnicity in a number of other factors including proteinuria, eclampsia, intrauterine fetal distress, intrauterine growth retardation, abruption, and recurrent preeclampsia.

RENO, NEV. — A retrospective study examining 473 pregnancies complicated by preeclampsia has uncovered a number of significant racial and ethnic differences in the expression of the disorder.

African American women with preeclampsia tend to have more severe hypertension and more often require antihypertensive medication than the population at large, according to a poster presentation by Amy Goodwin, M.D., of Case Western Reserve University, Cleveland, and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

While 37% of the full sample had severe hypertension at diagnosis, 45% of African American women had severe hypertension. African American women were also significantly more likely to require antihypertensive medication intrapartum (12% vs. 8.8%), post partum (18% vs. 13%), and at discharge (35% vs. 27%).

Non-Hispanic Caucasian women more frequently manifest severe hypertension with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. While 24% of the full sample exhibited HELLP, the rate among Caucasian women was 30%.

Hispanic women tend to present with preeclampsia later in gestation and with less severe disease than the rest of the population. They presented at a mean of 36 weeks of gestation vs. 34.4 weeks for the rest of the population, and a smaller proportion of them exhibited severe hypertension at diagnosis (27% vs. 37%).

The study found no significant differences by race or ethnicity in a number of other factors including proteinuria, eclampsia, intrauterine fetal distress, intrauterine growth retardation, abruption, and recurrent preeclampsia.

ORLANDO, FLA. — Pregnancy-induced hypertension and polycystic ovarian syndrome may be risk markers for later development of metabolic syndrome, Stephen Franks, M.D., said at an international conference on women, heart disease, and stroke.

The findings are important because they suggest that identification of those at risk for metabolic syndrome, and interventions to reduce that risk, can begin as early as adolescence, when polycystic ovarian syndrome (PCOS) typically emerges, said Dr. Franks of the Imperial College London.

The prevalence of metabolic syndrome in women is “staggeringly high,” and the hazard ratio for cardiovascular mortality in women with metabolic syndrome is nearly 2.8. For diabetes, the hazard ratio is 6.3.

“So there is an enormously increased risk of heart disease and diabetes; it would be very useful if we could try to predict [metabolic syndrome] and identify those factors that alert us to the possibility of a high risk for metabolic syndrome,” Dr. Franks said.

Several studies show that pregnancy-induced hypertension—including gestational hypertension and preeclampsia—is associated with increased prevalence of markers of metabolic syndrome as well as a higher lifetime risk of heart disease. In one study of nearly 2,700 women with prior gestational hypertension or preeclampsia and an average age of 31 years, the conditions were shown to be associated with increased systolic and diastolic blood pressure, as well as higher body mass index, waist-hip ratio, and other metabolic syndrome markers, compared with a reference population.

PCOS, which affects more than 5% of women of reproductive age, also appears to be associated with risk for metabolic syndrome. Since it presents so early, it may be the first identifiable sign predicting metabolic syndrome, Dr. Franks said.

The definitions of metabolic syndrome vary from study to study, so it is difficult to say just how common metabolic syndrome is in those with PCOS, but one review article suggests the prevalence is about 50% among obese women with PCOS, he said.

Obesity, which already is established as a marker for metabolic syndrome, appears to act as an amplifier of other etiologic factors, including pregnancy-induced hypertension and PCOS.

Furthermore, at least one study showed that PCOS patients who are obese in their teen years and who remain obese in adulthood have an even greater risk of developing metabolic syndrome.

A fundamental abnormality seen in obese PCOS patients is increased insulin resistance and higher insulin levels, compared with age- and weight-matched controls. In the normal population, as body mass index increases insulin levels also increase, but in PCOS this curve is steeper. In one study of more than 300 women with an average age of 57 years and a history of PCOS, the risk of diabetes was increased nearly threefold compared with controls.

Estimates of PCOS prevalence in young women range from 10% to 40% and the relationship between PCOS and obesity suggests the prevalence is set to increase.

“Adults are getting fatter, children are getting fatter, and obese children become obese adults,” Dr. Franks said.

But there is hope, because even modest reductions in weight with caloric restriction and exercise is proven to modify a woman's risk profile, he said.

Young women with PCOS or pregnancy-induced hypertension—particularly those who are obese—should be identified as being at risk for metabolic syndrome, and interventions should be initiated.

ORLANDO, FLA. — Pregnancy-induced hypertension and polycystic ovarian syndrome may be risk markers for later development of metabolic syndrome, Stephen Franks, M.D., said at an international conference on women, heart disease, and stroke.

The findings are important because they suggest that identification of those at risk for metabolic syndrome, and interventions to reduce that risk, can begin as early as adolescence, when polycystic ovarian syndrome (PCOS) typically emerges, said Dr. Franks of the Imperial College London.

The prevalence of metabolic syndrome in women is “staggeringly high,” and the hazard ratio for cardiovascular mortality in women with metabolic syndrome is nearly 2.8. For diabetes, the hazard ratio is 6.3.

“So there is an enormously increased risk of heart disease and diabetes; it would be very useful if we could try to predict [metabolic syndrome] and identify those factors that alert us to the possibility of a high risk for metabolic syndrome,” Dr. Franks said.

Several studies show that pregnancy-induced hypertension—including gestational hypertension and preeclampsia—is associated with increased prevalence of markers of metabolic syndrome as well as a higher lifetime risk of heart disease. In one study of nearly 2,700 women with prior gestational hypertension or preeclampsia and an average age of 31 years, the conditions were shown to be associated with increased systolic and diastolic blood pressure, as well as higher body mass index, waist-hip ratio, and other metabolic syndrome markers, compared with a reference population.

PCOS, which affects more than 5% of women of reproductive age, also appears to be associated with risk for metabolic syndrome. Since it presents so early, it may be the first identifiable sign predicting metabolic syndrome, Dr. Franks said.

The definitions of metabolic syndrome vary from study to study, so it is difficult to say just how common metabolic syndrome is in those with PCOS, but one review article suggests the prevalence is about 50% among obese women with PCOS, he said.

Obesity, which already is established as a marker for metabolic syndrome, appears to act as an amplifier of other etiologic factors, including pregnancy-induced hypertension and PCOS.

Furthermore, at least one study showed that PCOS patients who are obese in their teen years and who remain obese in adulthood have an even greater risk of developing metabolic syndrome.

A fundamental abnormality seen in obese PCOS patients is increased insulin resistance and higher insulin levels, compared with age- and weight-matched controls. In the normal population, as body mass index increases insulin levels also increase, but in PCOS this curve is steeper. In one study of more than 300 women with an average age of 57 years and a history of PCOS, the risk of diabetes was increased nearly threefold compared with controls.

Estimates of PCOS prevalence in young women range from 10% to 40% and the relationship between PCOS and obesity suggests the prevalence is set to increase.

“Adults are getting fatter, children are getting fatter, and obese children become obese adults,” Dr. Franks said.

But there is hope, because even modest reductions in weight with caloric restriction and exercise is proven to modify a woman's risk profile, he said.

Young women with PCOS or pregnancy-induced hypertension—particularly those who are obese—should be identified as being at risk for metabolic syndrome, and interventions should be initiated.

ORLANDO, FLA. — Pregnancy-induced hypertension and polycystic ovarian syndrome may be risk markers for later development of metabolic syndrome, Stephen Franks, M.D., said at an international conference on women, heart disease, and stroke.

The findings are important because they suggest that identification of those at risk for metabolic syndrome, and interventions to reduce that risk, can begin as early as adolescence, when polycystic ovarian syndrome (PCOS) typically emerges, said Dr. Franks of the Imperial College London.

The prevalence of metabolic syndrome in women is “staggeringly high,” and the hazard ratio for cardiovascular mortality in women with metabolic syndrome is nearly 2.8. For diabetes, the hazard ratio is 6.3.

“So there is an enormously increased risk of heart disease and diabetes; it would be very useful if we could try to predict [metabolic syndrome] and identify those factors that alert us to the possibility of a high risk for metabolic syndrome,” Dr. Franks said.

Several studies show that pregnancy-induced hypertension—including gestational hypertension and preeclampsia—is associated with increased prevalence of markers of metabolic syndrome as well as a higher lifetime risk of heart disease. In one study of nearly 2,700 women with prior gestational hypertension or preeclampsia and an average age of 31 years, the conditions were shown to be associated with increased systolic and diastolic blood pressure, as well as higher body mass index, waist-hip ratio, and other metabolic syndrome markers, compared with a reference population.

PCOS, which affects more than 5% of women of reproductive age, also appears to be associated with risk for metabolic syndrome. Since it presents so early, it may be the first identifiable sign predicting metabolic syndrome, Dr. Franks said.

The definitions of metabolic syndrome vary from study to study, so it is difficult to say just how common metabolic syndrome is in those with PCOS, but one review article suggests the prevalence is about 50% among obese women with PCOS, he said.

Obesity, which already is established as a marker for metabolic syndrome, appears to act as an amplifier of other etiologic factors, including pregnancy-induced hypertension and PCOS.

Furthermore, at least one study showed that PCOS patients who are obese in their teen years and who remain obese in adulthood have an even greater risk of developing metabolic syndrome.

A fundamental abnormality seen in obese PCOS patients is increased insulin resistance and higher insulin levels, compared with age- and weight-matched controls. In the normal population, as body mass index increases insulin levels also increase, but in PCOS this curve is steeper. In one study of more than 300 women with an average age of 57 years and a history of PCOS, the risk of diabetes was increased nearly threefold compared with controls.

Estimates of PCOS prevalence in young women range from 10% to 40% and the relationship between PCOS and obesity suggests the prevalence is set to increase.

“Adults are getting fatter, children are getting fatter, and obese children become obese adults,” Dr. Franks said.

But there is hope, because even modest reductions in weight with caloric restriction and exercise is proven to modify a woman's risk profile, he said.

Young women with PCOS or pregnancy-induced hypertension—particularly those who are obese—should be identified as being at risk for metabolic syndrome, and interventions should be initiated.

RENO, NEV. — A less-than-perfect score on a five-item, 10-point cardiovascular profile predicts a poorer outcome for a fetus with heart failure, according to a poster presented by Aleksandra Roczek, M.D., at the annual meeting of the Society for Maternal-Fetal Medicine.

Fetuses in this high-risk group warrant closer follow-up and management from both the obstetric and prenatal cardiology point of view, concluded Dr. Roczek of the University of South Florida, Tampa.

Poor scores on three of the five items—cardiomegaly, hydrops, and venous Doppler measurements—were especially predictive of mortality, Dr. Roczek noted.

She and her colleagues conducted a retrospective examination of 92 pregnancies where fetuses were judged to be at risk for heart failure on the basis of echocardiography and Doppler velocimetry. Of those fetuses, 53 (57%) survived and 39 (43%) did not.

The cardiovascular profile score awards two points each for absence of hydrops, normal venous Doppler, heart function, arterial Doppler, and heart size. The score in each domain is decreased by two points for severe signs and by one point for intermediate signs.

Fetuses with abnormal venous Doppler had a mortality rate of 64%. Mortality was 62.5% in fetuses with hydrops, and 60% in fetuses with cardiomegaly.

The other two factors were less predictive of mortality. Fetuses with abnormal heart function had a 33% mortality, and those with abnormal arterial Doppler had a 17% mortality.

RENO, NEV. — A less-than-perfect score on a five-item, 10-point cardiovascular profile predicts a poorer outcome for a fetus with heart failure, according to a poster presented by Aleksandra Roczek, M.D., at the annual meeting of the Society for Maternal-Fetal Medicine.

Fetuses in this high-risk group warrant closer follow-up and management from both the obstetric and prenatal cardiology point of view, concluded Dr. Roczek of the University of South Florida, Tampa.

Poor scores on three of the five items—cardiomegaly, hydrops, and venous Doppler measurements—were especially predictive of mortality, Dr. Roczek noted.

She and her colleagues conducted a retrospective examination of 92 pregnancies where fetuses were judged to be at risk for heart failure on the basis of echocardiography and Doppler velocimetry. Of those fetuses, 53 (57%) survived and 39 (43%) did not.

The cardiovascular profile score awards two points each for absence of hydrops, normal venous Doppler, heart function, arterial Doppler, and heart size. The score in each domain is decreased by two points for severe signs and by one point for intermediate signs.

Fetuses with abnormal venous Doppler had a mortality rate of 64%. Mortality was 62.5% in fetuses with hydrops, and 60% in fetuses with cardiomegaly.

The other two factors were less predictive of mortality. Fetuses with abnormal heart function had a 33% mortality, and those with abnormal arterial Doppler had a 17% mortality.

RENO, NEV. — A less-than-perfect score on a five-item, 10-point cardiovascular profile predicts a poorer outcome for a fetus with heart failure, according to a poster presented by Aleksandra Roczek, M.D., at the annual meeting of the Society for Maternal-Fetal Medicine.

Fetuses in this high-risk group warrant closer follow-up and management from both the obstetric and prenatal cardiology point of view, concluded Dr. Roczek of the University of South Florida, Tampa.

Poor scores on three of the five items—cardiomegaly, hydrops, and venous Doppler measurements—were especially predictive of mortality, Dr. Roczek noted.

She and her colleagues conducted a retrospective examination of 92 pregnancies where fetuses were judged to be at risk for heart failure on the basis of echocardiography and Doppler velocimetry. Of those fetuses, 53 (57%) survived and 39 (43%) did not.

The cardiovascular profile score awards two points each for absence of hydrops, normal venous Doppler, heart function, arterial Doppler, and heart size. The score in each domain is decreased by two points for severe signs and by one point for intermediate signs.

Fetuses with abnormal venous Doppler had a mortality rate of 64%. Mortality was 62.5% in fetuses with hydrops, and 60% in fetuses with cardiomegaly.

The other two factors were less predictive of mortality. Fetuses with abnormal heart function had a 33% mortality, and those with abnormal arterial Doppler had a 17% mortality.

RENO, NEV. — An increased nuchal translucency thickness can predict congenital heart disease in a euploid fetus and indicate pregnancies that should be referred for fetal echocardiography, according to data from the large First and Second Trimester Evaluation of Risk for Aneuploidy study.

When nuchal translucency thickness found on ultrasound in the first trimester is at least 2 multiples of the appropriate gestational median (MoM), the risk of a major congenital heart defect is 14 times higher than normal, Lynn L. Simpson, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

Moreover, as the MoM increased, so did the likelihood of having such a defect: When the MoM was at least 3, the risk was 51 times higher than normal.

Overall, the sensitivity of nuchal translucency screening for major congenital heart defects is low (less than 20%) and therefore is not a good screening test on its own, said Dr. Simpson of the department of obstetrics and gynecology at Columbia University, New York.

However, when nuchal translucency screening is added to the standard first trimester evaluation, it can pick up cases of major congenital heart defects that otherwise would have been missed.

With the cutoff of a nuchal thickness that is at least 2 MoM, about 1% of all infants would end up possibly being referred for fetal echocardiography, Dr. Simpson said.

The First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) study had 33,968 patients enrolled whose records could be reviewed for cardiac outcome. Among those, there were 195 cases of congenital heart disease (an incidence of 5.7/1,000), of which 43 were defined by the authors as major defects. Major defects were those associated with a poor perinatal outcome or ductal dependency after birth.

The majority of cases of major cardiac defect occurred in fetuses with a nuchal translucency thickness less than the 2 MoM cutoff (81%), hence the low sensitivity of the test. But because the specificity of the test is very high in the absence of aneuploidy, the negative predictive value of the test at the 2 MoM cutoff is greater than 99%, Dr. Simpson said.

RENO, NEV. — An increased nuchal translucency thickness can predict congenital heart disease in a euploid fetus and indicate pregnancies that should be referred for fetal echocardiography, according to data from the large First and Second Trimester Evaluation of Risk for Aneuploidy study.

When nuchal translucency thickness found on ultrasound in the first trimester is at least 2 multiples of the appropriate gestational median (MoM), the risk of a major congenital heart defect is 14 times higher than normal, Lynn L. Simpson, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

Moreover, as the MoM increased, so did the likelihood of having such a defect: When the MoM was at least 3, the risk was 51 times higher than normal.

Overall, the sensitivity of nuchal translucency screening for major congenital heart defects is low (less than 20%) and therefore is not a good screening test on its own, said Dr. Simpson of the department of obstetrics and gynecology at Columbia University, New York.

However, when nuchal translucency screening is added to the standard first trimester evaluation, it can pick up cases of major congenital heart defects that otherwise would have been missed.

With the cutoff of a nuchal thickness that is at least 2 MoM, about 1% of all infants would end up possibly being referred for fetal echocardiography, Dr. Simpson said.

The First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) study had 33,968 patients enrolled whose records could be reviewed for cardiac outcome. Among those, there were 195 cases of congenital heart disease (an incidence of 5.7/1,000), of which 43 were defined by the authors as major defects. Major defects were those associated with a poor perinatal outcome or ductal dependency after birth.

The majority of cases of major cardiac defect occurred in fetuses with a nuchal translucency thickness less than the 2 MoM cutoff (81%), hence the low sensitivity of the test. But because the specificity of the test is very high in the absence of aneuploidy, the negative predictive value of the test at the 2 MoM cutoff is greater than 99%, Dr. Simpson said.

RENO, NEV. — An increased nuchal translucency thickness can predict congenital heart disease in a euploid fetus and indicate pregnancies that should be referred for fetal echocardiography, according to data from the large First and Second Trimester Evaluation of Risk for Aneuploidy study.

When nuchal translucency thickness found on ultrasound in the first trimester is at least 2 multiples of the appropriate gestational median (MoM), the risk of a major congenital heart defect is 14 times higher than normal, Lynn L. Simpson, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

Moreover, as the MoM increased, so did the likelihood of having such a defect: When the MoM was at least 3, the risk was 51 times higher than normal.

Overall, the sensitivity of nuchal translucency screening for major congenital heart defects is low (less than 20%) and therefore is not a good screening test on its own, said Dr. Simpson of the department of obstetrics and gynecology at Columbia University, New York.

However, when nuchal translucency screening is added to the standard first trimester evaluation, it can pick up cases of major congenital heart defects that otherwise would have been missed.

With the cutoff of a nuchal thickness that is at least 2 MoM, about 1% of all infants would end up possibly being referred for fetal echocardiography, Dr. Simpson said.

The First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) study had 33,968 patients enrolled whose records could be reviewed for cardiac outcome. Among those, there were 195 cases of congenital heart disease (an incidence of 5.7/1,000), of which 43 were defined by the authors as major defects. Major defects were those associated with a poor perinatal outcome or ductal dependency after birth.

The majority of cases of major cardiac defect occurred in fetuses with a nuchal translucency thickness less than the 2 MoM cutoff (81%), hence the low sensitivity of the test. But because the specificity of the test is very high in the absence of aneuploidy, the negative predictive value of the test at the 2 MoM cutoff is greater than 99%, Dr. Simpson said.

RENO, NEV. — Saline amnioinfusion for labors with thickly meconium-stained amniotic fluid does not prevent meconium aspiration syndrome, William D. Fraser, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

In an international, randomized, prospective trial of laboring women with thickly stained fluid, there was a 4% rate of moderate or severe meconium aspiration syndrome or death in 985 neonates born after amnioinfusion, compared with a 3% rate in 988 neonates born to women who did not undergo the procedure, said Dr. Fraser of the University of Montreal.

“Our evidence does not support amnioinfusion,” Dr. Fraser said.

The findings of the current study run counter to those of some previous studies, including a recent metaanalysis of 12 trials, which concluded that the practice reduces by two-thirds the rate of meconium aspiration syndrome.

The metaanalysis, however, was dominated by a single study conducted in Zimbabwe, where modern labor and delivery practices usually aren't implemented, Dr. Fraser said, adding that the other studies that showed a positive benefit from amnioinfusion were much smaller than his.

His study was conducted in 56 different centers in 13 countries, including South Africa, Canada, and the United States, with the majority of patients enrolled in South Africa. There was no significant difference in results obtained from the various countries, Dr. Fraser said.

The study participants were at greater than 36 weeks' gestation and were stratified for randomization to one of two groups: one group with fetal heart-rate decelerations and one without decelerations. There was no significant difference in results between these two groups.

The investigators also saw a slight trend toward cesarean delivery in the group that received amnioinfusion (32% versus 29%), Dr. Fraser noted.

RENO, NEV. — Saline amnioinfusion for labors with thickly meconium-stained amniotic fluid does not prevent meconium aspiration syndrome, William D. Fraser, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

In an international, randomized, prospective trial of laboring women with thickly stained fluid, there was a 4% rate of moderate or severe meconium aspiration syndrome or death in 985 neonates born after amnioinfusion, compared with a 3% rate in 988 neonates born to women who did not undergo the procedure, said Dr. Fraser of the University of Montreal.

“Our evidence does not support amnioinfusion,” Dr. Fraser said.

The findings of the current study run counter to those of some previous studies, including a recent metaanalysis of 12 trials, which concluded that the practice reduces by two-thirds the rate of meconium aspiration syndrome.

The metaanalysis, however, was dominated by a single study conducted in Zimbabwe, where modern labor and delivery practices usually aren't implemented, Dr. Fraser said, adding that the other studies that showed a positive benefit from amnioinfusion were much smaller than his.

His study was conducted in 56 different centers in 13 countries, including South Africa, Canada, and the United States, with the majority of patients enrolled in South Africa. There was no significant difference in results obtained from the various countries, Dr. Fraser said.

The study participants were at greater than 36 weeks' gestation and were stratified for randomization to one of two groups: one group with fetal heart-rate decelerations and one without decelerations. There was no significant difference in results between these two groups.

The investigators also saw a slight trend toward cesarean delivery in the group that received amnioinfusion (32% versus 29%), Dr. Fraser noted.

RENO, NEV. — Saline amnioinfusion for labors with thickly meconium-stained amniotic fluid does not prevent meconium aspiration syndrome, William D. Fraser, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

In an international, randomized, prospective trial of laboring women with thickly stained fluid, there was a 4% rate of moderate or severe meconium aspiration syndrome or death in 985 neonates born after amnioinfusion, compared with a 3% rate in 988 neonates born to women who did not undergo the procedure, said Dr. Fraser of the University of Montreal.

“Our evidence does not support amnioinfusion,” Dr. Fraser said.

The findings of the current study run counter to those of some previous studies, including a recent metaanalysis of 12 trials, which concluded that the practice reduces by two-thirds the rate of meconium aspiration syndrome.

The metaanalysis, however, was dominated by a single study conducted in Zimbabwe, where modern labor and delivery practices usually aren't implemented, Dr. Fraser said, adding that the other studies that showed a positive benefit from amnioinfusion were much smaller than his.

His study was conducted in 56 different centers in 13 countries, including South Africa, Canada, and the United States, with the majority of patients enrolled in South Africa. There was no significant difference in results obtained from the various countries, Dr. Fraser said.

The study participants were at greater than 36 weeks' gestation and were stratified for randomization to one of two groups: one group with fetal heart-rate decelerations and one without decelerations. There was no significant difference in results between these two groups.

The investigators also saw a slight trend toward cesarean delivery in the group that received amnioinfusion (32% versus 29%), Dr. Fraser noted.

ATLANTA — Influenza vaccine recommendations for the 2005-2006 season will seek to minimize disruption in the event of another shortage and will strongly urge annual vaccination of health care workers against influenza.

A risk-based prioritization scheme for the inactivated (injectable) influenza vaccine and a stronger recommendation for immunization of health care workers with the live attenuated influenza vaccine (LAIV, or FluMist) are among the proposed changes to the yearly influenza vaccine statement discussed at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

There is no concrete information to suggest that there will be flu vaccine supply problems again next fall, but disruptions have occurred in four of the five previous seasons. Contributing factors have included production issues and regulatory actions. In addition, two manufacturers have left the market.

Thus “there is uncertainty about the 2005-2006 vaccine supply,” Keiji Fukuda, M.D., of the CDC's influenza branch, told the committee.

Although the final language was still being worked out at press time, ACIP voted in principle to support a three-tiered prioritization system in which high-risk groups are ranked based on rates of influenza-associated mortality and hospitalization in the United States. (See box.)

The tiering scheme applies only to the inactivated influenza vaccine, and the document is expected to contain a strong recommendation for the preferential use of LAIV for healthy persons aged 5-49 years—particularly health care workers—in the event of a shortage.

During periods of vaccine shortfall, persons listed in tier 1 should be vaccinated preferentially, followed by tiers 2 and 3. The subdivisions within tier 1 would be used only in the unlikely event that the local vaccine supply is extremely limited. Should that occur, state and local health officials should vaccinate the two populations in tier 1A—those aged 65 and older with comorbid conditions and long-term care facility residents—before all others.

In all other vaccine shortfall situations, populations falling into tiers 1A, 1B, and 1C should be considered equivalent and should be vaccinated simultaneously. Eligible individuals in tiers 1C, 2, and 3 should be encouraged to receive LAIV (those in tier 1C—health care personnel and close contacts of children less than 6 months of age—could receive either the injectable vaccine or LAIV, depending upon supply circumstances).

The committee also voted to include much stronger language about immunization of health care workers overall, regardless of vaccine supply status. Among the likely recommendations are that campaigns be organized to encourage workplace efforts to improve immunization rates among health care workers, and that such rates be regularly measured and reported.

“Giving the influenza vaccine to health care workers keeps them at work. It becomes a quality issue,” said ACIP member Jon S. Abramson, M.D. “When you increase the number of patients a nurse has to take care of [due to absenteeism], it affects patient outcome.”

Proposed Tiering in the Event of an Influenza Vaccine Shortage

Group 1A

▸ Aged 65 years and older with comorbid conditions.

▸ Long-term care facility residents.

Group 1B

▸ Pregnant women.

▸ Aged 2-64 years with comorbid conditions.

▸ Aged 65 years and older without comorbid conditions.

▸ Aged 6-23 months.

Group 1C

▸ Health care personnel.

▸ Close contacts of children less than 6 months of age.

Group 2

▸ Contacts of high-risk children and adults.

▸ Healthy persons aged 50-64 years.

Group 3

▸ Aged 2-49 years without high-risk conditions.

Source: Dr. Fukuda

ATLANTA — Influenza vaccine recommendations for the 2005-2006 season will seek to minimize disruption in the event of another shortage and will strongly urge annual vaccination of health care workers against influenza.

A risk-based prioritization scheme for the inactivated (injectable) influenza vaccine and a stronger recommendation for immunization of health care workers with the live attenuated influenza vaccine (LAIV, or FluMist) are among the proposed changes to the yearly influenza vaccine statement discussed at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

There is no concrete information to suggest that there will be flu vaccine supply problems again next fall, but disruptions have occurred in four of the five previous seasons. Contributing factors have included production issues and regulatory actions. In addition, two manufacturers have left the market.

Thus “there is uncertainty about the 2005-2006 vaccine supply,” Keiji Fukuda, M.D., of the CDC's influenza branch, told the committee.

Although the final language was still being worked out at press time, ACIP voted in principle to support a three-tiered prioritization system in which high-risk groups are ranked based on rates of influenza-associated mortality and hospitalization in the United States. (See box.)

The tiering scheme applies only to the inactivated influenza vaccine, and the document is expected to contain a strong recommendation for the preferential use of LAIV for healthy persons aged 5-49 years—particularly health care workers—in the event of a shortage.

During periods of vaccine shortfall, persons listed in tier 1 should be vaccinated preferentially, followed by tiers 2 and 3. The subdivisions within tier 1 would be used only in the unlikely event that the local vaccine supply is extremely limited. Should that occur, state and local health officials should vaccinate the two populations in tier 1A—those aged 65 and older with comorbid conditions and long-term care facility residents—before all others.

In all other vaccine shortfall situations, populations falling into tiers 1A, 1B, and 1C should be considered equivalent and should be vaccinated simultaneously. Eligible individuals in tiers 1C, 2, and 3 should be encouraged to receive LAIV (those in tier 1C—health care personnel and close contacts of children less than 6 months of age—could receive either the injectable vaccine or LAIV, depending upon supply circumstances).

The committee also voted to include much stronger language about immunization of health care workers overall, regardless of vaccine supply status. Among the likely recommendations are that campaigns be organized to encourage workplace efforts to improve immunization rates among health care workers, and that such rates be regularly measured and reported.

“Giving the influenza vaccine to health care workers keeps them at work. It becomes a quality issue,” said ACIP member Jon S. Abramson, M.D. “When you increase the number of patients a nurse has to take care of [due to absenteeism], it affects patient outcome.”

Proposed Tiering in the Event of an Influenza Vaccine Shortage

Group 1A

▸ Aged 65 years and older with comorbid conditions.

▸ Long-term care facility residents.

Group 1B

▸ Pregnant women.

▸ Aged 2-64 years with comorbid conditions.

▸ Aged 65 years and older without comorbid conditions.

▸ Aged 6-23 months.

Group 1C

▸ Health care personnel.

▸ Close contacts of children less than 6 months of age.

Group 2

▸ Contacts of high-risk children and adults.

▸ Healthy persons aged 50-64 years.

Group 3

▸ Aged 2-49 years without high-risk conditions.

Source: Dr. Fukuda

ATLANTA — Influenza vaccine recommendations for the 2005-2006 season will seek to minimize disruption in the event of another shortage and will strongly urge annual vaccination of health care workers against influenza.

A risk-based prioritization scheme for the inactivated (injectable) influenza vaccine and a stronger recommendation for immunization of health care workers with the live attenuated influenza vaccine (LAIV, or FluMist) are among the proposed changes to the yearly influenza vaccine statement discussed at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

There is no concrete information to suggest that there will be flu vaccine supply problems again next fall, but disruptions have occurred in four of the five previous seasons. Contributing factors have included production issues and regulatory actions. In addition, two manufacturers have left the market.

Thus “there is uncertainty about the 2005-2006 vaccine supply,” Keiji Fukuda, M.D., of the CDC's influenza branch, told the committee.

Although the final language was still being worked out at press time, ACIP voted in principle to support a three-tiered prioritization system in which high-risk groups are ranked based on rates of influenza-associated mortality and hospitalization in the United States. (See box.)

The tiering scheme applies only to the inactivated influenza vaccine, and the document is expected to contain a strong recommendation for the preferential use of LAIV for healthy persons aged 5-49 years—particularly health care workers—in the event of a shortage.

During periods of vaccine shortfall, persons listed in tier 1 should be vaccinated preferentially, followed by tiers 2 and 3. The subdivisions within tier 1 would be used only in the unlikely event that the local vaccine supply is extremely limited. Should that occur, state and local health officials should vaccinate the two populations in tier 1A—those aged 65 and older with comorbid conditions and long-term care facility residents—before all others.

In all other vaccine shortfall situations, populations falling into tiers 1A, 1B, and 1C should be considered equivalent and should be vaccinated simultaneously. Eligible individuals in tiers 1C, 2, and 3 should be encouraged to receive LAIV (those in tier 1C—health care personnel and close contacts of children less than 6 months of age—could receive either the injectable vaccine or LAIV, depending upon supply circumstances).

The committee also voted to include much stronger language about immunization of health care workers overall, regardless of vaccine supply status. Among the likely recommendations are that campaigns be organized to encourage workplace efforts to improve immunization rates among health care workers, and that such rates be regularly measured and reported.

“Giving the influenza vaccine to health care workers keeps them at work. It becomes a quality issue,” said ACIP member Jon S. Abramson, M.D. “When you increase the number of patients a nurse has to take care of [due to absenteeism], it affects patient outcome.”

Proposed Tiering in the Event of an Influenza Vaccine Shortage

Group 1A

▸ Aged 65 years and older with comorbid conditions.

▸ Long-term care facility residents.

Group 1B

▸ Pregnant women.

▸ Aged 2-64 years with comorbid conditions.

▸ Aged 65 years and older without comorbid conditions.

▸ Aged 6-23 months.

Group 1C

▸ Health care personnel.

▸ Close contacts of children less than 6 months of age.

Group 2

▸ Contacts of high-risk children and adults.

▸ Healthy persons aged 50-64 years.

Group 3

▸ Aged 2-49 years without high-risk conditions.

Source: Dr. Fukuda

RENO, NEV. — The inactivated influenza vaccine is safe and effective for women in the second half of pregnancy, results of a large prospective study suggest.

When given at least 2 weeks before exposure, the vaccine reduced the rate of influenza 19-fold, with no evidence of worsening in several obstetric and neonatal outcomes, including premature rupture of membranes, stillbirths, low birth weight, neonatal pneumonia, neonatal death, and major malformations.

The study, which was conducted at the University of Texas Southwestern Medical Center at Dallas, included 2,889 women who received the inactivatd influenza vaccine during the 2003-2004 flu season, which began earlier than usual and was moderately severe. They were compared with 1,988 gestational age-matched pregnant women who did not get vaccinated during the same time period, Jeanne S. Sheffield, M.D., and her associates wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

Six women in the vaccinated group (2.4 per 1,000 women) and 13 in the nonvaccinated group (6.5 per 1,000 women) developed laboratory-confirmed influenza, a statistically significant difference. The overall efficacy of the vaccine was 68%.

But when the analysis was restricted to women who developed influenza more than 2 weeks after vaccination (the time required to develop immunity), there was only one case of influenza (0.4 per 1,000 women), yielding an efficacy of 94%.

The relative risk of developing influenza decreased almost 19-fold when the vaccine was given 2 weeks before exposure.

There were some statistically significant differences between the groups, study co-investigator Scott W. Roberts, M.D., said in an interview with this newspaper.

Women in the vaccination group were seen more frequently than the controls. Those in the vaccination group also had more repeat cesarean deliveries and cases of dystocia, and larger body-mass indexes, the researchers said.

The estimated gestational age (EGA) at delivery was slightly, but significantly, higher in the vaccination group (39.6 weeks), compared with the unvaccinated group (39.4 weeks).

The vaccinated group had significantly fewer births with EGAs of 36 weeks or less, compared with the unvaccinated group. Infants whose mothers were vaccinated were significantly less likely to go to the intensive care nursery.

Women in the vaccinated group were significantly more likely to undergo a cesarean delivery (27% vs. 23%). Dr. Roberts said it is possible that most or all of these differences reflect the fact that the women who were seen in the clinic were more likely to choose getting the vaccination.

Women who were vaccinated had infants that were much less likely to be admitted to the intensive care nursery. Lynda Banzi

RENO, NEV. — The inactivated influenza vaccine is safe and effective for women in the second half of pregnancy, results of a large prospective study suggest.

When given at least 2 weeks before exposure, the vaccine reduced the rate of influenza 19-fold, with no evidence of worsening in several obstetric and neonatal outcomes, including premature rupture of membranes, stillbirths, low birth weight, neonatal pneumonia, neonatal death, and major malformations.

The study, which was conducted at the University of Texas Southwestern Medical Center at Dallas, included 2,889 women who received the inactivatd influenza vaccine during the 2003-2004 flu season, which began earlier than usual and was moderately severe. They were compared with 1,988 gestational age-matched pregnant women who did not get vaccinated during the same time period, Jeanne S. Sheffield, M.D., and her associates wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

Six women in the vaccinated group (2.4 per 1,000 women) and 13 in the nonvaccinated group (6.5 per 1,000 women) developed laboratory-confirmed influenza, a statistically significant difference. The overall efficacy of the vaccine was 68%.

But when the analysis was restricted to women who developed influenza more than 2 weeks after vaccination (the time required to develop immunity), there was only one case of influenza (0.4 per 1,000 women), yielding an efficacy of 94%.

The relative risk of developing influenza decreased almost 19-fold when the vaccine was given 2 weeks before exposure.

There were some statistically significant differences between the groups, study co-investigator Scott W. Roberts, M.D., said in an interview with this newspaper.

Women in the vaccination group were seen more frequently than the controls. Those in the vaccination group also had more repeat cesarean deliveries and cases of dystocia, and larger body-mass indexes, the researchers said.

The estimated gestational age (EGA) at delivery was slightly, but significantly, higher in the vaccination group (39.6 weeks), compared with the unvaccinated group (39.4 weeks).

The vaccinated group had significantly fewer births with EGAs of 36 weeks or less, compared with the unvaccinated group. Infants whose mothers were vaccinated were significantly less likely to go to the intensive care nursery.

Women in the vaccinated group were significantly more likely to undergo a cesarean delivery (27% vs. 23%). Dr. Roberts said it is possible that most or all of these differences reflect the fact that the women who were seen in the clinic were more likely to choose getting the vaccination.

Women who were vaccinated had infants that were much less likely to be admitted to the intensive care nursery. Lynda Banzi

RENO, NEV. — The inactivated influenza vaccine is safe and effective for women in the second half of pregnancy, results of a large prospective study suggest.

When given at least 2 weeks before exposure, the vaccine reduced the rate of influenza 19-fold, with no evidence of worsening in several obstetric and neonatal outcomes, including premature rupture of membranes, stillbirths, low birth weight, neonatal pneumonia, neonatal death, and major malformations.

The study, which was conducted at the University of Texas Southwestern Medical Center at Dallas, included 2,889 women who received the inactivatd influenza vaccine during the 2003-2004 flu season, which began earlier than usual and was moderately severe. They were compared with 1,988 gestational age-matched pregnant women who did not get vaccinated during the same time period, Jeanne S. Sheffield, M.D., and her associates wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

Six women in the vaccinated group (2.4 per 1,000 women) and 13 in the nonvaccinated group (6.5 per 1,000 women) developed laboratory-confirmed influenza, a statistically significant difference. The overall efficacy of the vaccine was 68%.

But when the analysis was restricted to women who developed influenza more than 2 weeks after vaccination (the time required to develop immunity), there was only one case of influenza (0.4 per 1,000 women), yielding an efficacy of 94%.

The relative risk of developing influenza decreased almost 19-fold when the vaccine was given 2 weeks before exposure.

There were some statistically significant differences between the groups, study co-investigator Scott W. Roberts, M.D., said in an interview with this newspaper.

Women in the vaccination group were seen more frequently than the controls. Those in the vaccination group also had more repeat cesarean deliveries and cases of dystocia, and larger body-mass indexes, the researchers said.

The estimated gestational age (EGA) at delivery was slightly, but significantly, higher in the vaccination group (39.6 weeks), compared with the unvaccinated group (39.4 weeks).

The vaccinated group had significantly fewer births with EGAs of 36 weeks or less, compared with the unvaccinated group. Infants whose mothers were vaccinated were significantly less likely to go to the intensive care nursery.

Women in the vaccinated group were significantly more likely to undergo a cesarean delivery (27% vs. 23%). Dr. Roberts said it is possible that most or all of these differences reflect the fact that the women who were seen in the clinic were more likely to choose getting the vaccination.

Women who were vaccinated had infants that were much less likely to be admitted to the intensive care nursery. Lynda Banzi

BRECKENRIDGE, COLO. — Hormonal evidence of polycystic ovary syndrome in patients on valproate is often reversed by a switch to one of the newer antiepileptic drugs, Jacci Bainbridge, Pharm.D., reported at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

Women with epilepsy are known to have an increased frequency of polycystic ovary syndrome (PCOS), a common complication of valproate therapy. Evidence that the associated adverse neuroendocrine changes are reversible with a change in seizure medication comes from a recent study by investigators at the University of Birmingham (England), said Dr. Bainbridge of the University of Colorado, Denver.

At the annual meeting of the American Epilepsy Society, the British investigators reported on 16 women with generalized epilepsy who had been taking valproate for longer than 2 years. They ranged in age from 16 to 27 years, and nine had been diagnosed with juvenile myoclonic epilepsy. All patients had the elevated testosterone and/or FSH levels that help define PCOS.

Patients were initially switched from valproate to lamotrigine (Lamictal). If their seizures worsened on the new medication, they were switched again, this time to levetiracetam (Keppra). Eleven women finished the study on lamotrigine. All five patients who were switched to levetiracetam became seizure free. Of the 16 patients, 15 lost hormonal evidence of PCOS during the switch from valproate.

Conference director Jose F. Cavazos, M.D., said that rather than doing routine hormone measurements in his valproate-treated patients in an effort to identify those with hyperandrogenism, he relies upon sudden weight gain as an early clinical tip-off to the presence of PCOS. Weight gain in this setting is often due to the insulin resistance that is one of the first manifestations of PCOS.

There are some data to suggest that there is a dose-dependent relationship between the use of valproate and PCOS. It may be possible to use the drug at lower doses without increasing the risk of the hormonal/metabolic disorder. That's welcome news because valproate remains a useful drug in certain circumstances.

“Patients with refractory primary generalized epilepsy are going to end up on multiple medications—and one of them is often Depakote [valproate],” noted Dr. Cavazos of the University of Texas at San Antonio.

Seizures can entail hypothalamic storm, with resultant long-term adverse effects on the hypothalamic-pituitary-ovarian axis. One outcome can be premature ovarian failure, which is more common in women with epilepsy. This helps explain the relatively low birth rate among women with epilepsy, he said.

Dr. Cavazos mentioned one study in which investigators evaluated 50 consecutive women with epilepsy aged 38-64 years whose seizures began prior to aged 41. A control group included 82 age-matched neurologically normal women. Of the women with epilepsy, 14% had onset of menopause prior to 42 years, compared with just 4% of controls (Epilepsia 2001;42:1584-9).

In another study, Cynthia L. Harden, M.D., of Columbia University, New York, demonstrated that seizure frequency and lifetime number of seizures were associated with earlier age at menopause, according to Dr. Cavazos.

She surveyed 68 women with epilepsy whose mean age at menopause was 47.8 years. The 15 women classified as having a low-seizure-frequency history had a mean age at menopause of 49.9 years, compared with 47.7 years in the intermediate-seizure-frequency group and 46.7 years in the 28 women with high seizure frequency. The age difference was statistically significant.

Potential confounders, including the use of the older enzyme-inducing antiepileptic drugs, smoking history, and number of pregnancies, didn't significantly affect the results (Neurology 2003;61:451-5).

BRECKENRIDGE, COLO. — Hormonal evidence of polycystic ovary syndrome in patients on valproate is often reversed by a switch to one of the newer antiepileptic drugs, Jacci Bainbridge, Pharm.D., reported at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

Women with epilepsy are known to have an increased frequency of polycystic ovary syndrome (PCOS), a common complication of valproate therapy. Evidence that the associated adverse neuroendocrine changes are reversible with a change in seizure medication comes from a recent study by investigators at the University of Birmingham (England), said Dr. Bainbridge of the University of Colorado, Denver.

At the annual meeting of the American Epilepsy Society, the British investigators reported on 16 women with generalized epilepsy who had been taking valproate for longer than 2 years. They ranged in age from 16 to 27 years, and nine had been diagnosed with juvenile myoclonic epilepsy. All patients had the elevated testosterone and/or FSH levels that help define PCOS.

Patients were initially switched from valproate to lamotrigine (Lamictal). If their seizures worsened on the new medication, they were switched again, this time to levetiracetam (Keppra). Eleven women finished the study on lamotrigine. All five patients who were switched to levetiracetam became seizure free. Of the 16 patients, 15 lost hormonal evidence of PCOS during the switch from valproate.

Conference director Jose F. Cavazos, M.D., said that rather than doing routine hormone measurements in his valproate-treated patients in an effort to identify those with hyperandrogenism, he relies upon sudden weight gain as an early clinical tip-off to the presence of PCOS. Weight gain in this setting is often due to the insulin resistance that is one of the first manifestations of PCOS.

There are some data to suggest that there is a dose-dependent relationship between the use of valproate and PCOS. It may be possible to use the drug at lower doses without increasing the risk of the hormonal/metabolic disorder. That's welcome news because valproate remains a useful drug in certain circumstances.

“Patients with refractory primary generalized epilepsy are going to end up on multiple medications—and one of them is often Depakote [valproate],” noted Dr. Cavazos of the University of Texas at San Antonio.

Seizures can entail hypothalamic storm, with resultant long-term adverse effects on the hypothalamic-pituitary-ovarian axis. One outcome can be premature ovarian failure, which is more common in women with epilepsy. This helps explain the relatively low birth rate among women with epilepsy, he said.

Dr. Cavazos mentioned one study in which investigators evaluated 50 consecutive women with epilepsy aged 38-64 years whose seizures began prior to aged 41. A control group included 82 age-matched neurologically normal women. Of the women with epilepsy, 14% had onset of menopause prior to 42 years, compared with just 4% of controls (Epilepsia 2001;42:1584-9).

In another study, Cynthia L. Harden, M.D., of Columbia University, New York, demonstrated that seizure frequency and lifetime number of seizures were associated with earlier age at menopause, according to Dr. Cavazos.

She surveyed 68 women with epilepsy whose mean age at menopause was 47.8 years. The 15 women classified as having a low-seizure-frequency history had a mean age at menopause of 49.9 years, compared with 47.7 years in the intermediate-seizure-frequency group and 46.7 years in the 28 women with high seizure frequency. The age difference was statistically significant.

Potential confounders, including the use of the older enzyme-inducing antiepileptic drugs, smoking history, and number of pregnancies, didn't significantly affect the results (Neurology 2003;61:451-5).

BRECKENRIDGE, COLO. — Hormonal evidence of polycystic ovary syndrome in patients on valproate is often reversed by a switch to one of the newer antiepileptic drugs, Jacci Bainbridge, Pharm.D., reported at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

Women with epilepsy are known to have an increased frequency of polycystic ovary syndrome (PCOS), a common complication of valproate therapy. Evidence that the associated adverse neuroendocrine changes are reversible with a change in seizure medication comes from a recent study by investigators at the University of Birmingham (England), said Dr. Bainbridge of the University of Colorado, Denver.

At the annual meeting of the American Epilepsy Society, the British investigators reported on 16 women with generalized epilepsy who had been taking valproate for longer than 2 years. They ranged in age from 16 to 27 years, and nine had been diagnosed with juvenile myoclonic epilepsy. All patients had the elevated testosterone and/or FSH levels that help define PCOS.

Patients were initially switched from valproate to lamotrigine (Lamictal). If their seizures worsened on the new medication, they were switched again, this time to levetiracetam (Keppra). Eleven women finished the study on lamotrigine. All five patients who were switched to levetiracetam became seizure free. Of the 16 patients, 15 lost hormonal evidence of PCOS during the switch from valproate.

Conference director Jose F. Cavazos, M.D., said that rather than doing routine hormone measurements in his valproate-treated patients in an effort to identify those with hyperandrogenism, he relies upon sudden weight gain as an early clinical tip-off to the presence of PCOS. Weight gain in this setting is often due to the insulin resistance that is one of the first manifestations of PCOS.

There are some data to suggest that there is a dose-dependent relationship between the use of valproate and PCOS. It may be possible to use the drug at lower doses without increasing the risk of the hormonal/metabolic disorder. That's welcome news because valproate remains a useful drug in certain circumstances.

“Patients with refractory primary generalized epilepsy are going to end up on multiple medications—and one of them is often Depakote [valproate],” noted Dr. Cavazos of the University of Texas at San Antonio.

Seizures can entail hypothalamic storm, with resultant long-term adverse effects on the hypothalamic-pituitary-ovarian axis. One outcome can be premature ovarian failure, which is more common in women with epilepsy. This helps explain the relatively low birth rate among women with epilepsy, he said.

Dr. Cavazos mentioned one study in which investigators evaluated 50 consecutive women with epilepsy aged 38-64 years whose seizures began prior to aged 41. A control group included 82 age-matched neurologically normal women. Of the women with epilepsy, 14% had onset of menopause prior to 42 years, compared with just 4% of controls (Epilepsia 2001;42:1584-9).

In another study, Cynthia L. Harden, M.D., of Columbia University, New York, demonstrated that seizure frequency and lifetime number of seizures were associated with earlier age at menopause, according to Dr. Cavazos.

She surveyed 68 women with epilepsy whose mean age at menopause was 47.8 years. The 15 women classified as having a low-seizure-frequency history had a mean age at menopause of 49.9 years, compared with 47.7 years in the intermediate-seizure-frequency group and 46.7 years in the 28 women with high seizure frequency. The age difference was statistically significant.

Potential confounders, including the use of the older enzyme-inducing antiepileptic drugs, smoking history, and number of pregnancies, didn't significantly affect the results (Neurology 2003;61:451-5).

BRECKENRIDGE, COLO. — Seizures in many epileptic women exhibit a stereotypic menses-related pattern that may have important treatment implications, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

How common is this catamenial exacerbation of seizures? In one recent study led by Andrew G. Herzog, M.D., of Harvard Medical School, Boston, 87 women with localization-related epilepsy charted their seizures in three menstrual cycles. Fully 39% showed one of three predefined catamenial patterns of seizure exacerbation during at least two of the three cycles.

The three patterns characteristic of catamenial epilepsy were perimenstrual or periovulatory exacerbations during normal cycles, and exacerbations during the second half of anovular cycles (Ann. Neurol. 2004;56:431-4).

The implication is that for the many women whose seizures follow a catamenial pattern, anticipatory short-term increases in antiepileptic drug dosing may help. Or patients can add an adjunctive anticonvulsant such as acetazolamide or a benzodiazepine for 3-4 days. Several days of clomiphene are another possibility, according to Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

To date, there have been no large prospective treatment studies in women with catamenial epilepsy. Reported therapeutic successes are strictly anecdotal, and there is no universally accepted therapy, the neurologist added.

The biologic basis of catamenial epilepsy is grounded in two well-established observations: Estrogens are mildly proconvulsant, whereas progesterones have a slight anticonvulsant effect. Animal studies have shown that a drop in serum levels of the endogenous neurosteroid allopregnanolone, a progesterone metabolite, lower the seizure threshold. But attempts to quell catamenial epilepsy via progesterone therapy have generally been thwarted by the finding that effective doses also result in depressive symptoms and other side effects, Dr. Cavazos continued.

Another etiologic factor in catamenial epilepsy is menstrual cycle-related alteration in hepatic metabolism of antiepileptic drugs. The perimenstrual decrease in sex hormones is associated with increased hepatic enzyme activity, which can result in lower serum anticonvulsant levels, he said.

BRECKENRIDGE, COLO. — Seizures in many epileptic women exhibit a stereotypic menses-related pattern that may have important treatment implications, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

How common is this catamenial exacerbation of seizures? In one recent study led by Andrew G. Herzog, M.D., of Harvard Medical School, Boston, 87 women with localization-related epilepsy charted their seizures in three menstrual cycles. Fully 39% showed one of three predefined catamenial patterns of seizure exacerbation during at least two of the three cycles.

The three patterns characteristic of catamenial epilepsy were perimenstrual or periovulatory exacerbations during normal cycles, and exacerbations during the second half of anovular cycles (Ann. Neurol. 2004;56:431-4).

The implication is that for the many women whose seizures follow a catamenial pattern, anticipatory short-term increases in antiepileptic drug dosing may help. Or patients can add an adjunctive anticonvulsant such as acetazolamide or a benzodiazepine for 3-4 days. Several days of clomiphene are another possibility, according to Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

To date, there have been no large prospective treatment studies in women with catamenial epilepsy. Reported therapeutic successes are strictly anecdotal, and there is no universally accepted therapy, the neurologist added.

The biologic basis of catamenial epilepsy is grounded in two well-established observations: Estrogens are mildly proconvulsant, whereas progesterones have a slight anticonvulsant effect. Animal studies have shown that a drop in serum levels of the endogenous neurosteroid allopregnanolone, a progesterone metabolite, lower the seizure threshold. But attempts to quell catamenial epilepsy via progesterone therapy have generally been thwarted by the finding that effective doses also result in depressive symptoms and other side effects, Dr. Cavazos continued.

Another etiologic factor in catamenial epilepsy is menstrual cycle-related alteration in hepatic metabolism of antiepileptic drugs. The perimenstrual decrease in sex hormones is associated with increased hepatic enzyme activity, which can result in lower serum anticonvulsant levels, he said.

BRECKENRIDGE, COLO. — Seizures in many epileptic women exhibit a stereotypic menses-related pattern that may have important treatment implications, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

How common is this catamenial exacerbation of seizures? In one recent study led by Andrew G. Herzog, M.D., of Harvard Medical School, Boston, 87 women with localization-related epilepsy charted their seizures in three menstrual cycles. Fully 39% showed one of three predefined catamenial patterns of seizure exacerbation during at least two of the three cycles.

The three patterns characteristic of catamenial epilepsy were perimenstrual or periovulatory exacerbations during normal cycles, and exacerbations during the second half of anovular cycles (Ann. Neurol. 2004;56:431-4).

The implication is that for the many women whose seizures follow a catamenial pattern, anticipatory short-term increases in antiepileptic drug dosing may help. Or patients can add an adjunctive anticonvulsant such as acetazolamide or a benzodiazepine for 3-4 days. Several days of clomiphene are another possibility, according to Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

To date, there have been no large prospective treatment studies in women with catamenial epilepsy. Reported therapeutic successes are strictly anecdotal, and there is no universally accepted therapy, the neurologist added.

The biologic basis of catamenial epilepsy is grounded in two well-established observations: Estrogens are mildly proconvulsant, whereas progesterones have a slight anticonvulsant effect. Animal studies have shown that a drop in serum levels of the endogenous neurosteroid allopregnanolone, a progesterone metabolite, lower the seizure threshold. But attempts to quell catamenial epilepsy via progesterone therapy have generally been thwarted by the finding that effective doses also result in depressive symptoms and other side effects, Dr. Cavazos continued.

Another etiologic factor in catamenial epilepsy is menstrual cycle-related alteration in hepatic metabolism of antiepileptic drugs. The perimenstrual decrease in sex hormones is associated with increased hepatic enzyme activity, which can result in lower serum anticonvulsant levels, he said.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, respectively, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health- sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, respectively, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health- sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, respectively, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health- sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users.