Miriam E. Tucker

VIENNA — The largest-ever systematic data review of the use of low-molecular- weight heparin during pregnancy suggests that it is safe and effective for both prophylaxis and treatment of venous thromboembolism, Catherine Nelson-Piercy, M.B., reported at the annual meeting of the International Society of Obstetric Medicine.

In recent years, low-molecular-weight heparin (LMWH) has become the standard therapy for both thromboprophylaxis and management of acute venous thromboembolism (VTE). “Thromboembolism is still the leading cause of maternal death in the U.K. For that reason, we are keen to promote the use of low-molecular-weight heparin for prophylaxis,” said Dr. Nelson-Piercy, an obstetrician at Guy's and St. Thomas' Hospitals Trust, London.

There are still no large randomized trials to help guide practice in this area, however. To overcome this lack of data, Dr. Nelson-Piercy and her associate Ian Greer, M.D., of Glasgow (Scotland) University, conducted a systematic electronic database review of all studies through December 2003 that investigated the use of LMWH during pregnancy. Exclusion of studies of women with artificial heart valves, those that did not provide data on LMWH administration, and a few others for methodologic reasons left a total of 2,659 pregnancies from 59 separate reports.

Prophylaxis of VTE was by far the most common indication for LMWH use, comprising 28 studies and 1,319 pregnancies. Prevention of recurrent pregnancy loss, a rapidly growing use for LMWH, was the indication in 370 pregnancies in 14 studies, while treatment of VTE was the indication for 174 pregnancies in 15 studies.

Enoxaparin was the most common low-molecular-weight heparin used (1,158 pregnancies, including 105 for treatment and 1,048 for prophylaxis), followed by dalteparin (783) and nadroparin (530).

The reason for LMWH prophylaxis use during pregnancy wasn't specified in all the studies, but those cases were still included in the safety analysis, Dr. Nelson-Piercy explained.

In the treatment studies, the rate of deep vein thrombosis among the 174 LMWH recipients was 1.15%, which was extremely low, compared with 5% for unfractionated heparin use among men and nonpregnant women. Bleeding complications occurred in a total of 1.72%, including prenatal bleeding in 0.57% and postpartum hemorrhage of more than 500 mL in 1.15%. Non-heparin-induced thrombocytopenia occurred in 0.57%.

Among the 2,485 pregnancies in which LMWH was used for thromboprophylaxis, 1.4% of the women had thrombosis, including 0.84% with VTE and 0.56% with arterial thrombosis. All the women who experienced arterial thrombosis were known to have antiphospholipid antibody syndrome.

Bleeding complications, including prenatal bleeding, postpartum hemorrhage, and wound hematoma occurred in 2.1%.

Thrombocytopenia was rare, occurring in just 0.08%. “I hope this provides the evidence that we can stop doing platelet counts 1 week after starting” LMWH, she said.

Allergic skin reactions to LMWH occurred in 1.15% during treatment and 1.9% with prophylaxis. This complication usually occurred at the site of injection and was most common with nadroparin and least with enoxaparin, with dalteparin falling between the two.

Heparin-induced osteoporosis was reported in just one patient, in whom dalteparin was used for thromboprophylaxis. However, a recent abstract from researchers in the United Kingdom reported three cases of osteoporosis associated with the use of tinzaparin during pregnancy. “Although our data are reassuring, we can't [ignore] osteoporosis,” she said.

There were no maternal deaths in the treatment or the prophylaxis group.

VIENNA — The largest-ever systematic data review of the use of low-molecular- weight heparin during pregnancy suggests that it is safe and effective for both prophylaxis and treatment of venous thromboembolism, Catherine Nelson-Piercy, M.B., reported at the annual meeting of the International Society of Obstetric Medicine.

In recent years, low-molecular-weight heparin (LMWH) has become the standard therapy for both thromboprophylaxis and management of acute venous thromboembolism (VTE). “Thromboembolism is still the leading cause of maternal death in the U.K. For that reason, we are keen to promote the use of low-molecular-weight heparin for prophylaxis,” said Dr. Nelson-Piercy, an obstetrician at Guy's and St. Thomas' Hospitals Trust, London.

There are still no large randomized trials to help guide practice in this area, however. To overcome this lack of data, Dr. Nelson-Piercy and her associate Ian Greer, M.D., of Glasgow (Scotland) University, conducted a systematic electronic database review of all studies through December 2003 that investigated the use of LMWH during pregnancy. Exclusion of studies of women with artificial heart valves, those that did not provide data on LMWH administration, and a few others for methodologic reasons left a total of 2,659 pregnancies from 59 separate reports.

Prophylaxis of VTE was by far the most common indication for LMWH use, comprising 28 studies and 1,319 pregnancies. Prevention of recurrent pregnancy loss, a rapidly growing use for LMWH, was the indication in 370 pregnancies in 14 studies, while treatment of VTE was the indication for 174 pregnancies in 15 studies.

Enoxaparin was the most common low-molecular-weight heparin used (1,158 pregnancies, including 105 for treatment and 1,048 for prophylaxis), followed by dalteparin (783) and nadroparin (530).

The reason for LMWH prophylaxis use during pregnancy wasn't specified in all the studies, but those cases were still included in the safety analysis, Dr. Nelson-Piercy explained.

In the treatment studies, the rate of deep vein thrombosis among the 174 LMWH recipients was 1.15%, which was extremely low, compared with 5% for unfractionated heparin use among men and nonpregnant women. Bleeding complications occurred in a total of 1.72%, including prenatal bleeding in 0.57% and postpartum hemorrhage of more than 500 mL in 1.15%. Non-heparin-induced thrombocytopenia occurred in 0.57%.

Among the 2,485 pregnancies in which LMWH was used for thromboprophylaxis, 1.4% of the women had thrombosis, including 0.84% with VTE and 0.56% with arterial thrombosis. All the women who experienced arterial thrombosis were known to have antiphospholipid antibody syndrome.

Bleeding complications, including prenatal bleeding, postpartum hemorrhage, and wound hematoma occurred in 2.1%.

Thrombocytopenia was rare, occurring in just 0.08%. “I hope this provides the evidence that we can stop doing platelet counts 1 week after starting” LMWH, she said.

Allergic skin reactions to LMWH occurred in 1.15% during treatment and 1.9% with prophylaxis. This complication usually occurred at the site of injection and was most common with nadroparin and least with enoxaparin, with dalteparin falling between the two.

Heparin-induced osteoporosis was reported in just one patient, in whom dalteparin was used for thromboprophylaxis. However, a recent abstract from researchers in the United Kingdom reported three cases of osteoporosis associated with the use of tinzaparin during pregnancy. “Although our data are reassuring, we can't [ignore] osteoporosis,” she said.

There were no maternal deaths in the treatment or the prophylaxis group.

VIENNA — The largest-ever systematic data review of the use of low-molecular- weight heparin during pregnancy suggests that it is safe and effective for both prophylaxis and treatment of venous thromboembolism, Catherine Nelson-Piercy, M.B., reported at the annual meeting of the International Society of Obstetric Medicine.

In recent years, low-molecular-weight heparin (LMWH) has become the standard therapy for both thromboprophylaxis and management of acute venous thromboembolism (VTE). “Thromboembolism is still the leading cause of maternal death in the U.K. For that reason, we are keen to promote the use of low-molecular-weight heparin for prophylaxis,” said Dr. Nelson-Piercy, an obstetrician at Guy's and St. Thomas' Hospitals Trust, London.

There are still no large randomized trials to help guide practice in this area, however. To overcome this lack of data, Dr. Nelson-Piercy and her associate Ian Greer, M.D., of Glasgow (Scotland) University, conducted a systematic electronic database review of all studies through December 2003 that investigated the use of LMWH during pregnancy. Exclusion of studies of women with artificial heart valves, those that did not provide data on LMWH administration, and a few others for methodologic reasons left a total of 2,659 pregnancies from 59 separate reports.

Prophylaxis of VTE was by far the most common indication for LMWH use, comprising 28 studies and 1,319 pregnancies. Prevention of recurrent pregnancy loss, a rapidly growing use for LMWH, was the indication in 370 pregnancies in 14 studies, while treatment of VTE was the indication for 174 pregnancies in 15 studies.

Enoxaparin was the most common low-molecular-weight heparin used (1,158 pregnancies, including 105 for treatment and 1,048 for prophylaxis), followed by dalteparin (783) and nadroparin (530).

The reason for LMWH prophylaxis use during pregnancy wasn't specified in all the studies, but those cases were still included in the safety analysis, Dr. Nelson-Piercy explained.

In the treatment studies, the rate of deep vein thrombosis among the 174 LMWH recipients was 1.15%, which was extremely low, compared with 5% for unfractionated heparin use among men and nonpregnant women. Bleeding complications occurred in a total of 1.72%, including prenatal bleeding in 0.57% and postpartum hemorrhage of more than 500 mL in 1.15%. Non-heparin-induced thrombocytopenia occurred in 0.57%.

Among the 2,485 pregnancies in which LMWH was used for thromboprophylaxis, 1.4% of the women had thrombosis, including 0.84% with VTE and 0.56% with arterial thrombosis. All the women who experienced arterial thrombosis were known to have antiphospholipid antibody syndrome.

Bleeding complications, including prenatal bleeding, postpartum hemorrhage, and wound hematoma occurred in 2.1%.

Thrombocytopenia was rare, occurring in just 0.08%. “I hope this provides the evidence that we can stop doing platelet counts 1 week after starting” LMWH, she said.

Allergic skin reactions to LMWH occurred in 1.15% during treatment and 1.9% with prophylaxis. This complication usually occurred at the site of injection and was most common with nadroparin and least with enoxaparin, with dalteparin falling between the two.

Heparin-induced osteoporosis was reported in just one patient, in whom dalteparin was used for thromboprophylaxis. However, a recent abstract from researchers in the United Kingdom reported three cases of osteoporosis associated with the use of tinzaparin during pregnancy. “Although our data are reassuring, we can't [ignore] osteoporosis,” she said.

There were no maternal deaths in the treatment or the prophylaxis group.

VIENNA — Guidelines are sorely needed for postpartum blood pressure management in women who experience hypertension during pregnancy, speakers said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“It's a problem we have very little guidance on and very little information about,” said Jason Waugh, a senior lecturer in the reproductive science section at the University of Leicester, England. He presented one of three studies highlighting the knowledge gaps regarding postpartum diagnosis and treatment of women with pregnancies complicated by hypertension.

Determining whether a woman has underlying chronic hypertension can be difficult. Professional societies such as the ISSHP and the American College of Obstetricians and Gynecologists define chronic hypertension in pregnancy as that occurring prior to pregnancy or diagnosed before 20 weeks' gestation.

But a study of 501 women with hypertension at delivery suggests that the 20-week cutoff is not a reliable one. Instead, thorough postnatal follow-up is essential for accurate diagnosis, Mr. Waugh said.

The women were given preliminary diagnoses at the time of delivery. They subsequently performed home blood pressure monitoring—during which they followed a strict protocol for medication dosage reduction—for 1-8 weeks and were given final diagnoses. Those with persistent hypertension were referred to cardiovascular physicians for follow-up of more than 1 year, during which none of the final diagnoses changed.

The final diagnoses were preeclampsia in 36% (178 women), gestational hypertension in 42% (210), new diagnosis of chronic hypertension in 10% (51), and preexisting hypertension in 12% (49 with essential hypertension and 13 with renal disease).

Standard risk factors were poor predictors of underlying hypertension during pregnancy: Among the 51 women with chronic hypertension not diagnosed prior to pregnancy, only parity and gestation diagnosis were predictive of the final diagnosis, with smoking also showing a strong but nonsignificant trend.

Age, weight, and body mass index were not related to the final diagnosis, nor was antenatal suspicion of hypertension. Of the 28 women with blood pressures greater than 140/90 mm Hg at less than 20 weeks' gestation, 16 (57%) were later proved to have only gestational hypertension, while 12 (43%) were ultimately found to have chronic hypertension. On the flip side, this means that of the 51 women newly diagnosed with chronic hypertension postnatally, just 12, or 24%, had been hypertensive prior to 20 weeks.

“We must proceed with great caution in both clinical and research practice if a postnatal confirmation of blood pressure is not available following antenatal hypertension,” Mr. Waugh remarked at the meeting.

Findings from another study suggest that gestational hypertension commonly persists post partum, particularly in older women.

Tiina Podymow, M.D., of the division of nephrology and hypertension at Weill Medical College, Cornell University, New York City, reviewed clinic charts of 29 women who developed gestational hypertension or preeclampsia; all had been normotensive prior to pregnancy.

The women had a mean age of 35 years. Hypertension had developed at gestational age 15-40 weeks, with 13 developing hypertension within 3 days of delivery and the remainder at 1-18 weeks prior to delivery. The average blood pressure was 161/94 mn Hg; the mean arterial pressure was 116. Eleven women were diagnosed with preeclampsia, and 25 were treated with antihypertensive drugs in the puerperium.

Blood pressure normalized between 0 and 4 weeks post partum in 12 women, between 5 and 12 weeks in 7, and between 13 and 20 weeks in 3. However, blood pressure remained elevated beyond 6 months in seven women, of whom one was found to have primary hyperaldosteronism. This finding suggests that secondary causes of hypertension should be considered in patients with hypertension persisting beyond 6 months, according to Dr. Podymow.

Age was a significant risk factor. The women who remained persistently hypertensive had a mean age of 41 years, compared with 33.5 years among those whose hypertension resolved, she reported.

And few data are available to guide physicians in treating these patients, Susan Sadeghi, M.D., of the University of British Columbia, Vancouver, reported in a poster presentation.

“Peak postpartum blood pressure occurs on days 3-6 after delivery, when most women have already been discharged home. [Yet] there is little information on how best to treat postpartum hypertension in order to minimize maternal hospital stay and optimize maternal safety,” she pointed out.

Indeed, in an extensive review of the literature dating back to 1980, only six randomized clinical trials involving 459 women addressed postpartum antihypertensive treatment with regard to maternal and neonatal efficacy and safety outcomes. The largest study involved 266 subjects and the smallest, just 18.

Three of the six trials looked at prevention of postpartum hypertension in a total of 315 women. All compared drug vs. placebo or no treatment; two involved oral furosemide 20-40 mg/day, and the other involved nifedipine capsules 10 mg every 4 hours. There were no cases of hypotension, serious maternal morbidity, or maternal death. Only one study—which included just 18 patients—examined maternal length of stay, finding an insignificant difference of 7.3 vs. 7.6 days.

The other three trials were treatment studies that included just 144 women. None compared antihypertensive medication with placebo or no treatment for mild to moderate hypertension. Two of the studies—involving 106 women—compared oral timolol or hydralazine with methyldopa for mild to moderate hypertension, and the third compared hydralazine plus nifedipine with nifedipine alone for severe postpartum hypertension.

There were no maternal deaths in the three treatment studies, and the need for additional antihypertensive therapy did not differ between groups.

Based on these minimal data, Dr. Sadeghi and her associates concluded: “If a clinician feels that antihypertensive therapy is needed, the agent used should be based on his/her familiarity with the drug.”

VIENNA — Guidelines are sorely needed for postpartum blood pressure management in women who experience hypertension during pregnancy, speakers said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“It's a problem we have very little guidance on and very little information about,” said Jason Waugh, a senior lecturer in the reproductive science section at the University of Leicester, England. He presented one of three studies highlighting the knowledge gaps regarding postpartum diagnosis and treatment of women with pregnancies complicated by hypertension.

Determining whether a woman has underlying chronic hypertension can be difficult. Professional societies such as the ISSHP and the American College of Obstetricians and Gynecologists define chronic hypertension in pregnancy as that occurring prior to pregnancy or diagnosed before 20 weeks' gestation.

But a study of 501 women with hypertension at delivery suggests that the 20-week cutoff is not a reliable one. Instead, thorough postnatal follow-up is essential for accurate diagnosis, Mr. Waugh said.

The women were given preliminary diagnoses at the time of delivery. They subsequently performed home blood pressure monitoring—during which they followed a strict protocol for medication dosage reduction—for 1-8 weeks and were given final diagnoses. Those with persistent hypertension were referred to cardiovascular physicians for follow-up of more than 1 year, during which none of the final diagnoses changed.

The final diagnoses were preeclampsia in 36% (178 women), gestational hypertension in 42% (210), new diagnosis of chronic hypertension in 10% (51), and preexisting hypertension in 12% (49 with essential hypertension and 13 with renal disease).

Standard risk factors were poor predictors of underlying hypertension during pregnancy: Among the 51 women with chronic hypertension not diagnosed prior to pregnancy, only parity and gestation diagnosis were predictive of the final diagnosis, with smoking also showing a strong but nonsignificant trend.

Age, weight, and body mass index were not related to the final diagnosis, nor was antenatal suspicion of hypertension. Of the 28 women with blood pressures greater than 140/90 mm Hg at less than 20 weeks' gestation, 16 (57%) were later proved to have only gestational hypertension, while 12 (43%) were ultimately found to have chronic hypertension. On the flip side, this means that of the 51 women newly diagnosed with chronic hypertension postnatally, just 12, or 24%, had been hypertensive prior to 20 weeks.

“We must proceed with great caution in both clinical and research practice if a postnatal confirmation of blood pressure is not available following antenatal hypertension,” Mr. Waugh remarked at the meeting.

Findings from another study suggest that gestational hypertension commonly persists post partum, particularly in older women.

Tiina Podymow, M.D., of the division of nephrology and hypertension at Weill Medical College, Cornell University, New York City, reviewed clinic charts of 29 women who developed gestational hypertension or preeclampsia; all had been normotensive prior to pregnancy.

The women had a mean age of 35 years. Hypertension had developed at gestational age 15-40 weeks, with 13 developing hypertension within 3 days of delivery and the remainder at 1-18 weeks prior to delivery. The average blood pressure was 161/94 mn Hg; the mean arterial pressure was 116. Eleven women were diagnosed with preeclampsia, and 25 were treated with antihypertensive drugs in the puerperium.

Blood pressure normalized between 0 and 4 weeks post partum in 12 women, between 5 and 12 weeks in 7, and between 13 and 20 weeks in 3. However, blood pressure remained elevated beyond 6 months in seven women, of whom one was found to have primary hyperaldosteronism. This finding suggests that secondary causes of hypertension should be considered in patients with hypertension persisting beyond 6 months, according to Dr. Podymow.

Age was a significant risk factor. The women who remained persistently hypertensive had a mean age of 41 years, compared with 33.5 years among those whose hypertension resolved, she reported.

And few data are available to guide physicians in treating these patients, Susan Sadeghi, M.D., of the University of British Columbia, Vancouver, reported in a poster presentation.

“Peak postpartum blood pressure occurs on days 3-6 after delivery, when most women have already been discharged home. [Yet] there is little information on how best to treat postpartum hypertension in order to minimize maternal hospital stay and optimize maternal safety,” she pointed out.

Indeed, in an extensive review of the literature dating back to 1980, only six randomized clinical trials involving 459 women addressed postpartum antihypertensive treatment with regard to maternal and neonatal efficacy and safety outcomes. The largest study involved 266 subjects and the smallest, just 18.

Three of the six trials looked at prevention of postpartum hypertension in a total of 315 women. All compared drug vs. placebo or no treatment; two involved oral furosemide 20-40 mg/day, and the other involved nifedipine capsules 10 mg every 4 hours. There were no cases of hypotension, serious maternal morbidity, or maternal death. Only one study—which included just 18 patients—examined maternal length of stay, finding an insignificant difference of 7.3 vs. 7.6 days.

The other three trials were treatment studies that included just 144 women. None compared antihypertensive medication with placebo or no treatment for mild to moderate hypertension. Two of the studies—involving 106 women—compared oral timolol or hydralazine with methyldopa for mild to moderate hypertension, and the third compared hydralazine plus nifedipine with nifedipine alone for severe postpartum hypertension.

There were no maternal deaths in the three treatment studies, and the need for additional antihypertensive therapy did not differ between groups.

Based on these minimal data, Dr. Sadeghi and her associates concluded: “If a clinician feels that antihypertensive therapy is needed, the agent used should be based on his/her familiarity with the drug.”

VIENNA — Guidelines are sorely needed for postpartum blood pressure management in women who experience hypertension during pregnancy, speakers said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“It's a problem we have very little guidance on and very little information about,” said Jason Waugh, a senior lecturer in the reproductive science section at the University of Leicester, England. He presented one of three studies highlighting the knowledge gaps regarding postpartum diagnosis and treatment of women with pregnancies complicated by hypertension.

Determining whether a woman has underlying chronic hypertension can be difficult. Professional societies such as the ISSHP and the American College of Obstetricians and Gynecologists define chronic hypertension in pregnancy as that occurring prior to pregnancy or diagnosed before 20 weeks' gestation.

But a study of 501 women with hypertension at delivery suggests that the 20-week cutoff is not a reliable one. Instead, thorough postnatal follow-up is essential for accurate diagnosis, Mr. Waugh said.

The women were given preliminary diagnoses at the time of delivery. They subsequently performed home blood pressure monitoring—during which they followed a strict protocol for medication dosage reduction—for 1-8 weeks and were given final diagnoses. Those with persistent hypertension were referred to cardiovascular physicians for follow-up of more than 1 year, during which none of the final diagnoses changed.

The final diagnoses were preeclampsia in 36% (178 women), gestational hypertension in 42% (210), new diagnosis of chronic hypertension in 10% (51), and preexisting hypertension in 12% (49 with essential hypertension and 13 with renal disease).

Standard risk factors were poor predictors of underlying hypertension during pregnancy: Among the 51 women with chronic hypertension not diagnosed prior to pregnancy, only parity and gestation diagnosis were predictive of the final diagnosis, with smoking also showing a strong but nonsignificant trend.

Age, weight, and body mass index were not related to the final diagnosis, nor was antenatal suspicion of hypertension. Of the 28 women with blood pressures greater than 140/90 mm Hg at less than 20 weeks' gestation, 16 (57%) were later proved to have only gestational hypertension, while 12 (43%) were ultimately found to have chronic hypertension. On the flip side, this means that of the 51 women newly diagnosed with chronic hypertension postnatally, just 12, or 24%, had been hypertensive prior to 20 weeks.

“We must proceed with great caution in both clinical and research practice if a postnatal confirmation of blood pressure is not available following antenatal hypertension,” Mr. Waugh remarked at the meeting.

Findings from another study suggest that gestational hypertension commonly persists post partum, particularly in older women.

Tiina Podymow, M.D., of the division of nephrology and hypertension at Weill Medical College, Cornell University, New York City, reviewed clinic charts of 29 women who developed gestational hypertension or preeclampsia; all had been normotensive prior to pregnancy.

The women had a mean age of 35 years. Hypertension had developed at gestational age 15-40 weeks, with 13 developing hypertension within 3 days of delivery and the remainder at 1-18 weeks prior to delivery. The average blood pressure was 161/94 mn Hg; the mean arterial pressure was 116. Eleven women were diagnosed with preeclampsia, and 25 were treated with antihypertensive drugs in the puerperium.

Blood pressure normalized between 0 and 4 weeks post partum in 12 women, between 5 and 12 weeks in 7, and between 13 and 20 weeks in 3. However, blood pressure remained elevated beyond 6 months in seven women, of whom one was found to have primary hyperaldosteronism. This finding suggests that secondary causes of hypertension should be considered in patients with hypertension persisting beyond 6 months, according to Dr. Podymow.

Age was a significant risk factor. The women who remained persistently hypertensive had a mean age of 41 years, compared with 33.5 years among those whose hypertension resolved, she reported.

And few data are available to guide physicians in treating these patients, Susan Sadeghi, M.D., of the University of British Columbia, Vancouver, reported in a poster presentation.

“Peak postpartum blood pressure occurs on days 3-6 after delivery, when most women have already been discharged home. [Yet] there is little information on how best to treat postpartum hypertension in order to minimize maternal hospital stay and optimize maternal safety,” she pointed out.

Indeed, in an extensive review of the literature dating back to 1980, only six randomized clinical trials involving 459 women addressed postpartum antihypertensive treatment with regard to maternal and neonatal efficacy and safety outcomes. The largest study involved 266 subjects and the smallest, just 18.

Three of the six trials looked at prevention of postpartum hypertension in a total of 315 women. All compared drug vs. placebo or no treatment; two involved oral furosemide 20-40 mg/day, and the other involved nifedipine capsules 10 mg every 4 hours. There were no cases of hypotension, serious maternal morbidity, or maternal death. Only one study—which included just 18 patients—examined maternal length of stay, finding an insignificant difference of 7.3 vs. 7.6 days.

The other three trials were treatment studies that included just 144 women. None compared antihypertensive medication with placebo or no treatment for mild to moderate hypertension. Two of the studies—involving 106 women—compared oral timolol or hydralazine with methyldopa for mild to moderate hypertension, and the third compared hydralazine plus nifedipine with nifedipine alone for severe postpartum hypertension.

There were no maternal deaths in the three treatment studies, and the need for additional antihypertensive therapy did not differ between groups.

Based on these minimal data, Dr. Sadeghi and her associates concluded: “If a clinician feels that antihypertensive therapy is needed, the agent used should be based on his/her familiarity with the drug.”

VIENNA — The use of low-molecular-weight heparin together with low-dose aspirin can improve pregnancy outcomes in women who previously had preeclampsia and low-birth-weight infants, Sergio Ferrazzani, M.D., reported.

Women with preeclampsia and low-birth-weight infants in their first pregnancy have double the recurrence rate of preeclampsia in their second pregnancy, compared with women who did not have preeclampsia previously. Infants of those subsequent pregnancies are at increased risk for fetal growth restriction and low birth weight. Data suggest that preeclampsia and fetal growth restriction might share one or more pathophysiologic mechanisms, said Dr. Ferrazzani of the Catholic University of the Sacred Heart, Rome.

An electronic database search of records from his hospital's high-risk pregnancy ward yielded data on 54 women with previous preeclampsia associated with low birth weight and/or intrauterine growth retardation who were negative for antiphospholipid antibody. The women had not been treated with aspirin during a previous pregnancy, he said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Of those 54 women, 23 gave birth during 1990-1996, when hospital policy called for thromboprophylaxis with low-dose (100 mg/day) aspirin alone (ASA); the 31 women who delivered during 1997-2003 were treated with the same daily dose of aspirin plus low-molecular-weight heparin (4,000 units subcutaneous enoxaparin).

Aspirin was prescribed from the 22nd day of the menstrual cycle and discontinued after 36 weeks' gestation. The low-molecular-weight heparin (LMWH) was prescribed after confirmation of a positive pregnancy test and continued until delivery.

The women were similar with regard to demographic and anthropomorphic characteristics. About 20% of the women in each group had chronic hypertension, and almost as many (17% in the ASA alone group and 19% in the ASA-LMWH group) had more than one previous pregnancy complicated by preeclampsia.

Gestational age at delivery of the treated pregnancy was higher in both groups, compared with the women's first pregnancies, but the improvement was greater for those in the ASA-LMWH group. The increase was 32.1 vs. 34.8 weeks for women treated with ASA alone, compared with 30.9 vs. 36.4 weeks for women treated with ASA-LMWH.

Similarly, the proportion of women with small-for-gestational-age fetuses, which was 100% among all the first pregnancies, dropped to just 35% with ASA treatment alone and 16% with ASA-LMWH treatment. Both groups showed a birth weight improvement, but the ASA-LWMH group's increase was nearly double that of the group treated with ASA alone (1,372 g vs. 2,017 g in the ASA group and 1,197 g vs. 2,600 g in the ASA-LMWH group).

In both groups, there were six intrauterine deaths among the first pregnancies and none in the treated pregnancies. Neonatal deaths fell from 6 to 3 with ASA and from 11 to 1 with ASA-LMWH. Only the ASA-LMWH drop was statistically significant.

Preeclampsia (in 100% of all the first pregnancies) occurred in 30% of the subsequent ASA-treated pregnancies, compared with just 3% of pregnancies treated with both ASA and LMWH.

Among the 11 patients with chronic hypertension, the mean gestational age at delivery and the mean birth weight were also significantly greater among the infants of the 6 patients from the ASA-LMWH group, compared with those of the 5 ASA patients, Dr. Ferrazzani added.

None of the women treated with ASA-LMWH developed heparin-induced thrombocytopenia or thrombotic episodes, and there was no clinical evidence of heparin-induced osteoporosis. Mild bruising at the injection site—which was considered to be confirmatory of self-administration of the anticoagulant—was the only complication noted with heparin therapy.

VIENNA — The use of low-molecular-weight heparin together with low-dose aspirin can improve pregnancy outcomes in women who previously had preeclampsia and low-birth-weight infants, Sergio Ferrazzani, M.D., reported.

Women with preeclampsia and low-birth-weight infants in their first pregnancy have double the recurrence rate of preeclampsia in their second pregnancy, compared with women who did not have preeclampsia previously. Infants of those subsequent pregnancies are at increased risk for fetal growth restriction and low birth weight. Data suggest that preeclampsia and fetal growth restriction might share one or more pathophysiologic mechanisms, said Dr. Ferrazzani of the Catholic University of the Sacred Heart, Rome.

An electronic database search of records from his hospital's high-risk pregnancy ward yielded data on 54 women with previous preeclampsia associated with low birth weight and/or intrauterine growth retardation who were negative for antiphospholipid antibody. The women had not been treated with aspirin during a previous pregnancy, he said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Of those 54 women, 23 gave birth during 1990-1996, when hospital policy called for thromboprophylaxis with low-dose (100 mg/day) aspirin alone (ASA); the 31 women who delivered during 1997-2003 were treated with the same daily dose of aspirin plus low-molecular-weight heparin (4,000 units subcutaneous enoxaparin).

Aspirin was prescribed from the 22nd day of the menstrual cycle and discontinued after 36 weeks' gestation. The low-molecular-weight heparin (LMWH) was prescribed after confirmation of a positive pregnancy test and continued until delivery.

The women were similar with regard to demographic and anthropomorphic characteristics. About 20% of the women in each group had chronic hypertension, and almost as many (17% in the ASA alone group and 19% in the ASA-LMWH group) had more than one previous pregnancy complicated by preeclampsia.

Gestational age at delivery of the treated pregnancy was higher in both groups, compared with the women's first pregnancies, but the improvement was greater for those in the ASA-LMWH group. The increase was 32.1 vs. 34.8 weeks for women treated with ASA alone, compared with 30.9 vs. 36.4 weeks for women treated with ASA-LMWH.

Similarly, the proportion of women with small-for-gestational-age fetuses, which was 100% among all the first pregnancies, dropped to just 35% with ASA treatment alone and 16% with ASA-LMWH treatment. Both groups showed a birth weight improvement, but the ASA-LWMH group's increase was nearly double that of the group treated with ASA alone (1,372 g vs. 2,017 g in the ASA group and 1,197 g vs. 2,600 g in the ASA-LMWH group).

In both groups, there were six intrauterine deaths among the first pregnancies and none in the treated pregnancies. Neonatal deaths fell from 6 to 3 with ASA and from 11 to 1 with ASA-LMWH. Only the ASA-LMWH drop was statistically significant.

Preeclampsia (in 100% of all the first pregnancies) occurred in 30% of the subsequent ASA-treated pregnancies, compared with just 3% of pregnancies treated with both ASA and LMWH.

Among the 11 patients with chronic hypertension, the mean gestational age at delivery and the mean birth weight were also significantly greater among the infants of the 6 patients from the ASA-LMWH group, compared with those of the 5 ASA patients, Dr. Ferrazzani added.

None of the women treated with ASA-LMWH developed heparin-induced thrombocytopenia or thrombotic episodes, and there was no clinical evidence of heparin-induced osteoporosis. Mild bruising at the injection site—which was considered to be confirmatory of self-administration of the anticoagulant—was the only complication noted with heparin therapy.

VIENNA — The use of low-molecular-weight heparin together with low-dose aspirin can improve pregnancy outcomes in women who previously had preeclampsia and low-birth-weight infants, Sergio Ferrazzani, M.D., reported.

Women with preeclampsia and low-birth-weight infants in their first pregnancy have double the recurrence rate of preeclampsia in their second pregnancy, compared with women who did not have preeclampsia previously. Infants of those subsequent pregnancies are at increased risk for fetal growth restriction and low birth weight. Data suggest that preeclampsia and fetal growth restriction might share one or more pathophysiologic mechanisms, said Dr. Ferrazzani of the Catholic University of the Sacred Heart, Rome.

An electronic database search of records from his hospital's high-risk pregnancy ward yielded data on 54 women with previous preeclampsia associated with low birth weight and/or intrauterine growth retardation who were negative for antiphospholipid antibody. The women had not been treated with aspirin during a previous pregnancy, he said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Of those 54 women, 23 gave birth during 1990-1996, when hospital policy called for thromboprophylaxis with low-dose (100 mg/day) aspirin alone (ASA); the 31 women who delivered during 1997-2003 were treated with the same daily dose of aspirin plus low-molecular-weight heparin (4,000 units subcutaneous enoxaparin).

Aspirin was prescribed from the 22nd day of the menstrual cycle and discontinued after 36 weeks' gestation. The low-molecular-weight heparin (LMWH) was prescribed after confirmation of a positive pregnancy test and continued until delivery.

The women were similar with regard to demographic and anthropomorphic characteristics. About 20% of the women in each group had chronic hypertension, and almost as many (17% in the ASA alone group and 19% in the ASA-LMWH group) had more than one previous pregnancy complicated by preeclampsia.

Gestational age at delivery of the treated pregnancy was higher in both groups, compared with the women's first pregnancies, but the improvement was greater for those in the ASA-LMWH group. The increase was 32.1 vs. 34.8 weeks for women treated with ASA alone, compared with 30.9 vs. 36.4 weeks for women treated with ASA-LMWH.

Similarly, the proportion of women with small-for-gestational-age fetuses, which was 100% among all the first pregnancies, dropped to just 35% with ASA treatment alone and 16% with ASA-LMWH treatment. Both groups showed a birth weight improvement, but the ASA-LWMH group's increase was nearly double that of the group treated with ASA alone (1,372 g vs. 2,017 g in the ASA group and 1,197 g vs. 2,600 g in the ASA-LMWH group).

In both groups, there were six intrauterine deaths among the first pregnancies and none in the treated pregnancies. Neonatal deaths fell from 6 to 3 with ASA and from 11 to 1 with ASA-LMWH. Only the ASA-LMWH drop was statistically significant.

Preeclampsia (in 100% of all the first pregnancies) occurred in 30% of the subsequent ASA-treated pregnancies, compared with just 3% of pregnancies treated with both ASA and LMWH.

Among the 11 patients with chronic hypertension, the mean gestational age at delivery and the mean birth weight were also significantly greater among the infants of the 6 patients from the ASA-LMWH group, compared with those of the 5 ASA patients, Dr. Ferrazzani added.

None of the women treated with ASA-LMWH developed heparin-induced thrombocytopenia or thrombotic episodes, and there was no clinical evidence of heparin-induced osteoporosis. Mild bruising at the injection site—which was considered to be confirmatory of self-administration of the anticoagulant—was the only complication noted with heparin therapy.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria (Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Pertussis is the only disease against which children are routinely immunized that is still increasing in the United States. That's because immunity from the vaccine wanes after about 10 years, and no pertussis vaccine is licensed for persons over age 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month postvaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” he remarked.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them.

Large areas of swelling at the injection site is an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects in this study—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were more frequent in the Tdap subjects (15.7% vs. 12.7%), with no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days post vaccination, he reported.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria (Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Pertussis is the only disease against which children are routinely immunized that is still increasing in the United States. That's because immunity from the vaccine wanes after about 10 years, and no pertussis vaccine is licensed for persons over age 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month postvaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” he remarked.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them.

Large areas of swelling at the injection site is an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects in this study—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were more frequent in the Tdap subjects (15.7% vs. 12.7%), with no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days post vaccination, he reported.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria (Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Pertussis is the only disease against which children are routinely immunized that is still increasing in the United States. That's because immunity from the vaccine wanes after about 10 years, and no pertussis vaccine is licensed for persons over age 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month postvaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” he remarked.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them.

Large areas of swelling at the injection site is an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects in this study—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were more frequent in the Tdap subjects (15.7% vs. 12.7%), with no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days post vaccination, he reported.

WASHINGTON — Enterococcal native valve endocarditis has a clinical picture distinct from that of other types of endocarditis and is generally associated with a better prognosis, Jay R. McDonald, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Enterococci account for 5%-20% of all episodes of infective endocarditis, but most descriptions of the condition in the literature have been limited to small sample sizes in just one or two centers and have not included useful comparison groups.

Now, for the first time, a merged database of the International Collaboration on Endocarditis has allowed for an examination of prospectively collected data on cases of infective endocarditis reported during 1970-1999 from seven sites in five countries (France, the United Kingdom, Spain, Sweden, and the United States.)

“The aging population and emerging antimicrobial resistance among enterococci make this a pathogen of increasing importance,” said Dr. McDonald of Duke University, Durham, N.C.

Of 1,285 patients aged 18 or older with left-sided native valve endocarditis (NVE), there were 107 infected with enterococcus, 314 with Staphylococcus aureus, 666 with streptococci, and 198 with other pathogens.

Another 296 patients had prosthetic valve endocarditis (PVE), of whom 45 had enterococcus.

The 512 patients from the database with right-sided NVE were excluded from this analysis because such patients have a distinct natural history and epidemiology (young IV drug users), he explained at the conference, sponsored by the American Society for Microbiology.

In-hospital mortality was significantly lower among patients with left-sided NVE due to enterococcus than among those with disease due to S. aureus (11.2% vs. 26.5%), despite the fact that the enterococcus group was older (66.4 vs. 60 years) and had similar rates of both heart failure (45.8% vs. 43.6%) and nosocomial acquisition (15.3% vs. 19.4%).

Moreover, the 11.2% rate of in-hospital mortality for the enterococcus group was similar to the 10.2% rate among those with streptococcal NVE, even though the latter were younger (57.8 vs. 66.4 years), had less disease associated with the aortic valve (28.6% vs. 44.4%), and were less likely to have heart failure (35.1% vs. 45.8%).

Compared with patients who had enterococcal prosthetic valve endocarditis, those with enterococcal NVE had significantly more new valve regurgitation (45.6% vs. 12.8%), fewer abscesses (6.3% vs. 20.1%), and similar rates of in-hospital mortality (12.6%/14.8%) and early surgery (31.1%/31.7%), Dr. McDonald reported.

In a multivariate analysis of all patients with left-sided NVE, factors that significantly increased the risk for in-hospital mortality included age in 10-year intervals, systemic embolization, infection with S. aureus, intracardiac abscess, and heart failure. In contrast, infection with either viridans streptococci or enterococcus increased the chance of survival.

Interestingly, unlike early studies of enterococcal endocarditis, the disease was rarely seen among young women. Of the total 107 with enterococcal NVE, women accounted for just 27%.

Of those 29 women, all but two were aged 50 and older, whereas 10 of the 78 men were under age 50 (including 3 in their 20s). This difference may be explained by improved antibiotic prophylaxis for gynecologic procedures, which was the major risk factor for enterococcal endocarditis among young women in the early studies, Dr. McDonald told this newspaper.

The International Collaboration on Endocarditis is planning a larger prospective study to better characterize the disorder, he said.

WASHINGTON — Enterococcal native valve endocarditis has a clinical picture distinct from that of other types of endocarditis and is generally associated with a better prognosis, Jay R. McDonald, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Enterococci account for 5%-20% of all episodes of infective endocarditis, but most descriptions of the condition in the literature have been limited to small sample sizes in just one or two centers and have not included useful comparison groups.

Now, for the first time, a merged database of the International Collaboration on Endocarditis has allowed for an examination of prospectively collected data on cases of infective endocarditis reported during 1970-1999 from seven sites in five countries (France, the United Kingdom, Spain, Sweden, and the United States.)

“The aging population and emerging antimicrobial resistance among enterococci make this a pathogen of increasing importance,” said Dr. McDonald of Duke University, Durham, N.C.

Of 1,285 patients aged 18 or older with left-sided native valve endocarditis (NVE), there were 107 infected with enterococcus, 314 with Staphylococcus aureus, 666 with streptococci, and 198 with other pathogens.

Another 296 patients had prosthetic valve endocarditis (PVE), of whom 45 had enterococcus.

The 512 patients from the database with right-sided NVE were excluded from this analysis because such patients have a distinct natural history and epidemiology (young IV drug users), he explained at the conference, sponsored by the American Society for Microbiology.

In-hospital mortality was significantly lower among patients with left-sided NVE due to enterococcus than among those with disease due to S. aureus (11.2% vs. 26.5%), despite the fact that the enterococcus group was older (66.4 vs. 60 years) and had similar rates of both heart failure (45.8% vs. 43.6%) and nosocomial acquisition (15.3% vs. 19.4%).

Moreover, the 11.2% rate of in-hospital mortality for the enterococcus group was similar to the 10.2% rate among those with streptococcal NVE, even though the latter were younger (57.8 vs. 66.4 years), had less disease associated with the aortic valve (28.6% vs. 44.4%), and were less likely to have heart failure (35.1% vs. 45.8%).

Compared with patients who had enterococcal prosthetic valve endocarditis, those with enterococcal NVE had significantly more new valve regurgitation (45.6% vs. 12.8%), fewer abscesses (6.3% vs. 20.1%), and similar rates of in-hospital mortality (12.6%/14.8%) and early surgery (31.1%/31.7%), Dr. McDonald reported.

In a multivariate analysis of all patients with left-sided NVE, factors that significantly increased the risk for in-hospital mortality included age in 10-year intervals, systemic embolization, infection with S. aureus, intracardiac abscess, and heart failure. In contrast, infection with either viridans streptococci or enterococcus increased the chance of survival.

Interestingly, unlike early studies of enterococcal endocarditis, the disease was rarely seen among young women. Of the total 107 with enterococcal NVE, women accounted for just 27%.

Of those 29 women, all but two were aged 50 and older, whereas 10 of the 78 men were under age 50 (including 3 in their 20s). This difference may be explained by improved antibiotic prophylaxis for gynecologic procedures, which was the major risk factor for enterococcal endocarditis among young women in the early studies, Dr. McDonald told this newspaper.

The International Collaboration on Endocarditis is planning a larger prospective study to better characterize the disorder, he said.

WASHINGTON — Enterococcal native valve endocarditis has a clinical picture distinct from that of other types of endocarditis and is generally associated with a better prognosis, Jay R. McDonald, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Enterococci account for 5%-20% of all episodes of infective endocarditis, but most descriptions of the condition in the literature have been limited to small sample sizes in just one or two centers and have not included useful comparison groups.

Now, for the first time, a merged database of the International Collaboration on Endocarditis has allowed for an examination of prospectively collected data on cases of infective endocarditis reported during 1970-1999 from seven sites in five countries (France, the United Kingdom, Spain, Sweden, and the United States.)

“The aging population and emerging antimicrobial resistance among enterococci make this a pathogen of increasing importance,” said Dr. McDonald of Duke University, Durham, N.C.

Of 1,285 patients aged 18 or older with left-sided native valve endocarditis (NVE), there were 107 infected with enterococcus, 314 with Staphylococcus aureus, 666 with streptococci, and 198 with other pathogens.

Another 296 patients had prosthetic valve endocarditis (PVE), of whom 45 had enterococcus.

The 512 patients from the database with right-sided NVE were excluded from this analysis because such patients have a distinct natural history and epidemiology (young IV drug users), he explained at the conference, sponsored by the American Society for Microbiology.

In-hospital mortality was significantly lower among patients with left-sided NVE due to enterococcus than among those with disease due to S. aureus (11.2% vs. 26.5%), despite the fact that the enterococcus group was older (66.4 vs. 60 years) and had similar rates of both heart failure (45.8% vs. 43.6%) and nosocomial acquisition (15.3% vs. 19.4%).

Moreover, the 11.2% rate of in-hospital mortality for the enterococcus group was similar to the 10.2% rate among those with streptococcal NVE, even though the latter were younger (57.8 vs. 66.4 years), had less disease associated with the aortic valve (28.6% vs. 44.4%), and were less likely to have heart failure (35.1% vs. 45.8%).

Compared with patients who had enterococcal prosthetic valve endocarditis, those with enterococcal NVE had significantly more new valve regurgitation (45.6% vs. 12.8%), fewer abscesses (6.3% vs. 20.1%), and similar rates of in-hospital mortality (12.6%/14.8%) and early surgery (31.1%/31.7%), Dr. McDonald reported.

In a multivariate analysis of all patients with left-sided NVE, factors that significantly increased the risk for in-hospital mortality included age in 10-year intervals, systemic embolization, infection with S. aureus, intracardiac abscess, and heart failure. In contrast, infection with either viridans streptococci or enterococcus increased the chance of survival.

Interestingly, unlike early studies of enterococcal endocarditis, the disease was rarely seen among young women. Of the total 107 with enterococcal NVE, women accounted for just 27%.

Of those 29 women, all but two were aged 50 and older, whereas 10 of the 78 men were under age 50 (including 3 in their 20s). This difference may be explained by improved antibiotic prophylaxis for gynecologic procedures, which was the major risk factor for enterococcal endocarditis among young women in the early studies, Dr. McDonald told this newspaper.

The International Collaboration on Endocarditis is planning a larger prospective study to better characterize the disorder, he said.

ORLANDO FLA – Pre- and postnatal depression in women influences neuroendocrine function in their infants, Laura R. Stroud, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Prenatal depression, reported in approximately 10% of all pregnant women, has been linked with deficits in infants such as attenuated response to social stimuli, excessive crying, increased sleep problems, and lower vagal tone. Moreover, women with prenatal depression are also at increased risk for postnatal depression, which has also been linked to adverse effects in infants. Little is known about the influence of pre- and early postnatal depression on infant neuroendocrine functioning, said Dr. Stroud of Brown University, Providence, R.I.

In the first of two studies, cortisol responses to the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) were measured in 1- to 2-day-old newborns of 49 nondepressed mothers and 13 mothers who scored high for depression (greater than 11) on the Beck Depression Inventory before delivery.

Baseline and poststress cortisol responses were significantly attenuated among the infants of the depressed mothers, compared with those of nondepressed mothers. These results persisted after maternal age, smoking, birth weight, and alcohol use were factored in, Dr. Stroud reported.

In a second study involving 62 different mother-infant pairs, scores higher than 17 on the Center for Epidemiologic Studies-Depression scale, which was used to evaluate postnatal depressive symptoms, were a better predictor than high prenatal depression of cortisol responses to stress in infants at 10-30 days of life. The 13 infants of mothers with high postnatal depression scores showed attenuated baseline but elevated poststress cortisol responses, compared with those of nondepressed mothers.

This study was funded by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

ORLANDO FLA – Pre- and postnatal depression in women influences neuroendocrine function in their infants, Laura R. Stroud, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Prenatal depression, reported in approximately 10% of all pregnant women, has been linked with deficits in infants such as attenuated response to social stimuli, excessive crying, increased sleep problems, and lower vagal tone. Moreover, women with prenatal depression are also at increased risk for postnatal depression, which has also been linked to adverse effects in infants. Little is known about the influence of pre- and early postnatal depression on infant neuroendocrine functioning, said Dr. Stroud of Brown University, Providence, R.I.

In the first of two studies, cortisol responses to the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) were measured in 1- to 2-day-old newborns of 49 nondepressed mothers and 13 mothers who scored high for depression (greater than 11) on the Beck Depression Inventory before delivery.

Baseline and poststress cortisol responses were significantly attenuated among the infants of the depressed mothers, compared with those of nondepressed mothers. These results persisted after maternal age, smoking, birth weight, and alcohol use were factored in, Dr. Stroud reported.

In a second study involving 62 different mother-infant pairs, scores higher than 17 on the Center for Epidemiologic Studies-Depression scale, which was used to evaluate postnatal depressive symptoms, were a better predictor than high prenatal depression of cortisol responses to stress in infants at 10-30 days of life. The 13 infants of mothers with high postnatal depression scores showed attenuated baseline but elevated poststress cortisol responses, compared with those of nondepressed mothers.

This study was funded by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

ORLANDO FLA – Pre- and postnatal depression in women influences neuroendocrine function in their infants, Laura R. Stroud, Ph.D., reported at the annual meeting of the American Psychosomatic Society.

Prenatal depression, reported in approximately 10% of all pregnant women, has been linked with deficits in infants such as attenuated response to social stimuli, excessive crying, increased sleep problems, and lower vagal tone. Moreover, women with prenatal depression are also at increased risk for postnatal depression, which has also been linked to adverse effects in infants. Little is known about the influence of pre- and early postnatal depression on infant neuroendocrine functioning, said Dr. Stroud of Brown University, Providence, R.I.

In the first of two studies, cortisol responses to the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) were measured in 1- to 2-day-old newborns of 49 nondepressed mothers and 13 mothers who scored high for depression (greater than 11) on the Beck Depression Inventory before delivery.

Baseline and poststress cortisol responses were significantly attenuated among the infants of the depressed mothers, compared with those of nondepressed mothers. These results persisted after maternal age, smoking, birth weight, and alcohol use were factored in, Dr. Stroud reported.

In a second study involving 62 different mother-infant pairs, scores higher than 17 on the Center for Epidemiologic Studies-Depression scale, which was used to evaluate postnatal depressive symptoms, were a better predictor than high prenatal depression of cortisol responses to stress in infants at 10-30 days of life. The 13 infants of mothers with high postnatal depression scores showed attenuated baseline but elevated poststress cortisol responses, compared with those of nondepressed mothers.

This study was funded by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

WASHINGTON — The safety profile of Aventis Pasteur's reduced-antigen tetanus-diphtheria-acellular pertussis vaccine in adolescents is similar to that of the currently-licensed tetanus-diphtheria vaccine, Michael E. Pichichero, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aventis Pasteur's reduced-antigen tetanus-diphtheria- acellular pertussis (Tdap) vaccine, called Adacel, has been licensed in Canada for booster immunization of adolescents and adults. It is under review by the Food and Drug Administration for use in individuals aged 11-64 years.

Two randomized multicenter U.S. trials included 2,990 adolescents aged 11-17 given Tdap and 792 given tetanus-diphtheria toxoid (Td), said Dr. Pichichero, a specialist in pediatric infectious diseases who practices in Rochester, N.Y.

Immediate reactions (within 30 minutes) were reported at comparably low frequencies in both the Tdap and Td groups (0.5%-0.6%). Most reactions were mild and resolved within a day. Also comparable were the frequency, intensity, and mean duration of fever of 38° C or greater (seen in 5.0%-5.2% with Tdap, 2.7% with Td) and injection site erythema and/or swelling (20.8%-24.3% with Tdap, 18.3%-19.7% with Td).

Pain at the injection site was slightly but significantly more frequent in the Tdap group (79.2% vs. 71.0%), but this pain was usually of mild intensity and its mean duration did not differ significantly between the two groups, Dr. Pichichero said at the conference, sponsored by the American Society for Microbiology.

Postvaccination limb circumference measurements within 2 weeks of vaccination were very similar between the two groups (increases of more than 3 cm occurred in roughly 5% of each group), and no study subjects had whole arm swelling. Headache, generalized body ache, and tiredness (mostly mild) were the three most commonly reported solicited systemic events, all in less than 30% of each group.

Unsolicited events such as pharyngitis, nasopharyngitis, and cough within 28 days of vaccination were reported with equal frequency, intensity, and type between the two groups. Most were mild or moderate and not related to vaccination. Serious events were rare (1% or less in both groups), comparable in frequency, and unrelated to vaccination, he said.

WASHINGTON — The safety profile of Aventis Pasteur's reduced-antigen tetanus-diphtheria-acellular pertussis vaccine in adolescents is similar to that of the currently-licensed tetanus-diphtheria vaccine, Michael E. Pichichero, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aventis Pasteur's reduced-antigen tetanus-diphtheria- acellular pertussis (Tdap) vaccine, called Adacel, has been licensed in Canada for booster immunization of adolescents and adults. It is under review by the Food and Drug Administration for use in individuals aged 11-64 years.

Two randomized multicenter U.S. trials included 2,990 adolescents aged 11-17 given Tdap and 792 given tetanus-diphtheria toxoid (Td), said Dr. Pichichero, a specialist in pediatric infectious diseases who practices in Rochester, N.Y.

Immediate reactions (within 30 minutes) were reported at comparably low frequencies in both the Tdap and Td groups (0.5%-0.6%). Most reactions were mild and resolved within a day. Also comparable were the frequency, intensity, and mean duration of fever of 38° C or greater (seen in 5.0%-5.2% with Tdap, 2.7% with Td) and injection site erythema and/or swelling (20.8%-24.3% with Tdap, 18.3%-19.7% with Td).

Pain at the injection site was slightly but significantly more frequent in the Tdap group (79.2% vs. 71.0%), but this pain was usually of mild intensity and its mean duration did not differ significantly between the two groups, Dr. Pichichero said at the conference, sponsored by the American Society for Microbiology.

Postvaccination limb circumference measurements within 2 weeks of vaccination were very similar between the two groups (increases of more than 3 cm occurred in roughly 5% of each group), and no study subjects had whole arm swelling. Headache, generalized body ache, and tiredness (mostly mild) were the three most commonly reported solicited systemic events, all in less than 30% of each group.

Unsolicited events such as pharyngitis, nasopharyngitis, and cough within 28 days of vaccination were reported with equal frequency, intensity, and type between the two groups. Most were mild or moderate and not related to vaccination. Serious events were rare (1% or less in both groups), comparable in frequency, and unrelated to vaccination, he said.

WASHINGTON — The safety profile of Aventis Pasteur's reduced-antigen tetanus-diphtheria-acellular pertussis vaccine in adolescents is similar to that of the currently-licensed tetanus-diphtheria vaccine, Michael E. Pichichero, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aventis Pasteur's reduced-antigen tetanus-diphtheria- acellular pertussis (Tdap) vaccine, called Adacel, has been licensed in Canada for booster immunization of adolescents and adults. It is under review by the Food and Drug Administration for use in individuals aged 11-64 years.

Two randomized multicenter U.S. trials included 2,990 adolescents aged 11-17 given Tdap and 792 given tetanus-diphtheria toxoid (Td), said Dr. Pichichero, a specialist in pediatric infectious diseases who practices in Rochester, N.Y.

Immediate reactions (within 30 minutes) were reported at comparably low frequencies in both the Tdap and Td groups (0.5%-0.6%). Most reactions were mild and resolved within a day. Also comparable were the frequency, intensity, and mean duration of fever of 38° C or greater (seen in 5.0%-5.2% with Tdap, 2.7% with Td) and injection site erythema and/or swelling (20.8%-24.3% with Tdap, 18.3%-19.7% with Td).

Pain at the injection site was slightly but significantly more frequent in the Tdap group (79.2% vs. 71.0%), but this pain was usually of mild intensity and its mean duration did not differ significantly between the two groups, Dr. Pichichero said at the conference, sponsored by the American Society for Microbiology.

Postvaccination limb circumference measurements within 2 weeks of vaccination were very similar between the two groups (increases of more than 3 cm occurred in roughly 5% of each group), and no study subjects had whole arm swelling. Headache, generalized body ache, and tiredness (mostly mild) were the three most commonly reported solicited systemic events, all in less than 30% of each group.

Unsolicited events such as pharyngitis, nasopharyngitis, and cough within 28 days of vaccination were reported with equal frequency, intensity, and type between the two groups. Most were mild or moderate and not related to vaccination. Serious events were rare (1% or less in both groups), comparable in frequency, and unrelated to vaccination, he said.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria toxoid(Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Of all the diseases against which children are routinely immunized in the United States, pertussis is the only one still increasing. That's because immunity from the childhood vaccine wanes after about 10 years, and there is currently no pertussis vaccine licensed for persons over the age of 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month post vaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” Dr. Friedland said.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them, he said.

Study subjects were instructed to immediately contact investigators if they developed large areas of swelling at the injection site, an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were slightly more frequent in the Tdap subjects (15.7% vs. 12.7%), but there were no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days after vaccination, Dr. Friedland reported.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria toxoid(Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Of all the diseases against which children are routinely immunized in the United States, pertussis is the only one still increasing. That's because immunity from the childhood vaccine wanes after about 10 years, and there is currently no pertussis vaccine licensed for persons over the age of 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month post vaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” Dr. Friedland said.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them, he said.

Study subjects were instructed to immediately contact investigators if they developed large areas of swelling at the injection site, an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were slightly more frequent in the Tdap subjects (15.7% vs. 12.7%), but there were no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days after vaccination, Dr. Friedland reported.

WASHINGTON — GlaxoSmithKline's candidate reduced-antigen content tetanus-diphtheria-acellular pertussis booster vaccine for adolescents compares favorably with other currently licensed vaccines, Leonard Friedland, M.D., reported during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a pivotal clinical study of 4,114 healthy 10-18 year olds, Boostrix (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed [Tdap]) was comparable in both immunogenicity and safety with a currently licensed tetanus-diphtheria toxoid(Td) vaccine and produced antibody responses at least as high as those seen in infants who receive the current higher-antigen DTaP vaccine, said Dr. Friedland, director of clinical research and development and medical affairs for GlaxoSmithKline's Vaccines North America division.

Of all the diseases against which children are routinely immunized in the United States, pertussis is the only one still increasing. That's because immunity from the childhood vaccine wanes after about 10 years, and there is currently no pertussis vaccine licensed for persons over the age of 7 years. In 2003, adolescents aged 10-19 made up 39% of all pertussis cases in the United States.

Boostrix is currently under review by the U.S. Food and Drug Adminstration for use as a single-dose booster in adolescents. If approved, it could replace the current Td booster, thereby protecting adolescents against pertussis without adding an extra injection, he noted at the conference, sponsored by the American Society for Microbiology.

All study subjects had previously received the routine childhood vaccinations against diphtheria, tetanus, and pertussis according to the recommended schedule. Most had received their first three doses as whole-cell pertussis vaccine. Some had received their fourth and/or fifth doses as acellular pertussis vaccine.

The proportion achieving a fourfold rise in titers of antidiphtheria antibody at 1 month post vaccination was 90.6% among the subjects who received Tdap, compared with 95.9% of those given Td. For antitetanus antibody, the proportions were 89.7% and 92.5%, respectively. Moreover, seroprotective levels of both antibodies were achieved in more than 99.9% of the subjects in both groups. These results met the pre-defined criteria for “noninferiority” of Tdap vs. Td, Dr. Friedland said.

Since there is no established serologic correlate of protection for pertussis, the antibody responses to each of the three pertussis antigens (PT, FHA, and PRN) of the subjects in this study were compared with those seen in infants following receipt of GlaxoSmithKline's DTaP vaccine (Infanrix). For each antigen, the geometric mean titers (enzyme-linked immunoabsorbent assay units/ml) were considerably higher in the adolescents following Tdap than among the infants who received DTaP (85.9 vs. 48.6 for PT, 617.3 vs. 89.1 for FHA, and 469.3 vs. 124.2 for PRN).

It is therefore “reasonable to assume that Tdap will be at least as effective as Infanrix for preventing pertussis in adolescents,” Dr. Friedland said.

Overall pain at the injection site did not differ between Tdap (75.3%) and Td (71.7%). The proportion reporting grade 2 or 3 pain was slightly greater in the Tdap group (51.2% vs. 42.5%), but the percentage with grade 3 pain—preventing normal activity—was less than 5% in both groups and not significantly different between them, he said.

Study subjects were instructed to immediately contact investigators if they developed large areas of swelling at the injection site, an adverse effect that has been observed in children receiving the DTaP booster. Only two subjects—one from each vaccine group—reported diffuse swelling. The swelling did not involve adjacent joints and resolved completely in both subjects, Dr. Friedland said.

Headaches preventing normal activity were slightly more frequent in the Tdap subjects (15.7% vs. 12.7%), but there were no differences in fever, fatigue, or GI symptoms. No serious events occurred in either group in the 31 days after vaccination, Dr. Friedland reported.

VIENNA — Both increasing severity and recurrence of gestational hypertension increase a woman's chances of developing ischemic heart disease later in life, Dr. Anna-Karin Wikström said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Long-term measures to prevent hypertension should be undertaken in women who experience severe or recurrent hypertension during pregnancy, said Dr. Wikström of Uppsala University, Stockholm.

Data from three Swedish medical databases were analyzed for more than 400,000 women with first births since 1973 and for more than 200,000 who gave birth to two infants between 1973 and 1982. Only singleton births were included. Women with chronic hypertension and/or diabetes were excluded.

After adjustment for maternal age, socioeconomic status, and hospital category, the relative risk of developing ischemic heart disease (IHD) after 19-28 years' follow-up was 1.6 for the women who had gestational hypertension without proteinuria in their first pregnancies, compared with those who did not have hypertension in their first pregnancies. Among women with preeclampsia the relative risk was 1.9, and among those with severe preeclampsia it was 2.8. All the between-group differences were statistically significant, she said.

In the group with two children, the women who had any degree of hypertensive disease during their first pregnancy but not during the second had a 1.9 relative risk of IHD, compared with those who did not have hypertension in either pregnancy. The relative risk of IHD for women with hypertension in the second pregnancy but not the first was 2.4, and for those with hypertension in both pregnancies, 2.8. The difference between the first-pregnancy and both-pregnancy groups was statistically significant, she noted.

“We don't think that [this] information must be given to all women with gestational hypertensive disease, since it could create a lot of anxiety in a large group of women who will never go on to develop ischemic heart disease,” Dr. Wikström said.

But she added that giving such information “could be considered in women with a history of severe or recurrent preeclampsia, or gestation with coexisting, avoidable independent risk factors such as smoking and obesity.”

VIENNA — Both increasing severity and recurrence of gestational hypertension increase a woman's chances of developing ischemic heart disease later in life, Dr. Anna-Karin Wikström said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Long-term measures to prevent hypertension should be undertaken in women who experience severe or recurrent hypertension during pregnancy, said Dr. Wikström of Uppsala University, Stockholm.

Data from three Swedish medical databases were analyzed for more than 400,000 women with first births since 1973 and for more than 200,000 who gave birth to two infants between 1973 and 1982. Only singleton births were included. Women with chronic hypertension and/or diabetes were excluded.

After adjustment for maternal age, socioeconomic status, and hospital category, the relative risk of developing ischemic heart disease (IHD) after 19-28 years' follow-up was 1.6 for the women who had gestational hypertension without proteinuria in their first pregnancies, compared with those who did not have hypertension in their first pregnancies. Among women with preeclampsia the relative risk was 1.9, and among those with severe preeclampsia it was 2.8. All the between-group differences were statistically significant, she said.

In the group with two children, the women who had any degree of hypertensive disease during their first pregnancy but not during the second had a 1.9 relative risk of IHD, compared with those who did not have hypertension in either pregnancy. The relative risk of IHD for women with hypertension in the second pregnancy but not the first was 2.4, and for those with hypertension in both pregnancies, 2.8. The difference between the first-pregnancy and both-pregnancy groups was statistically significant, she noted.

“We don't think that [this] information must be given to all women with gestational hypertensive disease, since it could create a lot of anxiety in a large group of women who will never go on to develop ischemic heart disease,” Dr. Wikström said.

But she added that giving such information “could be considered in women with a history of severe or recurrent preeclampsia, or gestation with coexisting, avoidable independent risk factors such as smoking and obesity.”

VIENNA — Both increasing severity and recurrence of gestational hypertension increase a woman's chances of developing ischemic heart disease later in life, Dr. Anna-Karin Wikström said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Long-term measures to prevent hypertension should be undertaken in women who experience severe or recurrent hypertension during pregnancy, said Dr. Wikström of Uppsala University, Stockholm.

Data from three Swedish medical databases were analyzed for more than 400,000 women with first births since 1973 and for more than 200,000 who gave birth to two infants between 1973 and 1982. Only singleton births were included. Women with chronic hypertension and/or diabetes were excluded.

After adjustment for maternal age, socioeconomic status, and hospital category, the relative risk of developing ischemic heart disease (IHD) after 19-28 years' follow-up was 1.6 for the women who had gestational hypertension without proteinuria in their first pregnancies, compared with those who did not have hypertension in their first pregnancies. Among women with preeclampsia the relative risk was 1.9, and among those with severe preeclampsia it was 2.8. All the between-group differences were statistically significant, she said.

In the group with two children, the women who had any degree of hypertensive disease during their first pregnancy but not during the second had a 1.9 relative risk of IHD, compared with those who did not have hypertension in either pregnancy. The relative risk of IHD for women with hypertension in the second pregnancy but not the first was 2.4, and for those with hypertension in both pregnancies, 2.8. The difference between the first-pregnancy and both-pregnancy groups was statistically significant, she noted.

“We don't think that [this] information must be given to all women with gestational hypertensive disease, since it could create a lot of anxiety in a large group of women who will never go on to develop ischemic heart disease,” Dr. Wikström said.

But she added that giving such information “could be considered in women with a history of severe or recurrent preeclampsia, or gestation with coexisting, avoidable independent risk factors such as smoking and obesity.”