Obstetrics

Almost three-quarters of children born extremely preterm showed mild or no neurodevelopmental disability at age 2.5 years, according to a population-based study published in the May 1 issue of JAMA.

In comparison, 78% of control subjects born at term showed no neurodevelopmental disability.

"Improved survival did not translate into increasing disability rates, and we, like others, believe that the neurodevelopmental outcome for extremely preterm children born in the 2000s will be better than for those born in the 1990s," said Dr. Fredrik Serenius of the department of women’s and children’s health, Uppsala University, and his associates in the Extremely Preterm Infants Study in Sweden (EXPRESS).

The investigators noted that their results may not be generalizable to other countries. Sweden has "a rather uniform society without extreme poverty. Antenatal care is easily accessible and utilized by close to 100% of mothers. All citizens are covered by general health insurance including a total of 480 days of parental leave after the child’s birth and additional benefits for severely sick children," they said.

EXPRESS is a national prospective study of all infants born in Sweden before 27 weeks’ gestation during 2004-2007. For this study, Dr. Serenius and his colleagues assessed neurological and developmental outcomes in 456 of these children who survived to 2.5 years of corrected age, as well as in 701 control children matched for residence, sex, day of birth, and mother’s country of origin.

Certified psychologists assessed the children’s cognitive, language, and motor development using the Bayley Scales of Infant and Toddler Development. In addition, specialists in pediatrics or pediatric neurology examined the preterm group for neuromotor function. Parents of children in both study groups were interviewed to ascertain parental education level and overall child health and development.

Among the preterm infants, 42% were neurodevelopmentally normal and 31% were mildly disabled. The remaining 27% were moderately or severely disabled, including four children who were blind and one who was blind and deaf. Seven percent of the preterm group had cerebral palsy – 13 with mild CP, 13 with moderate CP, and 6 with severe CP, the investigators said (JAMA 2013;309:1810-20).

In comparison, 78% of children in the control group were neurodevelopmentally normal and another 19% were mildly disabled. The remaining 3% were moderately or severely disabled, including one with severe CP.

The mean composite cognitive score for children in the preterm group was 94, compared with 104 for the control group. The mean composite language scores were 98 and 109, respectively, and the mean composite motor scores were 94 and 107, respectively.

In the preterm group, these scores rose with increasing gestational age at birth, so that cognitive scores were 2.5 points higher for every additional week of gestational age, language scores were 3.6 points higher for every additional week, and motor scores were 2.5 points higher for every additional week.

Overall, even though prematurity had a "large" impact on neurodevelopmental outcomes, most extremely preterm children emerged with no or only mild disability.

"These results are relevant for clinicians counseling families facing extremely preterm birth," Dr. Serenius and his associates said.

This study was supported in part by the Swedish Research Council. No financial conflicts of interest were reported.

Almost three-quarters of children born extremely preterm showed mild or no neurodevelopmental disability at age 2.5 years, according to a population-based study published in the May 1 issue of JAMA.

In comparison, 78% of control subjects born at term showed no neurodevelopmental disability.

"Improved survival did not translate into increasing disability rates, and we, like others, believe that the neurodevelopmental outcome for extremely preterm children born in the 2000s will be better than for those born in the 1990s," said Dr. Fredrik Serenius of the department of women’s and children’s health, Uppsala University, and his associates in the Extremely Preterm Infants Study in Sweden (EXPRESS).

The investigators noted that their results may not be generalizable to other countries. Sweden has "a rather uniform society without extreme poverty. Antenatal care is easily accessible and utilized by close to 100% of mothers. All citizens are covered by general health insurance including a total of 480 days of parental leave after the child’s birth and additional benefits for severely sick children," they said.

EXPRESS is a national prospective study of all infants born in Sweden before 27 weeks’ gestation during 2004-2007. For this study, Dr. Serenius and his colleagues assessed neurological and developmental outcomes in 456 of these children who survived to 2.5 years of corrected age, as well as in 701 control children matched for residence, sex, day of birth, and mother’s country of origin.

Certified psychologists assessed the children’s cognitive, language, and motor development using the Bayley Scales of Infant and Toddler Development. In addition, specialists in pediatrics or pediatric neurology examined the preterm group for neuromotor function. Parents of children in both study groups were interviewed to ascertain parental education level and overall child health and development.

Among the preterm infants, 42% were neurodevelopmentally normal and 31% were mildly disabled. The remaining 27% were moderately or severely disabled, including four children who were blind and one who was blind and deaf. Seven percent of the preterm group had cerebral palsy – 13 with mild CP, 13 with moderate CP, and 6 with severe CP, the investigators said (JAMA 2013;309:1810-20).

In comparison, 78% of children in the control group were neurodevelopmentally normal and another 19% were mildly disabled. The remaining 3% were moderately or severely disabled, including one with severe CP.

The mean composite cognitive score for children in the preterm group was 94, compared with 104 for the control group. The mean composite language scores were 98 and 109, respectively, and the mean composite motor scores were 94 and 107, respectively.

In the preterm group, these scores rose with increasing gestational age at birth, so that cognitive scores were 2.5 points higher for every additional week of gestational age, language scores were 3.6 points higher for every additional week, and motor scores were 2.5 points higher for every additional week.

Overall, even though prematurity had a "large" impact on neurodevelopmental outcomes, most extremely preterm children emerged with no or only mild disability.

"These results are relevant for clinicians counseling families facing extremely preterm birth," Dr. Serenius and his associates said.

This study was supported in part by the Swedish Research Council. No financial conflicts of interest were reported.

Almost three-quarters of children born extremely preterm showed mild or no neurodevelopmental disability at age 2.5 years, according to a population-based study published in the May 1 issue of JAMA.

In comparison, 78% of control subjects born at term showed no neurodevelopmental disability.

"Improved survival did not translate into increasing disability rates, and we, like others, believe that the neurodevelopmental outcome for extremely preterm children born in the 2000s will be better than for those born in the 1990s," said Dr. Fredrik Serenius of the department of women’s and children’s health, Uppsala University, and his associates in the Extremely Preterm Infants Study in Sweden (EXPRESS).

The investigators noted that their results may not be generalizable to other countries. Sweden has "a rather uniform society without extreme poverty. Antenatal care is easily accessible and utilized by close to 100% of mothers. All citizens are covered by general health insurance including a total of 480 days of parental leave after the child’s birth and additional benefits for severely sick children," they said.

EXPRESS is a national prospective study of all infants born in Sweden before 27 weeks’ gestation during 2004-2007. For this study, Dr. Serenius and his colleagues assessed neurological and developmental outcomes in 456 of these children who survived to 2.5 years of corrected age, as well as in 701 control children matched for residence, sex, day of birth, and mother’s country of origin.

Certified psychologists assessed the children’s cognitive, language, and motor development using the Bayley Scales of Infant and Toddler Development. In addition, specialists in pediatrics or pediatric neurology examined the preterm group for neuromotor function. Parents of children in both study groups were interviewed to ascertain parental education level and overall child health and development.

Among the preterm infants, 42% were neurodevelopmentally normal and 31% were mildly disabled. The remaining 27% were moderately or severely disabled, including four children who were blind and one who was blind and deaf. Seven percent of the preterm group had cerebral palsy – 13 with mild CP, 13 with moderate CP, and 6 with severe CP, the investigators said (JAMA 2013;309:1810-20).

In comparison, 78% of children in the control group were neurodevelopmentally normal and another 19% were mildly disabled. The remaining 3% were moderately or severely disabled, including one with severe CP.

The mean composite cognitive score for children in the preterm group was 94, compared with 104 for the control group. The mean composite language scores were 98 and 109, respectively, and the mean composite motor scores were 94 and 107, respectively.

In the preterm group, these scores rose with increasing gestational age at birth, so that cognitive scores were 2.5 points higher for every additional week of gestational age, language scores were 3.6 points higher for every additional week, and motor scores were 2.5 points higher for every additional week.

Overall, even though prematurity had a "large" impact on neurodevelopmental outcomes, most extremely preterm children emerged with no or only mild disability.

"These results are relevant for clinicians counseling families facing extremely preterm birth," Dr. Serenius and his associates said.

This study was supported in part by the Swedish Research Council. No financial conflicts of interest were reported.

All patients aged 15-65 years should be screened for HIV, regardless of their risk level, according to updated recommendations of the U.S. Preventive Services Task Force published online April 30 in the Annals of Internal Medicine.

The new strategy will substantially decrease the HIV disease burden across the country, dramatically reduce transmission of the virus, and markedly curtail infected patients’ progression to AIDS and death, said Dr. Virginia A. Moyer, chair of the USPSTF and professor of pediatrics at Baylor University and Texas Children’s Hospital, Houston, and her associates.

Amanda Mills/CDC

In its last set of HIV screening recommendations, issued in 2005, the USPSTF advised screening only at-risk patients. At that time, the task force cautioned that testing of the general population would cause undue psychological harm and that treatment before symptom onset would expose patients to serious adverse effects without exerting enough benefit to outweigh that disadvantage.

But 8 years later, new, convincing evidence shows "with high certainty" that identifying and treating HIV infection in asymptomatic people will substantially benefit public health as well as the health of those individual patients.

This change in screening recommendations is "of critical significance," because it brings the USPSTF into line with the Centers for Disease Control and Prevention on the issue of HIV screening, Dr. Moupali Das and Dr. Paul Volberding said in an editorial accompanying the new recommendations.

"Now, with an increasing consensus on population-wide screening, a growing belief in universal treatment, and the goal of near-universal access to medical care under the Affordable Care Act, we may ultimately awaken from the nightmare of the HIV/AIDS epidemic," Dr. Das and Dr. Volberding noted.

Three key research findings drove the task force to update HIV screening guidelines.

First, it is now known that 20% of people infected with HIV are not aware that they are infected. That means an estimated 236,400 people in the United States don’t know that they should take precautions against transmitting the virus and begin treatment to limit HIV-related illness and end-organ damage, Dr. Moyer and her colleagues said (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00645]).

Second, it has been proved that initiation of antiretroviral therapy before carriers become symptomatic – when CD4 counts are between 0.200 and 0.500 x 10⁹ cells/L – markedly reduces progression to AIDS and death.

"Hesitation in screening diminishes with the acceptance of HIV infection as a chronic disease that can be controlled by increasingly potent, convenient, and safe drugs," Dr. Das and Dr. Volberding said in their editorial (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00643]).

And third, the overall harms of screening the general population and treating those who are found to be HIV-positive are now considered "small." Both conventional and rapid screening tests are highly accurate, with sensitivities and specificities topping 99.5% – so the potential harms of false-negative and false-positive results are minimal. And treatment is highly effective, with benefits clearly outweighing adverse effects, Dr. Moyer and her associates said.

Accordingly, the USPSTF now recommends HIV screening for adolescents as young as 15 years and adults as old as 65 years, regardless of their risk status. And HIV screening remains advisable for patients of any age who are at risk.

The USPSTF also renewed its recommendation that all pregnant women should be screened for HIV, because identification and treatment "dramatically reduces the rate of mother-to-child transmission." Women screened during a previous pregnancy should be rescreened with every subsequent pregnancy.

"Both of these major U.S. treatment guidelines [the USPSTF’s and the CDC’s] now agree that all infected persons should be offered antiretroviral therapy ... to enable a more complete immune reconstitution with the goal of achieving a near-normal lifespan," said Dr. Das of the University of San Francisco and Dr. Volberding of the University of California San Francisco AIDS Research Institute. "Making an early diagnosis by screening asymptomatic persons is thus a vitally important entry into life-extending management."

The evidence is insufficient to establish what the optimal interval should be between screenings. However, it is "reasonable" to rescreen at-risk people at 1-year intervals. This includes patients who engage in high-risk behaviors and those who live in or receive medical care in high-prevalence settings such as correctional facilities, homeless shelters, TB clinics, sexually transmitted infection clinics, and clinics that serve men who have sex with men.

In addition, "the USPSTF concurs with the CDC’s recommendation that HIV screening should be voluntary and done only with the patient’s knowledge and understanding." Both organizations recommend that patients be fully informed about HIV infection and the meaning of test results and that they be screened unless they specifically decline (opt out of) HIV testing.

Although funded by the Agency for Healthcare Research and Quality under a congressional mandate, the USPSTF is a voluntary group of clinicians and public health experts that is independent of the federal government and compiles recommendations about preventive care for a range of health conditions.

Dr. Moyer and her associates reported no financial conflicts of interest. Dr. Das and Dr. Volberding also reported no financial conflicts of interest.

All patients aged 15-65 years should be screened for HIV, regardless of their risk level, according to updated recommendations of the U.S. Preventive Services Task Force published online April 30 in the Annals of Internal Medicine.

The new strategy will substantially decrease the HIV disease burden across the country, dramatically reduce transmission of the virus, and markedly curtail infected patients’ progression to AIDS and death, said Dr. Virginia A. Moyer, chair of the USPSTF and professor of pediatrics at Baylor University and Texas Children’s Hospital, Houston, and her associates.

Amanda Mills/CDC

In its last set of HIV screening recommendations, issued in 2005, the USPSTF advised screening only at-risk patients. At that time, the task force cautioned that testing of the general population would cause undue psychological harm and that treatment before symptom onset would expose patients to serious adverse effects without exerting enough benefit to outweigh that disadvantage.

But 8 years later, new, convincing evidence shows "with high certainty" that identifying and treating HIV infection in asymptomatic people will substantially benefit public health as well as the health of those individual patients.

This change in screening recommendations is "of critical significance," because it brings the USPSTF into line with the Centers for Disease Control and Prevention on the issue of HIV screening, Dr. Moupali Das and Dr. Paul Volberding said in an editorial accompanying the new recommendations.

"Now, with an increasing consensus on population-wide screening, a growing belief in universal treatment, and the goal of near-universal access to medical care under the Affordable Care Act, we may ultimately awaken from the nightmare of the HIV/AIDS epidemic," Dr. Das and Dr. Volberding noted.

Three key research findings drove the task force to update HIV screening guidelines.

First, it is now known that 20% of people infected with HIV are not aware that they are infected. That means an estimated 236,400 people in the United States don’t know that they should take precautions against transmitting the virus and begin treatment to limit HIV-related illness and end-organ damage, Dr. Moyer and her colleagues said (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00645]).

Second, it has been proved that initiation of antiretroviral therapy before carriers become symptomatic – when CD4 counts are between 0.200 and 0.500 x 10⁹ cells/L – markedly reduces progression to AIDS and death.

"Hesitation in screening diminishes with the acceptance of HIV infection as a chronic disease that can be controlled by increasingly potent, convenient, and safe drugs," Dr. Das and Dr. Volberding said in their editorial (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00643]).

And third, the overall harms of screening the general population and treating those who are found to be HIV-positive are now considered "small." Both conventional and rapid screening tests are highly accurate, with sensitivities and specificities topping 99.5% – so the potential harms of false-negative and false-positive results are minimal. And treatment is highly effective, with benefits clearly outweighing adverse effects, Dr. Moyer and her associates said.

Accordingly, the USPSTF now recommends HIV screening for adolescents as young as 15 years and adults as old as 65 years, regardless of their risk status. And HIV screening remains advisable for patients of any age who are at risk.

The USPSTF also renewed its recommendation that all pregnant women should be screened for HIV, because identification and treatment "dramatically reduces the rate of mother-to-child transmission." Women screened during a previous pregnancy should be rescreened with every subsequent pregnancy.

"Both of these major U.S. treatment guidelines [the USPSTF’s and the CDC’s] now agree that all infected persons should be offered antiretroviral therapy ... to enable a more complete immune reconstitution with the goal of achieving a near-normal lifespan," said Dr. Das of the University of San Francisco and Dr. Volberding of the University of California San Francisco AIDS Research Institute. "Making an early diagnosis by screening asymptomatic persons is thus a vitally important entry into life-extending management."

The evidence is insufficient to establish what the optimal interval should be between screenings. However, it is "reasonable" to rescreen at-risk people at 1-year intervals. This includes patients who engage in high-risk behaviors and those who live in or receive medical care in high-prevalence settings such as correctional facilities, homeless shelters, TB clinics, sexually transmitted infection clinics, and clinics that serve men who have sex with men.

In addition, "the USPSTF concurs with the CDC’s recommendation that HIV screening should be voluntary and done only with the patient’s knowledge and understanding." Both organizations recommend that patients be fully informed about HIV infection and the meaning of test results and that they be screened unless they specifically decline (opt out of) HIV testing.

Although funded by the Agency for Healthcare Research and Quality under a congressional mandate, the USPSTF is a voluntary group of clinicians and public health experts that is independent of the federal government and compiles recommendations about preventive care for a range of health conditions.

Dr. Moyer and her associates reported no financial conflicts of interest. Dr. Das and Dr. Volberding also reported no financial conflicts of interest.

All patients aged 15-65 years should be screened for HIV, regardless of their risk level, according to updated recommendations of the U.S. Preventive Services Task Force published online April 30 in the Annals of Internal Medicine.

The new strategy will substantially decrease the HIV disease burden across the country, dramatically reduce transmission of the virus, and markedly curtail infected patients’ progression to AIDS and death, said Dr. Virginia A. Moyer, chair of the USPSTF and professor of pediatrics at Baylor University and Texas Children’s Hospital, Houston, and her associates.

Amanda Mills/CDC

In its last set of HIV screening recommendations, issued in 2005, the USPSTF advised screening only at-risk patients. At that time, the task force cautioned that testing of the general population would cause undue psychological harm and that treatment before symptom onset would expose patients to serious adverse effects without exerting enough benefit to outweigh that disadvantage.

But 8 years later, new, convincing evidence shows "with high certainty" that identifying and treating HIV infection in asymptomatic people will substantially benefit public health as well as the health of those individual patients.

This change in screening recommendations is "of critical significance," because it brings the USPSTF into line with the Centers for Disease Control and Prevention on the issue of HIV screening, Dr. Moupali Das and Dr. Paul Volberding said in an editorial accompanying the new recommendations.

"Now, with an increasing consensus on population-wide screening, a growing belief in universal treatment, and the goal of near-universal access to medical care under the Affordable Care Act, we may ultimately awaken from the nightmare of the HIV/AIDS epidemic," Dr. Das and Dr. Volberding noted.

Three key research findings drove the task force to update HIV screening guidelines.

First, it is now known that 20% of people infected with HIV are not aware that they are infected. That means an estimated 236,400 people in the United States don’t know that they should take precautions against transmitting the virus and begin treatment to limit HIV-related illness and end-organ damage, Dr. Moyer and her colleagues said (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00645]).

Second, it has been proved that initiation of antiretroviral therapy before carriers become symptomatic – when CD4 counts are between 0.200 and 0.500 x 10⁹ cells/L – markedly reduces progression to AIDS and death.

"Hesitation in screening diminishes with the acceptance of HIV infection as a chronic disease that can be controlled by increasingly potent, convenient, and safe drugs," Dr. Das and Dr. Volberding said in their editorial (Ann. Intern. Med. 2013 [doi:10.7326/0003-4819-159-1-201307020-00643]).

And third, the overall harms of screening the general population and treating those who are found to be HIV-positive are now considered "small." Both conventional and rapid screening tests are highly accurate, with sensitivities and specificities topping 99.5% – so the potential harms of false-negative and false-positive results are minimal. And treatment is highly effective, with benefits clearly outweighing adverse effects, Dr. Moyer and her associates said.

Accordingly, the USPSTF now recommends HIV screening for adolescents as young as 15 years and adults as old as 65 years, regardless of their risk status. And HIV screening remains advisable for patients of any age who are at risk.

The USPSTF also renewed its recommendation that all pregnant women should be screened for HIV, because identification and treatment "dramatically reduces the rate of mother-to-child transmission." Women screened during a previous pregnancy should be rescreened with every subsequent pregnancy.

"Both of these major U.S. treatment guidelines [the USPSTF’s and the CDC’s] now agree that all infected persons should be offered antiretroviral therapy ... to enable a more complete immune reconstitution with the goal of achieving a near-normal lifespan," said Dr. Das of the University of San Francisco and Dr. Volberding of the University of California San Francisco AIDS Research Institute. "Making an early diagnosis by screening asymptomatic persons is thus a vitally important entry into life-extending management."

The evidence is insufficient to establish what the optimal interval should be between screenings. However, it is "reasonable" to rescreen at-risk people at 1-year intervals. This includes patients who engage in high-risk behaviors and those who live in or receive medical care in high-prevalence settings such as correctional facilities, homeless shelters, TB clinics, sexually transmitted infection clinics, and clinics that serve men who have sex with men.

In addition, "the USPSTF concurs with the CDC’s recommendation that HIV screening should be voluntary and done only with the patient’s knowledge and understanding." Both organizations recommend that patients be fully informed about HIV infection and the meaning of test results and that they be screened unless they specifically decline (opt out of) HIV testing.

Although funded by the Agency for Healthcare Research and Quality under a congressional mandate, the USPSTF is a voluntary group of clinicians and public health experts that is independent of the federal government and compiles recommendations about preventive care for a range of health conditions.

Dr. Moyer and her associates reported no financial conflicts of interest. Dr. Das and Dr. Volberding also reported no financial conflicts of interest.

ROME – The European Society of Hypertension is poised to endorse low-dose aspirin prophylaxis against preeclampsia for a large percent of pregnant women, according to a report at the annual meeting of the *European Association for Cardiovascular Prevention and Rehabilitation.

Endorsement of aspirin treatment for prophylaxis of preeclampsia in moderate- and high-risk women is part of new guidelines for managing hypertension prepared jointly by the European Society of Hypertension (ESH) and the European Society of Cardiology that will be unveiled at the hypertension society’s annual meeting in Milan in June, Dr. Renata Cifková said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"Aspirin, at a dosage of 75 mg/day, is recommended for the prevention of preeclampsia in women at high or moderate risk of preeclampsia from 12 weeks’ gestation until delivery," said Dr. Cifková, professor and head of the department of preventive cardiology at Thomayer University Hospital in Prague. The high- and moderate-risk categories together define a large proportion of women who become pregnant today.

The new guidelines define women at high risk who should receive aspirin prophylaxis as those who had gestational hypertension during a prior pregnancy, or women with chronic kidney disease, an autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome, type 1 or 2 diabetes, or chronic hypertension. The guidelines also say that women should receive aspirin prophylaxis if they have two or more of these moderate-risk factors for preeclampsia: first pregnancy, age 40 years or older, a prior pregnancy interval of more than 10 years, a body mass index of 30 kg/m² or greater, a family history of preeclampsia, or a multiple pregnancy.

These new ESH guidelines for preeclampsia prevention with aspirin follow exactly the recommendations made in August 2010 by the U.K.’s National Institute for Health and Clinical Excellence (NICE), noted Dr. Cifková. The most notable evidence supporting this approach came from a meta-analysis published in 2010 that included 27 studies involving more than 11,000 women and found that low-dose aspirin begun early in pregnancy cut the incidence of preeclampsia by about 50% (Ob.Gyn. 2010;116:402-14).

Another soon-to-appear guidance from the ESH, on appropriate patients for ambulatory blood pressure monitoring (ABPM), received a preview from Dr. Gianfranco Parati, professor of cardiovascular medicine at the University of Milan.

Mitchel L. Zoler/IMNG Medical Media

The new revision comes from an expert panel first convened 2 years ago by the ESH, Dr. Parati said at the meeting. The soon-to-be-published position on ABPM will not make recommendations that are as well defined as the ones for preeclampsia prophylaxis. "Is ABPM needed for every patient with hypertension? No, but it should be used in more patients," he said. Routine use of ABPM to confirm hypertension in all patients "is not suitable for every country because of its cost," he added.

Nonetheless, the new ESH consensus statement calls for using ABPM to confirm a diagnosis of hypertension or its absence, and thereby better avoid the twin nemeses of accurate hypertension assessment: white coat hypertension and masked hypertension, he said. ABPM also allows assessment of blood pressure control throughout 24 hours. The new guidelines say that ABPM is appropriate for selected elderly, children, and adolescent patients, and during pregnancy.

When high-risk patients or patients with nocturnal hypertension undergo ABPM, a follow-up, repeat examination should be done in 6 months. In most other patients, follow-up ABPM can occur after 1-2 years, Dr. Parati said.

Dr. Cifková reported no relevant financial disclosures. Dr. Parati has received honoraria from Bayer, Boegringer Ingelheim, Daiichi-Sankyo, Merck Serono, Menarini, Novartis, Recordati, Sanofi Aventis, and Takeda, and research support from Boehringer Ingelheim, Bayer, and Sanofi Aventis.

[email protected]

On Twitter @mitchelzoler

*Correction (5/29/13): A previous version of this story misstated the meeting name during which these presentations were made. This version has been updated. 

ROME – The European Society of Hypertension is poised to endorse low-dose aspirin prophylaxis against preeclampsia for a large percent of pregnant women, according to a report at the annual meeting of the *European Association for Cardiovascular Prevention and Rehabilitation.

Endorsement of aspirin treatment for prophylaxis of preeclampsia in moderate- and high-risk women is part of new guidelines for managing hypertension prepared jointly by the European Society of Hypertension (ESH) and the European Society of Cardiology that will be unveiled at the hypertension society’s annual meeting in Milan in June, Dr. Renata Cifková said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"Aspirin, at a dosage of 75 mg/day, is recommended for the prevention of preeclampsia in women at high or moderate risk of preeclampsia from 12 weeks’ gestation until delivery," said Dr. Cifková, professor and head of the department of preventive cardiology at Thomayer University Hospital in Prague. The high- and moderate-risk categories together define a large proportion of women who become pregnant today.

The new guidelines define women at high risk who should receive aspirin prophylaxis as those who had gestational hypertension during a prior pregnancy, or women with chronic kidney disease, an autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome, type 1 or 2 diabetes, or chronic hypertension. The guidelines also say that women should receive aspirin prophylaxis if they have two or more of these moderate-risk factors for preeclampsia: first pregnancy, age 40 years or older, a prior pregnancy interval of more than 10 years, a body mass index of 30 kg/m² or greater, a family history of preeclampsia, or a multiple pregnancy.

These new ESH guidelines for preeclampsia prevention with aspirin follow exactly the recommendations made in August 2010 by the U.K.’s National Institute for Health and Clinical Excellence (NICE), noted Dr. Cifková. The most notable evidence supporting this approach came from a meta-analysis published in 2010 that included 27 studies involving more than 11,000 women and found that low-dose aspirin begun early in pregnancy cut the incidence of preeclampsia by about 50% (Ob.Gyn. 2010;116:402-14).

Another soon-to-appear guidance from the ESH, on appropriate patients for ambulatory blood pressure monitoring (ABPM), received a preview from Dr. Gianfranco Parati, professor of cardiovascular medicine at the University of Milan.

Mitchel L. Zoler/IMNG Medical Media

The new revision comes from an expert panel first convened 2 years ago by the ESH, Dr. Parati said at the meeting. The soon-to-be-published position on ABPM will not make recommendations that are as well defined as the ones for preeclampsia prophylaxis. "Is ABPM needed for every patient with hypertension? No, but it should be used in more patients," he said. Routine use of ABPM to confirm hypertension in all patients "is not suitable for every country because of its cost," he added.

Nonetheless, the new ESH consensus statement calls for using ABPM to confirm a diagnosis of hypertension or its absence, and thereby better avoid the twin nemeses of accurate hypertension assessment: white coat hypertension and masked hypertension, he said. ABPM also allows assessment of blood pressure control throughout 24 hours. The new guidelines say that ABPM is appropriate for selected elderly, children, and adolescent patients, and during pregnancy.

When high-risk patients or patients with nocturnal hypertension undergo ABPM, a follow-up, repeat examination should be done in 6 months. In most other patients, follow-up ABPM can occur after 1-2 years, Dr. Parati said.

Dr. Cifková reported no relevant financial disclosures. Dr. Parati has received honoraria from Bayer, Boegringer Ingelheim, Daiichi-Sankyo, Merck Serono, Menarini, Novartis, Recordati, Sanofi Aventis, and Takeda, and research support from Boehringer Ingelheim, Bayer, and Sanofi Aventis.

[email protected]

On Twitter @mitchelzoler

*Correction (5/29/13): A previous version of this story misstated the meeting name during which these presentations were made. This version has been updated. 

ROME – The European Society of Hypertension is poised to endorse low-dose aspirin prophylaxis against preeclampsia for a large percent of pregnant women, according to a report at the annual meeting of the *European Association for Cardiovascular Prevention and Rehabilitation.

Endorsement of aspirin treatment for prophylaxis of preeclampsia in moderate- and high-risk women is part of new guidelines for managing hypertension prepared jointly by the European Society of Hypertension (ESH) and the European Society of Cardiology that will be unveiled at the hypertension society’s annual meeting in Milan in June, Dr. Renata Cifková said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"Aspirin, at a dosage of 75 mg/day, is recommended for the prevention of preeclampsia in women at high or moderate risk of preeclampsia from 12 weeks’ gestation until delivery," said Dr. Cifková, professor and head of the department of preventive cardiology at Thomayer University Hospital in Prague. The high- and moderate-risk categories together define a large proportion of women who become pregnant today.

The new guidelines define women at high risk who should receive aspirin prophylaxis as those who had gestational hypertension during a prior pregnancy, or women with chronic kidney disease, an autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome, type 1 or 2 diabetes, or chronic hypertension. The guidelines also say that women should receive aspirin prophylaxis if they have two or more of these moderate-risk factors for preeclampsia: first pregnancy, age 40 years or older, a prior pregnancy interval of more than 10 years, a body mass index of 30 kg/m² or greater, a family history of preeclampsia, or a multiple pregnancy.

These new ESH guidelines for preeclampsia prevention with aspirin follow exactly the recommendations made in August 2010 by the U.K.’s National Institute for Health and Clinical Excellence (NICE), noted Dr. Cifková. The most notable evidence supporting this approach came from a meta-analysis published in 2010 that included 27 studies involving more than 11,000 women and found that low-dose aspirin begun early in pregnancy cut the incidence of preeclampsia by about 50% (Ob.Gyn. 2010;116:402-14).

Another soon-to-appear guidance from the ESH, on appropriate patients for ambulatory blood pressure monitoring (ABPM), received a preview from Dr. Gianfranco Parati, professor of cardiovascular medicine at the University of Milan.

Mitchel L. Zoler/IMNG Medical Media

The new revision comes from an expert panel first convened 2 years ago by the ESH, Dr. Parati said at the meeting. The soon-to-be-published position on ABPM will not make recommendations that are as well defined as the ones for preeclampsia prophylaxis. "Is ABPM needed for every patient with hypertension? No, but it should be used in more patients," he said. Routine use of ABPM to confirm hypertension in all patients "is not suitable for every country because of its cost," he added.

Nonetheless, the new ESH consensus statement calls for using ABPM to confirm a diagnosis of hypertension or its absence, and thereby better avoid the twin nemeses of accurate hypertension assessment: white coat hypertension and masked hypertension, he said. ABPM also allows assessment of blood pressure control throughout 24 hours. The new guidelines say that ABPM is appropriate for selected elderly, children, and adolescent patients, and during pregnancy.

When high-risk patients or patients with nocturnal hypertension undergo ABPM, a follow-up, repeat examination should be done in 6 months. In most other patients, follow-up ABPM can occur after 1-2 years, Dr. Parati said.

Dr. Cifková reported no relevant financial disclosures. Dr. Parati has received honoraria from Bayer, Boegringer Ingelheim, Daiichi-Sankyo, Merck Serono, Menarini, Novartis, Recordati, Sanofi Aventis, and Takeda, and research support from Boehringer Ingelheim, Bayer, and Sanofi Aventis.

[email protected]

On Twitter @mitchelzoler

*Correction (5/29/13): A previous version of this story misstated the meeting name during which these presentations were made. This version has been updated. 

ORLANDO – Women with a history of severe preeclampsia show signs of small artery dysfunction as early as 2 years after delivery, an indication of cardiovascular disease later in life if not addressed by ob.gyns. and cardiologists early on, according to a small, unpublished study.

Researchers led by Dr. Karolina Kublickiene found that in women with a history of preeclampsia, endothelium-dependent dilation to flow was reduced, a change that could be due to nitric oxide contribution deficiency. The small arteries seen in the study group also exhibited increased myogenic tone, with enhanced sensitivity to the vasoconstrictor norepinephrine.

Dr. Louise Kenny, who moderated the session at the annual meeting of the Society for Gynecologic Investigation, said the study was "exquisitely executed."

"This is very basic science, but has massive clinical implications," said Dr. Kenny, a professor of obstetrics at the University College Cork, Ireland.

Several studies have shown that a history of preeclampsia is a risk factor for developing cardiovascular disease (Circulation 2012;125:1367-80). However, many women with preeclampsia go back to the community without proper follow-up with a cardiologist.

"I’m a high-risk maternal medicine obstetrician, and I’m very well aware that the long-term follow-up for women with preeclampsia is quite patchy," said Dr. Kenny. "We have a complete disconnect at several levels, and it is time to act."

Researchers hypothesized that functional and structural abnormalities in peripheral arteries are present as early as 2 years after delivery in mothers who had a pregnancy complicated by early-onset and severe preeclampsia.

They selected 15 women with a history of severe preeclampsia who had delivered between 2007 and 2011 at Karolinska University Hospital in Stockholm. They selected 15 closely matched controls who had normal pregnancies and gave birth during the same period. The women were on average 35 years old.

The investigators defined severe preeclampsia as systolic blood pressure of more than 160 mm Hg and/or diastolic blood pressure of more than 110 mm Hg on two occasions, at least 6 hours apart, and/or proteinuria of more than 5 g in a 24-hour period and/or organ damage.

The preeclampsia group and the control group were closely matched with regard to several biochemical characteristics, including the low-density lipoprotein to high-density lipoprotein (LDL/HDL) ratio (1.9 and 1.6, respectively). However, women in the preeclampsia group had higher blood pressure, insulin levels, and hemostatic model assessment index than did controls: The average diastolic blood pressure in the preeclampsia group was 74 mm Hg, versus 66 mm Hg in the control group. The average fasting insulin level in the preeclampsia group was almost twice as high as that of the control group (83 pmol/L vs. 44 pmol/L). Neither group showed evidence of early renal damage.

Researchers took subcutaneous fat biopsies from the women. They used pressure myography to compare the structure and function of the isolated small subcutaneous resistance arteries. They used immunostaining to compare endothelial nitric oxide synthase (eNOS) and lectin-like oxidized LDL receptor-1 (LOX-1) expression.

The arteries in both groups had similar diameters, wall thickness, wall-lumen ratio, and cross-sectional area.

Results showed that eNOS expression was similar in both groups, but LOX-1 expression was significantly enhanced in the study group. Inhibition of NOS had no effect on either group.

Myogenic tone was enhanced in the arteries of women with a history of preeclampsia, and was positively correlated with the LDL/HDL ratio, a change characterizing small artery dysfunction.

Basal tone in the study group also was positively correlated with the LDL/HDL ratio, triglycerides, glycated hemoglobin, and high-sensitivity C-reactive protein, and was negatively correlated with HDL. Basal tone at 60 mm Hg was 8 in the preeclampsia group, compared with 5 in the control group (P = .07).

Meanwhile, the study group had higher sensitivity to norepinephrine and angiotensin II, and showed reduced distensibility. Distensibility was negatively correlated with homocysteine level, which has been associated with cardiovascular disease, in the study group only.

"The changes in passive properties of vascular wall are characterized by reduced distensibility that will affect stiffness of the arteries in women with a history of preeclampsia," said Dr. Kublickiene, an associate professor of obstetrics and gynecology and senior researcher at the Karolinska Institute Hospital-Huddinge in Stockholm. She also leads the Center for Gender Medicine at the institute.

Endothelium-dependent dilation to bradykinin (BK) and NO donor compounds were similar between the two groups. But endothelium-dependent response to flow was significantly attenuated in the study group, which could mean possible impairment of flow detection and signaling, according to Dr. Kublickiene.

"Preserved relaxation and the contribution of NO to BK-induced responses to NO donor and eNOS expression between the groups further support the specific importance of NO deficiency in flow-mediated dilation," she said.

"The observed changes will contribute to an increased peripheral resistance and blood pressure, which are of critical importance for long-term women’s cardiovascular health," she said. Counseling following a preeclamptic pregnancy and preterm delivery should include a discussion about reproduction and cardiovascular risks, she said.

And, she emphasized, "Let’s work with cardiologists."

A 2012 study that focused on a different group of women showed that collaboration between cardiologists and ob.gyns. is indeed possible.

Dr. Kublickiene said that several questions remain: What are the appropriate preventive strategies? What screening schedules should be recommended? What are the clinical targets? And, what are the treatment regimens?

"I think now clinical trials of statins and other early interventions in these women are warranted," said Dr. Kenny.

Dr. Kublickiene and Dr. Kenny said they had no disclosures. The study was funded by the Center for Gender Medicine at the Karolinska Institute, by the Karolinska Institute, and by the ALF fund of the Stockholm County Council.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Women with a history of severe preeclampsia show signs of small artery dysfunction as early as 2 years after delivery, an indication of cardiovascular disease later in life if not addressed by ob.gyns. and cardiologists early on, according to a small, unpublished study.

Researchers led by Dr. Karolina Kublickiene found that in women with a history of preeclampsia, endothelium-dependent dilation to flow was reduced, a change that could be due to nitric oxide contribution deficiency. The small arteries seen in the study group also exhibited increased myogenic tone, with enhanced sensitivity to the vasoconstrictor norepinephrine.

Dr. Louise Kenny, who moderated the session at the annual meeting of the Society for Gynecologic Investigation, said the study was "exquisitely executed."

"This is very basic science, but has massive clinical implications," said Dr. Kenny, a professor of obstetrics at the University College Cork, Ireland.

Several studies have shown that a history of preeclampsia is a risk factor for developing cardiovascular disease (Circulation 2012;125:1367-80). However, many women with preeclampsia go back to the community without proper follow-up with a cardiologist.

"I’m a high-risk maternal medicine obstetrician, and I’m very well aware that the long-term follow-up for women with preeclampsia is quite patchy," said Dr. Kenny. "We have a complete disconnect at several levels, and it is time to act."

Researchers hypothesized that functional and structural abnormalities in peripheral arteries are present as early as 2 years after delivery in mothers who had a pregnancy complicated by early-onset and severe preeclampsia.

They selected 15 women with a history of severe preeclampsia who had delivered between 2007 and 2011 at Karolinska University Hospital in Stockholm. They selected 15 closely matched controls who had normal pregnancies and gave birth during the same period. The women were on average 35 years old.

The investigators defined severe preeclampsia as systolic blood pressure of more than 160 mm Hg and/or diastolic blood pressure of more than 110 mm Hg on two occasions, at least 6 hours apart, and/or proteinuria of more than 5 g in a 24-hour period and/or organ damage.

The preeclampsia group and the control group were closely matched with regard to several biochemical characteristics, including the low-density lipoprotein to high-density lipoprotein (LDL/HDL) ratio (1.9 and 1.6, respectively). However, women in the preeclampsia group had higher blood pressure, insulin levels, and hemostatic model assessment index than did controls: The average diastolic blood pressure in the preeclampsia group was 74 mm Hg, versus 66 mm Hg in the control group. The average fasting insulin level in the preeclampsia group was almost twice as high as that of the control group (83 pmol/L vs. 44 pmol/L). Neither group showed evidence of early renal damage.

Researchers took subcutaneous fat biopsies from the women. They used pressure myography to compare the structure and function of the isolated small subcutaneous resistance arteries. They used immunostaining to compare endothelial nitric oxide synthase (eNOS) and lectin-like oxidized LDL receptor-1 (LOX-1) expression.

The arteries in both groups had similar diameters, wall thickness, wall-lumen ratio, and cross-sectional area.

Results showed that eNOS expression was similar in both groups, but LOX-1 expression was significantly enhanced in the study group. Inhibition of NOS had no effect on either group.

Myogenic tone was enhanced in the arteries of women with a history of preeclampsia, and was positively correlated with the LDL/HDL ratio, a change characterizing small artery dysfunction.

Basal tone in the study group also was positively correlated with the LDL/HDL ratio, triglycerides, glycated hemoglobin, and high-sensitivity C-reactive protein, and was negatively correlated with HDL. Basal tone at 60 mm Hg was 8 in the preeclampsia group, compared with 5 in the control group (P = .07).

Meanwhile, the study group had higher sensitivity to norepinephrine and angiotensin II, and showed reduced distensibility. Distensibility was negatively correlated with homocysteine level, which has been associated with cardiovascular disease, in the study group only.

"The changes in passive properties of vascular wall are characterized by reduced distensibility that will affect stiffness of the arteries in women with a history of preeclampsia," said Dr. Kublickiene, an associate professor of obstetrics and gynecology and senior researcher at the Karolinska Institute Hospital-Huddinge in Stockholm. She also leads the Center for Gender Medicine at the institute.

Endothelium-dependent dilation to bradykinin (BK) and NO donor compounds were similar between the two groups. But endothelium-dependent response to flow was significantly attenuated in the study group, which could mean possible impairment of flow detection and signaling, according to Dr. Kublickiene.

"Preserved relaxation and the contribution of NO to BK-induced responses to NO donor and eNOS expression between the groups further support the specific importance of NO deficiency in flow-mediated dilation," she said.

"The observed changes will contribute to an increased peripheral resistance and blood pressure, which are of critical importance for long-term women’s cardiovascular health," she said. Counseling following a preeclamptic pregnancy and preterm delivery should include a discussion about reproduction and cardiovascular risks, she said.

And, she emphasized, "Let’s work with cardiologists."

A 2012 study that focused on a different group of women showed that collaboration between cardiologists and ob.gyns. is indeed possible.

Dr. Kublickiene said that several questions remain: What are the appropriate preventive strategies? What screening schedules should be recommended? What are the clinical targets? And, what are the treatment regimens?

"I think now clinical trials of statins and other early interventions in these women are warranted," said Dr. Kenny.

Dr. Kublickiene and Dr. Kenny said they had no disclosures. The study was funded by the Center for Gender Medicine at the Karolinska Institute, by the Karolinska Institute, and by the ALF fund of the Stockholm County Council.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Women with a history of severe preeclampsia show signs of small artery dysfunction as early as 2 years after delivery, an indication of cardiovascular disease later in life if not addressed by ob.gyns. and cardiologists early on, according to a small, unpublished study.

Researchers led by Dr. Karolina Kublickiene found that in women with a history of preeclampsia, endothelium-dependent dilation to flow was reduced, a change that could be due to nitric oxide contribution deficiency. The small arteries seen in the study group also exhibited increased myogenic tone, with enhanced sensitivity to the vasoconstrictor norepinephrine.

Dr. Louise Kenny, who moderated the session at the annual meeting of the Society for Gynecologic Investigation, said the study was "exquisitely executed."

"This is very basic science, but has massive clinical implications," said Dr. Kenny, a professor of obstetrics at the University College Cork, Ireland.

Several studies have shown that a history of preeclampsia is a risk factor for developing cardiovascular disease (Circulation 2012;125:1367-80). However, many women with preeclampsia go back to the community without proper follow-up with a cardiologist.

"I’m a high-risk maternal medicine obstetrician, and I’m very well aware that the long-term follow-up for women with preeclampsia is quite patchy," said Dr. Kenny. "We have a complete disconnect at several levels, and it is time to act."

Researchers hypothesized that functional and structural abnormalities in peripheral arteries are present as early as 2 years after delivery in mothers who had a pregnancy complicated by early-onset and severe preeclampsia.

They selected 15 women with a history of severe preeclampsia who had delivered between 2007 and 2011 at Karolinska University Hospital in Stockholm. They selected 15 closely matched controls who had normal pregnancies and gave birth during the same period. The women were on average 35 years old.

The investigators defined severe preeclampsia as systolic blood pressure of more than 160 mm Hg and/or diastolic blood pressure of more than 110 mm Hg on two occasions, at least 6 hours apart, and/or proteinuria of more than 5 g in a 24-hour period and/or organ damage.

The preeclampsia group and the control group were closely matched with regard to several biochemical characteristics, including the low-density lipoprotein to high-density lipoprotein (LDL/HDL) ratio (1.9 and 1.6, respectively). However, women in the preeclampsia group had higher blood pressure, insulin levels, and hemostatic model assessment index than did controls: The average diastolic blood pressure in the preeclampsia group was 74 mm Hg, versus 66 mm Hg in the control group. The average fasting insulin level in the preeclampsia group was almost twice as high as that of the control group (83 pmol/L vs. 44 pmol/L). Neither group showed evidence of early renal damage.

Researchers took subcutaneous fat biopsies from the women. They used pressure myography to compare the structure and function of the isolated small subcutaneous resistance arteries. They used immunostaining to compare endothelial nitric oxide synthase (eNOS) and lectin-like oxidized LDL receptor-1 (LOX-1) expression.

The arteries in both groups had similar diameters, wall thickness, wall-lumen ratio, and cross-sectional area.

Results showed that eNOS expression was similar in both groups, but LOX-1 expression was significantly enhanced in the study group. Inhibition of NOS had no effect on either group.

Myogenic tone was enhanced in the arteries of women with a history of preeclampsia, and was positively correlated with the LDL/HDL ratio, a change characterizing small artery dysfunction.

Basal tone in the study group also was positively correlated with the LDL/HDL ratio, triglycerides, glycated hemoglobin, and high-sensitivity C-reactive protein, and was negatively correlated with HDL. Basal tone at 60 mm Hg was 8 in the preeclampsia group, compared with 5 in the control group (P = .07).

Meanwhile, the study group had higher sensitivity to norepinephrine and angiotensin II, and showed reduced distensibility. Distensibility was negatively correlated with homocysteine level, which has been associated with cardiovascular disease, in the study group only.

"The changes in passive properties of vascular wall are characterized by reduced distensibility that will affect stiffness of the arteries in women with a history of preeclampsia," said Dr. Kublickiene, an associate professor of obstetrics and gynecology and senior researcher at the Karolinska Institute Hospital-Huddinge in Stockholm. She also leads the Center for Gender Medicine at the institute.

Endothelium-dependent dilation to bradykinin (BK) and NO donor compounds were similar between the two groups. But endothelium-dependent response to flow was significantly attenuated in the study group, which could mean possible impairment of flow detection and signaling, according to Dr. Kublickiene.

"Preserved relaxation and the contribution of NO to BK-induced responses to NO donor and eNOS expression between the groups further support the specific importance of NO deficiency in flow-mediated dilation," she said.

"The observed changes will contribute to an increased peripheral resistance and blood pressure, which are of critical importance for long-term women’s cardiovascular health," she said. Counseling following a preeclamptic pregnancy and preterm delivery should include a discussion about reproduction and cardiovascular risks, she said.

And, she emphasized, "Let’s work with cardiologists."

A 2012 study that focused on a different group of women showed that collaboration between cardiologists and ob.gyns. is indeed possible.

Dr. Kublickiene said that several questions remain: What are the appropriate preventive strategies? What screening schedules should be recommended? What are the clinical targets? And, what are the treatment regimens?

"I think now clinical trials of statins and other early interventions in these women are warranted," said Dr. Kenny.

Dr. Kublickiene and Dr. Kenny said they had no disclosures. The study was funded by the Center for Gender Medicine at the Karolinska Institute, by the Karolinska Institute, and by the ALF fund of the Stockholm County Council.

[email protected]

On Twitter @NaseemSMiller

The risk of having an autism spectrum disorder and childhood autism was significantly increased among children exposed prenatally to valproate, which persisted after researchers adjusted for parental psychiatric disease and maternal epilepsy in a Danish study that evaluated children up to age 14 years.

These risks were higher than the risks among the children whose mothers had stopped taking valproate before conceiving and also was elevated among the children of women who did not have epilepsy and took valproate, "indicating an association with valproate exposure," and that valproate may have a biological effect, said Jakob Christensen, Ph.D., of the department of neurology at Aarhus (Denmark) University Hospital, and his associates.

"For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control," they concluded (JAMA 2013;309:1696-703).

The population-based study used a birth registry of all children born alive in Denmark between January 1996 through Dec. 31, 2006, for a total of 655,107 children who had not been exposed to valproate and 508 exposed to valproate prenatally. At the end of follow-up, when the children were a mean age of almost 9 years (range, 4-14 years), 5,437 children had been diagnosed with autism spectrum disorder, including 2,067 with childhood autism. A national prescription registry was used to document exposure to antiepilepsy drugs (exposure during pregnancy was considered 30 days before conception to the day of birth) and a registry of psychiatric diagnoses was used to identify which children were diagnosed with autism.

Among the 508 children exposed to valproate, the incidence of autism spectrum disorder was 4.42% (hazard ratio, 2.9), and the incidence of childhood autism was 2.5% (HR, 5.2). The hazard ratios were adjusted for known autism risk factors, including age of the parents at conception, parental psychiatric history, and sex of the child.

Among the 432 children whose mothers had taken valproate for epilepsy (not another diagnosis treated with valproate), the incidence of autism spectrum disorder was 4.15% (HR, 1.7), and the incidence of childhood autism was 2.95% (HR, 2.9). Among the 6,152 children not exposed to valproate, the incidence of autism spectrum disorder was 2.44% and the incidence of childhood autism was 1.02%. The risks for both autism spectrum disorder and childhood autism were increased among women who took valproate during pregnancy, compared with the children whose mothers had taken valproate but had stopped taking it at least 30 days before they were conceived

The strengths of the study included the unlikely effect of selection bias because the investigators were able to follow-up most of the children born in the country over 14 years, and the high quality of autism diagnoses in the psychiatric registry. The possibility that some pregnancies exposed to valproate may have been missed was among the weaknesses of the study because the prescription registry only includes outpatient prescriptions.

The study was funded by grants from the European Research Council and the Danish Medical Research Council. Dr. Christensen received research support from the Danish Epilepsy Association and honoraria for serving on scientific advisory boards and lecture honoraria from UCB Nordic and Eisai AB, and received travel funding from UCB Nordic.

Dr. Meador received research support from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; Emory University received salary support from the Epilepsy Consortium, which gets funding from NeuroPace, Novartis, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals; and travel support from Sanofi Aventis. Dr. Loring received consulting fees from NeuroPace; grant support from NIH, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; and book royalties from Oxford University Press.

[email protected]

The risk of having an autism spectrum disorder and childhood autism was significantly increased among children exposed prenatally to valproate, which persisted after researchers adjusted for parental psychiatric disease and maternal epilepsy in a Danish study that evaluated children up to age 14 years.

These risks were higher than the risks among the children whose mothers had stopped taking valproate before conceiving and also was elevated among the children of women who did not have epilepsy and took valproate, "indicating an association with valproate exposure," and that valproate may have a biological effect, said Jakob Christensen, Ph.D., of the department of neurology at Aarhus (Denmark) University Hospital, and his associates.

"For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control," they concluded (JAMA 2013;309:1696-703).

The population-based study used a birth registry of all children born alive in Denmark between January 1996 through Dec. 31, 2006, for a total of 655,107 children who had not been exposed to valproate and 508 exposed to valproate prenatally. At the end of follow-up, when the children were a mean age of almost 9 years (range, 4-14 years), 5,437 children had been diagnosed with autism spectrum disorder, including 2,067 with childhood autism. A national prescription registry was used to document exposure to antiepilepsy drugs (exposure during pregnancy was considered 30 days before conception to the day of birth) and a registry of psychiatric diagnoses was used to identify which children were diagnosed with autism.

Among the 508 children exposed to valproate, the incidence of autism spectrum disorder was 4.42% (hazard ratio, 2.9), and the incidence of childhood autism was 2.5% (HR, 5.2). The hazard ratios were adjusted for known autism risk factors, including age of the parents at conception, parental psychiatric history, and sex of the child.

Among the 432 children whose mothers had taken valproate for epilepsy (not another diagnosis treated with valproate), the incidence of autism spectrum disorder was 4.15% (HR, 1.7), and the incidence of childhood autism was 2.95% (HR, 2.9). Among the 6,152 children not exposed to valproate, the incidence of autism spectrum disorder was 2.44% and the incidence of childhood autism was 1.02%. The risks for both autism spectrum disorder and childhood autism were increased among women who took valproate during pregnancy, compared with the children whose mothers had taken valproate but had stopped taking it at least 30 days before they were conceived

The strengths of the study included the unlikely effect of selection bias because the investigators were able to follow-up most of the children born in the country over 14 years, and the high quality of autism diagnoses in the psychiatric registry. The possibility that some pregnancies exposed to valproate may have been missed was among the weaknesses of the study because the prescription registry only includes outpatient prescriptions.

The study was funded by grants from the European Research Council and the Danish Medical Research Council. Dr. Christensen received research support from the Danish Epilepsy Association and honoraria for serving on scientific advisory boards and lecture honoraria from UCB Nordic and Eisai AB, and received travel funding from UCB Nordic.

Dr. Meador received research support from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; Emory University received salary support from the Epilepsy Consortium, which gets funding from NeuroPace, Novartis, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals; and travel support from Sanofi Aventis. Dr. Loring received consulting fees from NeuroPace; grant support from NIH, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; and book royalties from Oxford University Press.

[email protected]

The risk of having an autism spectrum disorder and childhood autism was significantly increased among children exposed prenatally to valproate, which persisted after researchers adjusted for parental psychiatric disease and maternal epilepsy in a Danish study that evaluated children up to age 14 years.

These risks were higher than the risks among the children whose mothers had stopped taking valproate before conceiving and also was elevated among the children of women who did not have epilepsy and took valproate, "indicating an association with valproate exposure," and that valproate may have a biological effect, said Jakob Christensen, Ph.D., of the department of neurology at Aarhus (Denmark) University Hospital, and his associates.

"For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control," they concluded (JAMA 2013;309:1696-703).

The population-based study used a birth registry of all children born alive in Denmark between January 1996 through Dec. 31, 2006, for a total of 655,107 children who had not been exposed to valproate and 508 exposed to valproate prenatally. At the end of follow-up, when the children were a mean age of almost 9 years (range, 4-14 years), 5,437 children had been diagnosed with autism spectrum disorder, including 2,067 with childhood autism. A national prescription registry was used to document exposure to antiepilepsy drugs (exposure during pregnancy was considered 30 days before conception to the day of birth) and a registry of psychiatric diagnoses was used to identify which children were diagnosed with autism.

Among the 508 children exposed to valproate, the incidence of autism spectrum disorder was 4.42% (hazard ratio, 2.9), and the incidence of childhood autism was 2.5% (HR, 5.2). The hazard ratios were adjusted for known autism risk factors, including age of the parents at conception, parental psychiatric history, and sex of the child.

Among the 432 children whose mothers had taken valproate for epilepsy (not another diagnosis treated with valproate), the incidence of autism spectrum disorder was 4.15% (HR, 1.7), and the incidence of childhood autism was 2.95% (HR, 2.9). Among the 6,152 children not exposed to valproate, the incidence of autism spectrum disorder was 2.44% and the incidence of childhood autism was 1.02%. The risks for both autism spectrum disorder and childhood autism were increased among women who took valproate during pregnancy, compared with the children whose mothers had taken valproate but had stopped taking it at least 30 days before they were conceived

The strengths of the study included the unlikely effect of selection bias because the investigators were able to follow-up most of the children born in the country over 14 years, and the high quality of autism diagnoses in the psychiatric registry. The possibility that some pregnancies exposed to valproate may have been missed was among the weaknesses of the study because the prescription registry only includes outpatient prescriptions.

The study was funded by grants from the European Research Council and the Danish Medical Research Council. Dr. Christensen received research support from the Danish Epilepsy Association and honoraria for serving on scientific advisory boards and lecture honoraria from UCB Nordic and Eisai AB, and received travel funding from UCB Nordic.

Dr. Meador received research support from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; Emory University received salary support from the Epilepsy Consortium, which gets funding from NeuroPace, Novartis, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals; and travel support from Sanofi Aventis. Dr. Loring received consulting fees from NeuroPace; grant support from NIH, the Patient-Centered Outcomes Research Institute, Pfizer, and UCB Pharma; and book royalties from Oxford University Press.

[email protected]

NEW YORK – What you screen and where you send your samples can have a tremendous impact on the usefulness of biomarkers to predict adverse pregnancy outcomes in patients with antiphospholipid syndrome, according to Dr. Michael D. Lockshin.

Women who have antiphospholipid antibodies are at high risk of developing adverse pregnancy outcomes (APOs), including preeclampsia, restricted fetal growth, prematurity, and fetal neonatal death. Antiphospholipid syndrome (APS) is defined by a clinical event (either thrombosis and/or recurrent pregnancy loss) plus the presence of an antiphospholipid antibody (either IgG or IgM anticardiolipin [aCL] and/or beta-2-glycoprotein I [beta-2 GPI]).

To see which serologic variables associated with APS may best identify women at highest risk of APO, researchers enrolled 144 pregnant patients with antiphospholipid antibodies (aPL) between 2003 and 2011 in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus) study. Twenty-eight (19%) had an APO. The results showed that 39% of the patients with lupus anticoagulant (LAC) had an APO, compared with 3% who did not have LAC (P = .0001).

A small percentage (5%) of women who were LAC negative but had high titers of IgG aCL antibody (at least 40 units/mL) had APOs. IgM aCL, IgG anti-beta-2 GPI, and IgM anti-beta-2 GPI were not predictive of APOs, according to Dr. Lockshin and his colleagues (Arthritis Rheum. 2012;64:2311-8).

Among women with high titers of IgG aCL, 8% of those who were LAC negative had an APO, compared with 43% who were LAC positive (P = .002).

"The only tests that made a difference in predicting APOs were lupus anticoagulant and IgG aCL," said Dr. Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Disease and professor of medicine and of obstetrics and gynecology at Weill Cornell Medical College, New York.

Similar patterns were seen in women with lupus who also had APS. In that population, 55% of those who were LAC positive and 12% who were LAC negative/high titer IgG aCL had an APO.

Dr. Lockshin then asked whether LAC screening methods differed in predicting the risk of APOs. He compared the positive and negative predictive values of the dilute prothrombin time test (dPT), the dilute Russell viper venom test (dRVVT), and the activated partial thromboplastin time test (APTT), as well as all tests combined, and found that using the results of all three tests together yielded the highest positive predictive value (all, 0.926; dPT, 0.808; dRVVT, 0.560; aPTT, 0.630). The test with the best negative predictive value was the dRVVT (0.910).

Making appropriate risk assessments for women with APS depends on accurate serological measurement. Dr. Lockshin reported that in a group of 610 women who were referred for SLE and/or aPL, 279 were found to be aPL positive by a referral laboratory. Upon reanalysis of the samples by a core laboratory, 147 of those deemed aPL positive by the referral laboratory were deemed to be aPL negative, yielding a 52% false positive rate. In a group of 196 referred as healthy controls, 2 were found to be aPL positive by the core lab, meaning that 2% of the controls were false negative for aPL. "Don’t just casually accept a commercial laboratory’s determination," Dr. Lockshin said at the meeting, sponsored by New York University.

In multivariate analysis, having SLE significantly increased the risk of having an APO (23% vs. 17%). Patients with prior thrombosis also were more likely to have an APO than were those without prior thrombosis (52% vs. 13%, P = .00005). Age, race, or prior pregnancy loss were not determinants of pregnancy problems.

Dr. Lockshin also addressed the question as to whether heparin mitigates the risk of an APO. He found that in patients who were LAC positive, there was no difference in the number of APOs in those given heparin (49%), compared with those not treated with heparin (50%). The rate of APOs was actually higher in women who were LAC negative but treated with heparin, compared with those who did not receive heparin (29% vs. 18%, no significant difference). Aspirin did reduce the occurrence of APOs (14% vs. 30%, P = .04), but neither hydroxychloroquine nor steroids had any protective effects.

At the meeting, Dr. Lockshin also reported the results of a pilot 12-month open-label phase II trial of rituximab for the noncriteria manifestations of APS (thrombocytopenia, cardiac valve disease, skin ulcers, aPL nephropathy, and/or cognitive dysfunction). After two doses of rituximab (1,000 mg) on days 1 and 15, dramatic improvements in leg ulcers were seen, and, for the first time ever, possible improvement in cognitive function, said Dr. Lockshin. No changes were noted in serology, cardiac valves, or abnormal imaging findings (Arthritis Rheum. 2013;65:464-471).

To encourage further investigation of APS, an international research network has been launched to organize well-designed, large-scale, multicenter clinical trials in aPL-positive patients, said Dr. Lockshin. The AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) has initiated two collaborative projects, one looking into the use of hydroxychloroquine for primary thrombosis prevention and the other a web-based registry of aPL-positive patients with or without systemic autoimmune diseases. For more information, go to www.apsaction.org.

Dr. Lockshin reported no financial disclosures.

NEW YORK – What you screen and where you send your samples can have a tremendous impact on the usefulness of biomarkers to predict adverse pregnancy outcomes in patients with antiphospholipid syndrome, according to Dr. Michael D. Lockshin.

Women who have antiphospholipid antibodies are at high risk of developing adverse pregnancy outcomes (APOs), including preeclampsia, restricted fetal growth, prematurity, and fetal neonatal death. Antiphospholipid syndrome (APS) is defined by a clinical event (either thrombosis and/or recurrent pregnancy loss) plus the presence of an antiphospholipid antibody (either IgG or IgM anticardiolipin [aCL] and/or beta-2-glycoprotein I [beta-2 GPI]).

To see which serologic variables associated with APS may best identify women at highest risk of APO, researchers enrolled 144 pregnant patients with antiphospholipid antibodies (aPL) between 2003 and 2011 in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus) study. Twenty-eight (19%) had an APO. The results showed that 39% of the patients with lupus anticoagulant (LAC) had an APO, compared with 3% who did not have LAC (P = .0001).

A small percentage (5%) of women who were LAC negative but had high titers of IgG aCL antibody (at least 40 units/mL) had APOs. IgM aCL, IgG anti-beta-2 GPI, and IgM anti-beta-2 GPI were not predictive of APOs, according to Dr. Lockshin and his colleagues (Arthritis Rheum. 2012;64:2311-8).

Among women with high titers of IgG aCL, 8% of those who were LAC negative had an APO, compared with 43% who were LAC positive (P = .002).

"The only tests that made a difference in predicting APOs were lupus anticoagulant and IgG aCL," said Dr. Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Disease and professor of medicine and of obstetrics and gynecology at Weill Cornell Medical College, New York.

Similar patterns were seen in women with lupus who also had APS. In that population, 55% of those who were LAC positive and 12% who were LAC negative/high titer IgG aCL had an APO.

Dr. Lockshin then asked whether LAC screening methods differed in predicting the risk of APOs. He compared the positive and negative predictive values of the dilute prothrombin time test (dPT), the dilute Russell viper venom test (dRVVT), and the activated partial thromboplastin time test (APTT), as well as all tests combined, and found that using the results of all three tests together yielded the highest positive predictive value (all, 0.926; dPT, 0.808; dRVVT, 0.560; aPTT, 0.630). The test with the best negative predictive value was the dRVVT (0.910).

Making appropriate risk assessments for women with APS depends on accurate serological measurement. Dr. Lockshin reported that in a group of 610 women who were referred for SLE and/or aPL, 279 were found to be aPL positive by a referral laboratory. Upon reanalysis of the samples by a core laboratory, 147 of those deemed aPL positive by the referral laboratory were deemed to be aPL negative, yielding a 52% false positive rate. In a group of 196 referred as healthy controls, 2 were found to be aPL positive by the core lab, meaning that 2% of the controls were false negative for aPL. "Don’t just casually accept a commercial laboratory’s determination," Dr. Lockshin said at the meeting, sponsored by New York University.

In multivariate analysis, having SLE significantly increased the risk of having an APO (23% vs. 17%). Patients with prior thrombosis also were more likely to have an APO than were those without prior thrombosis (52% vs. 13%, P = .00005). Age, race, or prior pregnancy loss were not determinants of pregnancy problems.

Dr. Lockshin also addressed the question as to whether heparin mitigates the risk of an APO. He found that in patients who were LAC positive, there was no difference in the number of APOs in those given heparin (49%), compared with those not treated with heparin (50%). The rate of APOs was actually higher in women who were LAC negative but treated with heparin, compared with those who did not receive heparin (29% vs. 18%, no significant difference). Aspirin did reduce the occurrence of APOs (14% vs. 30%, P = .04), but neither hydroxychloroquine nor steroids had any protective effects.

At the meeting, Dr. Lockshin also reported the results of a pilot 12-month open-label phase II trial of rituximab for the noncriteria manifestations of APS (thrombocytopenia, cardiac valve disease, skin ulcers, aPL nephropathy, and/or cognitive dysfunction). After two doses of rituximab (1,000 mg) on days 1 and 15, dramatic improvements in leg ulcers were seen, and, for the first time ever, possible improvement in cognitive function, said Dr. Lockshin. No changes were noted in serology, cardiac valves, or abnormal imaging findings (Arthritis Rheum. 2013;65:464-471).

To encourage further investigation of APS, an international research network has been launched to organize well-designed, large-scale, multicenter clinical trials in aPL-positive patients, said Dr. Lockshin. The AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) has initiated two collaborative projects, one looking into the use of hydroxychloroquine for primary thrombosis prevention and the other a web-based registry of aPL-positive patients with or without systemic autoimmune diseases. For more information, go to www.apsaction.org.

Dr. Lockshin reported no financial disclosures.

NEW YORK – What you screen and where you send your samples can have a tremendous impact on the usefulness of biomarkers to predict adverse pregnancy outcomes in patients with antiphospholipid syndrome, according to Dr. Michael D. Lockshin.

Women who have antiphospholipid antibodies are at high risk of developing adverse pregnancy outcomes (APOs), including preeclampsia, restricted fetal growth, prematurity, and fetal neonatal death. Antiphospholipid syndrome (APS) is defined by a clinical event (either thrombosis and/or recurrent pregnancy loss) plus the presence of an antiphospholipid antibody (either IgG or IgM anticardiolipin [aCL] and/or beta-2-glycoprotein I [beta-2 GPI]).

To see which serologic variables associated with APS may best identify women at highest risk of APO, researchers enrolled 144 pregnant patients with antiphospholipid antibodies (aPL) between 2003 and 2011 in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus) study. Twenty-eight (19%) had an APO. The results showed that 39% of the patients with lupus anticoagulant (LAC) had an APO, compared with 3% who did not have LAC (P = .0001).

A small percentage (5%) of women who were LAC negative but had high titers of IgG aCL antibody (at least 40 units/mL) had APOs. IgM aCL, IgG anti-beta-2 GPI, and IgM anti-beta-2 GPI were not predictive of APOs, according to Dr. Lockshin and his colleagues (Arthritis Rheum. 2012;64:2311-8).

Among women with high titers of IgG aCL, 8% of those who were LAC negative had an APO, compared with 43% who were LAC positive (P = .002).

"The only tests that made a difference in predicting APOs were lupus anticoagulant and IgG aCL," said Dr. Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Disease and professor of medicine and of obstetrics and gynecology at Weill Cornell Medical College, New York.

Similar patterns were seen in women with lupus who also had APS. In that population, 55% of those who were LAC positive and 12% who were LAC negative/high titer IgG aCL had an APO.

Dr. Lockshin then asked whether LAC screening methods differed in predicting the risk of APOs. He compared the positive and negative predictive values of the dilute prothrombin time test (dPT), the dilute Russell viper venom test (dRVVT), and the activated partial thromboplastin time test (APTT), as well as all tests combined, and found that using the results of all three tests together yielded the highest positive predictive value (all, 0.926; dPT, 0.808; dRVVT, 0.560; aPTT, 0.630). The test with the best negative predictive value was the dRVVT (0.910).

Making appropriate risk assessments for women with APS depends on accurate serological measurement. Dr. Lockshin reported that in a group of 610 women who were referred for SLE and/or aPL, 279 were found to be aPL positive by a referral laboratory. Upon reanalysis of the samples by a core laboratory, 147 of those deemed aPL positive by the referral laboratory were deemed to be aPL negative, yielding a 52% false positive rate. In a group of 196 referred as healthy controls, 2 were found to be aPL positive by the core lab, meaning that 2% of the controls were false negative for aPL. "Don’t just casually accept a commercial laboratory’s determination," Dr. Lockshin said at the meeting, sponsored by New York University.

In multivariate analysis, having SLE significantly increased the risk of having an APO (23% vs. 17%). Patients with prior thrombosis also were more likely to have an APO than were those without prior thrombosis (52% vs. 13%, P = .00005). Age, race, or prior pregnancy loss were not determinants of pregnancy problems.

Dr. Lockshin also addressed the question as to whether heparin mitigates the risk of an APO. He found that in patients who were LAC positive, there was no difference in the number of APOs in those given heparin (49%), compared with those not treated with heparin (50%). The rate of APOs was actually higher in women who were LAC negative but treated with heparin, compared with those who did not receive heparin (29% vs. 18%, no significant difference). Aspirin did reduce the occurrence of APOs (14% vs. 30%, P = .04), but neither hydroxychloroquine nor steroids had any protective effects.

At the meeting, Dr. Lockshin also reported the results of a pilot 12-month open-label phase II trial of rituximab for the noncriteria manifestations of APS (thrombocytopenia, cardiac valve disease, skin ulcers, aPL nephropathy, and/or cognitive dysfunction). After two doses of rituximab (1,000 mg) on days 1 and 15, dramatic improvements in leg ulcers were seen, and, for the first time ever, possible improvement in cognitive function, said Dr. Lockshin. No changes were noted in serology, cardiac valves, or abnormal imaging findings (Arthritis Rheum. 2013;65:464-471).

To encourage further investigation of APS, an international research network has been launched to organize well-designed, large-scale, multicenter clinical trials in aPL-positive patients, said Dr. Lockshin. The AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) has initiated two collaborative projects, one looking into the use of hydroxychloroquine for primary thrombosis prevention and the other a web-based registry of aPL-positive patients with or without systemic autoimmune diseases. For more information, go to www.apsaction.org.

Dr. Lockshin reported no financial disclosures.

LAS VEGAS – Until recently, residents and surgeons at the University of Cincinnati Medical Center routinely misdiagnosed normal postoperative fever after cesarean section as endometritis, significantly effecting the deep surgical site infection rates reported on websites such as Hospital Compare, according to an investigation by the medical center’s infectious disease experts.

All it took to fix the problem were a few Power Point presentations to make physicians aware of what was going on. Within months, the hospital’s deep-seated c-section infection rate dropped from 2.32 to 0.84 per 100 patients, according to Dr. Madhuri Sopirala, the center’s medical director of infection control, who led the investigation and subsequent educational efforts.

"I don’t believe this is unique to our institution. I am familiar with a lot of other hospitals and practices. This is not uncommon" or limited to c-sections, she said at the annual meeting of the Surgical Infection Society.

"Postoperative fevers happen in a majority of patients," resolve in a day or two, and usually have nothing to do with infection, she noted. Even so, they are often diagnosed and treated as infections out of an abundance of caution.

That’s a problem at a time when surgical site infection rates are among the hospital quality measures reported to the public and, increasingly, affecting the bottom line. Also, "giving antibiotics to patients who don’t need them is not a good thing," Dr. Sopirala added.

The investigation began after she and her colleagues noticed that postcesarean endometritis accounted for a significant proportion of the medical center’s deep surgical site infections.

They found that 78 patients were diagnosed with endometritis after vaginal deliveries or c-sections between January 2011 and June 2012. Forty-four patients were sent home after just a day or two of antibiotics; only 8 patients were readmitted within 30 days.

Most of the 20 post c-section endometritis cases diagnosed between July 2011 and June 2012 got just a few antibiotic doses, too; none of them returned to the hospital.

The numbers just didn’t add up, Dr. Sopirala said. Endometritis is a serious infection; if patients sent home after a dose or two of antibiotics truly had endometritis, more would have been back within a month, seriously ill.

They didn’t come back "because they didn’t need to. It wasn’t really endometritis. These patients most likely had postoperative fever," she said.

"Fever is the most common indication for antibiotics in this country. Whenever a patient has a fever, people give them antibiotics just in case, then find some reason to [justify it]. Endometritis is the most common thing that comes to mind in a patient that’s had a c-section," she said.

Residents and faculty were glad to be made aware of the problem. "The data speak for themselves," Dr. Sopirala said.

Instead of diagnosing postcesarean fevers as endometritis, they "started monitoring temperatures, and could see them coming down on their own. Before, when the fever came down, they assumed it was a response to the antibiotics," she said.

Following the educational efforts, there were no c-section endometritis cases diagnosed at the center between July 2012 and March 2013.

Dr. Sopirala said that she has no disclosures.

[email protected]

LAS VEGAS – Until recently, residents and surgeons at the University of Cincinnati Medical Center routinely misdiagnosed normal postoperative fever after cesarean section as endometritis, significantly effecting the deep surgical site infection rates reported on websites such as Hospital Compare, according to an investigation by the medical center’s infectious disease experts.

All it took to fix the problem were a few Power Point presentations to make physicians aware of what was going on. Within months, the hospital’s deep-seated c-section infection rate dropped from 2.32 to 0.84 per 100 patients, according to Dr. Madhuri Sopirala, the center’s medical director of infection control, who led the investigation and subsequent educational efforts.

"I don’t believe this is unique to our institution. I am familiar with a lot of other hospitals and practices. This is not uncommon" or limited to c-sections, she said at the annual meeting of the Surgical Infection Society.

"Postoperative fevers happen in a majority of patients," resolve in a day or two, and usually have nothing to do with infection, she noted. Even so, they are often diagnosed and treated as infections out of an abundance of caution.

That’s a problem at a time when surgical site infection rates are among the hospital quality measures reported to the public and, increasingly, affecting the bottom line. Also, "giving antibiotics to patients who don’t need them is not a good thing," Dr. Sopirala added.

The investigation began after she and her colleagues noticed that postcesarean endometritis accounted for a significant proportion of the medical center’s deep surgical site infections.

They found that 78 patients were diagnosed with endometritis after vaginal deliveries or c-sections between January 2011 and June 2012. Forty-four patients were sent home after just a day or two of antibiotics; only 8 patients were readmitted within 30 days.

Most of the 20 post c-section endometritis cases diagnosed between July 2011 and June 2012 got just a few antibiotic doses, too; none of them returned to the hospital.

The numbers just didn’t add up, Dr. Sopirala said. Endometritis is a serious infection; if patients sent home after a dose or two of antibiotics truly had endometritis, more would have been back within a month, seriously ill.

They didn’t come back "because they didn’t need to. It wasn’t really endometritis. These patients most likely had postoperative fever," she said.

"Fever is the most common indication for antibiotics in this country. Whenever a patient has a fever, people give them antibiotics just in case, then find some reason to [justify it]. Endometritis is the most common thing that comes to mind in a patient that’s had a c-section," she said.

Residents and faculty were glad to be made aware of the problem. "The data speak for themselves," Dr. Sopirala said.

Instead of diagnosing postcesarean fevers as endometritis, they "started monitoring temperatures, and could see them coming down on their own. Before, when the fever came down, they assumed it was a response to the antibiotics," she said.

Following the educational efforts, there were no c-section endometritis cases diagnosed at the center between July 2012 and March 2013.

Dr. Sopirala said that she has no disclosures.

[email protected]

LAS VEGAS – Until recently, residents and surgeons at the University of Cincinnati Medical Center routinely misdiagnosed normal postoperative fever after cesarean section as endometritis, significantly effecting the deep surgical site infection rates reported on websites such as Hospital Compare, according to an investigation by the medical center’s infectious disease experts.

All it took to fix the problem were a few Power Point presentations to make physicians aware of what was going on. Within months, the hospital’s deep-seated c-section infection rate dropped from 2.32 to 0.84 per 100 patients, according to Dr. Madhuri Sopirala, the center’s medical director of infection control, who led the investigation and subsequent educational efforts.

"I don’t believe this is unique to our institution. I am familiar with a lot of other hospitals and practices. This is not uncommon" or limited to c-sections, she said at the annual meeting of the Surgical Infection Society.

"Postoperative fevers happen in a majority of patients," resolve in a day or two, and usually have nothing to do with infection, she noted. Even so, they are often diagnosed and treated as infections out of an abundance of caution.

That’s a problem at a time when surgical site infection rates are among the hospital quality measures reported to the public and, increasingly, affecting the bottom line. Also, "giving antibiotics to patients who don’t need them is not a good thing," Dr. Sopirala added.

The investigation began after she and her colleagues noticed that postcesarean endometritis accounted for a significant proportion of the medical center’s deep surgical site infections.

They found that 78 patients were diagnosed with endometritis after vaginal deliveries or c-sections between January 2011 and June 2012. Forty-four patients were sent home after just a day or two of antibiotics; only 8 patients were readmitted within 30 days.

Most of the 20 post c-section endometritis cases diagnosed between July 2011 and June 2012 got just a few antibiotic doses, too; none of them returned to the hospital.

The numbers just didn’t add up, Dr. Sopirala said. Endometritis is a serious infection; if patients sent home after a dose or two of antibiotics truly had endometritis, more would have been back within a month, seriously ill.

They didn’t come back "because they didn’t need to. It wasn’t really endometritis. These patients most likely had postoperative fever," she said.

"Fever is the most common indication for antibiotics in this country. Whenever a patient has a fever, people give them antibiotics just in case, then find some reason to [justify it]. Endometritis is the most common thing that comes to mind in a patient that’s had a c-section," she said.

Residents and faculty were glad to be made aware of the problem. "The data speak for themselves," Dr. Sopirala said.

Instead of diagnosing postcesarean fevers as endometritis, they "started monitoring temperatures, and could see them coming down on their own. Before, when the fever came down, they assumed it was a response to the antibiotics," she said.

Following the educational efforts, there were no c-section endometritis cases diagnosed at the center between July 2012 and March 2013.

Dr. Sopirala said that she has no disclosures.

[email protected]

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

[email protected]

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

[email protected]

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

[email protected]

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

[email protected]

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

[email protected]

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

[email protected]