Whitney McKnight

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]

ARLINGTON, VA. – Low-income minority women recovering from cancer are also likely to face the paradoxical burden of obesity and hunger, a study has shown.

"It’s counterintuitive, this relationship that exists in this country where you can report having issues around hunger, food insecurity – where you don’t know where your next meal is going to come from, and whether it will be nutritious – and at the same time be obese or overweight," the poster’s presenter, Errol Philip, Ph.D., said in an interview at the annual meeting of the American Society of Preventive Oncology, where he presented the findings.

Add to that the strain of undergoing chemotherapy or other cancer interventions, and one’s quality of life is dramatically affected. Study participants whose body mass index (BMI) was near 30 kg/m², and who self-reported skipping meals or going an entire day without food because it was not available, also tended to have the lowest scores on the Functional Assessment of Cancer Therapy scale, which measures quality of life in cancer patients, reported Dr. Philip of Memorial Sloan Kettering Cancer Center, New York.

"This obesity-hunger paradox is thought to exist because of the change in our food environment over the past 50 years," he said, noting that images of hunger in days past were of underweight individuals. "Now, those who exist on aid, who have very little access to money, are purchasing cheap calories that are highly processed, malnutritious."

For this prospective, longitudinal assessment, Dr. Philip and his colleagues, including Dr. Francesca Gany, director of the Immigrant Health and Cancer Disparities Service at Memorial Sloan Kettering Cancer Center, analyzed the self-reported food insecurity and quality-of-life scores of 426 minority cancer patients (median age, 56 years), who had either been treated for cancer of any type or were at that time undergoing cancer treatment at one of 5 urban cancer centers. Food insecurity was measured according to the U.S. Department of Agriculture’s Core Food Security Module.

The majority of participants were women (70%), half of all participants were black, and just over a third were Hispanic. The most common diagnoses were breast cancer (44%) and gastrointestinal cancer (16%). More than three-quarters of the respondents reported income below the national poverty level.

The investigators found that two-thirds of all respondents were either overweight or obese (34% and 29% respectively), with nearly three-quarters (71%) reporting food insecurity, ranging from not knowing where the next nutritious meal would be found to not eating for an entire day.

Although the BMI of men in the study did not vary significantly according to whether they experienced food insecurity, the BMI of the women in the group did. Women who reported food insecurity along with moderate hunger had the highest BMI, while those who reported food insecurity and severe hunger had the lowest (27 vs. 26.6). Women who reported their food supply was secure had, on average, a BMI of 27.2.

The women with both food insecurity and obesity had the greatest measure of impaired quality of life. As for why women should be more affected than men, Dr. Philip said several hypotheses exist, including biomechanical ones such as women’s natural propensity to gain more weight than men, and women as caretakers forsaking their own meals in order to nourish others, but that no one knows for certain.

Overall, the implications are "troubling," said Dr. Philip. "In the general population, about 15% will endorse some kind of food insecurity. For individuals living below the poverty line, that number rises to about 40%. Among those individuals who also have cancer, the number rises to 70%."

Because many cancers have been associated with excess weight and low-quality nutrition, Dr. Philip said it was important for primary care providers to be aware that while these patients are vulnerable to begin with, dealing with cancer while also juggling the effects of both obesity and a lack of nutritious food means they are even more strained.

"Primary care providers can’t make the assumption that a patient who is overweight or obese is representative of that person having sufficient food," Dr. Philip said.

Dr. Philip did not report any relevant disclosures. Support for this research was provided by grants from the National Cancer Institute, the New York Community Trust, Susan G. Komen for the Cure (Greater New York City affiliate), and the Laurie M. Tisch Illumination Fund.

This article was updated March 19, 2014.

[email protected]

ARLINGTON, VA. – Low-income minority women recovering from cancer are also likely to face the paradoxical burden of obesity and hunger, a study has shown.

"It’s counterintuitive, this relationship that exists in this country where you can report having issues around hunger, food insecurity – where you don’t know where your next meal is going to come from, and whether it will be nutritious – and at the same time be obese or overweight," the poster’s presenter, Errol Philip, Ph.D., said in an interview at the annual meeting of the American Society of Preventive Oncology, where he presented the findings.

Add to that the strain of undergoing chemotherapy or other cancer interventions, and one’s quality of life is dramatically affected. Study participants whose body mass index (BMI) was near 30 kg/m², and who self-reported skipping meals or going an entire day without food because it was not available, also tended to have the lowest scores on the Functional Assessment of Cancer Therapy scale, which measures quality of life in cancer patients, reported Dr. Philip of Memorial Sloan Kettering Cancer Center, New York.

"This obesity-hunger paradox is thought to exist because of the change in our food environment over the past 50 years," he said, noting that images of hunger in days past were of underweight individuals. "Now, those who exist on aid, who have very little access to money, are purchasing cheap calories that are highly processed, malnutritious."

For this prospective, longitudinal assessment, Dr. Philip and his colleagues, including Dr. Francesca Gany, director of the Immigrant Health and Cancer Disparities Service at Memorial Sloan Kettering Cancer Center, analyzed the self-reported food insecurity and quality-of-life scores of 426 minority cancer patients (median age, 56 years), who had either been treated for cancer of any type or were at that time undergoing cancer treatment at one of 5 urban cancer centers. Food insecurity was measured according to the U.S. Department of Agriculture’s Core Food Security Module.

The majority of participants were women (70%), half of all participants were black, and just over a third were Hispanic. The most common diagnoses were breast cancer (44%) and gastrointestinal cancer (16%). More than three-quarters of the respondents reported income below the national poverty level.

The investigators found that two-thirds of all respondents were either overweight or obese (34% and 29% respectively), with nearly three-quarters (71%) reporting food insecurity, ranging from not knowing where the next nutritious meal would be found to not eating for an entire day.

Although the BMI of men in the study did not vary significantly according to whether they experienced food insecurity, the BMI of the women in the group did. Women who reported food insecurity along with moderate hunger had the highest BMI, while those who reported food insecurity and severe hunger had the lowest (27 vs. 26.6). Women who reported their food supply was secure had, on average, a BMI of 27.2.

The women with both food insecurity and obesity had the greatest measure of impaired quality of life. As for why women should be more affected than men, Dr. Philip said several hypotheses exist, including biomechanical ones such as women’s natural propensity to gain more weight than men, and women as caretakers forsaking their own meals in order to nourish others, but that no one knows for certain.

Overall, the implications are "troubling," said Dr. Philip. "In the general population, about 15% will endorse some kind of food insecurity. For individuals living below the poverty line, that number rises to about 40%. Among those individuals who also have cancer, the number rises to 70%."

Because many cancers have been associated with excess weight and low-quality nutrition, Dr. Philip said it was important for primary care providers to be aware that while these patients are vulnerable to begin with, dealing with cancer while also juggling the effects of both obesity and a lack of nutritious food means they are even more strained.

"Primary care providers can’t make the assumption that a patient who is overweight or obese is representative of that person having sufficient food," Dr. Philip said.

Dr. Philip did not report any relevant disclosures. Support for this research was provided by grants from the National Cancer Institute, the New York Community Trust, Susan G. Komen for the Cure (Greater New York City affiliate), and the Laurie M. Tisch Illumination Fund.

This article was updated March 19, 2014.

[email protected]

ARLINGTON, VA. – Low-income minority women recovering from cancer are also likely to face the paradoxical burden of obesity and hunger, a study has shown.

"It’s counterintuitive, this relationship that exists in this country where you can report having issues around hunger, food insecurity – where you don’t know where your next meal is going to come from, and whether it will be nutritious – and at the same time be obese or overweight," the poster’s presenter, Errol Philip, Ph.D., said in an interview at the annual meeting of the American Society of Preventive Oncology, where he presented the findings.

Add to that the strain of undergoing chemotherapy or other cancer interventions, and one’s quality of life is dramatically affected. Study participants whose body mass index (BMI) was near 30 kg/m², and who self-reported skipping meals or going an entire day without food because it was not available, also tended to have the lowest scores on the Functional Assessment of Cancer Therapy scale, which measures quality of life in cancer patients, reported Dr. Philip of Memorial Sloan Kettering Cancer Center, New York.

"This obesity-hunger paradox is thought to exist because of the change in our food environment over the past 50 years," he said, noting that images of hunger in days past were of underweight individuals. "Now, those who exist on aid, who have very little access to money, are purchasing cheap calories that are highly processed, malnutritious."

For this prospective, longitudinal assessment, Dr. Philip and his colleagues, including Dr. Francesca Gany, director of the Immigrant Health and Cancer Disparities Service at Memorial Sloan Kettering Cancer Center, analyzed the self-reported food insecurity and quality-of-life scores of 426 minority cancer patients (median age, 56 years), who had either been treated for cancer of any type or were at that time undergoing cancer treatment at one of 5 urban cancer centers. Food insecurity was measured according to the U.S. Department of Agriculture’s Core Food Security Module.

The majority of participants were women (70%), half of all participants were black, and just over a third were Hispanic. The most common diagnoses were breast cancer (44%) and gastrointestinal cancer (16%). More than three-quarters of the respondents reported income below the national poverty level.

The investigators found that two-thirds of all respondents were either overweight or obese (34% and 29% respectively), with nearly three-quarters (71%) reporting food insecurity, ranging from not knowing where the next nutritious meal would be found to not eating for an entire day.

Although the BMI of men in the study did not vary significantly according to whether they experienced food insecurity, the BMI of the women in the group did. Women who reported food insecurity along with moderate hunger had the highest BMI, while those who reported food insecurity and severe hunger had the lowest (27 vs. 26.6). Women who reported their food supply was secure had, on average, a BMI of 27.2.

The women with both food insecurity and obesity had the greatest measure of impaired quality of life. As for why women should be more affected than men, Dr. Philip said several hypotheses exist, including biomechanical ones such as women’s natural propensity to gain more weight than men, and women as caretakers forsaking their own meals in order to nourish others, but that no one knows for certain.

Overall, the implications are "troubling," said Dr. Philip. "In the general population, about 15% will endorse some kind of food insecurity. For individuals living below the poverty line, that number rises to about 40%. Among those individuals who also have cancer, the number rises to 70%."

Because many cancers have been associated with excess weight and low-quality nutrition, Dr. Philip said it was important for primary care providers to be aware that while these patients are vulnerable to begin with, dealing with cancer while also juggling the effects of both obesity and a lack of nutritious food means they are even more strained.

"Primary care providers can’t make the assumption that a patient who is overweight or obese is representative of that person having sufficient food," Dr. Philip said.

Dr. Philip did not report any relevant disclosures. Support for this research was provided by grants from the National Cancer Institute, the New York Community Trust, Susan G. Komen for the Cure (Greater New York City affiliate), and the Laurie M. Tisch Illumination Fund.

This article was updated March 19, 2014.

[email protected]

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

[email protected]

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

[email protected]

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

[email protected]

UPDATED 3/17/14*

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

Commentary – ‘Guidelines are a breath of fresh air’

Dr. Susan Millard comments: "I think the guidelines are a breath of fresh air. I feel they are very well thought out. More research needs to be done on the therapies for pulmonary hypertension, but the authors of these guidelines admit that there is a paucity of data in this area.

In addition, more collaboration is needed between our pulmonary, hematology, oncology, and cardiology specialties. Pulmonologists do not perform right heart catheterizations, but when we ask cardiologists about pulmonary hypertension concerns, we regularly get shot down by the ones who feel that echocardiograms are sufficient to look for this problem. Yet when we want help managing these patients, they don’t want to do that either because it is pulmonary hypertension. You need a dedicated group of people locally to work-up these patients.

There are not many experienced pulmonary hypertension centers easily accessible for both adult and pediatric patient referrals. It is difficult, for example, to refer patients out of state and get it approved by insurance companies.

Dr. Millard is a pediatric pulmonologist at Helen DeVos Children’s Hospital, Grand Rapids, Mich., and a CHEST board member.

*Dr. David Langleben responds: Cardiology input is essential [for patients with sickle cell disease being evaluated for pulmonary hypertension]. A multidisciplinary approach always benefits the patient. The patients may have high output cardiac failure, diastolic dysfunction, cardiomyopathies and myocardial ischemia. Heart catheterization is indispensable, as is echocardiography. They are complementary.

Dr. Langleben is professor of medicine at McGill University and director of cardiology and of the Centre for Pulmonary Vascular Disease at Jewish General Hospital, both in Montreal.

[email protected]

UPDATED 3/17/14*

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

Commentary – ‘Guidelines are a breath of fresh air’

Dr. Susan Millard comments: "I think the guidelines are a breath of fresh air. I feel they are very well thought out. More research needs to be done on the therapies for pulmonary hypertension, but the authors of these guidelines admit that there is a paucity of data in this area.

In addition, more collaboration is needed between our pulmonary, hematology, oncology, and cardiology specialties. Pulmonologists do not perform right heart catheterizations, but when we ask cardiologists about pulmonary hypertension concerns, we regularly get shot down by the ones who feel that echocardiograms are sufficient to look for this problem. Yet when we want help managing these patients, they don’t want to do that either because it is pulmonary hypertension. You need a dedicated group of people locally to work-up these patients.

There are not many experienced pulmonary hypertension centers easily accessible for both adult and pediatric patient referrals. It is difficult, for example, to refer patients out of state and get it approved by insurance companies.

Dr. Millard is a pediatric pulmonologist at Helen DeVos Children’s Hospital, Grand Rapids, Mich., and a CHEST board member.

*Dr. David Langleben responds: Cardiology input is essential [for patients with sickle cell disease being evaluated for pulmonary hypertension]. A multidisciplinary approach always benefits the patient. The patients may have high output cardiac failure, diastolic dysfunction, cardiomyopathies and myocardial ischemia. Heart catheterization is indispensable, as is echocardiography. They are complementary.

Dr. Langleben is professor of medicine at McGill University and director of cardiology and of the Centre for Pulmonary Vascular Disease at Jewish General Hospital, both in Montreal.

[email protected]

UPDATED 3/17/14*

The first treatment guidelines for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.

Because more effective treatments has extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.

The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine.

The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).

Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."

For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.

For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy. The same guidance was given for patients who have RHC-confirmed PH.

While the guidelines recommend against targeted therapies for RHC-confirmed PH, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.

The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement. "Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.

Dr. Klings receives support from NIH grant R21HL107993.

Commentary – ‘Guidelines are a breath of fresh air’

Dr. Susan Millard comments: "I think the guidelines are a breath of fresh air. I feel they are very well thought out. More research needs to be done on the therapies for pulmonary hypertension, but the authors of these guidelines admit that there is a paucity of data in this area.

In addition, more collaboration is needed between our pulmonary, hematology, oncology, and cardiology specialties. Pulmonologists do not perform right heart catheterizations, but when we ask cardiologists about pulmonary hypertension concerns, we regularly get shot down by the ones who feel that echocardiograms are sufficient to look for this problem. Yet when we want help managing these patients, they don’t want to do that either because it is pulmonary hypertension. You need a dedicated group of people locally to work-up these patients.

There are not many experienced pulmonary hypertension centers easily accessible for both adult and pediatric patient referrals. It is difficult, for example, to refer patients out of state and get it approved by insurance companies.

Dr. Millard is a pediatric pulmonologist at Helen DeVos Children’s Hospital, Grand Rapids, Mich., and a CHEST board member.

*Dr. David Langleben responds: Cardiology input is essential [for patients with sickle cell disease being evaluated for pulmonary hypertension]. A multidisciplinary approach always benefits the patient. The patients may have high output cardiac failure, diastolic dysfunction, cardiomyopathies and myocardial ischemia. Heart catheterization is indispensable, as is echocardiography. They are complementary.

Dr. Langleben is professor of medicine at McGill University and director of cardiology and of the Centre for Pulmonary Vascular Disease at Jewish General Hospital, both in Montreal.

[email protected]

At least a fifth of people with epilepsy, primarily children, engaged in hospital crossover over a 2-year period, a cross-sectional study of epilepsy patient data sets showed.

Health exchange information (HIE) technology has the potential to bridge the data gaps among the unaffiliated physicians who serve these patients, helping to "lower health care costs, reduce adverse events and medical errors, and improve population health," wrote Dr. Zachary M. Grinspan of Cornell University, New York, and New York Presbyterian Hospital and his coauthors. But the technology’s full value has yet to be studied.

To determine who among the epileptic community are most likely to use two or more hospitals (crossover), and why, Dr. Grinspan and his colleagues conducted a cross-sectional analysis of HIE patient-level data sets for 8,704 patients seen by seven New York City tertiary-care teaching hospitals. They examined demographics, encounter dates, and ICD-9 codes for outpatient, emergency department, inpatient, and radiology encounters for visits that occurred April 2009 through March 2012. All data were taken from the New York state–sponsored NYCLIX (New York Clinical Information Exchange), an "honest broker" of such information, and were deidentified prior to the analysis (Epilepsia 2014 March 5 [doi:10.1111/epi.12552]).

In all, 1,770 (22%) patients were found to engage in crossover during the study period. Compared with adults (median age, 36 years), children (between age 0 and 10 years) were more likely to be associated with crossover (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7), as were those who lived near the hospitals in the study (the borough of Manhattan vs. other New York boroughs (adjusted OR, 1.6; 95% CI, 1.4-1.8).

Crossover was also associated with significantly greater odds of more visits to emergency, radiology, inpatient, and outpatient settings (P less than .001 for each), and of having 6 or more days with a head CT scan (P less than .05 for 6-10 days and P less than .01 for 11 or more days). Both bivariate and multivariate analyses consistently associated an encephalopathy diagnosis with crossover (adjusted OR, 2.66; 95% CI, 2.14-3.29); any relationship between crossover and other comorbidities was uncertain.

Dr. Grinspan and his associates noted the possibility that their findings may actually reflect lower crossover than actually occurs, since there are 14 other hospitals in Manhattan that were not included in the data pool. Reasons for patients seeking care in multiple settings may include a desire for a second opinion or the need for emergency services in patients with uncontrolled epilepsy, wrote the authors. "Further research should investigate why hospital crossover occurs, how it affects care, and how HIE can most effectively mitigate the resultant fragmentation of medical records."

[email protected]

At least a fifth of people with epilepsy, primarily children, engaged in hospital crossover over a 2-year period, a cross-sectional study of epilepsy patient data sets showed.

Health exchange information (HIE) technology has the potential to bridge the data gaps among the unaffiliated physicians who serve these patients, helping to "lower health care costs, reduce adverse events and medical errors, and improve population health," wrote Dr. Zachary M. Grinspan of Cornell University, New York, and New York Presbyterian Hospital and his coauthors. But the technology’s full value has yet to be studied.

To determine who among the epileptic community are most likely to use two or more hospitals (crossover), and why, Dr. Grinspan and his colleagues conducted a cross-sectional analysis of HIE patient-level data sets for 8,704 patients seen by seven New York City tertiary-care teaching hospitals. They examined demographics, encounter dates, and ICD-9 codes for outpatient, emergency department, inpatient, and radiology encounters for visits that occurred April 2009 through March 2012. All data were taken from the New York state–sponsored NYCLIX (New York Clinical Information Exchange), an "honest broker" of such information, and were deidentified prior to the analysis (Epilepsia 2014 March 5 [doi:10.1111/epi.12552]).

In all, 1,770 (22%) patients were found to engage in crossover during the study period. Compared with adults (median age, 36 years), children (between age 0 and 10 years) were more likely to be associated with crossover (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7), as were those who lived near the hospitals in the study (the borough of Manhattan vs. other New York boroughs (adjusted OR, 1.6; 95% CI, 1.4-1.8).

Crossover was also associated with significantly greater odds of more visits to emergency, radiology, inpatient, and outpatient settings (P less than .001 for each), and of having 6 or more days with a head CT scan (P less than .05 for 6-10 days and P less than .01 for 11 or more days). Both bivariate and multivariate analyses consistently associated an encephalopathy diagnosis with crossover (adjusted OR, 2.66; 95% CI, 2.14-3.29); any relationship between crossover and other comorbidities was uncertain.

Dr. Grinspan and his associates noted the possibility that their findings may actually reflect lower crossover than actually occurs, since there are 14 other hospitals in Manhattan that were not included in the data pool. Reasons for patients seeking care in multiple settings may include a desire for a second opinion or the need for emergency services in patients with uncontrolled epilepsy, wrote the authors. "Further research should investigate why hospital crossover occurs, how it affects care, and how HIE can most effectively mitigate the resultant fragmentation of medical records."

[email protected]

At least a fifth of people with epilepsy, primarily children, engaged in hospital crossover over a 2-year period, a cross-sectional study of epilepsy patient data sets showed.

Health exchange information (HIE) technology has the potential to bridge the data gaps among the unaffiliated physicians who serve these patients, helping to "lower health care costs, reduce adverse events and medical errors, and improve population health," wrote Dr. Zachary M. Grinspan of Cornell University, New York, and New York Presbyterian Hospital and his coauthors. But the technology’s full value has yet to be studied.

To determine who among the epileptic community are most likely to use two or more hospitals (crossover), and why, Dr. Grinspan and his colleagues conducted a cross-sectional analysis of HIE patient-level data sets for 8,704 patients seen by seven New York City tertiary-care teaching hospitals. They examined demographics, encounter dates, and ICD-9 codes for outpatient, emergency department, inpatient, and radiology encounters for visits that occurred April 2009 through March 2012. All data were taken from the New York state–sponsored NYCLIX (New York Clinical Information Exchange), an "honest broker" of such information, and were deidentified prior to the analysis (Epilepsia 2014 March 5 [doi:10.1111/epi.12552]).

In all, 1,770 (22%) patients were found to engage in crossover during the study period. Compared with adults (median age, 36 years), children (between age 0 and 10 years) were more likely to be associated with crossover (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7), as were those who lived near the hospitals in the study (the borough of Manhattan vs. other New York boroughs (adjusted OR, 1.6; 95% CI, 1.4-1.8).

Crossover was also associated with significantly greater odds of more visits to emergency, radiology, inpatient, and outpatient settings (P less than .001 for each), and of having 6 or more days with a head CT scan (P less than .05 for 6-10 days and P less than .01 for 11 or more days). Both bivariate and multivariate analyses consistently associated an encephalopathy diagnosis with crossover (adjusted OR, 2.66; 95% CI, 2.14-3.29); any relationship between crossover and other comorbidities was uncertain.

Dr. Grinspan and his associates noted the possibility that their findings may actually reflect lower crossover than actually occurs, since there are 14 other hospitals in Manhattan that were not included in the data pool. Reasons for patients seeking care in multiple settings may include a desire for a second opinion or the need for emergency services in patients with uncontrolled epilepsy, wrote the authors. "Further research should investigate why hospital crossover occurs, how it affects care, and how HIE can most effectively mitigate the resultant fragmentation of medical records."

[email protected]

NEW ORLEANS – Laboring women had better overall pain relief satisfaction from epidurals than from remifentanil patient-controlled analgesia, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Although Dr. Liv Freeman, of Leiden (the Netherlands) University Medical Center, and her colleagues expected to find that the two pain relief methods would be equivalent, the results of their multisite, randomized controlled study instead showed a significantly higher pain appreciation (pain relief satisfaction) score in women who received epidural analgesia during delivery.

"This should be taken into account when pain relief is offered to women in labor," said Dr. Freeman, who noted that the study’s intention was to provide more definitive data about the two pain relief methods because previous studies were underpowered – with some data showing the two methods were comparable.

An advantage to using remifentanil, an opioid similar to pethidine, is that it is fast-acting, typically cycling within 3 minutes. This attribute allows the drug to be self-administered and lowers costs, said Dr. Freeman. There are maternal side effects, however, including respiratory depression, nausea and vomiting, and sedation.

Placental transfer also occurs with remifentanil, although "the drug is so short acting, it is cleared once the baby is born when discontinued in the second stage of labor," Dr. Freeman said.

As for the potential risks of using an epidural, Dr. Freeman said that although rare, epidural hematomas can occur, and that "about 1 in 100 women experience postspinal headache, and between 10% and 20% of mothers develop a fever during labor."

Before active labor began, 709 women were randomly assigned to the remifentanil patient-controlled analgesia (PCA) group, and 705 were assigned to the epidural group. The maternal age was about 31 years in each group, and other demographic baseline data also were similar. Nearly one-third more of the remifentanil PCA group, 402 women in all, opted to use the pain medication during labor, and 296 assigned to the epidural group chose to use it.

All women across the cohorts were asked hourly to rate their pain relief on a visual analog scale.

The total time-weighted pain appreciation score for the remifentanil PCA group was 25.7, versus 36.8 in the epidural group (P = .001).

Although the analysis was based on intention to treat, Dr. Freeman noted that 53 of the women in the self-administered pain relief group requested epidurals while in labor. Three women converted from an epidural to the self-administered pain medication.

The epidurals were performed according to local procedures across the 15 Dutch sites where the trial was conducted. Remifentanil PCA was 30 mcg administered intravenously with a 3-minute lockout time. The women had the option of increasing their dose to 40 mcg or decreasing it to 20 mcg.

The duration of analgesia was notably shorter in the remifentanil PCA group than in the epidural group: 236 minutes (interquartile range, 128-376 minutes) vs. 309 minutes (IQR, 181-454 minutes).

There were 22 elective cesarean deliveries in the remifentanil group and 29 in the epidural group. Three women in the epidural cohort were lost to follow-up, and two withdrew their consent.

There were no significant differences in important maternal and fetal outcomes, said Dr. Freeman. Because the safety profiles of remifentanil and epidural analgesia are essentially the same, physicians should counsel women about the pros and cons of each, she said.

This study was funded by ZonMw, the Netherlands Organisation for Health Research and Development. Dr. Freeman did not report any relevant financial disclosures.

[email protected]

NEW ORLEANS – Laboring women had better overall pain relief satisfaction from epidurals than from remifentanil patient-controlled analgesia, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Although Dr. Liv Freeman, of Leiden (the Netherlands) University Medical Center, and her colleagues expected to find that the two pain relief methods would be equivalent, the results of their multisite, randomized controlled study instead showed a significantly higher pain appreciation (pain relief satisfaction) score in women who received epidural analgesia during delivery.

"This should be taken into account when pain relief is offered to women in labor," said Dr. Freeman, who noted that the study’s intention was to provide more definitive data about the two pain relief methods because previous studies were underpowered – with some data showing the two methods were comparable.

An advantage to using remifentanil, an opioid similar to pethidine, is that it is fast-acting, typically cycling within 3 minutes. This attribute allows the drug to be self-administered and lowers costs, said Dr. Freeman. There are maternal side effects, however, including respiratory depression, nausea and vomiting, and sedation.

Placental transfer also occurs with remifentanil, although "the drug is so short acting, it is cleared once the baby is born when discontinued in the second stage of labor," Dr. Freeman said.

As for the potential risks of using an epidural, Dr. Freeman said that although rare, epidural hematomas can occur, and that "about 1 in 100 women experience postspinal headache, and between 10% and 20% of mothers develop a fever during labor."

Before active labor began, 709 women were randomly assigned to the remifentanil patient-controlled analgesia (PCA) group, and 705 were assigned to the epidural group. The maternal age was about 31 years in each group, and other demographic baseline data also were similar. Nearly one-third more of the remifentanil PCA group, 402 women in all, opted to use the pain medication during labor, and 296 assigned to the epidural group chose to use it.

All women across the cohorts were asked hourly to rate their pain relief on a visual analog scale.

The total time-weighted pain appreciation score for the remifentanil PCA group was 25.7, versus 36.8 in the epidural group (P = .001).

Although the analysis was based on intention to treat, Dr. Freeman noted that 53 of the women in the self-administered pain relief group requested epidurals while in labor. Three women converted from an epidural to the self-administered pain medication.

The epidurals were performed according to local procedures across the 15 Dutch sites where the trial was conducted. Remifentanil PCA was 30 mcg administered intravenously with a 3-minute lockout time. The women had the option of increasing their dose to 40 mcg or decreasing it to 20 mcg.

The duration of analgesia was notably shorter in the remifentanil PCA group than in the epidural group: 236 minutes (interquartile range, 128-376 minutes) vs. 309 minutes (IQR, 181-454 minutes).

There were 22 elective cesarean deliveries in the remifentanil group and 29 in the epidural group. Three women in the epidural cohort were lost to follow-up, and two withdrew their consent.

There were no significant differences in important maternal and fetal outcomes, said Dr. Freeman. Because the safety profiles of remifentanil and epidural analgesia are essentially the same, physicians should counsel women about the pros and cons of each, she said.

This study was funded by ZonMw, the Netherlands Organisation for Health Research and Development. Dr. Freeman did not report any relevant financial disclosures.

[email protected]

NEW ORLEANS – Laboring women had better overall pain relief satisfaction from epidurals than from remifentanil patient-controlled analgesia, according to results presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Although Dr. Liv Freeman, of Leiden (the Netherlands) University Medical Center, and her colleagues expected to find that the two pain relief methods would be equivalent, the results of their multisite, randomized controlled study instead showed a significantly higher pain appreciation (pain relief satisfaction) score in women who received epidural analgesia during delivery.

"This should be taken into account when pain relief is offered to women in labor," said Dr. Freeman, who noted that the study’s intention was to provide more definitive data about the two pain relief methods because previous studies were underpowered – with some data showing the two methods were comparable.

An advantage to using remifentanil, an opioid similar to pethidine, is that it is fast-acting, typically cycling within 3 minutes. This attribute allows the drug to be self-administered and lowers costs, said Dr. Freeman. There are maternal side effects, however, including respiratory depression, nausea and vomiting, and sedation.

Placental transfer also occurs with remifentanil, although "the drug is so short acting, it is cleared once the baby is born when discontinued in the second stage of labor," Dr. Freeman said.

As for the potential risks of using an epidural, Dr. Freeman said that although rare, epidural hematomas can occur, and that "about 1 in 100 women experience postspinal headache, and between 10% and 20% of mothers develop a fever during labor."

Before active labor began, 709 women were randomly assigned to the remifentanil patient-controlled analgesia (PCA) group, and 705 were assigned to the epidural group. The maternal age was about 31 years in each group, and other demographic baseline data also were similar. Nearly one-third more of the remifentanil PCA group, 402 women in all, opted to use the pain medication during labor, and 296 assigned to the epidural group chose to use it.

All women across the cohorts were asked hourly to rate their pain relief on a visual analog scale.

The total time-weighted pain appreciation score for the remifentanil PCA group was 25.7, versus 36.8 in the epidural group (P = .001).

Although the analysis was based on intention to treat, Dr. Freeman noted that 53 of the women in the self-administered pain relief group requested epidurals while in labor. Three women converted from an epidural to the self-administered pain medication.

The epidurals were performed according to local procedures across the 15 Dutch sites where the trial was conducted. Remifentanil PCA was 30 mcg administered intravenously with a 3-minute lockout time. The women had the option of increasing their dose to 40 mcg or decreasing it to 20 mcg.

The duration of analgesia was notably shorter in the remifentanil PCA group than in the epidural group: 236 minutes (interquartile range, 128-376 minutes) vs. 309 minutes (IQR, 181-454 minutes).

There were 22 elective cesarean deliveries in the remifentanil group and 29 in the epidural group. Three women in the epidural cohort were lost to follow-up, and two withdrew their consent.

There were no significant differences in important maternal and fetal outcomes, said Dr. Freeman. Because the safety profiles of remifentanil and epidural analgesia are essentially the same, physicians should counsel women about the pros and cons of each, she said.

This study was funded by ZonMw, the Netherlands Organisation for Health Research and Development. Dr. Freeman did not report any relevant financial disclosures.

[email protected]

NEW ORLEANS – Maternal obesity does not lessen the predictive value of noninvasive uterine electromyography monitoring, according to a poster presentation at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

"We wanted to see if in this subset of pregnant women, the noninvasive method was as effective as in other pregnant women," said Dr. Miha Lucovnik, a perinatologist at the University Medical Center, Ljubljana, Slovenia.

"Uterine contractions, at term or preterm, are one of the most common reasons for visits to obstetrical triage, but determining which patient with contractions is in true labor and needs to be admitted is, however, difficult," said Dr. Lucovnik. "The inability to accurately diagnose preterm labor leads to missed opportunities to improve outcomes of premature neonates, and also to unnecessary costs and side effects of treatments in women who would not deliver preterm regardless of intervention."

One of the more common monitoring methods – tocodynamometry – measures length and frequency of contractions but is often ineffective at detecting these signals in women with a BMI of 30 kg/m² and above, he said.

Electromyography (EMG) is more effective at monitoring the progression of true labor, because it can detect "the changes in cell excitability and coupling necessary for effective contractions," said Dr. Lucovnik.

To detect uterine activity, electrodes are placed on the patient’s abdomen with vertical and horizontal axes parallel to the patient’s vertical and horizontal axes, respectively, and with center-to-center distances between adjacent electrodes set about 5.0-5.5 cm apart. The uterine EMG is then measured for 30 minutes.

For the study, Dr. Lucovnik and his colleagues reviewed the predictive values of uterine EMG for preterm delivery in 88 women divided into three cohorts: 20 with a BMI of 30 or greater; 64 with a BMI of 25-29.9; and 4 with a BMI of 18.5-24.9.

The investigators did not find any significant difference between the cohorts in the area under the curve prediction of preterm delivery within 7 days (AUC was 0.95 in the normal and overweight cohorts, and 1 in the obese group; P = .08).

Six patients with low uterine EMG scores delivered prematurely within 7 days from the EMG measurement. No significant differences in BMI were reported between this false negative group (range, 26.13 plus or minus 1.03) and the combined true positive and true negative preterm labor groups (range, 28.04 plus or minus 3.77; P = .32).

"We know that predictive values of currently used methods to diagnose preterm labor are even lower in women with high BMI," said Dr. Lucovnik. "Our study showed that the accuracy of uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity in pregnant patients."

Dr. Lucovnik reported that he did not have any relevant disclosures.

[email protected]

NEW ORLEANS – Maternal obesity does not lessen the predictive value of noninvasive uterine electromyography monitoring, according to a poster presentation at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

"We wanted to see if in this subset of pregnant women, the noninvasive method was as effective as in other pregnant women," said Dr. Miha Lucovnik, a perinatologist at the University Medical Center, Ljubljana, Slovenia.

"Uterine contractions, at term or preterm, are one of the most common reasons for visits to obstetrical triage, but determining which patient with contractions is in true labor and needs to be admitted is, however, difficult," said Dr. Lucovnik. "The inability to accurately diagnose preterm labor leads to missed opportunities to improve outcomes of premature neonates, and also to unnecessary costs and side effects of treatments in women who would not deliver preterm regardless of intervention."

One of the more common monitoring methods – tocodynamometry – measures length and frequency of contractions but is often ineffective at detecting these signals in women with a BMI of 30 kg/m² and above, he said.

Electromyography (EMG) is more effective at monitoring the progression of true labor, because it can detect "the changes in cell excitability and coupling necessary for effective contractions," said Dr. Lucovnik.

To detect uterine activity, electrodes are placed on the patient’s abdomen with vertical and horizontal axes parallel to the patient’s vertical and horizontal axes, respectively, and with center-to-center distances between adjacent electrodes set about 5.0-5.5 cm apart. The uterine EMG is then measured for 30 minutes.

For the study, Dr. Lucovnik and his colleagues reviewed the predictive values of uterine EMG for preterm delivery in 88 women divided into three cohorts: 20 with a BMI of 30 or greater; 64 with a BMI of 25-29.9; and 4 with a BMI of 18.5-24.9.

The investigators did not find any significant difference between the cohorts in the area under the curve prediction of preterm delivery within 7 days (AUC was 0.95 in the normal and overweight cohorts, and 1 in the obese group; P = .08).

Six patients with low uterine EMG scores delivered prematurely within 7 days from the EMG measurement. No significant differences in BMI were reported between this false negative group (range, 26.13 plus or minus 1.03) and the combined true positive and true negative preterm labor groups (range, 28.04 plus or minus 3.77; P = .32).

"We know that predictive values of currently used methods to diagnose preterm labor are even lower in women with high BMI," said Dr. Lucovnik. "Our study showed that the accuracy of uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity in pregnant patients."

Dr. Lucovnik reported that he did not have any relevant disclosures.

[email protected]

NEW ORLEANS – Maternal obesity does not lessen the predictive value of noninvasive uterine electromyography monitoring, according to a poster presentation at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

"We wanted to see if in this subset of pregnant women, the noninvasive method was as effective as in other pregnant women," said Dr. Miha Lucovnik, a perinatologist at the University Medical Center, Ljubljana, Slovenia.

"Uterine contractions, at term or preterm, are one of the most common reasons for visits to obstetrical triage, but determining which patient with contractions is in true labor and needs to be admitted is, however, difficult," said Dr. Lucovnik. "The inability to accurately diagnose preterm labor leads to missed opportunities to improve outcomes of premature neonates, and also to unnecessary costs and side effects of treatments in women who would not deliver preterm regardless of intervention."

One of the more common monitoring methods – tocodynamometry – measures length and frequency of contractions but is often ineffective at detecting these signals in women with a BMI of 30 kg/m² and above, he said.

Electromyography (EMG) is more effective at monitoring the progression of true labor, because it can detect "the changes in cell excitability and coupling necessary for effective contractions," said Dr. Lucovnik.

To detect uterine activity, electrodes are placed on the patient’s abdomen with vertical and horizontal axes parallel to the patient’s vertical and horizontal axes, respectively, and with center-to-center distances between adjacent electrodes set about 5.0-5.5 cm apart. The uterine EMG is then measured for 30 minutes.

For the study, Dr. Lucovnik and his colleagues reviewed the predictive values of uterine EMG for preterm delivery in 88 women divided into three cohorts: 20 with a BMI of 30 or greater; 64 with a BMI of 25-29.9; and 4 with a BMI of 18.5-24.9.

The investigators did not find any significant difference between the cohorts in the area under the curve prediction of preterm delivery within 7 days (AUC was 0.95 in the normal and overweight cohorts, and 1 in the obese group; P = .08).

Six patients with low uterine EMG scores delivered prematurely within 7 days from the EMG measurement. No significant differences in BMI were reported between this false negative group (range, 26.13 plus or minus 1.03) and the combined true positive and true negative preterm labor groups (range, 28.04 plus or minus 3.77; P = .32).

"We know that predictive values of currently used methods to diagnose preterm labor are even lower in women with high BMI," said Dr. Lucovnik. "Our study showed that the accuracy of uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity in pregnant patients."

Dr. Lucovnik reported that he did not have any relevant disclosures.

[email protected]

The current prenatal screening standard of care for Down syndrome and other trisomies in low-risk pregnancies is more than three times as likely to return a false positive, compared with false positive rates from noninvasive, cell-free DNA testing, according to a new study.

The findings likely will strengthen public demand for the novel testing to become routine, according to Dr. Diana W. Bianchi, lead author of the CARE (Comparison of Aneuploidy Risk Evaluation) study.

"The pregnant women social media groups are very aware of the false positives. I think everybody knows somebody who has had one, since there’s 1 in 20 chance of that [happening]," Dr. Bianchi said in an interview.

Surprising results

Also revealed in the study was cell-free DNA testing’s essentially 100% negative predictive value for aneuploidies in low-risk populations.

The results are "very impressive," said Dr. Michael F. Greene, associate editor of the New England Journal of Medicine, in an interview. "I do think this is going to sweep the table in terms of what is offered to pregnant women," particularly if other studies demonstrate the same level of efficacy, he said. The study was published online (N. Engl. J. Med. 2014;370:799-808).

©iStock/thinkstockphotos.com

To compare false positive rates in the two methods of screening, Dr. Bianchi and her team analyzed test results from 1,914 women (average age, 30 years) enrolled from the general obstetrical population across 21 centers in 14 states. Participants either had or planned to have standard aneuploidy serum screening. All women were risk classified according to standard screening and had a singleton fetus without aneuploidy and a gestational age of at least 8 weeks. A second serum sample was taken from each woman, and massively parallel sequencing was used by laboratory personnel blinded to fetal karyotype to determine the chromosome dosage. Birth outcomes or karyotypes were used as the reference standard.

For trisomies 21 and 18, the false positive rates returned by cell-free DNA testing were significantly lower than those returned by standard screening: 6 patients vs. 69 out of 1,909 for trisomy 21 (0.3% vs. 3.6%; P less than .001), and 3 vs. 11 out of 1,905 for trisomy 18 (0.2% vs. 0.6%, P = .03).

The positive detection rate for cell-free DNA testing of all aneuploidies (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13) was 100% (95% confidence interval, 99.8-100). The positive predictive values for the cell-free DNA testing, compared with standard screening, were 45.5% vs. 4.2% for trisomy 21, and 40.0% vs. 8.3% for trisomy 18.

These positive predictive values, Dr. Greene and Dr. Elizabeth G. Phimister wrote in an accompanying editorial, "underscore the conclusion that assaying fetal DNA is a screening tool and not a diagnostic intervention." However, they concluded, "the observed negative predictive values of 100% with 95% confidence limits down to 99.8%, combined with the significantly and substantively lower false positive rates with cell-free DNA screening than with standard screening, augur well for pregnant women and their fetuses" (N. Engl. J. Med. 2014;370:874-5).

"I think it is going to surprise people when they see that the current standard of care has such a low positive predictive value in a general obstetrical population," said Dr. Bianchi, who also directs the Mother Infant Research Institute at Tufts Medical Center, Boston.

The primary outcome was determined by newborn physical examination in 1,857 patients (97.0%) and by karyotype in 57 patients (3.0%). Of these, chorionic villus sampling was performed in 10 patients, amniocentesis in 38, testing of the products of conception in 3, and postnatal evaluation in 6. The women whose cell-free DNA tests came back with false positive readings all had live births with normal physical examinations.

The secondary endpoint was a similar comparison of detection rates for trisomy 13 (Patau syndrome). There was one false positive result for trisomy 13 with cell-free DNA testing, as compared with six false positive results on standard screening, thus showing a trend toward significance (P = .059) in the 899 patients who underwent standard screening for trisomy 13.

Fetal fraction not maternal age–related

The researchers found that cell-free DNA testing had the same high-sensitivity detection rates in low-risk obstetrical populations as has been previously established in high-risk ones. Generally considered at higher risk for trisomy 21, women 35 years and older who were tested in either the first or second trimesters had results that were nearly identical to results from women under age 35 in terms of both their mean percentage of free fetal DNA and their standard screening results and/or cell-free DNA results (11.3% and 11.6%, respectively). For women tested in the third trimester, the fetal fraction was higher (mean, 24.6%).

This finding further strengthens the argument that the technology should be available to the general obstetric population. "The amount of the DNA was the same when we stratified the relatively high risk from the relatively low risk," said Dr. Bianchi. "That will be a surprise to some people who postulated that the high-risk women would have more DNA circulating. They don’t."

The consistent fetal fraction also lends itself to greater flexibility when prenatal screening occurs, allowing women to be screened anytime between 10 and 40 weeks gestational age. This could mean better prenatal care for women who do not have their first prenatal visit until late in the second trimester, for example. Because the current screening methods are specific to certain gestational times, if a woman is erratic with her prenatal visits, testing may be impossible.

Regarding its utility in women carrying multiple fetuses, Dr. Bianchi said that about 10% of the time, the fetal fraction per fetus tends to be too low to get an accurate reading.

‘Throwing down the gauntlet’

The test’s unparalleled accuracy could give greater peace of mind to women who might have had difficulty getting pregnant and so are wary of the miscarriage risks posed by invasive diagnostic testing, according to Dr. Bianchi. Fewer invasive diagnostic tests could also lower costs across the system.

When all results for trisomies 21 and 18 were combined, the researchers found that the false positive rates for standard screening were 4.2%, compared with 0.5% for cell-free DNA testing. "If all pregnant women had undergone cell-free DNA testing as a primary screening method and if all women with positive results had undergone post-test counseling and had decided to undergo an invasive procedure," wrote the authors, "there would have been a relative reduction of 89% in the number of diagnostic invasive procedures required to confirm a positive screening result."

The data should move professional societies to take action, according to Dr. Bianchi. "That’s kind of the gauntlet that we’re throwing down." More data are on the way, she said, which will "enable the professional societies to take a cumulative look and decide what their recommendations are going to be."

As it stands, the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists state that the testing be used only in women at higher risk for giving birth to children with aneuploidies, such as women aged 35 years or older or those with a history of pregnancy with trisomy, and that positive cell-free DNA results should be confirmed by invasive diagnostic testing.

For now, because the tests are not considered routine prenatal care, low-risk patients usually pay out of pocket for these tests, which Dr. Bianchi said many women are willing to do. The cost of the test ranges anywhere from $1,200 to upward of $2,700, although some careful Internet searching for deals can net tests at substantially lower prices, she said.

Market pressures

For some physicians in the field, this public demand for a screening test not subject to Food and Drug Administration (FDA) regulation has not outweighed the level of proof it offers in the clinical setting. One of these critics was, until recently, Dr. Greene.

"Companies have been free to build consumer demand for cell-free DNA testing by aggressively marketing the tests, emphasizing data that do not answer key questions," wrote Dr. Greene in July 2013, in an editorial he coauthored (N. Engl. J. Med. 2013;369:499-501). "As a result, cell-free DNA testing seems to be drifting into routine practice ahead of the evidence," stated Dr. Greene, who is also chief of obstetrics at Massachusetts General Hospital in Boston, and who wrote with his colleagues that the test’s positive predictive value, largely unreported by manufacturers, was still in question.

"The problem is that the proof-of-principle studies that all these companies have published to date have been with ratios of ‘Down’s’ to ‘normals’ ranging from 1 to 7, 1 to 13, or 1 to 20," said Dr. Greene in an interview. "All were done in retrospective populations at extraordinarily high risk."

However, with the CARE study, "what’s impressive is the positive predictive value in a low-incidence group of patients," he said.

Sponsored by Illumina/Verinata, the study puts pressure on other companies to publish their own data in peer-reviewed journals, said Dr. Greene. "Once this paper appears in print, [Verinata] will get a leg up, and the other companies won’t want to let them get too far ahead of them."

According to Dr. Bianchi, Verinata is now seeking FDA approval to market the testing as an in vitro diagnostic product. She expects demand for the testing to be led not by physicians but by patients. "People often ask me why the DNA testing took off so quickly," said Dr. Bianchi. "I think a factor is social media. I find there is a discrepancy between what the average patient knows and the general obstetrician knows because of the discussions [online]. "

Although some women will still need an invasive procedure to resolve a screen positive test, Dr. Bianchi said most pregnant women, including older women, are going to be reassured with the 100% negative predictive value.

"The younger woman’s benefit will primarily be the reduced false positive rate, because overwhelmingly, she is going to have a normal fetus, so her major benefit is not being made anxious and being sent for all the subsequent testing."

Dr. Bianchi and her coauthors disclosed relationships with Verinata/Illumina, maker of the Verifi cell-free DNA prenatal test. Dr. Bianchi is also on the clinical advisory board of Verinata. Dr. Greene stated that he had no conflict of interest disclosures. The study was sponsored by Illumina, ClinicalTrials.gov number NCT01663350.

[email protected]

The current prenatal screening standard of care for Down syndrome and other trisomies in low-risk pregnancies is more than three times as likely to return a false positive, compared with false positive rates from noninvasive, cell-free DNA testing, according to a new study.

The findings likely will strengthen public demand for the novel testing to become routine, according to Dr. Diana W. Bianchi, lead author of the CARE (Comparison of Aneuploidy Risk Evaluation) study.

"The pregnant women social media groups are very aware of the false positives. I think everybody knows somebody who has had one, since there’s 1 in 20 chance of that [happening]," Dr. Bianchi said in an interview.

Surprising results

Also revealed in the study was cell-free DNA testing’s essentially 100% negative predictive value for aneuploidies in low-risk populations.

The results are "very impressive," said Dr. Michael F. Greene, associate editor of the New England Journal of Medicine, in an interview. "I do think this is going to sweep the table in terms of what is offered to pregnant women," particularly if other studies demonstrate the same level of efficacy, he said. The study was published online (N. Engl. J. Med. 2014;370:799-808).

©iStock/thinkstockphotos.com

To compare false positive rates in the two methods of screening, Dr. Bianchi and her team analyzed test results from 1,914 women (average age, 30 years) enrolled from the general obstetrical population across 21 centers in 14 states. Participants either had or planned to have standard aneuploidy serum screening. All women were risk classified according to standard screening and had a singleton fetus without aneuploidy and a gestational age of at least 8 weeks. A second serum sample was taken from each woman, and massively parallel sequencing was used by laboratory personnel blinded to fetal karyotype to determine the chromosome dosage. Birth outcomes or karyotypes were used as the reference standard.

For trisomies 21 and 18, the false positive rates returned by cell-free DNA testing were significantly lower than those returned by standard screening: 6 patients vs. 69 out of 1,909 for trisomy 21 (0.3% vs. 3.6%; P less than .001), and 3 vs. 11 out of 1,905 for trisomy 18 (0.2% vs. 0.6%, P = .03).

The positive detection rate for cell-free DNA testing of all aneuploidies (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13) was 100% (95% confidence interval, 99.8-100). The positive predictive values for the cell-free DNA testing, compared with standard screening, were 45.5% vs. 4.2% for trisomy 21, and 40.0% vs. 8.3% for trisomy 18.

These positive predictive values, Dr. Greene and Dr. Elizabeth G. Phimister wrote in an accompanying editorial, "underscore the conclusion that assaying fetal DNA is a screening tool and not a diagnostic intervention." However, they concluded, "the observed negative predictive values of 100% with 95% confidence limits down to 99.8%, combined with the significantly and substantively lower false positive rates with cell-free DNA screening than with standard screening, augur well for pregnant women and their fetuses" (N. Engl. J. Med. 2014;370:874-5).

"I think it is going to surprise people when they see that the current standard of care has such a low positive predictive value in a general obstetrical population," said Dr. Bianchi, who also directs the Mother Infant Research Institute at Tufts Medical Center, Boston.

The primary outcome was determined by newborn physical examination in 1,857 patients (97.0%) and by karyotype in 57 patients (3.0%). Of these, chorionic villus sampling was performed in 10 patients, amniocentesis in 38, testing of the products of conception in 3, and postnatal evaluation in 6. The women whose cell-free DNA tests came back with false positive readings all had live births with normal physical examinations.

The secondary endpoint was a similar comparison of detection rates for trisomy 13 (Patau syndrome). There was one false positive result for trisomy 13 with cell-free DNA testing, as compared with six false positive results on standard screening, thus showing a trend toward significance (P = .059) in the 899 patients who underwent standard screening for trisomy 13.

Fetal fraction not maternal age–related

The researchers found that cell-free DNA testing had the same high-sensitivity detection rates in low-risk obstetrical populations as has been previously established in high-risk ones. Generally considered at higher risk for trisomy 21, women 35 years and older who were tested in either the first or second trimesters had results that were nearly identical to results from women under age 35 in terms of both their mean percentage of free fetal DNA and their standard screening results and/or cell-free DNA results (11.3% and 11.6%, respectively). For women tested in the third trimester, the fetal fraction was higher (mean, 24.6%).

This finding further strengthens the argument that the technology should be available to the general obstetric population. "The amount of the DNA was the same when we stratified the relatively high risk from the relatively low risk," said Dr. Bianchi. "That will be a surprise to some people who postulated that the high-risk women would have more DNA circulating. They don’t."

The consistent fetal fraction also lends itself to greater flexibility when prenatal screening occurs, allowing women to be screened anytime between 10 and 40 weeks gestational age. This could mean better prenatal care for women who do not have their first prenatal visit until late in the second trimester, for example. Because the current screening methods are specific to certain gestational times, if a woman is erratic with her prenatal visits, testing may be impossible.

Regarding its utility in women carrying multiple fetuses, Dr. Bianchi said that about 10% of the time, the fetal fraction per fetus tends to be too low to get an accurate reading.

‘Throwing down the gauntlet’

The test’s unparalleled accuracy could give greater peace of mind to women who might have had difficulty getting pregnant and so are wary of the miscarriage risks posed by invasive diagnostic testing, according to Dr. Bianchi. Fewer invasive diagnostic tests could also lower costs across the system.

When all results for trisomies 21 and 18 were combined, the researchers found that the false positive rates for standard screening were 4.2%, compared with 0.5% for cell-free DNA testing. "If all pregnant women had undergone cell-free DNA testing as a primary screening method and if all women with positive results had undergone post-test counseling and had decided to undergo an invasive procedure," wrote the authors, "there would have been a relative reduction of 89% in the number of diagnostic invasive procedures required to confirm a positive screening result."

The data should move professional societies to take action, according to Dr. Bianchi. "That’s kind of the gauntlet that we’re throwing down." More data are on the way, she said, which will "enable the professional societies to take a cumulative look and decide what their recommendations are going to be."

As it stands, the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists state that the testing be used only in women at higher risk for giving birth to children with aneuploidies, such as women aged 35 years or older or those with a history of pregnancy with trisomy, and that positive cell-free DNA results should be confirmed by invasive diagnostic testing.

For now, because the tests are not considered routine prenatal care, low-risk patients usually pay out of pocket for these tests, which Dr. Bianchi said many women are willing to do. The cost of the test ranges anywhere from $1,200 to upward of $2,700, although some careful Internet searching for deals can net tests at substantially lower prices, she said.

Market pressures

For some physicians in the field, this public demand for a screening test not subject to Food and Drug Administration (FDA) regulation has not outweighed the level of proof it offers in the clinical setting. One of these critics was, until recently, Dr. Greene.

"Companies have been free to build consumer demand for cell-free DNA testing by aggressively marketing the tests, emphasizing data that do not answer key questions," wrote Dr. Greene in July 2013, in an editorial he coauthored (N. Engl. J. Med. 2013;369:499-501). "As a result, cell-free DNA testing seems to be drifting into routine practice ahead of the evidence," stated Dr. Greene, who is also chief of obstetrics at Massachusetts General Hospital in Boston, and who wrote with his colleagues that the test’s positive predictive value, largely unreported by manufacturers, was still in question.

"The problem is that the proof-of-principle studies that all these companies have published to date have been with ratios of ‘Down’s’ to ‘normals’ ranging from 1 to 7, 1 to 13, or 1 to 20," said Dr. Greene in an interview. "All were done in retrospective populations at extraordinarily high risk."

However, with the CARE study, "what’s impressive is the positive predictive value in a low-incidence group of patients," he said.

Sponsored by Illumina/Verinata, the study puts pressure on other companies to publish their own data in peer-reviewed journals, said Dr. Greene. "Once this paper appears in print, [Verinata] will get a leg up, and the other companies won’t want to let them get too far ahead of them."

According to Dr. Bianchi, Verinata is now seeking FDA approval to market the testing as an in vitro diagnostic product. She expects demand for the testing to be led not by physicians but by patients. "People often ask me why the DNA testing took off so quickly," said Dr. Bianchi. "I think a factor is social media. I find there is a discrepancy between what the average patient knows and the general obstetrician knows because of the discussions [online]. "

Although some women will still need an invasive procedure to resolve a screen positive test, Dr. Bianchi said most pregnant women, including older women, are going to be reassured with the 100% negative predictive value.

"The younger woman’s benefit will primarily be the reduced false positive rate, because overwhelmingly, she is going to have a normal fetus, so her major benefit is not being made anxious and being sent for all the subsequent testing."

Dr. Bianchi and her coauthors disclosed relationships with Verinata/Illumina, maker of the Verifi cell-free DNA prenatal test. Dr. Bianchi is also on the clinical advisory board of Verinata. Dr. Greene stated that he had no conflict of interest disclosures. The study was sponsored by Illumina, ClinicalTrials.gov number NCT01663350.

[email protected]

The current prenatal screening standard of care for Down syndrome and other trisomies in low-risk pregnancies is more than three times as likely to return a false positive, compared with false positive rates from noninvasive, cell-free DNA testing, according to a new study.

The findings likely will strengthen public demand for the novel testing to become routine, according to Dr. Diana W. Bianchi, lead author of the CARE (Comparison of Aneuploidy Risk Evaluation) study.

"The pregnant women social media groups are very aware of the false positives. I think everybody knows somebody who has had one, since there’s 1 in 20 chance of that [happening]," Dr. Bianchi said in an interview.

Surprising results

Also revealed in the study was cell-free DNA testing’s essentially 100% negative predictive value for aneuploidies in low-risk populations.

The results are "very impressive," said Dr. Michael F. Greene, associate editor of the New England Journal of Medicine, in an interview. "I do think this is going to sweep the table in terms of what is offered to pregnant women," particularly if other studies demonstrate the same level of efficacy, he said. The study was published online (N. Engl. J. Med. 2014;370:799-808).

©iStock/thinkstockphotos.com

To compare false positive rates in the two methods of screening, Dr. Bianchi and her team analyzed test results from 1,914 women (average age, 30 years) enrolled from the general obstetrical population across 21 centers in 14 states. Participants either had or planned to have standard aneuploidy serum screening. All women were risk classified according to standard screening and had a singleton fetus without aneuploidy and a gestational age of at least 8 weeks. A second serum sample was taken from each woman, and massively parallel sequencing was used by laboratory personnel blinded to fetal karyotype to determine the chromosome dosage. Birth outcomes or karyotypes were used as the reference standard.

For trisomies 21 and 18, the false positive rates returned by cell-free DNA testing were significantly lower than those returned by standard screening: 6 patients vs. 69 out of 1,909 for trisomy 21 (0.3% vs. 3.6%; P less than .001), and 3 vs. 11 out of 1,905 for trisomy 18 (0.2% vs. 0.6%, P = .03).

The positive detection rate for cell-free DNA testing of all aneuploidies (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13) was 100% (95% confidence interval, 99.8-100). The positive predictive values for the cell-free DNA testing, compared with standard screening, were 45.5% vs. 4.2% for trisomy 21, and 40.0% vs. 8.3% for trisomy 18.

These positive predictive values, Dr. Greene and Dr. Elizabeth G. Phimister wrote in an accompanying editorial, "underscore the conclusion that assaying fetal DNA is a screening tool and not a diagnostic intervention." However, they concluded, "the observed negative predictive values of 100% with 95% confidence limits down to 99.8%, combined with the significantly and substantively lower false positive rates with cell-free DNA screening than with standard screening, augur well for pregnant women and their fetuses" (N. Engl. J. Med. 2014;370:874-5).

"I think it is going to surprise people when they see that the current standard of care has such a low positive predictive value in a general obstetrical population," said Dr. Bianchi, who also directs the Mother Infant Research Institute at Tufts Medical Center, Boston.

The primary outcome was determined by newborn physical examination in 1,857 patients (97.0%) and by karyotype in 57 patients (3.0%). Of these, chorionic villus sampling was performed in 10 patients, amniocentesis in 38, testing of the products of conception in 3, and postnatal evaluation in 6. The women whose cell-free DNA tests came back with false positive readings all had live births with normal physical examinations.

The secondary endpoint was a similar comparison of detection rates for trisomy 13 (Patau syndrome). There was one false positive result for trisomy 13 with cell-free DNA testing, as compared with six false positive results on standard screening, thus showing a trend toward significance (P = .059) in the 899 patients who underwent standard screening for trisomy 13.

Fetal fraction not maternal age–related

The researchers found that cell-free DNA testing had the same high-sensitivity detection rates in low-risk obstetrical populations as has been previously established in high-risk ones. Generally considered at higher risk for trisomy 21, women 35 years and older who were tested in either the first or second trimesters had results that were nearly identical to results from women under age 35 in terms of both their mean percentage of free fetal DNA and their standard screening results and/or cell-free DNA results (11.3% and 11.6%, respectively). For women tested in the third trimester, the fetal fraction was higher (mean, 24.6%).

This finding further strengthens the argument that the technology should be available to the general obstetric population. "The amount of the DNA was the same when we stratified the relatively high risk from the relatively low risk," said Dr. Bianchi. "That will be a surprise to some people who postulated that the high-risk women would have more DNA circulating. They don’t."

The consistent fetal fraction also lends itself to greater flexibility when prenatal screening occurs, allowing women to be screened anytime between 10 and 40 weeks gestational age. This could mean better prenatal care for women who do not have their first prenatal visit until late in the second trimester, for example. Because the current screening methods are specific to certain gestational times, if a woman is erratic with her prenatal visits, testing may be impossible.

Regarding its utility in women carrying multiple fetuses, Dr. Bianchi said that about 10% of the time, the fetal fraction per fetus tends to be too low to get an accurate reading.

‘Throwing down the gauntlet’

The test’s unparalleled accuracy could give greater peace of mind to women who might have had difficulty getting pregnant and so are wary of the miscarriage risks posed by invasive diagnostic testing, according to Dr. Bianchi. Fewer invasive diagnostic tests could also lower costs across the system.

When all results for trisomies 21 and 18 were combined, the researchers found that the false positive rates for standard screening were 4.2%, compared with 0.5% for cell-free DNA testing. "If all pregnant women had undergone cell-free DNA testing as a primary screening method and if all women with positive results had undergone post-test counseling and had decided to undergo an invasive procedure," wrote the authors, "there would have been a relative reduction of 89% in the number of diagnostic invasive procedures required to confirm a positive screening result."

The data should move professional societies to take action, according to Dr. Bianchi. "That’s kind of the gauntlet that we’re throwing down." More data are on the way, she said, which will "enable the professional societies to take a cumulative look and decide what their recommendations are going to be."

As it stands, the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists state that the testing be used only in women at higher risk for giving birth to children with aneuploidies, such as women aged 35 years or older or those with a history of pregnancy with trisomy, and that positive cell-free DNA results should be confirmed by invasive diagnostic testing.

For now, because the tests are not considered routine prenatal care, low-risk patients usually pay out of pocket for these tests, which Dr. Bianchi said many women are willing to do. The cost of the test ranges anywhere from $1,200 to upward of $2,700, although some careful Internet searching for deals can net tests at substantially lower prices, she said.

Market pressures

For some physicians in the field, this public demand for a screening test not subject to Food and Drug Administration (FDA) regulation has not outweighed the level of proof it offers in the clinical setting. One of these critics was, until recently, Dr. Greene.

"Companies have been free to build consumer demand for cell-free DNA testing by aggressively marketing the tests, emphasizing data that do not answer key questions," wrote Dr. Greene in July 2013, in an editorial he coauthored (N. Engl. J. Med. 2013;369:499-501). "As a result, cell-free DNA testing seems to be drifting into routine practice ahead of the evidence," stated Dr. Greene, who is also chief of obstetrics at Massachusetts General Hospital in Boston, and who wrote with his colleagues that the test’s positive predictive value, largely unreported by manufacturers, was still in question.

"The problem is that the proof-of-principle studies that all these companies have published to date have been with ratios of ‘Down’s’ to ‘normals’ ranging from 1 to 7, 1 to 13, or 1 to 20," said Dr. Greene in an interview. "All were done in retrospective populations at extraordinarily high risk."

However, with the CARE study, "what’s impressive is the positive predictive value in a low-incidence group of patients," he said.

Sponsored by Illumina/Verinata, the study puts pressure on other companies to publish their own data in peer-reviewed journals, said Dr. Greene. "Once this paper appears in print, [Verinata] will get a leg up, and the other companies won’t want to let them get too far ahead of them."

According to Dr. Bianchi, Verinata is now seeking FDA approval to market the testing as an in vitro diagnostic product. She expects demand for the testing to be led not by physicians but by patients. "People often ask me why the DNA testing took off so quickly," said Dr. Bianchi. "I think a factor is social media. I find there is a discrepancy between what the average patient knows and the general obstetrician knows because of the discussions [online]. "

Although some women will still need an invasive procedure to resolve a screen positive test, Dr. Bianchi said most pregnant women, including older women, are going to be reassured with the 100% negative predictive value.

"The younger woman’s benefit will primarily be the reduced false positive rate, because overwhelmingly, she is going to have a normal fetus, so her major benefit is not being made anxious and being sent for all the subsequent testing."

Dr. Bianchi and her coauthors disclosed relationships with Verinata/Illumina, maker of the Verifi cell-free DNA prenatal test. Dr. Bianchi is also on the clinical advisory board of Verinata. Dr. Greene stated that he had no conflict of interest disclosures. The study was sponsored by Illumina, ClinicalTrials.gov number NCT01663350.

[email protected]

NEW ORLEANS – The link between labor induction and cesarean deliveries was found to be negatively correlated, according to data presented at this year’s Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

The findings that a woman’s odds of delivering by C-section are 30% greater (confidence interval, 1.26-1.31; P = less than .01) if she delivers at a hospital with low rates of labor induction, independent of other obstetric risk factors and hospital characteristics, were unexpected by the study’s presenter, Dr. Sarah E. Little of Brigham and Women’s Hospital in Boston. "I was quite surprised by the findings. It suggests to me that inductions themselves may not be the culprit behind the rising rate of cesarean delivery in the United States."

Dr. Little and her colleagues conducted the research to help close the gap between this commonly held belief that an overreliance on induction is at least in part responsible for why the rate of C-section deliveries performed in the United States rose from 20.7% in 1996 to 32.8% in 2011, making it the most commonly performed surgical procedure in the nation. The increased risk has not been shown in prospective trials because the control group would be women with expectant management, according to Dr. Little.

"In retrospective trials, the comparison group is often spontaneous labor, but you can’t choose to be in spontaneous labor," she said. "During expectant management, things can arise – the babies get bigger, the placentas get worse, moms can develop bleeding or preeclampsia – all of which increase the risk of cesarean section, so if you don’t take this into account, then inductions look worse."

For the study, Dr. Little and her colleagues calculated hospital rates of C-sections using the 2010 Nationwide Inpatient Sample of 813,693 deliveries at 604 hospitals. The sample was representative of roughly 20% of all American hospitals, according to Dr. Little and included women at low risk for emergency C-section, and those with no preexisting comorbidities.

The investigators classified hospital level inductions as any induction; low-risk inductions, excluding anyone with preexisting comorbidities; and elective inductions if they were performed when not medically indicated, according to Joint Commission guidelines.

Hospitals in the study were characterized according to location, number of beds, and whether they were teaching facilities. Hospitals that performed fewer than 100 C-sections or did not perform labor inductions were excluded.

The researchers then conducted unadjusted and adjusted hospital cesarean rates according to hospital induction quartile. They also conducted a logistic regression analysis across quartiles to determine the correlation between the hospital rate of induction and the individual’s risk for C-section.

Dr. Little and her team found that hospitals had an average cesarean rate of 31%, with a range of 5.1%-75.7% (mean, 30.5%); rates of labor induction varied from 0% to 50% (mean 19.1%).

Hospitals with high induction rates had lower cesarean delivery rates (Pearson, –0.18; P = less than .001), a negative correlation that held even when only low-risk C-sections and low-risk inductions were studied (Pearson –0.31; P = less than .001). Hospitals in the highest quartile of labor inductions had an average cesarean rate of 32.6%, compared with 29.7% at hospitals in the lowest quartile of inductions.

"There is wide variation in the induction rates across hospitals," said Dr. Little. "I think this speaks to the wide variation in physician practices across the U.S."

The findings were presented during a time when the society is actively encouraging physicians to think twice before inducing labor and is conducting workshops that specifically draw a connection between the two procedures. "This study provides helpful information, and is potentially reassuring to those who require labor induction, but I would continue to encourage a practice of limiting labor induction to those with an indication for delivery and no contraindication to labor," Dr. Brian Mercer, the society’s immediate past president, responded when asked about the results.

The society’s suggested protocols are outlined in the paper, "Preventing the first cesarean delivery" (Obstet. Gynecol. 2012;120:1181-93), which includes an algorithm for when to induce labor – typically, only when medically indicated, such as in the case of membrane rupture.

"I think [our study] supports the SMFM initiative as there is clearly a large variation in practice which could potentially be targeted for change," said Dr. Little. "Also, there are other downsides to labor induction – iatrogenic prematurity if done prior to 39 weeks and increased cost and resource utilization. So even if inductions don’t lead to increased cesareans directly, there are a number of reasons you might want to avoid them."

Because birth certificate data is not kept at the hospital level, the investigators used billing data from the Nationwide Inpatient Sample. "This is not perfect, as it lacks some covariates, such as parity and gestational age, but it is the best national data available currently at the hospital level," Dr. Little said. "The next step might be to look at data sets, which combine birth certificate and discharge data, or collect this data prospectively at a hospital level."

[email protected]

NEW ORLEANS – The link between labor induction and cesarean deliveries was found to be negatively correlated, according to data presented at this year’s Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

The findings that a woman’s odds of delivering by C-section are 30% greater (confidence interval, 1.26-1.31; P = less than .01) if she delivers at a hospital with low rates of labor induction, independent of other obstetric risk factors and hospital characteristics, were unexpected by the study’s presenter, Dr. Sarah E. Little of Brigham and Women’s Hospital in Boston. "I was quite surprised by the findings. It suggests to me that inductions themselves may not be the culprit behind the rising rate of cesarean delivery in the United States."

Dr. Little and her colleagues conducted the research to help close the gap between this commonly held belief that an overreliance on induction is at least in part responsible for why the rate of C-section deliveries performed in the United States rose from 20.7% in 1996 to 32.8% in 2011, making it the most commonly performed surgical procedure in the nation. The increased risk has not been shown in prospective trials because the control group would be women with expectant management, according to Dr. Little.

"In retrospective trials, the comparison group is often spontaneous labor, but you can’t choose to be in spontaneous labor," she said. "During expectant management, things can arise – the babies get bigger, the placentas get worse, moms can develop bleeding or preeclampsia – all of which increase the risk of cesarean section, so if you don’t take this into account, then inductions look worse."

For the study, Dr. Little and her colleagues calculated hospital rates of C-sections using the 2010 Nationwide Inpatient Sample of 813,693 deliveries at 604 hospitals. The sample was representative of roughly 20% of all American hospitals, according to Dr. Little and included women at low risk for emergency C-section, and those with no preexisting comorbidities.

The investigators classified hospital level inductions as any induction; low-risk inductions, excluding anyone with preexisting comorbidities; and elective inductions if they were performed when not medically indicated, according to Joint Commission guidelines.

Hospitals in the study were characterized according to location, number of beds, and whether they were teaching facilities. Hospitals that performed fewer than 100 C-sections or did not perform labor inductions were excluded.

The researchers then conducted unadjusted and adjusted hospital cesarean rates according to hospital induction quartile. They also conducted a logistic regression analysis across quartiles to determine the correlation between the hospital rate of induction and the individual’s risk for C-section.

Dr. Little and her team found that hospitals had an average cesarean rate of 31%, with a range of 5.1%-75.7% (mean, 30.5%); rates of labor induction varied from 0% to 50% (mean 19.1%).

Hospitals with high induction rates had lower cesarean delivery rates (Pearson, –0.18; P = less than .001), a negative correlation that held even when only low-risk C-sections and low-risk inductions were studied (Pearson –0.31; P = less than .001). Hospitals in the highest quartile of labor inductions had an average cesarean rate of 32.6%, compared with 29.7% at hospitals in the lowest quartile of inductions.

"There is wide variation in the induction rates across hospitals," said Dr. Little. "I think this speaks to the wide variation in physician practices across the U.S."

The findings were presented during a time when the society is actively encouraging physicians to think twice before inducing labor and is conducting workshops that specifically draw a connection between the two procedures. "This study provides helpful information, and is potentially reassuring to those who require labor induction, but I would continue to encourage a practice of limiting labor induction to those with an indication for delivery and no contraindication to labor," Dr. Brian Mercer, the society’s immediate past president, responded when asked about the results.

The society’s suggested protocols are outlined in the paper, "Preventing the first cesarean delivery" (Obstet. Gynecol. 2012;120:1181-93), which includes an algorithm for when to induce labor – typically, only when medically indicated, such as in the case of membrane rupture.

"I think [our study] supports the SMFM initiative as there is clearly a large variation in practice which could potentially be targeted for change," said Dr. Little. "Also, there are other downsides to labor induction – iatrogenic prematurity if done prior to 39 weeks and increased cost and resource utilization. So even if inductions don’t lead to increased cesareans directly, there are a number of reasons you might want to avoid them."

Because birth certificate data is not kept at the hospital level, the investigators used billing data from the Nationwide Inpatient Sample. "This is not perfect, as it lacks some covariates, such as parity and gestational age, but it is the best national data available currently at the hospital level," Dr. Little said. "The next step might be to look at data sets, which combine birth certificate and discharge data, or collect this data prospectively at a hospital level."

[email protected]

NEW ORLEANS – The link between labor induction and cesarean deliveries was found to be negatively correlated, according to data presented at this year’s Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

The findings that a woman’s odds of delivering by C-section are 30% greater (confidence interval, 1.26-1.31; P = less than .01) if she delivers at a hospital with low rates of labor induction, independent of other obstetric risk factors and hospital characteristics, were unexpected by the study’s presenter, Dr. Sarah E. Little of Brigham and Women’s Hospital in Boston. "I was quite surprised by the findings. It suggests to me that inductions themselves may not be the culprit behind the rising rate of cesarean delivery in the United States."

Dr. Little and her colleagues conducted the research to help close the gap between this commonly held belief that an overreliance on induction is at least in part responsible for why the rate of C-section deliveries performed in the United States rose from 20.7% in 1996 to 32.8% in 2011, making it the most commonly performed surgical procedure in the nation. The increased risk has not been shown in prospective trials because the control group would be women with expectant management, according to Dr. Little.

"In retrospective trials, the comparison group is often spontaneous labor, but you can’t choose to be in spontaneous labor," she said. "During expectant management, things can arise – the babies get bigger, the placentas get worse, moms can develop bleeding or preeclampsia – all of which increase the risk of cesarean section, so if you don’t take this into account, then inductions look worse."

For the study, Dr. Little and her colleagues calculated hospital rates of C-sections using the 2010 Nationwide Inpatient Sample of 813,693 deliveries at 604 hospitals. The sample was representative of roughly 20% of all American hospitals, according to Dr. Little and included women at low risk for emergency C-section, and those with no preexisting comorbidities.

The investigators classified hospital level inductions as any induction; low-risk inductions, excluding anyone with preexisting comorbidities; and elective inductions if they were performed when not medically indicated, according to Joint Commission guidelines.

Hospitals in the study were characterized according to location, number of beds, and whether they were teaching facilities. Hospitals that performed fewer than 100 C-sections or did not perform labor inductions were excluded.

The researchers then conducted unadjusted and adjusted hospital cesarean rates according to hospital induction quartile. They also conducted a logistic regression analysis across quartiles to determine the correlation between the hospital rate of induction and the individual’s risk for C-section.

Dr. Little and her team found that hospitals had an average cesarean rate of 31%, with a range of 5.1%-75.7% (mean, 30.5%); rates of labor induction varied from 0% to 50% (mean 19.1%).

Hospitals with high induction rates had lower cesarean delivery rates (Pearson, –0.18; P = less than .001), a negative correlation that held even when only low-risk C-sections and low-risk inductions were studied (Pearson –0.31; P = less than .001). Hospitals in the highest quartile of labor inductions had an average cesarean rate of 32.6%, compared with 29.7% at hospitals in the lowest quartile of inductions.

"There is wide variation in the induction rates across hospitals," said Dr. Little. "I think this speaks to the wide variation in physician practices across the U.S."

The findings were presented during a time when the society is actively encouraging physicians to think twice before inducing labor and is conducting workshops that specifically draw a connection between the two procedures. "This study provides helpful information, and is potentially reassuring to those who require labor induction, but I would continue to encourage a practice of limiting labor induction to those with an indication for delivery and no contraindication to labor," Dr. Brian Mercer, the society’s immediate past president, responded when asked about the results.

The society’s suggested protocols are outlined in the paper, "Preventing the first cesarean delivery" (Obstet. Gynecol. 2012;120:1181-93), which includes an algorithm for when to induce labor – typically, only when medically indicated, such as in the case of membrane rupture.

"I think [our study] supports the SMFM initiative as there is clearly a large variation in practice which could potentially be targeted for change," said Dr. Little. "Also, there are other downsides to labor induction – iatrogenic prematurity if done prior to 39 weeks and increased cost and resource utilization. So even if inductions don’t lead to increased cesareans directly, there are a number of reasons you might want to avoid them."

Because birth certificate data is not kept at the hospital level, the investigators used billing data from the Nationwide Inpatient Sample. "This is not perfect, as it lacks some covariates, such as parity and gestational age, but it is the best national data available currently at the hospital level," Dr. Little said. "The next step might be to look at data sets, which combine birth certificate and discharge data, or collect this data prospectively at a hospital level."

[email protected]

WASHINGTON – Longer labors lead to fewer cesarean sections.

That’s according to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine who have jointly issued the Obstetric Care Consensus guideline, urging physicians to allow women with low-risk pregnancies to remain in latent labor longer before elevating their delivery to surgical status. The report and the consensus guideline appear in the March issue of Obstetrics & Gynecology (Obstet. Gynecol. 2014;123:693-711).

"Evidence now shows that labor actually progresses slower than we thought in the past, so many women might just need a little more time to labor and deliver vaginally instead of moving to a cesarean delivery," Dr. Aaron B. Caughey, a member of ACOG’s Committee on Obstetric Practice, said in a statement.

The document calls on physicians to consider that active labor has begun at 6 cm of cervical dilation, rather than 4, and stresses that doctors should allow more time for progression of labor during the active phase. Whether a woman chooses to use an epidural should also be factored into laboring times because the analgesia can slow contractions.

Although no absolute specific time for allowing a woman to remain in the active labor phase has been determined, the document states that women who have never delivered should be given at least 3 hours to push, while women who have delivered previously should be given a minimum of 2 hours.

‘Fear and convenience’

The recommendations are specifically concerned with avoiding the primary cesarean section because more than one-third of all births in the United States are cesarean deliveries, two-thirds of which are among nulliparous women. Avoiding the first cesarean section is important, "because if the woman labors with a scar from a previous C-section, there is a risk that the uterus will rupture," SMFM president Dr. Vincenzo Berghella, director of maternal-fetal medicine at Thomas Jefferson Medical Center in Philadelphia, said in an interview. "It only happens one-half to one percent [of the time], but it can be catastrophic. The baby could even die. A lot of women, understandably, are afraid of [that]."

In addition, sometimes the procedure is medically indicated, as in the case of placenta previa or uterine rupture. However, according to the document, in most pregnancies, which are typically low risk, cesarean delivery carries with it greater overall severe morbidity and mortality risks for the mother compared with vaginal delivery: 9.2% vs. 8.6% and 2.7% vs. 0.9%, respectively.

A combination of fear of being sued for malpractice, convenience, and lack of manpower, are partially responsible for the astronomical rise in C-sections, now the most common surgical procedure performed in the United States, according to the Centers for Disease Control and Prevention.

Dr. Berghella said a scenario that plays out in a physician’s mind could run along the lines of, "You know what, maybe 99% of things are fine here, but I am just worried a little bit here. So I am just going to do a C-section just to cover my behind."

In the past, solo practitioners also were pressed in ways that today’s doctors who belong to an entire practice are not, said Dr. Berghella.

"There are many, many factors that can lead to a longer labor," Dr. Berghella said, adding it was his "hope" that the document will help doctors make decisions based on the patient and how she presents as an individual. "This is to empower doctors, and reassure everyone on the team, including that patient, that if everything is going well, there is no rush."

Redefining active labor and ‘failed’ induction

The use of alternative methods to assist with stalled labors, such as vaginally delivering the baby with forceps or vacuum, is no longer as common as it once was. So residents were taught these techniques less and less. But now Dr. Berghella and his colleagues at the college and the society are urging residency training programs to offer more training in these techniques, including with vacuum birth simulations. "It’s better to do it the first time on a simulator than to try it out on the patient and put the woman at risk. But [residents] need to learn how to do these things," he said.

Physicians also are urged in the statement to reconsider whether there is a failed induction, noting that if the maternal and fetal status allow, cesarean deliveries should be postponed up to 24 hours or longer, and that "oxytocin [should] be administered for at least 12-18 hours after membrane rupture before deeming induction a failure"

A commonly held misperception is that induction and C-section rates are positively correlated, according to the document. "That is a big, big change. The better data seem to say that if you get to 39 weeks, if you do an induction, it actually decreases the chance for a cesarean," said Dr. Berghella. "It was painted as a terrible thing, but if you do it at the right time, it is beneficial."

Into practice

Prenatal counseling should stress weight maintenance, because more than a third of women of reproductive age in the United States are obese, a factor that Dr. Berghella said contributes to the rise in C-sections. Infection risk is higher in this population, and the abundance of adipose tissues makes it harder for the baby to be delivered vaginally. "The higher your weight, the higher your chance of C-section," said Dr. Berghella.

In addition to tort reform, which the document states is "necessary" to prompt physicians to overcome their fears of being sued in case of an adverse event during vaginal delivery, Dr. Berghella said that the culture change rests on communication between office-based obstetricians, midwives, nurse practitioners, and their patients. "Doing a better job of educating women [prenatally] about labor in general, including that it can take a while, will prepare them and help avoid frustration and impatience because they will know what is going on," he said, noting that even a woman who has given birth before can have a completely different experience the next time.

Dr. Berghella said he had no relevant financial disclosures.

[email protected]

WASHINGTON – Longer labors lead to fewer cesarean sections.

That’s according to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine who have jointly issued the Obstetric Care Consensus guideline, urging physicians to allow women with low-risk pregnancies to remain in latent labor longer before elevating their delivery to surgical status. The report and the consensus guideline appear in the March issue of Obstetrics & Gynecology (Obstet. Gynecol. 2014;123:693-711).

"Evidence now shows that labor actually progresses slower than we thought in the past, so many women might just need a little more time to labor and deliver vaginally instead of moving to a cesarean delivery," Dr. Aaron B. Caughey, a member of ACOG’s Committee on Obstetric Practice, said in a statement.

The document calls on physicians to consider that active labor has begun at 6 cm of cervical dilation, rather than 4, and stresses that doctors should allow more time for progression of labor during the active phase. Whether a woman chooses to use an epidural should also be factored into laboring times because the analgesia can slow contractions.

Although no absolute specific time for allowing a woman to remain in the active labor phase has been determined, the document states that women who have never delivered should be given at least 3 hours to push, while women who have delivered previously should be given a minimum of 2 hours.

‘Fear and convenience’

The recommendations are specifically concerned with avoiding the primary cesarean section because more than one-third of all births in the United States are cesarean deliveries, two-thirds of which are among nulliparous women. Avoiding the first cesarean section is important, "because if the woman labors with a scar from a previous C-section, there is a risk that the uterus will rupture," SMFM president Dr. Vincenzo Berghella, director of maternal-fetal medicine at Thomas Jefferson Medical Center in Philadelphia, said in an interview. "It only happens one-half to one percent [of the time], but it can be catastrophic. The baby could even die. A lot of women, understandably, are afraid of [that]."

In addition, sometimes the procedure is medically indicated, as in the case of placenta previa or uterine rupture. However, according to the document, in most pregnancies, which are typically low risk, cesarean delivery carries with it greater overall severe morbidity and mortality risks for the mother compared with vaginal delivery: 9.2% vs. 8.6% and 2.7% vs. 0.9%, respectively.

A combination of fear of being sued for malpractice, convenience, and lack of manpower, are partially responsible for the astronomical rise in C-sections, now the most common surgical procedure performed in the United States, according to the Centers for Disease Control and Prevention.

Dr. Berghella said a scenario that plays out in a physician’s mind could run along the lines of, "You know what, maybe 99% of things are fine here, but I am just worried a little bit here. So I am just going to do a C-section just to cover my behind."

In the past, solo practitioners also were pressed in ways that today’s doctors who belong to an entire practice are not, said Dr. Berghella.

"There are many, many factors that can lead to a longer labor," Dr. Berghella said, adding it was his "hope" that the document will help doctors make decisions based on the patient and how she presents as an individual. "This is to empower doctors, and reassure everyone on the team, including that patient, that if everything is going well, there is no rush."

Redefining active labor and ‘failed’ induction

The use of alternative methods to assist with stalled labors, such as vaginally delivering the baby with forceps or vacuum, is no longer as common as it once was. So residents were taught these techniques less and less. But now Dr. Berghella and his colleagues at the college and the society are urging residency training programs to offer more training in these techniques, including with vacuum birth simulations. "It’s better to do it the first time on a simulator than to try it out on the patient and put the woman at risk. But [residents] need to learn how to do these things," he said.

Physicians also are urged in the statement to reconsider whether there is a failed induction, noting that if the maternal and fetal status allow, cesarean deliveries should be postponed up to 24 hours or longer, and that "oxytocin [should] be administered for at least 12-18 hours after membrane rupture before deeming induction a failure"

A commonly held misperception is that induction and C-section rates are positively correlated, according to the document. "That is a big, big change. The better data seem to say that if you get to 39 weeks, if you do an induction, it actually decreases the chance for a cesarean," said Dr. Berghella. "It was painted as a terrible thing, but if you do it at the right time, it is beneficial."

Into practice

Prenatal counseling should stress weight maintenance, because more than a third of women of reproductive age in the United States are obese, a factor that Dr. Berghella said contributes to the rise in C-sections. Infection risk is higher in this population, and the abundance of adipose tissues makes it harder for the baby to be delivered vaginally. "The higher your weight, the higher your chance of C-section," said Dr. Berghella.

In addition to tort reform, which the document states is "necessary" to prompt physicians to overcome their fears of being sued in case of an adverse event during vaginal delivery, Dr. Berghella said that the culture change rests on communication between office-based obstetricians, midwives, nurse practitioners, and their patients. "Doing a better job of educating women [prenatally] about labor in general, including that it can take a while, will prepare them and help avoid frustration and impatience because they will know what is going on," he said, noting that even a woman who has given birth before can have a completely different experience the next time.

Dr. Berghella said he had no relevant financial disclosures.

[email protected]

WASHINGTON – Longer labors lead to fewer cesarean sections.

That’s according to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine who have jointly issued the Obstetric Care Consensus guideline, urging physicians to allow women with low-risk pregnancies to remain in latent labor longer before elevating their delivery to surgical status. The report and the consensus guideline appear in the March issue of Obstetrics & Gynecology (Obstet. Gynecol. 2014;123:693-711).

"Evidence now shows that labor actually progresses slower than we thought in the past, so many women might just need a little more time to labor and deliver vaginally instead of moving to a cesarean delivery," Dr. Aaron B. Caughey, a member of ACOG’s Committee on Obstetric Practice, said in a statement.

The document calls on physicians to consider that active labor has begun at 6 cm of cervical dilation, rather than 4, and stresses that doctors should allow more time for progression of labor during the active phase. Whether a woman chooses to use an epidural should also be factored into laboring times because the analgesia can slow contractions.

Although no absolute specific time for allowing a woman to remain in the active labor phase has been determined, the document states that women who have never delivered should be given at least 3 hours to push, while women who have delivered previously should be given a minimum of 2 hours.

‘Fear and convenience’

The recommendations are specifically concerned with avoiding the primary cesarean section because more than one-third of all births in the United States are cesarean deliveries, two-thirds of which are among nulliparous women. Avoiding the first cesarean section is important, "because if the woman labors with a scar from a previous C-section, there is a risk that the uterus will rupture," SMFM president Dr. Vincenzo Berghella, director of maternal-fetal medicine at Thomas Jefferson Medical Center in Philadelphia, said in an interview. "It only happens one-half to one percent [of the time], but it can be catastrophic. The baby could even die. A lot of women, understandably, are afraid of [that]."

In addition, sometimes the procedure is medically indicated, as in the case of placenta previa or uterine rupture. However, according to the document, in most pregnancies, which are typically low risk, cesarean delivery carries with it greater overall severe morbidity and mortality risks for the mother compared with vaginal delivery: 9.2% vs. 8.6% and 2.7% vs. 0.9%, respectively.

A combination of fear of being sued for malpractice, convenience, and lack of manpower, are partially responsible for the astronomical rise in C-sections, now the most common surgical procedure performed in the United States, according to the Centers for Disease Control and Prevention.

Dr. Berghella said a scenario that plays out in a physician’s mind could run along the lines of, "You know what, maybe 99% of things are fine here, but I am just worried a little bit here. So I am just going to do a C-section just to cover my behind."

In the past, solo practitioners also were pressed in ways that today’s doctors who belong to an entire practice are not, said Dr. Berghella.

"There are many, many factors that can lead to a longer labor," Dr. Berghella said, adding it was his "hope" that the document will help doctors make decisions based on the patient and how she presents as an individual. "This is to empower doctors, and reassure everyone on the team, including that patient, that if everything is going well, there is no rush."

Redefining active labor and ‘failed’ induction

The use of alternative methods to assist with stalled labors, such as vaginally delivering the baby with forceps or vacuum, is no longer as common as it once was. So residents were taught these techniques less and less. But now Dr. Berghella and his colleagues at the college and the society are urging residency training programs to offer more training in these techniques, including with vacuum birth simulations. "It’s better to do it the first time on a simulator than to try it out on the patient and put the woman at risk. But [residents] need to learn how to do these things," he said.

Physicians also are urged in the statement to reconsider whether there is a failed induction, noting that if the maternal and fetal status allow, cesarean deliveries should be postponed up to 24 hours or longer, and that "oxytocin [should] be administered for at least 12-18 hours after membrane rupture before deeming induction a failure"

A commonly held misperception is that induction and C-section rates are positively correlated, according to the document. "That is a big, big change. The better data seem to say that if you get to 39 weeks, if you do an induction, it actually decreases the chance for a cesarean," said Dr. Berghella. "It was painted as a terrible thing, but if you do it at the right time, it is beneficial."

Into practice

Prenatal counseling should stress weight maintenance, because more than a third of women of reproductive age in the United States are obese, a factor that Dr. Berghella said contributes to the rise in C-sections. Infection risk is higher in this population, and the abundance of adipose tissues makes it harder for the baby to be delivered vaginally. "The higher your weight, the higher your chance of C-section," said Dr. Berghella.

In addition to tort reform, which the document states is "necessary" to prompt physicians to overcome their fears of being sued in case of an adverse event during vaginal delivery, Dr. Berghella said that the culture change rests on communication between office-based obstetricians, midwives, nurse practitioners, and their patients. "Doing a better job of educating women [prenatally] about labor in general, including that it can take a while, will prepare them and help avoid frustration and impatience because they will know what is going on," he said, noting that even a woman who has given birth before can have a completely different experience the next time.

Dr. Berghella said he had no relevant financial disclosures.

[email protected]