SMFM Annual Meeting 2013

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Grobman disclosed no relevant financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Grobman disclosed no relevant financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Grobman disclosed no relevant financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Saade disclosed no relevant financial conflicts of interest.

obnews@elsevier.com

Some women who have experienced a pregnancy loss can increase their odds of a live birth in the next pregnancy simply by taking aspirin, investigators reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

A team led by Enrique F. Schisterman, Ph.D., conducted a randomized trial of 1,228 healthy young women who had had up to two prior pregnancy losses, but did not have infertility and were attempting to conceive again.

©jimdeli/Fotolia.com

The women were assigned evenly to take low-dose aspirin (81 mg) or placebo daily, along with folic acid, for up to six menstrual cycles or, if they conceived, up to the 36th week of pregnancy.

Results showed that low-dose aspirin was associated with an absolute 9.2% increase in the rate of live birth among the subset of women who met restricted criteria for pregnancy loss, namely a single pregnancy loss before 20 weeks’ gestation in the past year, reported Dr. Schisterman, who is a senior investigator and chief of the epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md.

The benefit was mainly due to early effects. "There was an effect on becoming pregnant and early pregnancy [maintenance], but there were no differences after that," he elaborated. "The implications of that are not only that aspirin will help women become pregnant, but if you start too late, then the effects of aspirin are not there any more."

Analyses in the group with restricted criteria suggested that only about 11 women would need to be treated with low-dose aspirin to achieve one additional live birth.

In contrast, there was no significant benefit of low-dose aspirin among the subset of women who met general criteria for pregnancy loss that required one or two pregnancy losses at any time in the past, but excluded those meeting restricted criteria.

Low-dose aspirin was associated with somewhat higher rates of minor vaginal bleeding and minor gastrointestinal upset, but the drug was not associated with pregnancy loss or with an increased risk of major fetal, neonatal, or maternal complications.

An attendee wondered about the difference between the two subsets of women having differing histories of pregnancy loss, saying, "You would expect more or less the same effect."

Dr. Schisterman maintained that the two groups were not all that similar. "I am not sure I would expect the same result, although when we did some analyses in which we compared those who had a single loss in the restricted stratum to those who had a single loss in the general stratum, we found attenuated but in a similar direction results in the general stratum," he commented. "So it seems that the number of losses is the driving force. But we are still analyzing that data."

Another attendee raised the issue of the timing of the previous pregnancy loss in the subset meeting restricted criteria. "Were you able to identify any influence of the gestational age of the previous loss on the effectiveness of aspirin in the next pregnancy, the randomized pregnancy?" he asked.

"Not yet," Dr. Schisterman replied, noting that all of the losses were fairly early. However, here too, analyses are still ongoing.

Giving some background to the trial, he noted, "We know that inflammation and abnormal blood flow, especially in the uterus, endometrium, ovaries, and placenta, ... are unifying features of outcomes like infertility, pregnancy loss, preeclampsia, preterm delivery, and small for gestational age. So clearly, an ideal therapy that would reduce inflammation and improve blood flow will be the one that we are looking for. Low-dose aspirin could be such a therapy."

The drug has seldom been studied when given in the preconceptional period, but there is a strong rationale for such use, he maintained.

"It impacts endometrial vascularization and placentation. It has very well documented anti-inflammatory effects. It has very few maternal and fetal side effects. It’s safe, widely available, and more importantly, it’s cheap – it costs $2 for the whole pregnancy to treat a woman," he elaborated.

Women enrolled in the trial, known as EAGeR (The Effects of Aspirin in Gestation and Reproduction), were aged 18-39 years. They were roughly evenly split between meeting the restricted criteria and the general criteria for previous pregnancy loss.

On average, the women were 29 years old and had a body mass index of about 27 kg/m². Most were married and white.

Overall, there was only a trend toward a higher rate of live births in the low-dose aspirin group compared with the placebo group (57.8% vs. 52.7%, P = .09), reported Dr. Schisterman.

In stratified analyses, there was a significant benefit of low-dose aspirin in the subset meeting the restricted pregnancy loss criteria (62.4% vs. 53.2%, P = .04) but not in the subset meeting the general pregnancy loss criteria (53.9% vs. 52.2%).

When the investigators more closely assessed the reason for benefit in the women meeting restricted criteria, they found a higher rate of achieving a positive pregnancy test with low-dose aspirin (70.5% vs. 61.7%, P = .03). Rates of progression thereafter to confirmed pregnancy by ultrasound at 6 weeks and ultimately to live birth were similar for the two treatment groups.

Dr. Schisterman disclosed no relevant conflicts of interest.

obnews@elsevier.com

Some women who have experienced a pregnancy loss can increase their odds of a live birth in the next pregnancy simply by taking aspirin, investigators reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

A team led by Enrique F. Schisterman, Ph.D., conducted a randomized trial of 1,228 healthy young women who had had up to two prior pregnancy losses, but did not have infertility and were attempting to conceive again.

©jimdeli/Fotolia.com

The women were assigned evenly to take low-dose aspirin (81 mg) or placebo daily, along with folic acid, for up to six menstrual cycles or, if they conceived, up to the 36th week of pregnancy.

Results showed that low-dose aspirin was associated with an absolute 9.2% increase in the rate of live birth among the subset of women who met restricted criteria for pregnancy loss, namely a single pregnancy loss before 20 weeks’ gestation in the past year, reported Dr. Schisterman, who is a senior investigator and chief of the epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md.

The benefit was mainly due to early effects. "There was an effect on becoming pregnant and early pregnancy [maintenance], but there were no differences after that," he elaborated. "The implications of that are not only that aspirin will help women become pregnant, but if you start too late, then the effects of aspirin are not there any more."

Analyses in the group with restricted criteria suggested that only about 11 women would need to be treated with low-dose aspirin to achieve one additional live birth.

In contrast, there was no significant benefit of low-dose aspirin among the subset of women who met general criteria for pregnancy loss that required one or two pregnancy losses at any time in the past, but excluded those meeting restricted criteria.

Low-dose aspirin was associated with somewhat higher rates of minor vaginal bleeding and minor gastrointestinal upset, but the drug was not associated with pregnancy loss or with an increased risk of major fetal, neonatal, or maternal complications.

An attendee wondered about the difference between the two subsets of women having differing histories of pregnancy loss, saying, "You would expect more or less the same effect."

Dr. Schisterman maintained that the two groups were not all that similar. "I am not sure I would expect the same result, although when we did some analyses in which we compared those who had a single loss in the restricted stratum to those who had a single loss in the general stratum, we found attenuated but in a similar direction results in the general stratum," he commented. "So it seems that the number of losses is the driving force. But we are still analyzing that data."

Another attendee raised the issue of the timing of the previous pregnancy loss in the subset meeting restricted criteria. "Were you able to identify any influence of the gestational age of the previous loss on the effectiveness of aspirin in the next pregnancy, the randomized pregnancy?" he asked.

"Not yet," Dr. Schisterman replied, noting that all of the losses were fairly early. However, here too, analyses are still ongoing.

Giving some background to the trial, he noted, "We know that inflammation and abnormal blood flow, especially in the uterus, endometrium, ovaries, and placenta, ... are unifying features of outcomes like infertility, pregnancy loss, preeclampsia, preterm delivery, and small for gestational age. So clearly, an ideal therapy that would reduce inflammation and improve blood flow will be the one that we are looking for. Low-dose aspirin could be such a therapy."

The drug has seldom been studied when given in the preconceptional period, but there is a strong rationale for such use, he maintained.

"It impacts endometrial vascularization and placentation. It has very well documented anti-inflammatory effects. It has very few maternal and fetal side effects. It’s safe, widely available, and more importantly, it’s cheap – it costs $2 for the whole pregnancy to treat a woman," he elaborated.

Women enrolled in the trial, known as EAGeR (The Effects of Aspirin in Gestation and Reproduction), were aged 18-39 years. They were roughly evenly split between meeting the restricted criteria and the general criteria for previous pregnancy loss.

On average, the women were 29 years old and had a body mass index of about 27 kg/m². Most were married and white.

Overall, there was only a trend toward a higher rate of live births in the low-dose aspirin group compared with the placebo group (57.8% vs. 52.7%, P = .09), reported Dr. Schisterman.

In stratified analyses, there was a significant benefit of low-dose aspirin in the subset meeting the restricted pregnancy loss criteria (62.4% vs. 53.2%, P = .04) but not in the subset meeting the general pregnancy loss criteria (53.9% vs. 52.2%).

When the investigators more closely assessed the reason for benefit in the women meeting restricted criteria, they found a higher rate of achieving a positive pregnancy test with low-dose aspirin (70.5% vs. 61.7%, P = .03). Rates of progression thereafter to confirmed pregnancy by ultrasound at 6 weeks and ultimately to live birth were similar for the two treatment groups.

Dr. Schisterman disclosed no relevant conflicts of interest.

obnews@elsevier.com

Some women who have experienced a pregnancy loss can increase their odds of a live birth in the next pregnancy simply by taking aspirin, investigators reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

A team led by Enrique F. Schisterman, Ph.D., conducted a randomized trial of 1,228 healthy young women who had had up to two prior pregnancy losses, but did not have infertility and were attempting to conceive again.

©jimdeli/Fotolia.com

The women were assigned evenly to take low-dose aspirin (81 mg) or placebo daily, along with folic acid, for up to six menstrual cycles or, if they conceived, up to the 36th week of pregnancy.

Results showed that low-dose aspirin was associated with an absolute 9.2% increase in the rate of live birth among the subset of women who met restricted criteria for pregnancy loss, namely a single pregnancy loss before 20 weeks’ gestation in the past year, reported Dr. Schisterman, who is a senior investigator and chief of the epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md.

The benefit was mainly due to early effects. "There was an effect on becoming pregnant and early pregnancy [maintenance], but there were no differences after that," he elaborated. "The implications of that are not only that aspirin will help women become pregnant, but if you start too late, then the effects of aspirin are not there any more."

Analyses in the group with restricted criteria suggested that only about 11 women would need to be treated with low-dose aspirin to achieve one additional live birth.

In contrast, there was no significant benefit of low-dose aspirin among the subset of women who met general criteria for pregnancy loss that required one or two pregnancy losses at any time in the past, but excluded those meeting restricted criteria.

Low-dose aspirin was associated with somewhat higher rates of minor vaginal bleeding and minor gastrointestinal upset, but the drug was not associated with pregnancy loss or with an increased risk of major fetal, neonatal, or maternal complications.

An attendee wondered about the difference between the two subsets of women having differing histories of pregnancy loss, saying, "You would expect more or less the same effect."

Dr. Schisterman maintained that the two groups were not all that similar. "I am not sure I would expect the same result, although when we did some analyses in which we compared those who had a single loss in the restricted stratum to those who had a single loss in the general stratum, we found attenuated but in a similar direction results in the general stratum," he commented. "So it seems that the number of losses is the driving force. But we are still analyzing that data."

Another attendee raised the issue of the timing of the previous pregnancy loss in the subset meeting restricted criteria. "Were you able to identify any influence of the gestational age of the previous loss on the effectiveness of aspirin in the next pregnancy, the randomized pregnancy?" he asked.

"Not yet," Dr. Schisterman replied, noting that all of the losses were fairly early. However, here too, analyses are still ongoing.

Giving some background to the trial, he noted, "We know that inflammation and abnormal blood flow, especially in the uterus, endometrium, ovaries, and placenta, ... are unifying features of outcomes like infertility, pregnancy loss, preeclampsia, preterm delivery, and small for gestational age. So clearly, an ideal therapy that would reduce inflammation and improve blood flow will be the one that we are looking for. Low-dose aspirin could be such a therapy."

The drug has seldom been studied when given in the preconceptional period, but there is a strong rationale for such use, he maintained.

"It impacts endometrial vascularization and placentation. It has very well documented anti-inflammatory effects. It has very few maternal and fetal side effects. It’s safe, widely available, and more importantly, it’s cheap – it costs $2 for the whole pregnancy to treat a woman," he elaborated.

Women enrolled in the trial, known as EAGeR (The Effects of Aspirin in Gestation and Reproduction), were aged 18-39 years. They were roughly evenly split between meeting the restricted criteria and the general criteria for previous pregnancy loss.

On average, the women were 29 years old and had a body mass index of about 27 kg/m². Most were married and white.

Overall, there was only a trend toward a higher rate of live births in the low-dose aspirin group compared with the placebo group (57.8% vs. 52.7%, P = .09), reported Dr. Schisterman.

In stratified analyses, there was a significant benefit of low-dose aspirin in the subset meeting the restricted pregnancy loss criteria (62.4% vs. 53.2%, P = .04) but not in the subset meeting the general pregnancy loss criteria (53.9% vs. 52.2%).

When the investigators more closely assessed the reason for benefit in the women meeting restricted criteria, they found a higher rate of achieving a positive pregnancy test with low-dose aspirin (70.5% vs. 61.7%, P = .03). Rates of progression thereafter to confirmed pregnancy by ultrasound at 6 weeks and ultimately to live birth were similar for the two treatment groups.

Dr. Schisterman disclosed no relevant conflicts of interest.

obnews@elsevier.com