SMFM Annual Meeting 2013

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

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

Susan London/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

obnews@frontlinemedcom.com

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

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

Susan London/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

obnews@frontlinemedcom.com

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

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

Susan London/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

obnews@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen 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 – 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.

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.