Susan London

SAN FRANCISCO – Women found to be infected with high-risk types of human papillomavirus early in pregnancy are more than twice as likely to develop preeclampsia, according to a retrospective cohort study reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"This study supports an association between high-risk human papillomavirus and preeclampsia, which is consistent with the association that was previously seen between high-risk HPV and cardiovascular disease," lead investigator Dr. Mollie McDonnold commented.

"If this is confirmed in future prospective studies or larger cohorts, it may suggest a potential role for HPV vaccination in preeclampsia prevention," she added.

Using study data and data on the population prevalence of high-risk HPV infection, the investigators estimated that if all women received the quadrivalent vaccine (which prevents about two-thirds of such infections), the rate of preeclampsia would fall from 5,189 to 5,020 cases per 100,000 women.

"When you are doing a preeclampsia study like this, the clinical diagnosis in multiparas has a high degree of uncertainty. So did you look separately at your nulliparas?" one attendee asked.

"In order to achieve numbers, we did include nulliparous and multiparous women in our study. We haven’t looked specifically at this, but in our regression model, we did control for nulliparity. We could certainly, hopefully with more numbers, look exclusively at nulliparas," replied Dr. McDonnold, who is an obstetrician-gynecologist at the University of Texas Medical Branch in Galveston.

Another attendee noted that Pap test results were often used as a surrogate for HPV status. "Could you separate out the effect of HPV status from the effect of Pap status – the difference between the groups could not only be HPV driven but also Pap driven?" he wondered.

Women did not necessarily have HPV testing unless it was clinically indicated, Dr. McDonnold acknowledged. And some classified as noninfected may have had HPV infection. "The reason why we asked to have two normal Pap smears was to increase the sensitivity and specificity of the Pap smear of being negative for HPV. But certainly you could say that this was Pap smear data only."

Giving some study background, she noted that high-risk HPV has been previously implicated in both adverse pregnancy outcomes and adverse cardiovascular outcomes.

"This association between HPV and cardiovascular disease is relevant in pregnancy, as preeclampsia and cardiovascular disease share a similar pathophysiology," including endothelial dysfunction and inflammation, as well as vascular risk factors such as obesity, hypertension, diabetes, and dyslipidemia, Dr. McDonnold elaborated.

High-risk HPV transfects trophoblasts, causing changes that interfere with normal placentation, and also disables tumor suppressor proteins, accelerating unfavorable vascular changes typically seen in atherosclerosis.

"So we believe there is a biologic plausibility to support a role of high-risk HPV and preeclampsia," Dr. McDonnold said.

For the study, the investigators classified women as having high-risk HPV if they had atypical squamous cells of undetermined significance (ASCUS) plus detection of a high-risk type on reflex DNA testing, or if they had a cervical pathology known to be associated with this infection. A total of 314 pregnant women were classified as having high-risk HPV.

The investigators matched each infected woman by delivery date with two noninfected women who had negative Pap test results both before and during the pregnancy.

The groups were similar with respect to obstetric risk factors such as chronic hypertension and twin gestations, according to Dr. McDonnold.

Women infected with high-risk HPV had a higher rate of preeclampsia than their noninfected counterparts did (10.2% vs. 4.9%, P = .004). They also tended to have a higher rate of severe preeclampsia (5.1% vs. 2.7%, P = .09).

After adjustment for age, nulliparity, blood pressure at entry to care, and smoking, the difference corresponded to a more than doubling of the odds of preeclampsia for the high-risk HPV group (odds ratio, 2.29), according to data reported at the meeting.

The women with high-risk HPV also were significantly more likely to have a spontaneous preterm birth before 37 weeks (OR 1.83), any preterm birth before 35 weeks (2.58), and spontaneous preterm birth before 35 weeks (6.85).

However, the two groups were statistically indistinguishable with respect to the outcomes of gestational hypertension, gestational diabetes, intrauterine growth restriction, and cesarean delivery.

Dr. McDonnold disclosed no relevant conflicts of interest.

SAN FRANCISCO – Women found to be infected with high-risk types of human papillomavirus early in pregnancy are more than twice as likely to develop preeclampsia, according to a retrospective cohort study reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"This study supports an association between high-risk human papillomavirus and preeclampsia, which is consistent with the association that was previously seen between high-risk HPV and cardiovascular disease," lead investigator Dr. Mollie McDonnold commented.

"If this is confirmed in future prospective studies or larger cohorts, it may suggest a potential role for HPV vaccination in preeclampsia prevention," she added.

Using study data and data on the population prevalence of high-risk HPV infection, the investigators estimated that if all women received the quadrivalent vaccine (which prevents about two-thirds of such infections), the rate of preeclampsia would fall from 5,189 to 5,020 cases per 100,000 women.

"When you are doing a preeclampsia study like this, the clinical diagnosis in multiparas has a high degree of uncertainty. So did you look separately at your nulliparas?" one attendee asked.

"In order to achieve numbers, we did include nulliparous and multiparous women in our study. We haven’t looked specifically at this, but in our regression model, we did control for nulliparity. We could certainly, hopefully with more numbers, look exclusively at nulliparas," replied Dr. McDonnold, who is an obstetrician-gynecologist at the University of Texas Medical Branch in Galveston.

Another attendee noted that Pap test results were often used as a surrogate for HPV status. "Could you separate out the effect of HPV status from the effect of Pap status – the difference between the groups could not only be HPV driven but also Pap driven?" he wondered.

Women did not necessarily have HPV testing unless it was clinically indicated, Dr. McDonnold acknowledged. And some classified as noninfected may have had HPV infection. "The reason why we asked to have two normal Pap smears was to increase the sensitivity and specificity of the Pap smear of being negative for HPV. But certainly you could say that this was Pap smear data only."

Giving some study background, she noted that high-risk HPV has been previously implicated in both adverse pregnancy outcomes and adverse cardiovascular outcomes.

"This association between HPV and cardiovascular disease is relevant in pregnancy, as preeclampsia and cardiovascular disease share a similar pathophysiology," including endothelial dysfunction and inflammation, as well as vascular risk factors such as obesity, hypertension, diabetes, and dyslipidemia, Dr. McDonnold elaborated.

High-risk HPV transfects trophoblasts, causing changes that interfere with normal placentation, and also disables tumor suppressor proteins, accelerating unfavorable vascular changes typically seen in atherosclerosis.

"So we believe there is a biologic plausibility to support a role of high-risk HPV and preeclampsia," Dr. McDonnold said.

For the study, the investigators classified women as having high-risk HPV if they had atypical squamous cells of undetermined significance (ASCUS) plus detection of a high-risk type on reflex DNA testing, or if they had a cervical pathology known to be associated with this infection. A total of 314 pregnant women were classified as having high-risk HPV.

The investigators matched each infected woman by delivery date with two noninfected women who had negative Pap test results both before and during the pregnancy.

The groups were similar with respect to obstetric risk factors such as chronic hypertension and twin gestations, according to Dr. McDonnold.

Women infected with high-risk HPV had a higher rate of preeclampsia than their noninfected counterparts did (10.2% vs. 4.9%, P = .004). They also tended to have a higher rate of severe preeclampsia (5.1% vs. 2.7%, P = .09).

After adjustment for age, nulliparity, blood pressure at entry to care, and smoking, the difference corresponded to a more than doubling of the odds of preeclampsia for the high-risk HPV group (odds ratio, 2.29), according to data reported at the meeting.

The women with high-risk HPV also were significantly more likely to have a spontaneous preterm birth before 37 weeks (OR 1.83), any preterm birth before 35 weeks (2.58), and spontaneous preterm birth before 35 weeks (6.85).

However, the two groups were statistically indistinguishable with respect to the outcomes of gestational hypertension, gestational diabetes, intrauterine growth restriction, and cesarean delivery.

Dr. McDonnold disclosed no relevant conflicts of interest.

SAN FRANCISCO – Women found to be infected with high-risk types of human papillomavirus early in pregnancy are more than twice as likely to develop preeclampsia, according to a retrospective cohort study reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"This study supports an association between high-risk human papillomavirus and preeclampsia, which is consistent with the association that was previously seen between high-risk HPV and cardiovascular disease," lead investigator Dr. Mollie McDonnold commented.

"If this is confirmed in future prospective studies or larger cohorts, it may suggest a potential role for HPV vaccination in preeclampsia prevention," she added.

Using study data and data on the population prevalence of high-risk HPV infection, the investigators estimated that if all women received the quadrivalent vaccine (which prevents about two-thirds of such infections), the rate of preeclampsia would fall from 5,189 to 5,020 cases per 100,000 women.

"When you are doing a preeclampsia study like this, the clinical diagnosis in multiparas has a high degree of uncertainty. So did you look separately at your nulliparas?" one attendee asked.

"In order to achieve numbers, we did include nulliparous and multiparous women in our study. We haven’t looked specifically at this, but in our regression model, we did control for nulliparity. We could certainly, hopefully with more numbers, look exclusively at nulliparas," replied Dr. McDonnold, who is an obstetrician-gynecologist at the University of Texas Medical Branch in Galveston.

Another attendee noted that Pap test results were often used as a surrogate for HPV status. "Could you separate out the effect of HPV status from the effect of Pap status – the difference between the groups could not only be HPV driven but also Pap driven?" he wondered.

Women did not necessarily have HPV testing unless it was clinically indicated, Dr. McDonnold acknowledged. And some classified as noninfected may have had HPV infection. "The reason why we asked to have two normal Pap smears was to increase the sensitivity and specificity of the Pap smear of being negative for HPV. But certainly you could say that this was Pap smear data only."

Giving some study background, she noted that high-risk HPV has been previously implicated in both adverse pregnancy outcomes and adverse cardiovascular outcomes.

"This association between HPV and cardiovascular disease is relevant in pregnancy, as preeclampsia and cardiovascular disease share a similar pathophysiology," including endothelial dysfunction and inflammation, as well as vascular risk factors such as obesity, hypertension, diabetes, and dyslipidemia, Dr. McDonnold elaborated.

High-risk HPV transfects trophoblasts, causing changes that interfere with normal placentation, and also disables tumor suppressor proteins, accelerating unfavorable vascular changes typically seen in atherosclerosis.

"So we believe there is a biologic plausibility to support a role of high-risk HPV and preeclampsia," Dr. McDonnold said.

For the study, the investigators classified women as having high-risk HPV if they had atypical squamous cells of undetermined significance (ASCUS) plus detection of a high-risk type on reflex DNA testing, or if they had a cervical pathology known to be associated with this infection. A total of 314 pregnant women were classified as having high-risk HPV.

The investigators matched each infected woman by delivery date with two noninfected women who had negative Pap test results both before and during the pregnancy.

The groups were similar with respect to obstetric risk factors such as chronic hypertension and twin gestations, according to Dr. McDonnold.

Women infected with high-risk HPV had a higher rate of preeclampsia than their noninfected counterparts did (10.2% vs. 4.9%, P = .004). They also tended to have a higher rate of severe preeclampsia (5.1% vs. 2.7%, P = .09).

After adjustment for age, nulliparity, blood pressure at entry to care, and smoking, the difference corresponded to a more than doubling of the odds of preeclampsia for the high-risk HPV group (odds ratio, 2.29), according to data reported at the meeting.

The women with high-risk HPV also were significantly more likely to have a spontaneous preterm birth before 37 weeks (OR 1.83), any preterm birth before 35 weeks (2.58), and spontaneous preterm birth before 35 weeks (6.85).

However, the two groups were statistically indistinguishable with respect to the outcomes of gestational hypertension, gestational diabetes, intrauterine growth restriction, and cesarean delivery.

Dr. McDonnold disclosed no relevant conflicts of interest.

SAN FRANCISCO – A new vaginal prostaglandin product speeds the time to delivery in women needing labor induction and does not appear to compromise safety, according to a phase III trial reported at the Pregnancy Meeting, the annual meeting of the Society of Maternal-Fetal Medicine.

The randomized trial, known as EXPEDITE, enrolled 1,358 women, all of whom had uncomplicated term or near-term pregnancies and needed cervical ripening and labor induction.

The main results showed that the time between study drug insertion and vaginal delivery (the trial’s primary outcome) was 21.5 hours with an investigational misoprostol vaginal insert delivering 200 mcg of the drug (MVI 200), compared with 32.8 hours with the commercially available dinoprostone vaginal insert (DVI), lead investigator Dr. Deborah A. Wing reported.

In terms of safety, about a quarter of women had a cesarean delivery, with no significant difference between groups, although the trial unexpectedly lacked sufficient power to assess this difference. The rate of intrapartum adverse events thought to be related to the study drug was higher with MVI 200.

"Use of MVI 200 reduced the time to vaginal delivery by more than 11 hours compared with DVI," she commented. "Both treatments had similar cesarean delivery rates. Abnormal labor affecting the fetus and fetal heart rate disorder considered related to the study drug were more common with MVI 200."

An attendee asked, "Why do you think that while the labor was shortened, there wasn’t a reduction in the risk of cesarean delivery?"

"I think it’s because we have developed an agent or a device with an agent that is very good at getting the process of human parturition to be turned on. There are still myriad factors that we do not understand about what makes human parturition be successful if one agrees that success is defined as vaginal delivery," replied Dr. Wing, who is a maternal-fetal medicine specialist at the University of California, Irvine.

Another attendee disagreed with the choice of the trial’s primary outcome, saying, "You chose time as a primary outcome over patient safety – that outcome is a secondary one – and I’m afraid that your study is really underpowered to rule out a difference in neonatal outcomes. So why didn’t you use neonatal and maternal outcomes as the primary ones to be sure that we are not harming the kids by these fast deliveries, because I think that’s what’s happening – we are pushing them out early and some of them are eventually harmed by that."

"There is no doubt in my mind and no doubt in the sponsor’s mind that safety – both maternal and neonatal – is number one. You are correct, these trials I don’t think can be conducted in any way, shape, or form in today’s world of sufficient magnitude to be able to address the issues of maternal or neonatal safety," Dr. Wing said.

She noted, for example, that a recent analysis included in a Cochrane review on the use of oral misoprostol for labor induction suggested that adequately assessing the outcome of maternal death would require 160,000 women per treatment arm. "Clearly, there are other things that happen more commonly, but the magnitude of those trials is still on the order of tens of thousands of women. ... So, yes, safety is a primary concern. Efficacy has also been a concern, and part of the focus has been guided by the U.S. Food and Drug Administration and their many years of working with [the manufacturer] to get us where we are."

A third attendee said, "My understanding is that the MVI is a 24-hour drug and that the DVI is a 12-hour drug, and in this blinded trial, they have each received the drug for 24 hours. So technically, if I’m thinking correctly, the DVI group went 12 hours with no treatment and delivered 11 hours later. How can you address that with the time difference?"

"Yes, the package insert for the Cervidil [the brand name of the DVI] says 12 hours, but the protocol was designed for 24 hours of exposure to the DVI, with the blessing of the U.S. Food and Drug Administration, so that all women in both groups had the opportunity to be exposed to the drug for up to a day," Dr. Wing said.

Women participating in the trial were from multiple institutions in North America and had a gestation of at least 36 weeks, a modified Bishop score of 4 or less, and a parity of 3 or less. Two-thirds were nulliparous.

They were randomized evenly to receive MVI 200 or the DVI (Cervidil, which delivers 10 mg of the drug). The inserts were placed transversely, high in the posterior vaginal fornix, and left in place until the onset of active labor, other events requiring removal, or 24 hours.

The main indications for labor induction were prolonged pregnancy, hypertensive complications, and oligohydramnios, Dr. Wing.

In analyses with censoring for cesarean delivery and for nondelivery, women in the MVI 200 group had a median time to vaginal delivery that was 11.3 hours shorter than for the DVI group (P less than .001). The difference was 6.5 hours in parous women and 14.0 hours in nulliparous women.

The MVI 200 group also had a shorter median time to any delivery (18.3 vs. 27.3 hours) and a shorter median time to active labor (12.1 vs. 18.6 hours), and this group was less likely to be given oxytocin before delivery (48% vs. 74%; P less than .001 for all three outcomes).

The rate of cesarean delivery was 26% in the MVI 200 group and 27% in the DVI group, a nonsignificant difference; however, the latter value fell short of the anticipated 30% needed for adequate power. "The indications for c-section were similar between the groups," Dr. Wing noted.

The MVI 200 group had a higher incidence of intrapartum drug-related adverse events (13% vs. 4%) – mainly driven by fetal heart rate disorder and abnormal labor affecting the fetus (arrest of dilatation or descent).

Rates of maternal postpartum drug-related adverse events were identical; rates of neonatal drug-related adverse events were low generally but higher with MVI 200 (0.7% vs. 0.1%).

Dr. Wing disclosed that she is a principal investigator for and consultant to Ferring Pharmaceuticals. The trial was supported by Ferring.

SAN FRANCISCO – A new vaginal prostaglandin product speeds the time to delivery in women needing labor induction and does not appear to compromise safety, according to a phase III trial reported at the Pregnancy Meeting, the annual meeting of the Society of Maternal-Fetal Medicine.

The randomized trial, known as EXPEDITE, enrolled 1,358 women, all of whom had uncomplicated term or near-term pregnancies and needed cervical ripening and labor induction.

The main results showed that the time between study drug insertion and vaginal delivery (the trial’s primary outcome) was 21.5 hours with an investigational misoprostol vaginal insert delivering 200 mcg of the drug (MVI 200), compared with 32.8 hours with the commercially available dinoprostone vaginal insert (DVI), lead investigator Dr. Deborah A. Wing reported.

In terms of safety, about a quarter of women had a cesarean delivery, with no significant difference between groups, although the trial unexpectedly lacked sufficient power to assess this difference. The rate of intrapartum adverse events thought to be related to the study drug was higher with MVI 200.

"Use of MVI 200 reduced the time to vaginal delivery by more than 11 hours compared with DVI," she commented. "Both treatments had similar cesarean delivery rates. Abnormal labor affecting the fetus and fetal heart rate disorder considered related to the study drug were more common with MVI 200."

An attendee asked, "Why do you think that while the labor was shortened, there wasn’t a reduction in the risk of cesarean delivery?"

"I think it’s because we have developed an agent or a device with an agent that is very good at getting the process of human parturition to be turned on. There are still myriad factors that we do not understand about what makes human parturition be successful if one agrees that success is defined as vaginal delivery," replied Dr. Wing, who is a maternal-fetal medicine specialist at the University of California, Irvine.

Another attendee disagreed with the choice of the trial’s primary outcome, saying, "You chose time as a primary outcome over patient safety – that outcome is a secondary one – and I’m afraid that your study is really underpowered to rule out a difference in neonatal outcomes. So why didn’t you use neonatal and maternal outcomes as the primary ones to be sure that we are not harming the kids by these fast deliveries, because I think that’s what’s happening – we are pushing them out early and some of them are eventually harmed by that."

"There is no doubt in my mind and no doubt in the sponsor’s mind that safety – both maternal and neonatal – is number one. You are correct, these trials I don’t think can be conducted in any way, shape, or form in today’s world of sufficient magnitude to be able to address the issues of maternal or neonatal safety," Dr. Wing said.

She noted, for example, that a recent analysis included in a Cochrane review on the use of oral misoprostol for labor induction suggested that adequately assessing the outcome of maternal death would require 160,000 women per treatment arm. "Clearly, there are other things that happen more commonly, but the magnitude of those trials is still on the order of tens of thousands of women. ... So, yes, safety is a primary concern. Efficacy has also been a concern, and part of the focus has been guided by the U.S. Food and Drug Administration and their many years of working with [the manufacturer] to get us where we are."

A third attendee said, "My understanding is that the MVI is a 24-hour drug and that the DVI is a 12-hour drug, and in this blinded trial, they have each received the drug for 24 hours. So technically, if I’m thinking correctly, the DVI group went 12 hours with no treatment and delivered 11 hours later. How can you address that with the time difference?"

"Yes, the package insert for the Cervidil [the brand name of the DVI] says 12 hours, but the protocol was designed for 24 hours of exposure to the DVI, with the blessing of the U.S. Food and Drug Administration, so that all women in both groups had the opportunity to be exposed to the drug for up to a day," Dr. Wing said.

Women participating in the trial were from multiple institutions in North America and had a gestation of at least 36 weeks, a modified Bishop score of 4 or less, and a parity of 3 or less. Two-thirds were nulliparous.

They were randomized evenly to receive MVI 200 or the DVI (Cervidil, which delivers 10 mg of the drug). The inserts were placed transversely, high in the posterior vaginal fornix, and left in place until the onset of active labor, other events requiring removal, or 24 hours.

The main indications for labor induction were prolonged pregnancy, hypertensive complications, and oligohydramnios, Dr. Wing.

In analyses with censoring for cesarean delivery and for nondelivery, women in the MVI 200 group had a median time to vaginal delivery that was 11.3 hours shorter than for the DVI group (P less than .001). The difference was 6.5 hours in parous women and 14.0 hours in nulliparous women.

The MVI 200 group also had a shorter median time to any delivery (18.3 vs. 27.3 hours) and a shorter median time to active labor (12.1 vs. 18.6 hours), and this group was less likely to be given oxytocin before delivery (48% vs. 74%; P less than .001 for all three outcomes).

The rate of cesarean delivery was 26% in the MVI 200 group and 27% in the DVI group, a nonsignificant difference; however, the latter value fell short of the anticipated 30% needed for adequate power. "The indications for c-section were similar between the groups," Dr. Wing noted.

The MVI 200 group had a higher incidence of intrapartum drug-related adverse events (13% vs. 4%) – mainly driven by fetal heart rate disorder and abnormal labor affecting the fetus (arrest of dilatation or descent).

Rates of maternal postpartum drug-related adverse events were identical; rates of neonatal drug-related adverse events were low generally but higher with MVI 200 (0.7% vs. 0.1%).

Dr. Wing disclosed that she is a principal investigator for and consultant to Ferring Pharmaceuticals. The trial was supported by Ferring.

SAN FRANCISCO – A new vaginal prostaglandin product speeds the time to delivery in women needing labor induction and does not appear to compromise safety, according to a phase III trial reported at the Pregnancy Meeting, the annual meeting of the Society of Maternal-Fetal Medicine.

The randomized trial, known as EXPEDITE, enrolled 1,358 women, all of whom had uncomplicated term or near-term pregnancies and needed cervical ripening and labor induction.

The main results showed that the time between study drug insertion and vaginal delivery (the trial’s primary outcome) was 21.5 hours with an investigational misoprostol vaginal insert delivering 200 mcg of the drug (MVI 200), compared with 32.8 hours with the commercially available dinoprostone vaginal insert (DVI), lead investigator Dr. Deborah A. Wing reported.

In terms of safety, about a quarter of women had a cesarean delivery, with no significant difference between groups, although the trial unexpectedly lacked sufficient power to assess this difference. The rate of intrapartum adverse events thought to be related to the study drug was higher with MVI 200.

"Use of MVI 200 reduced the time to vaginal delivery by more than 11 hours compared with DVI," she commented. "Both treatments had similar cesarean delivery rates. Abnormal labor affecting the fetus and fetal heart rate disorder considered related to the study drug were more common with MVI 200."

An attendee asked, "Why do you think that while the labor was shortened, there wasn’t a reduction in the risk of cesarean delivery?"

"I think it’s because we have developed an agent or a device with an agent that is very good at getting the process of human parturition to be turned on. There are still myriad factors that we do not understand about what makes human parturition be successful if one agrees that success is defined as vaginal delivery," replied Dr. Wing, who is a maternal-fetal medicine specialist at the University of California, Irvine.

Another attendee disagreed with the choice of the trial’s primary outcome, saying, "You chose time as a primary outcome over patient safety – that outcome is a secondary one – and I’m afraid that your study is really underpowered to rule out a difference in neonatal outcomes. So why didn’t you use neonatal and maternal outcomes as the primary ones to be sure that we are not harming the kids by these fast deliveries, because I think that’s what’s happening – we are pushing them out early and some of them are eventually harmed by that."

"There is no doubt in my mind and no doubt in the sponsor’s mind that safety – both maternal and neonatal – is number one. You are correct, these trials I don’t think can be conducted in any way, shape, or form in today’s world of sufficient magnitude to be able to address the issues of maternal or neonatal safety," Dr. Wing said.

She noted, for example, that a recent analysis included in a Cochrane review on the use of oral misoprostol for labor induction suggested that adequately assessing the outcome of maternal death would require 160,000 women per treatment arm. "Clearly, there are other things that happen more commonly, but the magnitude of those trials is still on the order of tens of thousands of women. ... So, yes, safety is a primary concern. Efficacy has also been a concern, and part of the focus has been guided by the U.S. Food and Drug Administration and their many years of working with [the manufacturer] to get us where we are."

A third attendee said, "My understanding is that the MVI is a 24-hour drug and that the DVI is a 12-hour drug, and in this blinded trial, they have each received the drug for 24 hours. So technically, if I’m thinking correctly, the DVI group went 12 hours with no treatment and delivered 11 hours later. How can you address that with the time difference?"

"Yes, the package insert for the Cervidil [the brand name of the DVI] says 12 hours, but the protocol was designed for 24 hours of exposure to the DVI, with the blessing of the U.S. Food and Drug Administration, so that all women in both groups had the opportunity to be exposed to the drug for up to a day," Dr. Wing said.

Women participating in the trial were from multiple institutions in North America and had a gestation of at least 36 weeks, a modified Bishop score of 4 or less, and a parity of 3 or less. Two-thirds were nulliparous.

They were randomized evenly to receive MVI 200 or the DVI (Cervidil, which delivers 10 mg of the drug). The inserts were placed transversely, high in the posterior vaginal fornix, and left in place until the onset of active labor, other events requiring removal, or 24 hours.

The main indications for labor induction were prolonged pregnancy, hypertensive complications, and oligohydramnios, Dr. Wing.

In analyses with censoring for cesarean delivery and for nondelivery, women in the MVI 200 group had a median time to vaginal delivery that was 11.3 hours shorter than for the DVI group (P less than .001). The difference was 6.5 hours in parous women and 14.0 hours in nulliparous women.

The MVI 200 group also had a shorter median time to any delivery (18.3 vs. 27.3 hours) and a shorter median time to active labor (12.1 vs. 18.6 hours), and this group was less likely to be given oxytocin before delivery (48% vs. 74%; P less than .001 for all three outcomes).

The rate of cesarean delivery was 26% in the MVI 200 group and 27% in the DVI group, a nonsignificant difference; however, the latter value fell short of the anticipated 30% needed for adequate power. "The indications for c-section were similar between the groups," Dr. Wing noted.

The MVI 200 group had a higher incidence of intrapartum drug-related adverse events (13% vs. 4%) – mainly driven by fetal heart rate disorder and abnormal labor affecting the fetus (arrest of dilatation or descent).

Rates of maternal postpartum drug-related adverse events were identical; rates of neonatal drug-related adverse events were low generally but higher with MVI 200 (0.7% vs. 0.1%).

Dr. Wing disclosed that she is a principal investigator for and consultant to Ferring Pharmaceuticals. The trial was supported by Ferring.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Guideline-adherent treatment can make the difference between life and death in patients with ovarian cancer, and it often hinges on where and from whom patients receive care, new data suggest.

In a retrospective, population-based study of more than 13,000 patients with epithelial ovarian cancer, only about 40% of patients received treatment adhering to that recommended by the National Comprehensive Cancer Network (NCCN).

Patients were more likely to receive guideline-adherent treatment if they went to high-volume hospitals (those treating at least 20 such patients each year) and high-volume physicians (those treating at least 10 such patients each year), according to results reported at the annual meeting of the Society of Gynecologic Oncology*. Still, in absolute terms, only about half of patients treated in high-volume hospitals or by high-volume surgeons received adherent treatment.

Compared with their counterparts who received guideline-adherent treatment, patients who received nonadherent treatment had a 33% higher risk of dying from their disease in the subsequent 5 years.

"NCCN guideline adherence predicts improved survival," lead investigator Dr. Robert E. Bristow commented in an interview. "A minority of patients is getting access to guideline care, and increased efforts to direct ovarian cancer patients to high-volume providers are warranted."

From a population-based perspective, much greater gains in survival can be achieved by centralizing ovarian cancer care to gynecologic oncologists and high-volume hospitals than through new chemotherapy drugs or experimental treatments, according to Dr. Bristow, who is director of the division of gynecologic oncology at the University of California, Irvine, medical center. The success of this model "has been demonstrated in Norway, where nonaccredited providers are not paid for any ovarian cancer care they deliver."

That said, the data cannot be used to discern the reasons for the overall poor rate of guideline adherence.

"In population-based data sets, you don’t have the granularity of data to tease out the nuances that might contribute to risk, like an infirm 85-year-old woman who can’t tolerate major surgery and aggressive surgery. We were not able to control for that," Dr. Bristow noted. Yet "only about 20% of patients had access to high-volume providers, and since high-volume providers are more likely to deliver appropriate care, the lack of access to these physicians and hospitals is probably the biggest reason (for nonadherence). By ensuring that we do everything possible to get ovarian cancer patients to the physicians and centers that are best equipped to take care of them, we will maximize each patient’s chance for the best possible outcome."

Analyses were based on 13,321 patients with epithelial ovarian cancer having data in the California Cancer Registry for the years 1999 through 2006. They had a median age of 61 years; 70% had stage III or IV disease, and 42% had serous tumor histology.

Among patients having data on these measures, 81% were treated at low-volume hospitals and 79% by low-volume surgeons. In multivariate analyses, patients were significantly more likely to receive nonadherent treatment if they were treated in low-volume hospitals (odds ratio, 1.83) or by low-volume physicians (OR, 1.19).

Overall, 37% of the patients received treatment recommended by NCCN guidelines. The 5-year disease-specific survival rate was 45% for the cohort overall. In multivariate analyses, patients had significantly higher odds of ovarian cancer death if they received nonadherent treatment (hazard ratio, 1.33), and if they were treated at a low-volume hospital (HR, 1.08) or by a low-volume physician (HR, 1.18).

"We are in the infancy of defining quality care for ovarian cancer," concluded Dr. Bristow. "We need to develop risk-adjusted models for comparison, to make sure we are comparing apples to apples, so to speak. We need to become more sophisticated in our measurement and reporting. Ideally, one day, everyone’s quality performance measures will be publicly available and patients and payers can choose for themselves where to go for care."

The investigators plan future research on such models and on universal reporting requirements. "There are also critical issues of racial and socioeconomic disparities in ovarian cancer care and outcomes that we are investigating," he said.

Dr. Bristow disclosed no relevant conflicts of interest.

Correction, 3/28/2013: An earlier version of this story misstated the name of the Society of Gynecologic Oncology.

LOS ANGELES – Guideline-adherent treatment can make the difference between life and death in patients with ovarian cancer, and it often hinges on where and from whom patients receive care, new data suggest.

In a retrospective, population-based study of more than 13,000 patients with epithelial ovarian cancer, only about 40% of patients received treatment adhering to that recommended by the National Comprehensive Cancer Network (NCCN).

Patients were more likely to receive guideline-adherent treatment if they went to high-volume hospitals (those treating at least 20 such patients each year) and high-volume physicians (those treating at least 10 such patients each year), according to results reported at the annual meeting of the Society of Gynecologic Oncology*. Still, in absolute terms, only about half of patients treated in high-volume hospitals or by high-volume surgeons received adherent treatment.

Compared with their counterparts who received guideline-adherent treatment, patients who received nonadherent treatment had a 33% higher risk of dying from their disease in the subsequent 5 years.

"NCCN guideline adherence predicts improved survival," lead investigator Dr. Robert E. Bristow commented in an interview. "A minority of patients is getting access to guideline care, and increased efforts to direct ovarian cancer patients to high-volume providers are warranted."

From a population-based perspective, much greater gains in survival can be achieved by centralizing ovarian cancer care to gynecologic oncologists and high-volume hospitals than through new chemotherapy drugs or experimental treatments, according to Dr. Bristow, who is director of the division of gynecologic oncology at the University of California, Irvine, medical center. The success of this model "has been demonstrated in Norway, where nonaccredited providers are not paid for any ovarian cancer care they deliver."

That said, the data cannot be used to discern the reasons for the overall poor rate of guideline adherence.

"In population-based data sets, you don’t have the granularity of data to tease out the nuances that might contribute to risk, like an infirm 85-year-old woman who can’t tolerate major surgery and aggressive surgery. We were not able to control for that," Dr. Bristow noted. Yet "only about 20% of patients had access to high-volume providers, and since high-volume providers are more likely to deliver appropriate care, the lack of access to these physicians and hospitals is probably the biggest reason (for nonadherence). By ensuring that we do everything possible to get ovarian cancer patients to the physicians and centers that are best equipped to take care of them, we will maximize each patient’s chance for the best possible outcome."

Analyses were based on 13,321 patients with epithelial ovarian cancer having data in the California Cancer Registry for the years 1999 through 2006. They had a median age of 61 years; 70% had stage III or IV disease, and 42% had serous tumor histology.

Among patients having data on these measures, 81% were treated at low-volume hospitals and 79% by low-volume surgeons. In multivariate analyses, patients were significantly more likely to receive nonadherent treatment if they were treated in low-volume hospitals (odds ratio, 1.83) or by low-volume physicians (OR, 1.19).

Overall, 37% of the patients received treatment recommended by NCCN guidelines. The 5-year disease-specific survival rate was 45% for the cohort overall. In multivariate analyses, patients had significantly higher odds of ovarian cancer death if they received nonadherent treatment (hazard ratio, 1.33), and if they were treated at a low-volume hospital (HR, 1.08) or by a low-volume physician (HR, 1.18).

"We are in the infancy of defining quality care for ovarian cancer," concluded Dr. Bristow. "We need to develop risk-adjusted models for comparison, to make sure we are comparing apples to apples, so to speak. We need to become more sophisticated in our measurement and reporting. Ideally, one day, everyone’s quality performance measures will be publicly available and patients and payers can choose for themselves where to go for care."

The investigators plan future research on such models and on universal reporting requirements. "There are also critical issues of racial and socioeconomic disparities in ovarian cancer care and outcomes that we are investigating," he said.

Dr. Bristow disclosed no relevant conflicts of interest.

Correction, 3/28/2013: An earlier version of this story misstated the name of the Society of Gynecologic Oncology.

LOS ANGELES – Guideline-adherent treatment can make the difference between life and death in patients with ovarian cancer, and it often hinges on where and from whom patients receive care, new data suggest.

In a retrospective, population-based study of more than 13,000 patients with epithelial ovarian cancer, only about 40% of patients received treatment adhering to that recommended by the National Comprehensive Cancer Network (NCCN).

Patients were more likely to receive guideline-adherent treatment if they went to high-volume hospitals (those treating at least 20 such patients each year) and high-volume physicians (those treating at least 10 such patients each year), according to results reported at the annual meeting of the Society of Gynecologic Oncology*. Still, in absolute terms, only about half of patients treated in high-volume hospitals or by high-volume surgeons received adherent treatment.

Compared with their counterparts who received guideline-adherent treatment, patients who received nonadherent treatment had a 33% higher risk of dying from their disease in the subsequent 5 years.

"NCCN guideline adherence predicts improved survival," lead investigator Dr. Robert E. Bristow commented in an interview. "A minority of patients is getting access to guideline care, and increased efforts to direct ovarian cancer patients to high-volume providers are warranted."

From a population-based perspective, much greater gains in survival can be achieved by centralizing ovarian cancer care to gynecologic oncologists and high-volume hospitals than through new chemotherapy drugs or experimental treatments, according to Dr. Bristow, who is director of the division of gynecologic oncology at the University of California, Irvine, medical center. The success of this model "has been demonstrated in Norway, where nonaccredited providers are not paid for any ovarian cancer care they deliver."

That said, the data cannot be used to discern the reasons for the overall poor rate of guideline adherence.

"In population-based data sets, you don’t have the granularity of data to tease out the nuances that might contribute to risk, like an infirm 85-year-old woman who can’t tolerate major surgery and aggressive surgery. We were not able to control for that," Dr. Bristow noted. Yet "only about 20% of patients had access to high-volume providers, and since high-volume providers are more likely to deliver appropriate care, the lack of access to these physicians and hospitals is probably the biggest reason (for nonadherence). By ensuring that we do everything possible to get ovarian cancer patients to the physicians and centers that are best equipped to take care of them, we will maximize each patient’s chance for the best possible outcome."

Analyses were based on 13,321 patients with epithelial ovarian cancer having data in the California Cancer Registry for the years 1999 through 2006. They had a median age of 61 years; 70% had stage III or IV disease, and 42% had serous tumor histology.

Among patients having data on these measures, 81% were treated at low-volume hospitals and 79% by low-volume surgeons. In multivariate analyses, patients were significantly more likely to receive nonadherent treatment if they were treated in low-volume hospitals (odds ratio, 1.83) or by low-volume physicians (OR, 1.19).

Overall, 37% of the patients received treatment recommended by NCCN guidelines. The 5-year disease-specific survival rate was 45% for the cohort overall. In multivariate analyses, patients had significantly higher odds of ovarian cancer death if they received nonadherent treatment (hazard ratio, 1.33), and if they were treated at a low-volume hospital (HR, 1.08) or by a low-volume physician (HR, 1.18).

"We are in the infancy of defining quality care for ovarian cancer," concluded Dr. Bristow. "We need to develop risk-adjusted models for comparison, to make sure we are comparing apples to apples, so to speak. We need to become more sophisticated in our measurement and reporting. Ideally, one day, everyone’s quality performance measures will be publicly available and patients and payers can choose for themselves where to go for care."

The investigators plan future research on such models and on universal reporting requirements. "There are also critical issues of racial and socioeconomic disparities in ovarian cancer care and outcomes that we are investigating," he said.

Dr. Bristow disclosed no relevant conflicts of interest.

Correction, 3/28/2013: An earlier version of this story misstated the name of the Society of Gynecologic Oncology.

SAN FRANCISCO – Prophylactically placing a pessary around the cervix during the second trimester reduces the risk of preterm birth in women with a multiple pregnancy who have a shorter cervix, a randomized trial conducted in the Netherlands has shown.

Pessaries were ineffective when compared with usual care among the entire population of 813 women with a multiple pregnancy studied, according to data reported at the annual meeting of the Society for Maternal-Fetal Medicine.

But among the subgroup with a cervix measuring less than the 25th percentile – which corresponded to 38 mm in the study population – the use of pessaries cut the risk of a composite of poor perinatal outcomes by 60%, the risk of death before discharge by 86%, and the risk of delivery before 32 weeks by 51%.

"In unselected women with a multiple pregnancy, prophylactic use of a pessary does not reduce poor perinatal outcome. However, in women with a multiple pregnancy and a cervical length below 38 mm at 16-22 weeks, the pessary reduced both poor perinatal outcome and preterm birth rates," commented lead investigator Dr. Sophie Liem, an ob.gyn. with the Academic Medical Center in Amsterdam.

Attendee Dr. B. Anthony Armson of Dalhousie University in Halifax, N.S, commented, "Most of us would consider 38 mm normal length. I wonder if you were to extrapolate that into a recommendation, would you have us all identify what our 25th percentile is or select our usual standard of less than 25 mm?

"Initially, we planned a subgroup analysis for women with a cervical length below 25 mm." However, "we found we had only nine women with a cervical length below 25 mm. So prior to analysis, we changed the cutoff to the 25th percentile," Dr. Liem explained. "I don’t know if the distribution of the cervical length in the United States would be the same as in the Netherlands."

An attendee from Houston noted, "When I put a pessary in pregnant women, one of the things is that they are not having sex. Did you assess sexual activity in those in the placebo group versus those in the pessary group? Do you think this might be related to sexual activity because those with the pessary were not having sex, compared to those in the placebo group?"

"Unfortunately, we didn’t record sexual behavior, so we do not have data on that," Dr. Liem replied.

Attendee Dr. Arnold Cohen of the Einstein Medical Center in Philadelphia, said, "The [Arabin] pessary that was used, from the diagram, seems to be circular around the cervix. That isn’t the type of pessary we use in the United States routinely. Can you comment on whether it was basically a cerclage effect of what you used, or would other pessaries work in the same way?"

"The exact working mechanism is not known," Dr. Liem said. "It has been hypothesized that the pessary changes the angle of the cervical canal and therefore maybe pressure on the internal os, and prevents deterioration of the cervical mucous plug or the loss of it. I don’t know if other pessaries would work the same."

Providing some background to the study, she noted that previous research has shown that progestagens, bed rest, and cerclage are all ineffective for preventing preterm birth in multiple pregnancies. "Several studies suggest that the pessary could prevent preterm birth; however, most studies were small and not randomized," she said.

Women enrolled in the new study, known as the ProTWIN trial, had a multiple pregnancy (monochorionic or dichorionic) with a gestational age of 12-20 weeks. They did not have fetuses with congenital disorders, stillbirth, twin-to-twin transfusion syndrome, or placenta previa.

The women were randomized evenly to placement of an Arabin pessary at 16-20 weeks or usual care. In the former group, the pessary was removed at 36 weeks, or earlier in the case of premature rupture of membranes, vaginal bleeding, severe painful contraction, or other discomfort.

Overall, 55% of the women were nulliparous, and 6% had a previous preterm delivery, Dr. Liem reported. The mean cervical length was 44 mm.

In the trial population as a whole, the rate of the primary outcome – a composite of eight adverse perinatal outcomes – was 13% in the pessary group and 14% in the usual care group, a nonsignificant difference. The pattern was the same for each component individually.

The two groups were also statistically indistinguishable with respect to the time to delivery, the number of days spent in the neonatal intensive care unit, and various measures of maternal morbidity.

However, in the preplanned subgroup analysis among women falling below the 25th percentile for cervical length (38 mm) at 16-22 weeks’ gestation, the rate of the composite of poor perinatal outcomes was 12% in the pessary group, significantly lower than the 29% in the usual care group (relative risk, 0.40). There was also a significant reduction in the risk of the component measure of death before discharge (RR, 0.14).

Additionally, in this subgroup of women, pessaries significantly prolonged the time to delivery (P = .01), leading to an older median gestational age (36³/₇ vs. 35 weeks in the usual care group) and reducing the risk of delivery before 32 weeks (RR, 0.49) and before 28 weeks (RR, 0.23).

"We are starting to look at the optimal cutoff [of cervical length for pessary placement] in post hoc analyses," Dr. Liem noted.

She disclosed no relevant financial conflicts.

SAN FRANCISCO – Prophylactically placing a pessary around the cervix during the second trimester reduces the risk of preterm birth in women with a multiple pregnancy who have a shorter cervix, a randomized trial conducted in the Netherlands has shown.

Pessaries were ineffective when compared with usual care among the entire population of 813 women with a multiple pregnancy studied, according to data reported at the annual meeting of the Society for Maternal-Fetal Medicine.

But among the subgroup with a cervix measuring less than the 25th percentile – which corresponded to 38 mm in the study population – the use of pessaries cut the risk of a composite of poor perinatal outcomes by 60%, the risk of death before discharge by 86%, and the risk of delivery before 32 weeks by 51%.

"In unselected women with a multiple pregnancy, prophylactic use of a pessary does not reduce poor perinatal outcome. However, in women with a multiple pregnancy and a cervical length below 38 mm at 16-22 weeks, the pessary reduced both poor perinatal outcome and preterm birth rates," commented lead investigator Dr. Sophie Liem, an ob.gyn. with the Academic Medical Center in Amsterdam.

Attendee Dr. B. Anthony Armson of Dalhousie University in Halifax, N.S, commented, "Most of us would consider 38 mm normal length. I wonder if you were to extrapolate that into a recommendation, would you have us all identify what our 25th percentile is or select our usual standard of less than 25 mm?

"Initially, we planned a subgroup analysis for women with a cervical length below 25 mm." However, "we found we had only nine women with a cervical length below 25 mm. So prior to analysis, we changed the cutoff to the 25th percentile," Dr. Liem explained. "I don’t know if the distribution of the cervical length in the United States would be the same as in the Netherlands."

An attendee from Houston noted, "When I put a pessary in pregnant women, one of the things is that they are not having sex. Did you assess sexual activity in those in the placebo group versus those in the pessary group? Do you think this might be related to sexual activity because those with the pessary were not having sex, compared to those in the placebo group?"

"Unfortunately, we didn’t record sexual behavior, so we do not have data on that," Dr. Liem replied.

Attendee Dr. Arnold Cohen of the Einstein Medical Center in Philadelphia, said, "The [Arabin] pessary that was used, from the diagram, seems to be circular around the cervix. That isn’t the type of pessary we use in the United States routinely. Can you comment on whether it was basically a cerclage effect of what you used, or would other pessaries work in the same way?"

"The exact working mechanism is not known," Dr. Liem said. "It has been hypothesized that the pessary changes the angle of the cervical canal and therefore maybe pressure on the internal os, and prevents deterioration of the cervical mucous plug or the loss of it. I don’t know if other pessaries would work the same."

Providing some background to the study, she noted that previous research has shown that progestagens, bed rest, and cerclage are all ineffective for preventing preterm birth in multiple pregnancies. "Several studies suggest that the pessary could prevent preterm birth; however, most studies were small and not randomized," she said.

Women enrolled in the new study, known as the ProTWIN trial, had a multiple pregnancy (monochorionic or dichorionic) with a gestational age of 12-20 weeks. They did not have fetuses with congenital disorders, stillbirth, twin-to-twin transfusion syndrome, or placenta previa.

The women were randomized evenly to placement of an Arabin pessary at 16-20 weeks or usual care. In the former group, the pessary was removed at 36 weeks, or earlier in the case of premature rupture of membranes, vaginal bleeding, severe painful contraction, or other discomfort.

Overall, 55% of the women were nulliparous, and 6% had a previous preterm delivery, Dr. Liem reported. The mean cervical length was 44 mm.

In the trial population as a whole, the rate of the primary outcome – a composite of eight adverse perinatal outcomes – was 13% in the pessary group and 14% in the usual care group, a nonsignificant difference. The pattern was the same for each component individually.

The two groups were also statistically indistinguishable with respect to the time to delivery, the number of days spent in the neonatal intensive care unit, and various measures of maternal morbidity.

However, in the preplanned subgroup analysis among women falling below the 25th percentile for cervical length (38 mm) at 16-22 weeks’ gestation, the rate of the composite of poor perinatal outcomes was 12% in the pessary group, significantly lower than the 29% in the usual care group (relative risk, 0.40). There was also a significant reduction in the risk of the component measure of death before discharge (RR, 0.14).

Additionally, in this subgroup of women, pessaries significantly prolonged the time to delivery (P = .01), leading to an older median gestational age (36³/₇ vs. 35 weeks in the usual care group) and reducing the risk of delivery before 32 weeks (RR, 0.49) and before 28 weeks (RR, 0.23).

"We are starting to look at the optimal cutoff [of cervical length for pessary placement] in post hoc analyses," Dr. Liem noted.

She disclosed no relevant financial conflicts.

SAN FRANCISCO – Prophylactically placing a pessary around the cervix during the second trimester reduces the risk of preterm birth in women with a multiple pregnancy who have a shorter cervix, a randomized trial conducted in the Netherlands has shown.

Pessaries were ineffective when compared with usual care among the entire population of 813 women with a multiple pregnancy studied, according to data reported at the annual meeting of the Society for Maternal-Fetal Medicine.

But among the subgroup with a cervix measuring less than the 25th percentile – which corresponded to 38 mm in the study population – the use of pessaries cut the risk of a composite of poor perinatal outcomes by 60%, the risk of death before discharge by 86%, and the risk of delivery before 32 weeks by 51%.

"In unselected women with a multiple pregnancy, prophylactic use of a pessary does not reduce poor perinatal outcome. However, in women with a multiple pregnancy and a cervical length below 38 mm at 16-22 weeks, the pessary reduced both poor perinatal outcome and preterm birth rates," commented lead investigator Dr. Sophie Liem, an ob.gyn. with the Academic Medical Center in Amsterdam.

Attendee Dr. B. Anthony Armson of Dalhousie University in Halifax, N.S, commented, "Most of us would consider 38 mm normal length. I wonder if you were to extrapolate that into a recommendation, would you have us all identify what our 25th percentile is or select our usual standard of less than 25 mm?

"Initially, we planned a subgroup analysis for women with a cervical length below 25 mm." However, "we found we had only nine women with a cervical length below 25 mm. So prior to analysis, we changed the cutoff to the 25th percentile," Dr. Liem explained. "I don’t know if the distribution of the cervical length in the United States would be the same as in the Netherlands."

An attendee from Houston noted, "When I put a pessary in pregnant women, one of the things is that they are not having sex. Did you assess sexual activity in those in the placebo group versus those in the pessary group? Do you think this might be related to sexual activity because those with the pessary were not having sex, compared to those in the placebo group?"

"Unfortunately, we didn’t record sexual behavior, so we do not have data on that," Dr. Liem replied.

Attendee Dr. Arnold Cohen of the Einstein Medical Center in Philadelphia, said, "The [Arabin] pessary that was used, from the diagram, seems to be circular around the cervix. That isn’t the type of pessary we use in the United States routinely. Can you comment on whether it was basically a cerclage effect of what you used, or would other pessaries work in the same way?"

"The exact working mechanism is not known," Dr. Liem said. "It has been hypothesized that the pessary changes the angle of the cervical canal and therefore maybe pressure on the internal os, and prevents deterioration of the cervical mucous plug or the loss of it. I don’t know if other pessaries would work the same."

Providing some background to the study, she noted that previous research has shown that progestagens, bed rest, and cerclage are all ineffective for preventing preterm birth in multiple pregnancies. "Several studies suggest that the pessary could prevent preterm birth; however, most studies were small and not randomized," she said.

Women enrolled in the new study, known as the ProTWIN trial, had a multiple pregnancy (monochorionic or dichorionic) with a gestational age of 12-20 weeks. They did not have fetuses with congenital disorders, stillbirth, twin-to-twin transfusion syndrome, or placenta previa.

The women were randomized evenly to placement of an Arabin pessary at 16-20 weeks or usual care. In the former group, the pessary was removed at 36 weeks, or earlier in the case of premature rupture of membranes, vaginal bleeding, severe painful contraction, or other discomfort.

Overall, 55% of the women were nulliparous, and 6% had a previous preterm delivery, Dr. Liem reported. The mean cervical length was 44 mm.

In the trial population as a whole, the rate of the primary outcome – a composite of eight adverse perinatal outcomes – was 13% in the pessary group and 14% in the usual care group, a nonsignificant difference. The pattern was the same for each component individually.

The two groups were also statistically indistinguishable with respect to the time to delivery, the number of days spent in the neonatal intensive care unit, and various measures of maternal morbidity.

However, in the preplanned subgroup analysis among women falling below the 25th percentile for cervical length (38 mm) at 16-22 weeks’ gestation, the rate of the composite of poor perinatal outcomes was 12% in the pessary group, significantly lower than the 29% in the usual care group (relative risk, 0.40). There was also a significant reduction in the risk of the component measure of death before discharge (RR, 0.14).

Additionally, in this subgroup of women, pessaries significantly prolonged the time to delivery (P = .01), leading to an older median gestational age (36³/₇ vs. 35 weeks in the usual care group) and reducing the risk of delivery before 32 weeks (RR, 0.49) and before 28 weeks (RR, 0.23).

"We are starting to look at the optimal cutoff [of cervical length for pessary placement] in post hoc analyses," Dr. Liem noted.

She disclosed no relevant financial conflicts.

SAN FRANCISCO – Few women in a general U.S. obstetric practice are given a trial of labor after a previous cesarean birth, but the majority do have a vaginal delivery, a study has shown.

A team led by Dr. Kirsten Salmeen, a fellow in maternal-fetal medicine at the University of California, San Francisco, retrospectively studied a cohort of more than 1.1 million nonanomalous singleton term pregnancies in women with a history of cesarean delivery. The results, reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one in eight women were given a trial of labor. But two-thirds of this group succeeded in having a vaginal delivery.

Susan London/IMNG Medical Media

"Overall, VBAC [vaginal birth after cesarean] rates are high" in routine clinical practice – "maybe not quite as high as in studies of VBAC, but still, very good success rates overall. However, the number of women attempting a trial of labor in this country is very, very low compared to the women who are likely to succeed," Dr. Salmeen said in an interview.

Resistance to a trial of labor after cesarean is complicated and multifactorial.

"Sometimes hospital policy comes into it. Sometimes provider comfort," she said. "Also, there is a lot out there among women in the community about the safety and the benefits and the pros and the cons. I think that a lot of women who are pregnant ... are sort of under the impression that it’s much safer for them to have a C-section. Starting to chisel away at that myth and really trying to educate women might go far."

Women in the study had especially good odds of having a vaginal delivery if they had had at least one previous vaginal delivery.

For hospitals that have policies against a trial of labor, or that are prohibitive in terms of a trial of labor, one category that can be viewed very differently is that of women with a history of previous vaginal birth, Dr. Salmeen said. She suggested that hospitals adjust their policies accordingly. If a woman has a 6.2 increase in the odds of having a successful vaginal birth, and nearly 90% of such women go on to have a successful VBAC – as was the case for those who had had at least three previous vaginal births – "maybe we can adjust those policies a little bit for those women," Dr. Salmeen said.

On the other hand, women had reduced odds of having a vaginal delivery if they had certain common medical conditions, but the reduction was relatively small, she noted.

In the case of gestational diabetes, for example, "a lot of people assume that those women are much less likely to have a successful VBAC, and it’s a very big part of our population," she said. Given their adjusted odds of success, "they were about 20% less likely to succeed than women who didn’t have gestational diabetes. But they weren’t, say, 80% or 90% less likely to succeed. So it was relatively small."

In the larger context, new models incorporating factors such as these may go a long way in predicting a woman’s odds of successful VBAC. "This data set has the potential to sort of test some of those models and see if they really stand up in a national population," Dr. Salmeen maintained.

She and her coinvestigators analyzed data from the U.S. Certificate of Live Birth data set for women giving birth between 2005 and 2009. Results reported at the meeting were based on 1,162,197 pregnancies among women having at least one previous cesarean delivery.

Overall, 13% had a trial of labor, reported Dr. Salmeen.

In a multivariate analysis, women were significantly more likely to be given a trial if they were black (odds ratio, 1.17); had less than a high school education (1.20); and especially if they had had one, two, or three or more previous vaginal deliveries (2.69, 4.22, and 6.09, respectively).

They were significantly less likely to be given a trial of labor if they were younger than age 20 (0.91) or aged 35 or older (0.95), were Hispanic (0.95), had pregestational diabetes (0.67) or gestational diabetes (0.81), or had chronic hypertension (0.71) or gestational hypertension (0.82).

Overall, 67% of the group given a trial of labor had a vaginal birth. This compares with roughly 70% in studies, Dr. Salmeen noted.

In a multivariate analysis, women were significantly more likely to succeed in being delivered vaginally if they had less than a high school education (odds ratio, 1.28) and especially if they had had one, two, or three or more previous vaginal deliveries (2.97, 4.50, and 6.23, respectively).

They were significantly less likely to succeed in being delivered vaginally if they were black, Hispanic, or Asian (odds ratios, 0.80, 0.92, and 0.86); were younger than age 20 (0.72); had pregestational diabetes (0.50) or gestational diabetes (0.81); or had chronic hypertension (0.56) or gestational hypertension (0.70).

SAN FRANCISCO – Few women in a general U.S. obstetric practice are given a trial of labor after a previous cesarean birth, but the majority do have a vaginal delivery, a study has shown.

A team led by Dr. Kirsten Salmeen, a fellow in maternal-fetal medicine at the University of California, San Francisco, retrospectively studied a cohort of more than 1.1 million nonanomalous singleton term pregnancies in women with a history of cesarean delivery. The results, reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one in eight women were given a trial of labor. But two-thirds of this group succeeded in having a vaginal delivery.

Susan London/IMNG Medical Media

"Overall, VBAC [vaginal birth after cesarean] rates are high" in routine clinical practice – "maybe not quite as high as in studies of VBAC, but still, very good success rates overall. However, the number of women attempting a trial of labor in this country is very, very low compared to the women who are likely to succeed," Dr. Salmeen said in an interview.

Resistance to a trial of labor after cesarean is complicated and multifactorial.

"Sometimes hospital policy comes into it. Sometimes provider comfort," she said. "Also, there is a lot out there among women in the community about the safety and the benefits and the pros and the cons. I think that a lot of women who are pregnant ... are sort of under the impression that it’s much safer for them to have a C-section. Starting to chisel away at that myth and really trying to educate women might go far."

Women in the study had especially good odds of having a vaginal delivery if they had had at least one previous vaginal delivery.

For hospitals that have policies against a trial of labor, or that are prohibitive in terms of a trial of labor, one category that can be viewed very differently is that of women with a history of previous vaginal birth, Dr. Salmeen said. She suggested that hospitals adjust their policies accordingly. If a woman has a 6.2 increase in the odds of having a successful vaginal birth, and nearly 90% of such women go on to have a successful VBAC – as was the case for those who had had at least three previous vaginal births – "maybe we can adjust those policies a little bit for those women," Dr. Salmeen said.

On the other hand, women had reduced odds of having a vaginal delivery if they had certain common medical conditions, but the reduction was relatively small, she noted.

In the case of gestational diabetes, for example, "a lot of people assume that those women are much less likely to have a successful VBAC, and it’s a very big part of our population," she said. Given their adjusted odds of success, "they were about 20% less likely to succeed than women who didn’t have gestational diabetes. But they weren’t, say, 80% or 90% less likely to succeed. So it was relatively small."

In the larger context, new models incorporating factors such as these may go a long way in predicting a woman’s odds of successful VBAC. "This data set has the potential to sort of test some of those models and see if they really stand up in a national population," Dr. Salmeen maintained.

She and her coinvestigators analyzed data from the U.S. Certificate of Live Birth data set for women giving birth between 2005 and 2009. Results reported at the meeting were based on 1,162,197 pregnancies among women having at least one previous cesarean delivery.

Overall, 13% had a trial of labor, reported Dr. Salmeen.

In a multivariate analysis, women were significantly more likely to be given a trial if they were black (odds ratio, 1.17); had less than a high school education (1.20); and especially if they had had one, two, or three or more previous vaginal deliveries (2.69, 4.22, and 6.09, respectively).

They were significantly less likely to be given a trial of labor if they were younger than age 20 (0.91) or aged 35 or older (0.95), were Hispanic (0.95), had pregestational diabetes (0.67) or gestational diabetes (0.81), or had chronic hypertension (0.71) or gestational hypertension (0.82).

Overall, 67% of the group given a trial of labor had a vaginal birth. This compares with roughly 70% in studies, Dr. Salmeen noted.

In a multivariate analysis, women were significantly more likely to succeed in being delivered vaginally if they had less than a high school education (odds ratio, 1.28) and especially if they had had one, two, or three or more previous vaginal deliveries (2.97, 4.50, and 6.23, respectively).

They were significantly less likely to succeed in being delivered vaginally if they were black, Hispanic, or Asian (odds ratios, 0.80, 0.92, and 0.86); were younger than age 20 (0.72); had pregestational diabetes (0.50) or gestational diabetes (0.81); or had chronic hypertension (0.56) or gestational hypertension (0.70).

SAN FRANCISCO – Few women in a general U.S. obstetric practice are given a trial of labor after a previous cesarean birth, but the majority do have a vaginal delivery, a study has shown.

A team led by Dr. Kirsten Salmeen, a fellow in maternal-fetal medicine at the University of California, San Francisco, retrospectively studied a cohort of more than 1.1 million nonanomalous singleton term pregnancies in women with a history of cesarean delivery. The results, reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one in eight women were given a trial of labor. But two-thirds of this group succeeded in having a vaginal delivery.

Susan London/IMNG Medical Media

"Overall, VBAC [vaginal birth after cesarean] rates are high" in routine clinical practice – "maybe not quite as high as in studies of VBAC, but still, very good success rates overall. However, the number of women attempting a trial of labor in this country is very, very low compared to the women who are likely to succeed," Dr. Salmeen said in an interview.

Resistance to a trial of labor after cesarean is complicated and multifactorial.

"Sometimes hospital policy comes into it. Sometimes provider comfort," she said. "Also, there is a lot out there among women in the community about the safety and the benefits and the pros and the cons. I think that a lot of women who are pregnant ... are sort of under the impression that it’s much safer for them to have a C-section. Starting to chisel away at that myth and really trying to educate women might go far."

Women in the study had especially good odds of having a vaginal delivery if they had had at least one previous vaginal delivery.

For hospitals that have policies against a trial of labor, or that are prohibitive in terms of a trial of labor, one category that can be viewed very differently is that of women with a history of previous vaginal birth, Dr. Salmeen said. She suggested that hospitals adjust their policies accordingly. If a woman has a 6.2 increase in the odds of having a successful vaginal birth, and nearly 90% of such women go on to have a successful VBAC – as was the case for those who had had at least three previous vaginal births – "maybe we can adjust those policies a little bit for those women," Dr. Salmeen said.

On the other hand, women had reduced odds of having a vaginal delivery if they had certain common medical conditions, but the reduction was relatively small, she noted.

In the case of gestational diabetes, for example, "a lot of people assume that those women are much less likely to have a successful VBAC, and it’s a very big part of our population," she said. Given their adjusted odds of success, "they were about 20% less likely to succeed than women who didn’t have gestational diabetes. But they weren’t, say, 80% or 90% less likely to succeed. So it was relatively small."

In the larger context, new models incorporating factors such as these may go a long way in predicting a woman’s odds of successful VBAC. "This data set has the potential to sort of test some of those models and see if they really stand up in a national population," Dr. Salmeen maintained.

She and her coinvestigators analyzed data from the U.S. Certificate of Live Birth data set for women giving birth between 2005 and 2009. Results reported at the meeting were based on 1,162,197 pregnancies among women having at least one previous cesarean delivery.

Overall, 13% had a trial of labor, reported Dr. Salmeen.

In a multivariate analysis, women were significantly more likely to be given a trial if they were black (odds ratio, 1.17); had less than a high school education (1.20); and especially if they had had one, two, or three or more previous vaginal deliveries (2.69, 4.22, and 6.09, respectively).

They were significantly less likely to be given a trial of labor if they were younger than age 20 (0.91) or aged 35 or older (0.95), were Hispanic (0.95), had pregestational diabetes (0.67) or gestational diabetes (0.81), or had chronic hypertension (0.71) or gestational hypertension (0.82).

Overall, 67% of the group given a trial of labor had a vaginal birth. This compares with roughly 70% in studies, Dr. Salmeen noted.

In a multivariate analysis, women were significantly more likely to succeed in being delivered vaginally if they had less than a high school education (odds ratio, 1.28) and especially if they had had one, two, or three or more previous vaginal deliveries (2.97, 4.50, and 6.23, respectively).

They were significantly less likely to succeed in being delivered vaginally if they were black, Hispanic, or Asian (odds ratios, 0.80, 0.92, and 0.86); were younger than age 20 (0.72); had pregestational diabetes (0.50) or gestational diabetes (0.81); or had chronic hypertension (0.56) or gestational hypertension (0.70).

Women who have had an abortion are no longer at increased risk for preterm birth in subsequent pregnancies, and it may be time to adjust counseling guidelines accordingly, a study has shown.

In a cohort study among 416,301 nulliparous Scottish women with a first singleton birth between 1992 and 2008, those who had had a previous induced abortion had a significant 12% increase in the adjusted odds of spontaneous preterm birth, lead investigator Clare Oliver-Williams reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, more-detailed analyses stratified by time period showed that the association weakened over time and disappeared as of about 2000.

This trend coincided with a shift toward the use of abortion practices less likely to injure the cervix: a sharp decrease to almost 0 in surgical abortions performed without cervical pretreatment and a sharp increase in medical abortions.

"We think the reason why there has been a loss of association [between previous abortion and preterm birth] is because of this change in practice: There are no longer surgical abortions without cervical pretreatment, and that was driving the association all along," Ms. Oliver-Williams said in an interview.

"If women have chosen to have an abortion previously and then go on to have an intended pregnancy, this should be reassuring to them," she said. And the findings have related implications for preabortion counseling.

Current U.K. guidelines recommend that women be advised before the procedure about a subsequent increase in the risk of preterm birth, she noted. "That might not be the most appropriate thing to tell women anymore given that the majority of abortions [now] occur through medical means or surgical means with cervical pretreatment."

Cervical pretreatment in the United Kingdom usually involves the use of a prostaglandin, and practices may differ across countries, said Ms. Oliver-Williams, a PhD candidate in the department of public health and primary care at the University of Cambridge (England). But it is reasonable to assume that other countries are also getting away from more-injurious procedures.

"The theory holds up that mechanical dilation would damage the cervix and lead to spontaneous preterm birth" in a later pregnancy, she said. "So, in a cautious way, I would suggest that the association would still exist in other countries if there was a decrease in these surgical abortions without cervical pretreatment."

Nulliparous women were chosen for analysis in part because there are fewer complicating factors for this group, such as the timing of abortions relative to births, according to Ms. Oliver-Williams. But the findings would likely be similar for multiparous women, too. "I can’t imagine why multiparity would have any impact," she said.

The main results showed that women with a previous induced abortion had significantly higher odds of spontaneous preterm birth after other factors were considered (odds ratio, 1.12), reported Ms. Oliver-Williams.

There was a dose-response relationship between the number of previous abortions and risk: Women who had had one, two, and three previous abortions had 7%, 24%, and 37% higher odds, respectively, of spontaneous preterm birth (P less than .001 for trend).

In time period–stratified analysis, the odds were elevated for women giving birth during 1992-1995 and during 1996-1999. But they were no longer so thereafter.

During the same overall study period, the proportion of all abortions that were surgical and performed without cervical pretreatment fell sharply (from 31% to less than 1%), and the proportion that were performed with medication rose sharply (from 18% to 68%).

In additional study findings, previous abortion was not associated with a significant increase in the risk of various other adverse outcomes: antepartum stillbirth, intrapartum stillbirth, neonatal death, small-for-gestational-age birth, induced preterm birth due to any reason, or induced preterm birth specifically due to preeclampsia.

Ms. Oliver-Williams disclosed no relevant financial conflicts.

Women who have had an abortion are no longer at increased risk for preterm birth in subsequent pregnancies, and it may be time to adjust counseling guidelines accordingly, a study has shown.

In a cohort study among 416,301 nulliparous Scottish women with a first singleton birth between 1992 and 2008, those who had had a previous induced abortion had a significant 12% increase in the adjusted odds of spontaneous preterm birth, lead investigator Clare Oliver-Williams reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, more-detailed analyses stratified by time period showed that the association weakened over time and disappeared as of about 2000.

This trend coincided with a shift toward the use of abortion practices less likely to injure the cervix: a sharp decrease to almost 0 in surgical abortions performed without cervical pretreatment and a sharp increase in medical abortions.

"We think the reason why there has been a loss of association [between previous abortion and preterm birth] is because of this change in practice: There are no longer surgical abortions without cervical pretreatment, and that was driving the association all along," Ms. Oliver-Williams said in an interview.

"If women have chosen to have an abortion previously and then go on to have an intended pregnancy, this should be reassuring to them," she said. And the findings have related implications for preabortion counseling.

Current U.K. guidelines recommend that women be advised before the procedure about a subsequent increase in the risk of preterm birth, she noted. "That might not be the most appropriate thing to tell women anymore given that the majority of abortions [now] occur through medical means or surgical means with cervical pretreatment."

Cervical pretreatment in the United Kingdom usually involves the use of a prostaglandin, and practices may differ across countries, said Ms. Oliver-Williams, a PhD candidate in the department of public health and primary care at the University of Cambridge (England). But it is reasonable to assume that other countries are also getting away from more-injurious procedures.

"The theory holds up that mechanical dilation would damage the cervix and lead to spontaneous preterm birth" in a later pregnancy, she said. "So, in a cautious way, I would suggest that the association would still exist in other countries if there was a decrease in these surgical abortions without cervical pretreatment."

Nulliparous women were chosen for analysis in part because there are fewer complicating factors for this group, such as the timing of abortions relative to births, according to Ms. Oliver-Williams. But the findings would likely be similar for multiparous women, too. "I can’t imagine why multiparity would have any impact," she said.

The main results showed that women with a previous induced abortion had significantly higher odds of spontaneous preterm birth after other factors were considered (odds ratio, 1.12), reported Ms. Oliver-Williams.

There was a dose-response relationship between the number of previous abortions and risk: Women who had had one, two, and three previous abortions had 7%, 24%, and 37% higher odds, respectively, of spontaneous preterm birth (P less than .001 for trend).

In time period–stratified analysis, the odds were elevated for women giving birth during 1992-1995 and during 1996-1999. But they were no longer so thereafter.

During the same overall study period, the proportion of all abortions that were surgical and performed without cervical pretreatment fell sharply (from 31% to less than 1%), and the proportion that were performed with medication rose sharply (from 18% to 68%).

In additional study findings, previous abortion was not associated with a significant increase in the risk of various other adverse outcomes: antepartum stillbirth, intrapartum stillbirth, neonatal death, small-for-gestational-age birth, induced preterm birth due to any reason, or induced preterm birth specifically due to preeclampsia.

Ms. Oliver-Williams disclosed no relevant financial conflicts.

Women who have had an abortion are no longer at increased risk for preterm birth in subsequent pregnancies, and it may be time to adjust counseling guidelines accordingly, a study has shown.

In a cohort study among 416,301 nulliparous Scottish women with a first singleton birth between 1992 and 2008, those who had had a previous induced abortion had a significant 12% increase in the adjusted odds of spontaneous preterm birth, lead investigator Clare Oliver-Williams reported in a poster session at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, more-detailed analyses stratified by time period showed that the association weakened over time and disappeared as of about 2000.

This trend coincided with a shift toward the use of abortion practices less likely to injure the cervix: a sharp decrease to almost 0 in surgical abortions performed without cervical pretreatment and a sharp increase in medical abortions.

"We think the reason why there has been a loss of association [between previous abortion and preterm birth] is because of this change in practice: There are no longer surgical abortions without cervical pretreatment, and that was driving the association all along," Ms. Oliver-Williams said in an interview.

"If women have chosen to have an abortion previously and then go on to have an intended pregnancy, this should be reassuring to them," she said. And the findings have related implications for preabortion counseling.

Current U.K. guidelines recommend that women be advised before the procedure about a subsequent increase in the risk of preterm birth, she noted. "That might not be the most appropriate thing to tell women anymore given that the majority of abortions [now] occur through medical means or surgical means with cervical pretreatment."

Cervical pretreatment in the United Kingdom usually involves the use of a prostaglandin, and practices may differ across countries, said Ms. Oliver-Williams, a PhD candidate in the department of public health and primary care at the University of Cambridge (England). But it is reasonable to assume that other countries are also getting away from more-injurious procedures.

"The theory holds up that mechanical dilation would damage the cervix and lead to spontaneous preterm birth" in a later pregnancy, she said. "So, in a cautious way, I would suggest that the association would still exist in other countries if there was a decrease in these surgical abortions without cervical pretreatment."

Nulliparous women were chosen for analysis in part because there are fewer complicating factors for this group, such as the timing of abortions relative to births, according to Ms. Oliver-Williams. But the findings would likely be similar for multiparous women, too. "I can’t imagine why multiparity would have any impact," she said.

The main results showed that women with a previous induced abortion had significantly higher odds of spontaneous preterm birth after other factors were considered (odds ratio, 1.12), reported Ms. Oliver-Williams.

There was a dose-response relationship between the number of previous abortions and risk: Women who had had one, two, and three previous abortions had 7%, 24%, and 37% higher odds, respectively, of spontaneous preterm birth (P less than .001 for trend).

In time period–stratified analysis, the odds were elevated for women giving birth during 1992-1995 and during 1996-1999. But they were no longer so thereafter.

During the same overall study period, the proportion of all abortions that were surgical and performed without cervical pretreatment fell sharply (from 31% to less than 1%), and the proportion that were performed with medication rose sharply (from 18% to 68%).

In additional study findings, previous abortion was not associated with a significant increase in the risk of various other adverse outcomes: antepartum stillbirth, intrapartum stillbirth, neonatal death, small-for-gestational-age birth, induced preterm birth due to any reason, or induced preterm birth specifically due to preeclampsia.

Ms. Oliver-Williams disclosed no relevant financial conflicts.

Restricting physical activity does not reduce the odds of preterm birth in asymptomatic nulliparous women with a singleton pregnancy who have a short cervix, and doing so may even be harmful, a study has shown.

More than a third of the 646 women with a short cervix who were studied were placed on some kind of activity restriction, despite the general lack of evidence and guideline endorsement for the practice in this context, Dr. William Grobman reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Compared with their counterparts who were not placed on any kind of activity restriction, women who rested had a more than doubling of the odds of giving birth before 37 weeks after other factors, including cervical length, were considered.

"To me, the key important point is that there is no evidence of benefit, [and there are] multiple potential paths of harm," said Dr. Grobman, who is a maternal-fetal medicine specialist at Northwestern Memorial Hospital in Chicago.

"Even if there is not harm for preterm birth, there probably is harm in other regards – in terms of deconditioning, in terms of bone loss," he said. Placing such women on activity restriction, sometimes in the hospital, also has major implications for resource use and lost productivity.

The findings are consistent with earlier research, he added. "There’s no good evidence from any study that [activity restriction] makes a difference. ... Personally, [at my institution], we never did put women on activity restriction," given the lack of compelling evidence of benefit. That’s just been the cultural practice in obstetrics, he said.

The new data should temper current screening trends, according to Dr. Grobman. "There has been increasing emphasis on the value of screening asymptomatic women and how that might be beneficial," he explained. "But oftentimes, what is not accounted for in that are the unintended consequences that you bring." The study is not arguing against screening, "but it suggests that if we screen, we have to be very cognizant of that."

In the larger context, about three-fourths of such women with a short cervix will not be delivered preterm, and those who do often give birth many weeks after the condition is first detected, according to Dr. Grobman.

In addition, especially when women are receiving prenatal care, there is usually sufficient opportunity to detect early labor and intervene. "I can remember in 20 years, one woman coming in at 24 weeks in preterm labor and us not having the opportunity to give her steroids or whatever," he commented.

The women studied were participants in the SCAN trial of progesterone for preventing preterm birth in nulliparous women with a short cervix. Those with prolapsing membranes were excluded.

All had a cervix measuring less than 30 mm on second-trimester transvaginal ultrasound, with an interquartile range of about 19-28 mm, Dr. Grobman reported on behalf of investigators with the maternal-fetal medicine unit (MFMU) network of the National Institute of Child Health and Human Development.

Study results, presented in a poster session, showed that 39% of the women were put on some type of activity restriction, meaning pelvic rest (prohibition of sexual activity), reduction of work activity, and/or reduction of nonwork activity. The majority were put on all three types and usually at home, on an outpatient basis.

After adjustment for potential confounders, relative to their peers who were not put on activity restriction, women who were had significantly higher odds of being delivered before 37 weeks (odds ratio, 2.4) and before 34 weeks (OR, 2.8).

The numbers were generally too small to look at associations for individual types of activity restriction, as most women were prescribed all three types, according to Dr. Grobman.

"I think the message is when people get plunked on bed rest, they get shut down," he commented. But analyses among the subset placed solely on work restrictions yielded the same results.

In closing, Dr. Grobman cautioned that the results apply only to the population studied. "I’m not talking about bed rest for anyone, ever, for anything. These are asymptomatic women in a study [who were] found to have a short cervix," he said.

Dr. Grobman disclosed no relevant financial conflicts.

Restricting physical activity does not reduce the odds of preterm birth in asymptomatic nulliparous women with a singleton pregnancy who have a short cervix, and doing so may even be harmful, a study has shown.

More than a third of the 646 women with a short cervix who were studied were placed on some kind of activity restriction, despite the general lack of evidence and guideline endorsement for the practice in this context, Dr. William Grobman reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Compared with their counterparts who were not placed on any kind of activity restriction, women who rested had a more than doubling of the odds of giving birth before 37 weeks after other factors, including cervical length, were considered.

"To me, the key important point is that there is no evidence of benefit, [and there are] multiple potential paths of harm," said Dr. Grobman, who is a maternal-fetal medicine specialist at Northwestern Memorial Hospital in Chicago.

"Even if there is not harm for preterm birth, there probably is harm in other regards – in terms of deconditioning, in terms of bone loss," he said. Placing such women on activity restriction, sometimes in the hospital, also has major implications for resource use and lost productivity.

The findings are consistent with earlier research, he added. "There’s no good evidence from any study that [activity restriction] makes a difference. ... Personally, [at my institution], we never did put women on activity restriction," given the lack of compelling evidence of benefit. That’s just been the cultural practice in obstetrics, he said.

The new data should temper current screening trends, according to Dr. Grobman. "There has been increasing emphasis on the value of screening asymptomatic women and how that might be beneficial," he explained. "But oftentimes, what is not accounted for in that are the unintended consequences that you bring." The study is not arguing against screening, "but it suggests that if we screen, we have to be very cognizant of that."

In the larger context, about three-fourths of such women with a short cervix will not be delivered preterm, and those who do often give birth many weeks after the condition is first detected, according to Dr. Grobman.

In addition, especially when women are receiving prenatal care, there is usually sufficient opportunity to detect early labor and intervene. "I can remember in 20 years, one woman coming in at 24 weeks in preterm labor and us not having the opportunity to give her steroids or whatever," he commented.

The women studied were participants in the SCAN trial of progesterone for preventing preterm birth in nulliparous women with a short cervix. Those with prolapsing membranes were excluded.

All had a cervix measuring less than 30 mm on second-trimester transvaginal ultrasound, with an interquartile range of about 19-28 mm, Dr. Grobman reported on behalf of investigators with the maternal-fetal medicine unit (MFMU) network of the National Institute of Child Health and Human Development.

Study results, presented in a poster session, showed that 39% of the women were put on some type of activity restriction, meaning pelvic rest (prohibition of sexual activity), reduction of work activity, and/or reduction of nonwork activity. The majority were put on all three types and usually at home, on an outpatient basis.

After adjustment for potential confounders, relative to their peers who were not put on activity restriction, women who were had significantly higher odds of being delivered before 37 weeks (odds ratio, 2.4) and before 34 weeks (OR, 2.8).

The numbers were generally too small to look at associations for individual types of activity restriction, as most women were prescribed all three types, according to Dr. Grobman.

"I think the message is when people get plunked on bed rest, they get shut down," he commented. But analyses among the subset placed solely on work restrictions yielded the same results.

In closing, Dr. Grobman cautioned that the results apply only to the population studied. "I’m not talking about bed rest for anyone, ever, for anything. These are asymptomatic women in a study [who were] found to have a short cervix," he said.

Dr. Grobman disclosed no relevant financial conflicts.

Restricting physical activity does not reduce the odds of preterm birth in asymptomatic nulliparous women with a singleton pregnancy who have a short cervix, and doing so may even be harmful, a study has shown.

More than a third of the 646 women with a short cervix who were studied were placed on some kind of activity restriction, despite the general lack of evidence and guideline endorsement for the practice in this context, Dr. William Grobman reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Compared with their counterparts who were not placed on any kind of activity restriction, women who rested had a more than doubling of the odds of giving birth before 37 weeks after other factors, including cervical length, were considered.

"To me, the key important point is that there is no evidence of benefit, [and there are] multiple potential paths of harm," said Dr. Grobman, who is a maternal-fetal medicine specialist at Northwestern Memorial Hospital in Chicago.

"Even if there is not harm for preterm birth, there probably is harm in other regards – in terms of deconditioning, in terms of bone loss," he said. Placing such women on activity restriction, sometimes in the hospital, also has major implications for resource use and lost productivity.

The findings are consistent with earlier research, he added. "There’s no good evidence from any study that [activity restriction] makes a difference. ... Personally, [at my institution], we never did put women on activity restriction," given the lack of compelling evidence of benefit. That’s just been the cultural practice in obstetrics, he said.

The new data should temper current screening trends, according to Dr. Grobman. "There has been increasing emphasis on the value of screening asymptomatic women and how that might be beneficial," he explained. "But oftentimes, what is not accounted for in that are the unintended consequences that you bring." The study is not arguing against screening, "but it suggests that if we screen, we have to be very cognizant of that."

In the larger context, about three-fourths of such women with a short cervix will not be delivered preterm, and those who do often give birth many weeks after the condition is first detected, according to Dr. Grobman.

In addition, especially when women are receiving prenatal care, there is usually sufficient opportunity to detect early labor and intervene. "I can remember in 20 years, one woman coming in at 24 weeks in preterm labor and us not having the opportunity to give her steroids or whatever," he commented.

The women studied were participants in the SCAN trial of progesterone for preventing preterm birth in nulliparous women with a short cervix. Those with prolapsing membranes were excluded.

All had a cervix measuring less than 30 mm on second-trimester transvaginal ultrasound, with an interquartile range of about 19-28 mm, Dr. Grobman reported on behalf of investigators with the maternal-fetal medicine unit (MFMU) network of the National Institute of Child Health and Human Development.

Study results, presented in a poster session, showed that 39% of the women were put on some type of activity restriction, meaning pelvic rest (prohibition of sexual activity), reduction of work activity, and/or reduction of nonwork activity. The majority were put on all three types and usually at home, on an outpatient basis.

After adjustment for potential confounders, relative to their peers who were not put on activity restriction, women who were had significantly higher odds of being delivered before 37 weeks (odds ratio, 2.4) and before 34 weeks (OR, 2.8).

The numbers were generally too small to look at associations for individual types of activity restriction, as most women were prescribed all three types, according to Dr. Grobman.

"I think the message is when people get plunked on bed rest, they get shut down," he commented. But analyses among the subset placed solely on work restrictions yielded the same results.

In closing, Dr. Grobman cautioned that the results apply only to the population studied. "I’m not talking about bed rest for anyone, ever, for anything. These are asymptomatic women in a study [who were] found to have a short cervix," he said.

Dr. Grobman disclosed no relevant financial conflicts.

SAN FRANCISCO – Intra-amniotic debris is a strong independent risk factor for early preterm birth in asymptomatic nulliparous women who have a short cervix, finds a study presented at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

In the secondary analysis of 657 women participating in a randomized prevention trial, those who had intra-amniotic debris (sometimes called sludge) on ultrasound were about twice as likely to deliver before 35 weeks’ gestation and before 34 weeks, and three times as likely to deliver before 32 weeks.

The women with intra-amniotic debris also had higher odds of giving birth to an infant with perinatal problems, such as a low Apgar score or need for neonatal intensive care admission. But this association vanished after adjustment for gestational age.

"Intra-amniotic debris increases the risk of early preterm birth independently of the cervical length," lead investigator Dr. George R. Saade, professor of obstetrics and gynecology at the University of Texas Medical Branch, Galveston, commented. "Presence of debris is associated with worse perinatal outcome through its effect on preterm birth."

One attendee said, "I’m curious as to whether you have data on infectious complications among women with debris compared to those without, such as chorioamnionitis."

Those analyses are still ongoing, and the mechanism behind the association of debris with preterm birth remains unclear, according to Dr. Saade, who was presenting the study’s results on behalf of investigators with the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

"The rate of severe growth restriction, which we should consider as indicated preterm birth, was actually lower in the group with debris. So it must be something else with the debris that’s causing these preterm births," he added.

The women studied were participants in the SCAN trial of progesterone to prevent preterm birth in nulliparous women with a short cervix. All were between 16 and 22 weeks of a singleton gestation and had a cervical length of less than 30 mm on transvaginal ultrasound but no other risk factors for preterm birth.

During the ultrasound to measure cervical length, the sonographer also assessed the presence of cervical funneling and intra-amniotic debris.

All sonographers were trained according to published methods (N. Engl. J. Med. 1996;334:567-72) and certified by central image review before the study, Dr. Saade said, noting that other studies have been limited by a lack of standardized training.

Main trials results, previously reported, showed no significant benefit of progesterone in reducing preterm birth (Am. J. Obstet. Gynecol. 2012;207:390.e1-8).

In the secondary analysis, ultrasound revealed that 24% of the women had cervical funneling, 12% had intra-amniotic debris, and 7% had both.

Relative to other women, women who had funneling and/or debris were older and more likely to be of minority race/ethnicity, and had a higher prepregnancy body mass index. They also were more likely to have had a prior pregnancy loss before 20 weeks’ gestation, an older gestational age at trial screening, and a shorter cervical length.

Cervical funneling and intra-amniotic debris were each significantly associated with a higher rate of preterm birth at multiple gestational cutoffs in an unadjusted analysis and in an adjusted analysis that took into account progesterone treatment.

After further adjustment for cervical length, cervical funneling no longer predicted preterm birth at any cutoff. But intra-amniotic debris still predicted preterm birth before 35 weeks (odds ratio, 1.90), before 34 weeks (2.04), and before 32 weeks (3.10).

In absolute terms, 27% of women having intra-amniotic debris on ultrasound delivered before 32 weeks’ gestation, compared with just 7% of their counterparts without debris, according to Dr. Saade.

Intra-amniotic debris also was associated with a composite of eight adverse perinatal outcomes in the infant in an analysis adjusted for progesterone treatment. But the association was no longer significant after additional adjustment for cervical length and gestational age.

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

SAN FRANCISCO – Intra-amniotic debris is a strong independent risk factor for early preterm birth in asymptomatic nulliparous women who have a short cervix, finds a study presented at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

In the secondary analysis of 657 women participating in a randomized prevention trial, those who had intra-amniotic debris (sometimes called sludge) on ultrasound were about twice as likely to deliver before 35 weeks’ gestation and before 34 weeks, and three times as likely to deliver before 32 weeks.

The women with intra-amniotic debris also had higher odds of giving birth to an infant with perinatal problems, such as a low Apgar score or need for neonatal intensive care admission. But this association vanished after adjustment for gestational age.

"Intra-amniotic debris increases the risk of early preterm birth independently of the cervical length," lead investigator Dr. George R. Saade, professor of obstetrics and gynecology at the University of Texas Medical Branch, Galveston, commented. "Presence of debris is associated with worse perinatal outcome through its effect on preterm birth."

One attendee said, "I’m curious as to whether you have data on infectious complications among women with debris compared to those without, such as chorioamnionitis."

Those analyses are still ongoing, and the mechanism behind the association of debris with preterm birth remains unclear, according to Dr. Saade, who was presenting the study’s results on behalf of investigators with the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

"The rate of severe growth restriction, which we should consider as indicated preterm birth, was actually lower in the group with debris. So it must be something else with the debris that’s causing these preterm births," he added.

The women studied were participants in the SCAN trial of progesterone to prevent preterm birth in nulliparous women with a short cervix. All were between 16 and 22 weeks of a singleton gestation and had a cervical length of less than 30 mm on transvaginal ultrasound but no other risk factors for preterm birth.

During the ultrasound to measure cervical length, the sonographer also assessed the presence of cervical funneling and intra-amniotic debris.

All sonographers were trained according to published methods (N. Engl. J. Med. 1996;334:567-72) and certified by central image review before the study, Dr. Saade said, noting that other studies have been limited by a lack of standardized training.

Main trials results, previously reported, showed no significant benefit of progesterone in reducing preterm birth (Am. J. Obstet. Gynecol. 2012;207:390.e1-8).

In the secondary analysis, ultrasound revealed that 24% of the women had cervical funneling, 12% had intra-amniotic debris, and 7% had both.

Relative to other women, women who had funneling and/or debris were older and more likely to be of minority race/ethnicity, and had a higher prepregnancy body mass index. They also were more likely to have had a prior pregnancy loss before 20 weeks’ gestation, an older gestational age at trial screening, and a shorter cervical length.

Cervical funneling and intra-amniotic debris were each significantly associated with a higher rate of preterm birth at multiple gestational cutoffs in an unadjusted analysis and in an adjusted analysis that took into account progesterone treatment.

After further adjustment for cervical length, cervical funneling no longer predicted preterm birth at any cutoff. But intra-amniotic debris still predicted preterm birth before 35 weeks (odds ratio, 1.90), before 34 weeks (2.04), and before 32 weeks (3.10).

In absolute terms, 27% of women having intra-amniotic debris on ultrasound delivered before 32 weeks’ gestation, compared with just 7% of their counterparts without debris, according to Dr. Saade.

Intra-amniotic debris also was associated with a composite of eight adverse perinatal outcomes in the infant in an analysis adjusted for progesterone treatment. But the association was no longer significant after additional adjustment for cervical length and gestational age.

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

SAN FRANCISCO – Intra-amniotic debris is a strong independent risk factor for early preterm birth in asymptomatic nulliparous women who have a short cervix, finds a study presented at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

In the secondary analysis of 657 women participating in a randomized prevention trial, those who had intra-amniotic debris (sometimes called sludge) on ultrasound were about twice as likely to deliver before 35 weeks’ gestation and before 34 weeks, and three times as likely to deliver before 32 weeks.

The women with intra-amniotic debris also had higher odds of giving birth to an infant with perinatal problems, such as a low Apgar score or need for neonatal intensive care admission. But this association vanished after adjustment for gestational age.

"Intra-amniotic debris increases the risk of early preterm birth independently of the cervical length," lead investigator Dr. George R. Saade, professor of obstetrics and gynecology at the University of Texas Medical Branch, Galveston, commented. "Presence of debris is associated with worse perinatal outcome through its effect on preterm birth."

One attendee said, "I’m curious as to whether you have data on infectious complications among women with debris compared to those without, such as chorioamnionitis."

Those analyses are still ongoing, and the mechanism behind the association of debris with preterm birth remains unclear, according to Dr. Saade, who was presenting the study’s results on behalf of investigators with the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

"The rate of severe growth restriction, which we should consider as indicated preterm birth, was actually lower in the group with debris. So it must be something else with the debris that’s causing these preterm births," he added.

The women studied were participants in the SCAN trial of progesterone to prevent preterm birth in nulliparous women with a short cervix. All were between 16 and 22 weeks of a singleton gestation and had a cervical length of less than 30 mm on transvaginal ultrasound but no other risk factors for preterm birth.

During the ultrasound to measure cervical length, the sonographer also assessed the presence of cervical funneling and intra-amniotic debris.

All sonographers were trained according to published methods (N. Engl. J. Med. 1996;334:567-72) and certified by central image review before the study, Dr. Saade said, noting that other studies have been limited by a lack of standardized training.

Main trials results, previously reported, showed no significant benefit of progesterone in reducing preterm birth (Am. J. Obstet. Gynecol. 2012;207:390.e1-8).

In the secondary analysis, ultrasound revealed that 24% of the women had cervical funneling, 12% had intra-amniotic debris, and 7% had both.

Relative to other women, women who had funneling and/or debris were older and more likely to be of minority race/ethnicity, and had a higher prepregnancy body mass index. They also were more likely to have had a prior pregnancy loss before 20 weeks’ gestation, an older gestational age at trial screening, and a shorter cervical length.

Cervical funneling and intra-amniotic debris were each significantly associated with a higher rate of preterm birth at multiple gestational cutoffs in an unadjusted analysis and in an adjusted analysis that took into account progesterone treatment.

After further adjustment for cervical length, cervical funneling no longer predicted preterm birth at any cutoff. But intra-amniotic debris still predicted preterm birth before 35 weeks (odds ratio, 1.90), before 34 weeks (2.04), and before 32 weeks (3.10).

In absolute terms, 27% of women having intra-amniotic debris on ultrasound delivered before 32 weeks’ gestation, compared with just 7% of their counterparts without debris, according to Dr. Saade.

Intra-amniotic debris also was associated with a composite of eight adverse perinatal outcomes in the infant in an analysis adjusted for progesterone treatment. But the association was no longer significant after additional adjustment for cervical length and gestational age.

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

cardiologynews@elsevier.com

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

cardiologynews@elsevier.com

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

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