SMFM Annual Meeting 2012

DALLAS – Compared with expectant management, labor induction for cases involving a suspected large-for-dates fetus was associated with a threefold reduction in the risk of neonatal trauma and an improved likelihood of spontaneous vaginal birth in a randomized controlled trial involving 817 women.

Induction did not increase the cesarean section rate, compared with expectant management, but neonates in the induction group did have a higher rate of severe icterus, Dr. Michel Boulvain reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of neonatal trauma were 2.2% in the 407 women who were randomized to be induced, and 6.6% in 410 controls who underwent expectant management (relative risk, 0.34). The likelihood of a spontaneous vaginal delivery also was significantly higher in the induction group (RR, 1.14), said Dr. Boulvain of University Hospitals of Geneva, Switzerland.

The cesarean section rates in the induction and expectant management groups were 28% and 31.7%, respectively.

Women in the induction group delivered a mean of 9 days earlier, and birth weight in that group was 300 g less than in the expectant management group.

The study was conducted in collaboration with 20 teaching hospitals that are members of the Research Group in Obstetrics and Gynecology (GROG) in France, Switzerland, and Belgium. Study participants were women who underwent a clinical screening at 36-38 weeks’ gestation indicating an estimated fetal weight above the 90th percentile, and who then underwent sonography indicating an estimated fetal weight above the 95th percentile. Those randomized to induction were induced within 3 days.

Women with diabetes treated with insulin, and those with a history of cesarean section or shoulder dystocia were excluded.

Baseline characteristics were similar in the induction and expectant management groups, and no differences were seen with respect to very severe outcomes, Dr. Boulvain said.

The findings with respect to the individual outcomes from the composite neonatal trauma outcome – such as shoulder dystocia, brachial plexus injury, and fractures – each were improved in the induction group, compared with the expectant management group, which is encouraging, he noted.

The increase in the rate of icterus, however, is disturbing, and might be explained by fact that the induction group delivered more than a week earlier, or by increased attention to that outcome in the induction group, he said.

It could also be a direct effect of the oxytocin, he suggested.

Nonetheless, the conclusion of the findings is that induction of labor at 37-38 weeks’ gestation when estimated fetal weight is above the 95th percentile decreases risk of outcomes such as shoulder dystocia and fracture without increasing the risk of cesarean section, and increases the likelihood of spontaneous vaginal delivery, he said.

He added that decisions about management should be made with consideration of the characteristic and preference of the patient, keeping in mind that prior cesarean section and other conditions can preclude induction, and also keeping in mind that icterus is a potential concern.

Dr. Boulvain said he had no relevant financial disclosures.

DALLAS – Compared with expectant management, labor induction for cases involving a suspected large-for-dates fetus was associated with a threefold reduction in the risk of neonatal trauma and an improved likelihood of spontaneous vaginal birth in a randomized controlled trial involving 817 women.

Induction did not increase the cesarean section rate, compared with expectant management, but neonates in the induction group did have a higher rate of severe icterus, Dr. Michel Boulvain reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of neonatal trauma were 2.2% in the 407 women who were randomized to be induced, and 6.6% in 410 controls who underwent expectant management (relative risk, 0.34). The likelihood of a spontaneous vaginal delivery also was significantly higher in the induction group (RR, 1.14), said Dr. Boulvain of University Hospitals of Geneva, Switzerland.

The cesarean section rates in the induction and expectant management groups were 28% and 31.7%, respectively.

Women in the induction group delivered a mean of 9 days earlier, and birth weight in that group was 300 g less than in the expectant management group.

The study was conducted in collaboration with 20 teaching hospitals that are members of the Research Group in Obstetrics and Gynecology (GROG) in France, Switzerland, and Belgium. Study participants were women who underwent a clinical screening at 36-38 weeks’ gestation indicating an estimated fetal weight above the 90th percentile, and who then underwent sonography indicating an estimated fetal weight above the 95th percentile. Those randomized to induction were induced within 3 days.

Women with diabetes treated with insulin, and those with a history of cesarean section or shoulder dystocia were excluded.

Baseline characteristics were similar in the induction and expectant management groups, and no differences were seen with respect to very severe outcomes, Dr. Boulvain said.

The findings with respect to the individual outcomes from the composite neonatal trauma outcome – such as shoulder dystocia, brachial plexus injury, and fractures – each were improved in the induction group, compared with the expectant management group, which is encouraging, he noted.

The increase in the rate of icterus, however, is disturbing, and might be explained by fact that the induction group delivered more than a week earlier, or by increased attention to that outcome in the induction group, he said.

It could also be a direct effect of the oxytocin, he suggested.

Nonetheless, the conclusion of the findings is that induction of labor at 37-38 weeks’ gestation when estimated fetal weight is above the 95th percentile decreases risk of outcomes such as shoulder dystocia and fracture without increasing the risk of cesarean section, and increases the likelihood of spontaneous vaginal delivery, he said.

He added that decisions about management should be made with consideration of the characteristic and preference of the patient, keeping in mind that prior cesarean section and other conditions can preclude induction, and also keeping in mind that icterus is a potential concern.

Dr. Boulvain said he had no relevant financial disclosures.

DALLAS – Compared with expectant management, labor induction for cases involving a suspected large-for-dates fetus was associated with a threefold reduction in the risk of neonatal trauma and an improved likelihood of spontaneous vaginal birth in a randomized controlled trial involving 817 women.

Induction did not increase the cesarean section rate, compared with expectant management, but neonates in the induction group did have a higher rate of severe icterus, Dr. Michel Boulvain reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of neonatal trauma were 2.2% in the 407 women who were randomized to be induced, and 6.6% in 410 controls who underwent expectant management (relative risk, 0.34). The likelihood of a spontaneous vaginal delivery also was significantly higher in the induction group (RR, 1.14), said Dr. Boulvain of University Hospitals of Geneva, Switzerland.

The cesarean section rates in the induction and expectant management groups were 28% and 31.7%, respectively.

Women in the induction group delivered a mean of 9 days earlier, and birth weight in that group was 300 g less than in the expectant management group.

The study was conducted in collaboration with 20 teaching hospitals that are members of the Research Group in Obstetrics and Gynecology (GROG) in France, Switzerland, and Belgium. Study participants were women who underwent a clinical screening at 36-38 weeks’ gestation indicating an estimated fetal weight above the 90th percentile, and who then underwent sonography indicating an estimated fetal weight above the 95th percentile. Those randomized to induction were induced within 3 days.

Women with diabetes treated with insulin, and those with a history of cesarean section or shoulder dystocia were excluded.

Baseline characteristics were similar in the induction and expectant management groups, and no differences were seen with respect to very severe outcomes, Dr. Boulvain said.

The findings with respect to the individual outcomes from the composite neonatal trauma outcome – such as shoulder dystocia, brachial plexus injury, and fractures – each were improved in the induction group, compared with the expectant management group, which is encouraging, he noted.

The increase in the rate of icterus, however, is disturbing, and might be explained by fact that the induction group delivered more than a week earlier, or by increased attention to that outcome in the induction group, he said.

It could also be a direct effect of the oxytocin, he suggested.

Nonetheless, the conclusion of the findings is that induction of labor at 37-38 weeks’ gestation when estimated fetal weight is above the 95th percentile decreases risk of outcomes such as shoulder dystocia and fracture without increasing the risk of cesarean section, and increases the likelihood of spontaneous vaginal delivery, he said.

He added that decisions about management should be made with consideration of the characteristic and preference of the patient, keeping in mind that prior cesarean section and other conditions can preclude induction, and also keeping in mind that icterus is a potential concern.

Dr. Boulvain said he had no relevant financial disclosures.

DALLAS – Biweekly injections of 17-alpha-hydroxyprogesterone caproate, or 17P, did not significantly prolong pregnancy in a randomized open-label French study involving 188 women with an episode of successfully arrested preterm labor and a short cervix.

The median time from randomization to delivery was 64 days in 94 women who received 17P, and 67 days in 94 control subjects, Dr. Patrick Rozenberg reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of delivery prior to 37, 34, and 32 weeks’ gestation also did not differ significantly between the groups, with 39% and 38%, 16% and 20%, and 9% and 14% in the treatment and control groups, respectively, delivering at those time points, said Dr. Rozenberg of Poissy (France) Saint-Germain Hospital.

The findings contrast with those from several smaller trials that suggested 17P might reduce the risk of preterm delivery in women with preterm labor arrested by tocolysis.

Women in the current study had singleton pregnancies at 24-32 weeks’ gestation and a cervical length less than 25 mm, and were admitted at one of 13 French university hospitals with preterm labor. All were successfully treated with 12 mg of intramuscular betamethasone, which was repeated after 24 hours. The women were then randomized to receive or not receive 17P.

The 17P treatment group received 500 mg of intramuscular 17P beginning after tocolysis ended, and then twice weekly until 36 weeks’ gestation or until delivery. The control group received no progesterone, but all other management in both groups was left to the discretion of the attending physician, Dr. Rozenberg said, noting that clinical characteristics, including gestational age and cervical length, were similar in both the treatment and control groups, as were additional management, need for readmission for preterm labor, and tocolysis.

Neonatal outcomes, including birth weight and complications, also were similar between the groups, and there were no adverse effects associated with treatment.

Although several studies suggest that progesterone can reduce the rate of prematurity, many questions remain about optimal timing, mode of administration, dosing, and indications, Dr. Rozenberg noted. The findings of this study, however, do not support its use in women with a short cervix and an episode of preterm labor successfully treated with tocolysis.

"We could say that treatment with progesterone in patients with preterm labor and a short cervix below 25 mm did not prolong pregnancy, did not reduce the rate of prematurity and related complications, and was not associated with adverse effects. In conclusion, once the pathologic process of preterm labor begins, progesterone is no longer effective," he said.

Dr. Rozenberg said he had no relevant financial disclosures.

DALLAS – Biweekly injections of 17-alpha-hydroxyprogesterone caproate, or 17P, did not significantly prolong pregnancy in a randomized open-label French study involving 188 women with an episode of successfully arrested preterm labor and a short cervix.

The median time from randomization to delivery was 64 days in 94 women who received 17P, and 67 days in 94 control subjects, Dr. Patrick Rozenberg reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of delivery prior to 37, 34, and 32 weeks’ gestation also did not differ significantly between the groups, with 39% and 38%, 16% and 20%, and 9% and 14% in the treatment and control groups, respectively, delivering at those time points, said Dr. Rozenberg of Poissy (France) Saint-Germain Hospital.

The findings contrast with those from several smaller trials that suggested 17P might reduce the risk of preterm delivery in women with preterm labor arrested by tocolysis.

Women in the current study had singleton pregnancies at 24-32 weeks’ gestation and a cervical length less than 25 mm, and were admitted at one of 13 French university hospitals with preterm labor. All were successfully treated with 12 mg of intramuscular betamethasone, which was repeated after 24 hours. The women were then randomized to receive or not receive 17P.

The 17P treatment group received 500 mg of intramuscular 17P beginning after tocolysis ended, and then twice weekly until 36 weeks’ gestation or until delivery. The control group received no progesterone, but all other management in both groups was left to the discretion of the attending physician, Dr. Rozenberg said, noting that clinical characteristics, including gestational age and cervical length, were similar in both the treatment and control groups, as were additional management, need for readmission for preterm labor, and tocolysis.

Neonatal outcomes, including birth weight and complications, also were similar between the groups, and there were no adverse effects associated with treatment.

Although several studies suggest that progesterone can reduce the rate of prematurity, many questions remain about optimal timing, mode of administration, dosing, and indications, Dr. Rozenberg noted. The findings of this study, however, do not support its use in women with a short cervix and an episode of preterm labor successfully treated with tocolysis.

"We could say that treatment with progesterone in patients with preterm labor and a short cervix below 25 mm did not prolong pregnancy, did not reduce the rate of prematurity and related complications, and was not associated with adverse effects. In conclusion, once the pathologic process of preterm labor begins, progesterone is no longer effective," he said.

Dr. Rozenberg said he had no relevant financial disclosures.

DALLAS – Biweekly injections of 17-alpha-hydroxyprogesterone caproate, or 17P, did not significantly prolong pregnancy in a randomized open-label French study involving 188 women with an episode of successfully arrested preterm labor and a short cervix.

The median time from randomization to delivery was 64 days in 94 women who received 17P, and 67 days in 94 control subjects, Dr. Patrick Rozenberg reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The rates of delivery prior to 37, 34, and 32 weeks’ gestation also did not differ significantly between the groups, with 39% and 38%, 16% and 20%, and 9% and 14% in the treatment and control groups, respectively, delivering at those time points, said Dr. Rozenberg of Poissy (France) Saint-Germain Hospital.

The findings contrast with those from several smaller trials that suggested 17P might reduce the risk of preterm delivery in women with preterm labor arrested by tocolysis.

Women in the current study had singleton pregnancies at 24-32 weeks’ gestation and a cervical length less than 25 mm, and were admitted at one of 13 French university hospitals with preterm labor. All were successfully treated with 12 mg of intramuscular betamethasone, which was repeated after 24 hours. The women were then randomized to receive or not receive 17P.

The 17P treatment group received 500 mg of intramuscular 17P beginning after tocolysis ended, and then twice weekly until 36 weeks’ gestation or until delivery. The control group received no progesterone, but all other management in both groups was left to the discretion of the attending physician, Dr. Rozenberg said, noting that clinical characteristics, including gestational age and cervical length, were similar in both the treatment and control groups, as were additional management, need for readmission for preterm labor, and tocolysis.

Neonatal outcomes, including birth weight and complications, also were similar between the groups, and there were no adverse effects associated with treatment.

Although several studies suggest that progesterone can reduce the rate of prematurity, many questions remain about optimal timing, mode of administration, dosing, and indications, Dr. Rozenberg noted. The findings of this study, however, do not support its use in women with a short cervix and an episode of preterm labor successfully treated with tocolysis.

"We could say that treatment with progesterone in patients with preterm labor and a short cervix below 25 mm did not prolong pregnancy, did not reduce the rate of prematurity and related complications, and was not associated with adverse effects. In conclusion, once the pathologic process of preterm labor begins, progesterone is no longer effective," he said.

Dr. Rozenberg said he had no relevant financial disclosures.

DALLAS – MicroRNA 210 is strongly associated with the presence of preeclampsia, and predicts the condition months prior to its onset, according to findings in a subset of women from a case-control study and women from a separate prospective cohort.

If validated as a reliable biomarker in larger studies, microRNA 210 (MIR210) could be used to risk-stratify women for development of hypertensive disorders of pregnancy, including preeclampsia, Dr. Michal A. Elovitz reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The levels of MIR210, as well as levels of MIR517a and MIR517c, were first analyzed in 28 maternal serum samples from women with preeclampsia who were enrolled in the Preeclampsia: Mechanisms and Consequences study. The microRNA levels were compared with those from samples collected from 14 control patients without preeclampsia at the time of delivery. Samples in the cases were collected either at the time of diagnosis or at the time of delivery, said Dr. Elovitz of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia.

The MIR517a and MIR517c levels did not differ between the groups, but MIR210 levels differed significantly in the cases and controls. In fact, each 1-unit increase in MIR210 was associated with a 9.5-fold increase in the odds of being a case vs. a control, Dr. Elovitz said, noting that controlling for race did not change the effect size, and that MIR210 had a "very high" predictive ability for being a case.

As expected, the gestational age at delivery was lower in the cases than the controls, but there were no significant differences in the rates of chronic hypertension, the number of African American women, and the number of fetuses with intrauterine growth restriction between the groups.

MIR210 levels also differed significantly in 38 cases and 57 controls from a separate prospective cohort of women undergoing integrated or sequential screening. Serum samples in that cohort were collected during the second trimester, at 15-17 weeks’ gestation.

Each 1-unit increase in MIR210 was associated in this cohort with a 2.9-fold increase in the likelihood of developing a hypertensive disease of pregnancy, Dr. Elovitz said, adding that the MIR210 in this population had "fair" predictive ability. When analysis was limited just to those who eventually developed preeclampsia, however, each 1-unit increase in MIR210 was associated with a 3.8-fold increase in the odds of developing preeclampsia.

Because there was such a wide range of MIR210 levels, she and her colleagues also looked at a 10-unit increase, and found that each of these units was associated with a 6.7-fold increase in the risk of preeclampsia. MIR210 in this scenario had a "fairly good" predictive value, she said.

In this portion of the study, no differences were seen between cases and controls with respect to gestational age at time of blood draw, number of African American women, rate of intrauterine fetal death, or rate of preterm birth at less than 37 weeks’ gestation.

MicroRNAs have emerged as critical players in many biological systems and in certain disease states, Dr. Elovitz explained.

MIR515a and MIR515c were included in the current analyses because they have previously been shown to be uniquely expressed in placental tissues, and increased in placental tissues from women with preeclampsia, compared with controls. MIR210 has been found to be very highly expressed in placental tissues, and is known to be highly involved in hypoxic conditions and to be a promising biomarker in other disease states, she said.

The current findings are important because preeclampsia is a leading cause of morbidity and mortality in pregnancy, and remains the leading cause of medically indicated preterm birth.

"Several randomized, controlled trials have failed to identify successful preventative strategies to decrease development of preeclampsia. Indeed, the pathogenesis of preeclampsia has not been revealed," she said, adding that consequently, the ability to identify those at risk is poor, and the ability to offer interventions based on the true pathogenesis of the disease has not been achieved.

The findings – although limited by the case-cohort design, small study populations, and the lack of a panel of microRNAs – suggest that MIR210 is a reliable biomarker for hypertensive disorders of pregnancy, including preeclampsia. The findings are strengthened by the focus on specific microRNAs and by the use of two cohorts.

"Further work is obviously necessary. We need to validate MIR210 as a reliable biomarker, and we need to unravel the role of MIR210 and other microRNAs in the pathogenesis of preeclampsia," Dr. Elovitz concluded.

Dr. Elovitz said she had no conflicts to disclose.

DALLAS – MicroRNA 210 is strongly associated with the presence of preeclampsia, and predicts the condition months prior to its onset, according to findings in a subset of women from a case-control study and women from a separate prospective cohort.

If validated as a reliable biomarker in larger studies, microRNA 210 (MIR210) could be used to risk-stratify women for development of hypertensive disorders of pregnancy, including preeclampsia, Dr. Michal A. Elovitz reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The levels of MIR210, as well as levels of MIR517a and MIR517c, were first analyzed in 28 maternal serum samples from women with preeclampsia who were enrolled in the Preeclampsia: Mechanisms and Consequences study. The microRNA levels were compared with those from samples collected from 14 control patients without preeclampsia at the time of delivery. Samples in the cases were collected either at the time of diagnosis or at the time of delivery, said Dr. Elovitz of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia.

The MIR517a and MIR517c levels did not differ between the groups, but MIR210 levels differed significantly in the cases and controls. In fact, each 1-unit increase in MIR210 was associated with a 9.5-fold increase in the odds of being a case vs. a control, Dr. Elovitz said, noting that controlling for race did not change the effect size, and that MIR210 had a "very high" predictive ability for being a case.

As expected, the gestational age at delivery was lower in the cases than the controls, but there were no significant differences in the rates of chronic hypertension, the number of African American women, and the number of fetuses with intrauterine growth restriction between the groups.

MIR210 levels also differed significantly in 38 cases and 57 controls from a separate prospective cohort of women undergoing integrated or sequential screening. Serum samples in that cohort were collected during the second trimester, at 15-17 weeks’ gestation.

Each 1-unit increase in MIR210 was associated in this cohort with a 2.9-fold increase in the likelihood of developing a hypertensive disease of pregnancy, Dr. Elovitz said, adding that the MIR210 in this population had "fair" predictive ability. When analysis was limited just to those who eventually developed preeclampsia, however, each 1-unit increase in MIR210 was associated with a 3.8-fold increase in the odds of developing preeclampsia.

Because there was such a wide range of MIR210 levels, she and her colleagues also looked at a 10-unit increase, and found that each of these units was associated with a 6.7-fold increase in the risk of preeclampsia. MIR210 in this scenario had a "fairly good" predictive value, she said.

In this portion of the study, no differences were seen between cases and controls with respect to gestational age at time of blood draw, number of African American women, rate of intrauterine fetal death, or rate of preterm birth at less than 37 weeks’ gestation.

MicroRNAs have emerged as critical players in many biological systems and in certain disease states, Dr. Elovitz explained.

MIR515a and MIR515c were included in the current analyses because they have previously been shown to be uniquely expressed in placental tissues, and increased in placental tissues from women with preeclampsia, compared with controls. MIR210 has been found to be very highly expressed in placental tissues, and is known to be highly involved in hypoxic conditions and to be a promising biomarker in other disease states, she said.

The current findings are important because preeclampsia is a leading cause of morbidity and mortality in pregnancy, and remains the leading cause of medically indicated preterm birth.

"Several randomized, controlled trials have failed to identify successful preventative strategies to decrease development of preeclampsia. Indeed, the pathogenesis of preeclampsia has not been revealed," she said, adding that consequently, the ability to identify those at risk is poor, and the ability to offer interventions based on the true pathogenesis of the disease has not been achieved.

The findings – although limited by the case-cohort design, small study populations, and the lack of a panel of microRNAs – suggest that MIR210 is a reliable biomarker for hypertensive disorders of pregnancy, including preeclampsia. The findings are strengthened by the focus on specific microRNAs and by the use of two cohorts.

"Further work is obviously necessary. We need to validate MIR210 as a reliable biomarker, and we need to unravel the role of MIR210 and other microRNAs in the pathogenesis of preeclampsia," Dr. Elovitz concluded.

Dr. Elovitz said she had no conflicts to disclose.

DALLAS – MicroRNA 210 is strongly associated with the presence of preeclampsia, and predicts the condition months prior to its onset, according to findings in a subset of women from a case-control study and women from a separate prospective cohort.

If validated as a reliable biomarker in larger studies, microRNA 210 (MIR210) could be used to risk-stratify women for development of hypertensive disorders of pregnancy, including preeclampsia, Dr. Michal A. Elovitz reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The levels of MIR210, as well as levels of MIR517a and MIR517c, were first analyzed in 28 maternal serum samples from women with preeclampsia who were enrolled in the Preeclampsia: Mechanisms and Consequences study. The microRNA levels were compared with those from samples collected from 14 control patients without preeclampsia at the time of delivery. Samples in the cases were collected either at the time of diagnosis or at the time of delivery, said Dr. Elovitz of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia.

The MIR517a and MIR517c levels did not differ between the groups, but MIR210 levels differed significantly in the cases and controls. In fact, each 1-unit increase in MIR210 was associated with a 9.5-fold increase in the odds of being a case vs. a control, Dr. Elovitz said, noting that controlling for race did not change the effect size, and that MIR210 had a "very high" predictive ability for being a case.

As expected, the gestational age at delivery was lower in the cases than the controls, but there were no significant differences in the rates of chronic hypertension, the number of African American women, and the number of fetuses with intrauterine growth restriction between the groups.

MIR210 levels also differed significantly in 38 cases and 57 controls from a separate prospective cohort of women undergoing integrated or sequential screening. Serum samples in that cohort were collected during the second trimester, at 15-17 weeks’ gestation.

Each 1-unit increase in MIR210 was associated in this cohort with a 2.9-fold increase in the likelihood of developing a hypertensive disease of pregnancy, Dr. Elovitz said, adding that the MIR210 in this population had "fair" predictive ability. When analysis was limited just to those who eventually developed preeclampsia, however, each 1-unit increase in MIR210 was associated with a 3.8-fold increase in the odds of developing preeclampsia.

Because there was such a wide range of MIR210 levels, she and her colleagues also looked at a 10-unit increase, and found that each of these units was associated with a 6.7-fold increase in the risk of preeclampsia. MIR210 in this scenario had a "fairly good" predictive value, she said.

In this portion of the study, no differences were seen between cases and controls with respect to gestational age at time of blood draw, number of African American women, rate of intrauterine fetal death, or rate of preterm birth at less than 37 weeks’ gestation.

MicroRNAs have emerged as critical players in many biological systems and in certain disease states, Dr. Elovitz explained.

MIR515a and MIR515c were included in the current analyses because they have previously been shown to be uniquely expressed in placental tissues, and increased in placental tissues from women with preeclampsia, compared with controls. MIR210 has been found to be very highly expressed in placental tissues, and is known to be highly involved in hypoxic conditions and to be a promising biomarker in other disease states, she said.

The current findings are important because preeclampsia is a leading cause of morbidity and mortality in pregnancy, and remains the leading cause of medically indicated preterm birth.

"Several randomized, controlled trials have failed to identify successful preventative strategies to decrease development of preeclampsia. Indeed, the pathogenesis of preeclampsia has not been revealed," she said, adding that consequently, the ability to identify those at risk is poor, and the ability to offer interventions based on the true pathogenesis of the disease has not been achieved.

The findings – although limited by the case-cohort design, small study populations, and the lack of a panel of microRNAs – suggest that MIR210 is a reliable biomarker for hypertensive disorders of pregnancy, including preeclampsia. The findings are strengthened by the focus on specific microRNAs and by the use of two cohorts.

"Further work is obviously necessary. We need to validate MIR210 as a reliable biomarker, and we need to unravel the role of MIR210 and other microRNAs in the pathogenesis of preeclampsia," Dr. Elovitz concluded.

Dr. Elovitz said she had no conflicts to disclose.

DALLAS – Numerous prescription drugs inhibit the metabolism of 17-alpha hydroxyprogesterone caproate, or 17P, and could impact its efficacy for the prevention of preterm delivery, according to findings from a study evaluating the effects of 25 specific medications.

Of the 25 medications tested, 16 were found to inhibit the metabolism of 17P, Dr. Courtney Cuppett reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Those with the strongest inhibitory effects were the asthma drug montelukast (Singulair), and the protease inhibitors nelfinavir (Viracept) and ritonavir (Norvir), which were associated with 90%-100% inhibition of 17P.

Drugs associated with moderate (50%-80%) inhibition of 17P were fluconazole (Diflucan), itraconazole (Sporanox), diltiazem, esomeprazole (Nexium), tacrolimus, and bergamottin. Those with weak (30%-50%) inhibitory effects included fluticasone, voriconazole (Vfend), nifedipine, erythromycin, sertraline (Zoloft), haloperidol (Haldol), and trazodone, and those with negligible (less than 20%) inhibitory effects included midazolam (Versed), quetiapine (Seroquel), venlafaxine (Effexor), citalopram (Celexa), clarithromycin (Biaxin), metronidazole (Flagyl), cyclosporine, sirolimus (Rapamune), and ondansetron (Zofran), said Dr. Cuppett, a fellow in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh’s Magee-Women’s Hospital.

The hormonal agent 17P has been shown to reduce the incidence of recurrent preterm birth by 33% in a high risk population of women. In 2011, it became the first medication to receive Food and Drug Administration approval for prevention of preterm birth. Its use has become widespread, and it is currently indicated in patients with a history of spontaneous preterm birth. It is administered at a weekly dosage of 250 mg given intramuscularly at 16-36 weeks’ gestation, Dr. Cuppett noted.

"Although this drug is routinely prescribed, there is so much we don’t understand," including the optimal dose and dosing interval and the definition of therapeutic concentration; in addition, "importantly, both the site and mechanism of action are still largely unknown," she said.

One thing that is known, however, is that there is very large interindividual variability in plasma concentrations (range, 5-40 ng/mL) in those receiving a standard dose, she said, noting that such variability can potentially affect efficacy, and may be one reason why only a third of the target population benefited from treatment in trials.

She and her colleagues also found that 17P is metabolized by the drug-metabolizing enzyme CYP3A4, which is primarily found in the liver, but is also found in other tissues, including the placenta, uterus, and cervix. CYP3A4 also is responsible for the metabolism of more than half of all prescription medications.

"Thus, we hypothesized that prescription medications may alter the metabolism of 17P," she said.

Using ideal drug concentrations and incubation conditions identified as part of the study, they incubated pooled human CYP3A4 microsomes with 17P alone and with each of the 25 medications known to be substrates and or inhibitors of CYP3A4.

The finding that the metabolism of 17P is significantly inhibited by several of the prescription medications suggests that these drug-drug interactions may contribute to the large interindividual variability in 17P plasma concentrations observed in patients treated with the standard 17P dose, Dr. Cuppett said.

The clinical implications of the findings are unclear, as the therapeutic window for 17P has not been defined.

"However, if in the future we are able to define the therapeutic window for 17P, the dose and/or dosing interval may be adjusted in women who also take medications that are substrates, inhibitors, and/or inducers of CYP3A4," she said.

Importantly, it should also be considered that if prescription medications inhibit 17P, the converse also could be true.

In the future, it will be important to look for the converse drug-drug interactions and potential for 17P to inhibit prescription medications – particularly those with narrow therapeutic windows – because inhibition of metabolism of such drugs could lead to toxicity.

An example is the protease inhibitors that were shown in this study to inhibit 17P by 90%-100%. If the converse interaction proved true, patients using these drugs would need to be monitored more closely for signs of toxicity, and doses may potentially require adjustment, Dr. Cuppett said.

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Cuppett said she had no relevant financial disclosures.

DALLAS – Numerous prescription drugs inhibit the metabolism of 17-alpha hydroxyprogesterone caproate, or 17P, and could impact its efficacy for the prevention of preterm delivery, according to findings from a study evaluating the effects of 25 specific medications.

Of the 25 medications tested, 16 were found to inhibit the metabolism of 17P, Dr. Courtney Cuppett reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Those with the strongest inhibitory effects were the asthma drug montelukast (Singulair), and the protease inhibitors nelfinavir (Viracept) and ritonavir (Norvir), which were associated with 90%-100% inhibition of 17P.

Drugs associated with moderate (50%-80%) inhibition of 17P were fluconazole (Diflucan), itraconazole (Sporanox), diltiazem, esomeprazole (Nexium), tacrolimus, and bergamottin. Those with weak (30%-50%) inhibitory effects included fluticasone, voriconazole (Vfend), nifedipine, erythromycin, sertraline (Zoloft), haloperidol (Haldol), and trazodone, and those with negligible (less than 20%) inhibitory effects included midazolam (Versed), quetiapine (Seroquel), venlafaxine (Effexor), citalopram (Celexa), clarithromycin (Biaxin), metronidazole (Flagyl), cyclosporine, sirolimus (Rapamune), and ondansetron (Zofran), said Dr. Cuppett, a fellow in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh’s Magee-Women’s Hospital.

The hormonal agent 17P has been shown to reduce the incidence of recurrent preterm birth by 33% in a high risk population of women. In 2011, it became the first medication to receive Food and Drug Administration approval for prevention of preterm birth. Its use has become widespread, and it is currently indicated in patients with a history of spontaneous preterm birth. It is administered at a weekly dosage of 250 mg given intramuscularly at 16-36 weeks’ gestation, Dr. Cuppett noted.

"Although this drug is routinely prescribed, there is so much we don’t understand," including the optimal dose and dosing interval and the definition of therapeutic concentration; in addition, "importantly, both the site and mechanism of action are still largely unknown," she said.

One thing that is known, however, is that there is very large interindividual variability in plasma concentrations (range, 5-40 ng/mL) in those receiving a standard dose, she said, noting that such variability can potentially affect efficacy, and may be one reason why only a third of the target population benefited from treatment in trials.

She and her colleagues also found that 17P is metabolized by the drug-metabolizing enzyme CYP3A4, which is primarily found in the liver, but is also found in other tissues, including the placenta, uterus, and cervix. CYP3A4 also is responsible for the metabolism of more than half of all prescription medications.

"Thus, we hypothesized that prescription medications may alter the metabolism of 17P," she said.

Using ideal drug concentrations and incubation conditions identified as part of the study, they incubated pooled human CYP3A4 microsomes with 17P alone and with each of the 25 medications known to be substrates and or inhibitors of CYP3A4.

The finding that the metabolism of 17P is significantly inhibited by several of the prescription medications suggests that these drug-drug interactions may contribute to the large interindividual variability in 17P plasma concentrations observed in patients treated with the standard 17P dose, Dr. Cuppett said.

The clinical implications of the findings are unclear, as the therapeutic window for 17P has not been defined.

"However, if in the future we are able to define the therapeutic window for 17P, the dose and/or dosing interval may be adjusted in women who also take medications that are substrates, inhibitors, and/or inducers of CYP3A4," she said.

Importantly, it should also be considered that if prescription medications inhibit 17P, the converse also could be true.

In the future, it will be important to look for the converse drug-drug interactions and potential for 17P to inhibit prescription medications – particularly those with narrow therapeutic windows – because inhibition of metabolism of such drugs could lead to toxicity.

An example is the protease inhibitors that were shown in this study to inhibit 17P by 90%-100%. If the converse interaction proved true, patients using these drugs would need to be monitored more closely for signs of toxicity, and doses may potentially require adjustment, Dr. Cuppett said.

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Cuppett said she had no relevant financial disclosures.

DALLAS – Numerous prescription drugs inhibit the metabolism of 17-alpha hydroxyprogesterone caproate, or 17P, and could impact its efficacy for the prevention of preterm delivery, according to findings from a study evaluating the effects of 25 specific medications.

Of the 25 medications tested, 16 were found to inhibit the metabolism of 17P, Dr. Courtney Cuppett reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Those with the strongest inhibitory effects were the asthma drug montelukast (Singulair), and the protease inhibitors nelfinavir (Viracept) and ritonavir (Norvir), which were associated with 90%-100% inhibition of 17P.

Drugs associated with moderate (50%-80%) inhibition of 17P were fluconazole (Diflucan), itraconazole (Sporanox), diltiazem, esomeprazole (Nexium), tacrolimus, and bergamottin. Those with weak (30%-50%) inhibitory effects included fluticasone, voriconazole (Vfend), nifedipine, erythromycin, sertraline (Zoloft), haloperidol (Haldol), and trazodone, and those with negligible (less than 20%) inhibitory effects included midazolam (Versed), quetiapine (Seroquel), venlafaxine (Effexor), citalopram (Celexa), clarithromycin (Biaxin), metronidazole (Flagyl), cyclosporine, sirolimus (Rapamune), and ondansetron (Zofran), said Dr. Cuppett, a fellow in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh’s Magee-Women’s Hospital.

The hormonal agent 17P has been shown to reduce the incidence of recurrent preterm birth by 33% in a high risk population of women. In 2011, it became the first medication to receive Food and Drug Administration approval for prevention of preterm birth. Its use has become widespread, and it is currently indicated in patients with a history of spontaneous preterm birth. It is administered at a weekly dosage of 250 mg given intramuscularly at 16-36 weeks’ gestation, Dr. Cuppett noted.

"Although this drug is routinely prescribed, there is so much we don’t understand," including the optimal dose and dosing interval and the definition of therapeutic concentration; in addition, "importantly, both the site and mechanism of action are still largely unknown," she said.

One thing that is known, however, is that there is very large interindividual variability in plasma concentrations (range, 5-40 ng/mL) in those receiving a standard dose, she said, noting that such variability can potentially affect efficacy, and may be one reason why only a third of the target population benefited from treatment in trials.

She and her colleagues also found that 17P is metabolized by the drug-metabolizing enzyme CYP3A4, which is primarily found in the liver, but is also found in other tissues, including the placenta, uterus, and cervix. CYP3A4 also is responsible for the metabolism of more than half of all prescription medications.

"Thus, we hypothesized that prescription medications may alter the metabolism of 17P," she said.

Using ideal drug concentrations and incubation conditions identified as part of the study, they incubated pooled human CYP3A4 microsomes with 17P alone and with each of the 25 medications known to be substrates and or inhibitors of CYP3A4.

The finding that the metabolism of 17P is significantly inhibited by several of the prescription medications suggests that these drug-drug interactions may contribute to the large interindividual variability in 17P plasma concentrations observed in patients treated with the standard 17P dose, Dr. Cuppett said.

The clinical implications of the findings are unclear, as the therapeutic window for 17P has not been defined.

"However, if in the future we are able to define the therapeutic window for 17P, the dose and/or dosing interval may be adjusted in women who also take medications that are substrates, inhibitors, and/or inducers of CYP3A4," she said.

Importantly, it should also be considered that if prescription medications inhibit 17P, the converse also could be true.

In the future, it will be important to look for the converse drug-drug interactions and potential for 17P to inhibit prescription medications – particularly those with narrow therapeutic windows – because inhibition of metabolism of such drugs could lead to toxicity.

An example is the protease inhibitors that were shown in this study to inhibit 17P by 90%-100%. If the converse interaction proved true, patients using these drugs would need to be monitored more closely for signs of toxicity, and doses may potentially require adjustment, Dr. Cuppett said.

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Cuppett said she had no relevant financial disclosures.

DALLAS – Slow progression of labor beyond 7 cm of dilation in women attempting a trial of labor after cesarean section may signal risk for uterine rupture, findings from a case-control study suggest.

In 99 women who experienced uterine rupture while attempting a trial of labor after cesarean section (TOLAC) and 309 controls who did not experience uterine rupture during TOLAC, the time to progress 1 cm of dilation – after adjustment for prior vaginal delivery – was similar until 7 cm of dilation. Once the women reached 7 cm of dilation, however, a 1 cm progression took significantly longer in those who experienced rupture.

For example, progression from 7 cm to 8 cm took a median of 0.33 vs. 0.15 hours in the uterine rupture patients and the controls, respectively, and the progression from 8 cm to 9 cm took a median of 0.24 vs. 0.1 hours in the groups, respectively, Dr. Lorie Harper of Washington University in St. Louis reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This works out to approx 10-13 minutes longer for the median time to progress 1 cm in the uterine rupture group," she said, noting that the differences were particularly striking at the 95th percentile of time per 1 cm of dilation; for women with a successful trial of labor, each 1 cm of dilation after 7 cm took less than 1 hour, while at the 95th percentile, progression of each 1 cm of dilation after 7 cm took at least 1 hour.

The findings are from a secondary analysis of data from a nested case-control study of women attempting TOLAC within a 17-center retrospective cohort study of women with a prior low transverse cesarean section. Cases included women who experienced uterine rupture, and controls included women attempting TOLAC who reached 10 cm dilation. An additional reference group included 110 women with a failed TOLAC who ultimately underwent repeat cesarean section, and no significant difference was seen between this group and the cases in terms of time to progress after 7 cm. All subjects had only one prior cesarean section.

Uterine rupture for this study was explicitly defined, a priori, as a full-thickness disruption of the uterine wall accompanied by clinical signs, Dr. Harper said.

The cases and controls from both reference groups were similar with respect to age, gravidity, diabetes, hypertension, and type of hospital, although the rate of prior vaginal delivery and black race both were more common in the reference groups. The three groups also were comparable with respect to intrapartum characteristics such as epidural use and gestational age at delivery, although those who experienced uterine rupture were more likely to have been induced and to have received Pitocin, she noted.

Although the case-control design of this study has inherent limitations such as possible selection bias, the study also has strengths, including the large study population of nearly 14,000 women in the original retrospective cohort, she said.

The findings suggest that a protracted labor prior to 7 cm of dilation does not necessarily signify uterine rupture in women attempting a TOLAC, as it was not uncommon during this period for the women to require 2 hours to progress 1 cm, and some still reached 10 cm, Dr. Harper said.

After 7 cm, however, labor dystocia should raise suspicion for uterine rupture in this population, she said.

Although the findings don’t necessarily suggest that intervention such as cesarean delivery is indicated in those with slow progression after 7 cm, they do underscore the need for more careful and frequent monitoring for signs of uterine rupture during active labor in women attempting a TOLAC.

"Instead of waiting 2 hours to check them, maybe they should be checked in an hour to make sure they’re progressing," she said.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Harper said she had no relevant financial disclosures.

DALLAS – Slow progression of labor beyond 7 cm of dilation in women attempting a trial of labor after cesarean section may signal risk for uterine rupture, findings from a case-control study suggest.

In 99 women who experienced uterine rupture while attempting a trial of labor after cesarean section (TOLAC) and 309 controls who did not experience uterine rupture during TOLAC, the time to progress 1 cm of dilation – after adjustment for prior vaginal delivery – was similar until 7 cm of dilation. Once the women reached 7 cm of dilation, however, a 1 cm progression took significantly longer in those who experienced rupture.

For example, progression from 7 cm to 8 cm took a median of 0.33 vs. 0.15 hours in the uterine rupture patients and the controls, respectively, and the progression from 8 cm to 9 cm took a median of 0.24 vs. 0.1 hours in the groups, respectively, Dr. Lorie Harper of Washington University in St. Louis reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This works out to approx 10-13 minutes longer for the median time to progress 1 cm in the uterine rupture group," she said, noting that the differences were particularly striking at the 95th percentile of time per 1 cm of dilation; for women with a successful trial of labor, each 1 cm of dilation after 7 cm took less than 1 hour, while at the 95th percentile, progression of each 1 cm of dilation after 7 cm took at least 1 hour.

The findings are from a secondary analysis of data from a nested case-control study of women attempting TOLAC within a 17-center retrospective cohort study of women with a prior low transverse cesarean section. Cases included women who experienced uterine rupture, and controls included women attempting TOLAC who reached 10 cm dilation. An additional reference group included 110 women with a failed TOLAC who ultimately underwent repeat cesarean section, and no significant difference was seen between this group and the cases in terms of time to progress after 7 cm. All subjects had only one prior cesarean section.

Uterine rupture for this study was explicitly defined, a priori, as a full-thickness disruption of the uterine wall accompanied by clinical signs, Dr. Harper said.

The cases and controls from both reference groups were similar with respect to age, gravidity, diabetes, hypertension, and type of hospital, although the rate of prior vaginal delivery and black race both were more common in the reference groups. The three groups also were comparable with respect to intrapartum characteristics such as epidural use and gestational age at delivery, although those who experienced uterine rupture were more likely to have been induced and to have received Pitocin, she noted.

Although the case-control design of this study has inherent limitations such as possible selection bias, the study also has strengths, including the large study population of nearly 14,000 women in the original retrospective cohort, she said.

The findings suggest that a protracted labor prior to 7 cm of dilation does not necessarily signify uterine rupture in women attempting a TOLAC, as it was not uncommon during this period for the women to require 2 hours to progress 1 cm, and some still reached 10 cm, Dr. Harper said.

After 7 cm, however, labor dystocia should raise suspicion for uterine rupture in this population, she said.

Although the findings don’t necessarily suggest that intervention such as cesarean delivery is indicated in those with slow progression after 7 cm, they do underscore the need for more careful and frequent monitoring for signs of uterine rupture during active labor in women attempting a TOLAC.

"Instead of waiting 2 hours to check them, maybe they should be checked in an hour to make sure they’re progressing," she said.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Harper said she had no relevant financial disclosures.

DALLAS – Slow progression of labor beyond 7 cm of dilation in women attempting a trial of labor after cesarean section may signal risk for uterine rupture, findings from a case-control study suggest.

In 99 women who experienced uterine rupture while attempting a trial of labor after cesarean section (TOLAC) and 309 controls who did not experience uterine rupture during TOLAC, the time to progress 1 cm of dilation – after adjustment for prior vaginal delivery – was similar until 7 cm of dilation. Once the women reached 7 cm of dilation, however, a 1 cm progression took significantly longer in those who experienced rupture.

For example, progression from 7 cm to 8 cm took a median of 0.33 vs. 0.15 hours in the uterine rupture patients and the controls, respectively, and the progression from 8 cm to 9 cm took a median of 0.24 vs. 0.1 hours in the groups, respectively, Dr. Lorie Harper of Washington University in St. Louis reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This works out to approx 10-13 minutes longer for the median time to progress 1 cm in the uterine rupture group," she said, noting that the differences were particularly striking at the 95th percentile of time per 1 cm of dilation; for women with a successful trial of labor, each 1 cm of dilation after 7 cm took less than 1 hour, while at the 95th percentile, progression of each 1 cm of dilation after 7 cm took at least 1 hour.

The findings are from a secondary analysis of data from a nested case-control study of women attempting TOLAC within a 17-center retrospective cohort study of women with a prior low transverse cesarean section. Cases included women who experienced uterine rupture, and controls included women attempting TOLAC who reached 10 cm dilation. An additional reference group included 110 women with a failed TOLAC who ultimately underwent repeat cesarean section, and no significant difference was seen between this group and the cases in terms of time to progress after 7 cm. All subjects had only one prior cesarean section.

Uterine rupture for this study was explicitly defined, a priori, as a full-thickness disruption of the uterine wall accompanied by clinical signs, Dr. Harper said.

The cases and controls from both reference groups were similar with respect to age, gravidity, diabetes, hypertension, and type of hospital, although the rate of prior vaginal delivery and black race both were more common in the reference groups. The three groups also were comparable with respect to intrapartum characteristics such as epidural use and gestational age at delivery, although those who experienced uterine rupture were more likely to have been induced and to have received Pitocin, she noted.

Although the case-control design of this study has inherent limitations such as possible selection bias, the study also has strengths, including the large study population of nearly 14,000 women in the original retrospective cohort, she said.

The findings suggest that a protracted labor prior to 7 cm of dilation does not necessarily signify uterine rupture in women attempting a TOLAC, as it was not uncommon during this period for the women to require 2 hours to progress 1 cm, and some still reached 10 cm, Dr. Harper said.

After 7 cm, however, labor dystocia should raise suspicion for uterine rupture in this population, she said.

Although the findings don’t necessarily suggest that intervention such as cesarean delivery is indicated in those with slow progression after 7 cm, they do underscore the need for more careful and frequent monitoring for signs of uterine rupture during active labor in women attempting a TOLAC.

"Instead of waiting 2 hours to check them, maybe they should be checked in an hour to make sure they’re progressing," she said.

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Harper said she had no relevant financial disclosures.

DALLAS – The drug 17-hydroxyprogesterone caproate, or 17P, is not effective for reducing the risk of preterm delivery in nulliparous women with a cervix length less than the 10th percentile, findings from a randomized placebo-controlled study involving 657 women have shown.

Based on findings from prior studies, 17P is indicated in women with a cervical length of 10-20 mm, which represents only a very small proportion of patients. The objective of the current study was to determine if the benefits of 17P might extend to those with a "longer short cervix," Dr. William Grobman said at the annual meeting of the Society for Maternal-Fetal Medicine.

"Using a cervical length cutoff of the 10th percentile potentially expands the benefits of progesterone to a larger proportion of the population," said Dr. Grobman of the department of obstetrics and gynecology at Northwestern University, Chicago, who was speaking on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

Between 16 and 22 weeks’ gestation, when routine anatomic surveys are performed, the 10th percentile for cervical length is 30 mm, he explained.

Of 15,436 women screened at the 14 centers that are part of the Maternal-Fetal Medicine Units Network, 1,588 had a cervical length of less than 30 mm, and 657 consented to randomization. The frequency of preterm birth, defined as delivery prior to 37 weeks’ gestation, was 25.1% in 327 women randomized to receive 17P, and 24.5% in the 330 who received placebo.

There also were no differences in the rates of preterm birth at less than 32 weeks and less than 28 weeks, and no difference in the survival curve – defined as the number of days the women remained pregnant following 17P injection, Dr. Grobman said.

Based on these findings, enrollment in the study was stopped at the third interim analysis, he noted.

As for neonatal outcomes, no difference was seen between the treatment and placebo groups in regard to a composite outcome including, but not limited to, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, retinopathy of prematurity, and perinatal death.

When neonatal outcomes were analyzed individually, a significant difference was seen between the treatment and placebo groups with regard to sepsis; those in the 17P group had a lower risk of developing sepsis, Dr. Grobman noted.

Women in this study had a singleton pregnancy, and were screened between 16 and 22³/₇ weeks by a certified sonographer. They had no major fetal anomalies, no increased probability of indicated preterm birth, and no prior loop electrosurgical excision procedure or müllerian anomalies.

Those who consented to participate received an injection of 1 mL of placebo, and those who returned at least 3 days later but before 23 weeks’ gestation were randomized to receive 250 mg of intramuscular 17P weekly, or identically appearing placebo. All received weekly injections until delivery or 37 weeks.

Those in the treatment group were slightly, but significantly older. All other characteristics, including body mass index, race/ethnicity, and estimated gestational age at randomization were similar in the treatment and placebo groups.

The mean cervical length was 24 mm in both groups; less than 10% had a cervical length less than 15 mm, and less than 20% of those had the cervical funnel visualized, Dr. Grobman said.

"Based on these data, we do conclude that weekly intramuscular 17P does not reduce the frequency of preterm birth in nulliparous women with a cervix less than 30 mm," he concluded.

"This is really a study more than anything of women with a longer short cervix," he added, explaining during a question and answer session that the study isn’t powered to look at outcomes for those with other cervical lengths, for example, less than 20 mm or less than 15 mm. About 85% of women in this study had a cervical length between 25 and 30 mm.

Dr. Grobman said he had no relevant financial disclosures.

DALLAS – The drug 17-hydroxyprogesterone caproate, or 17P, is not effective for reducing the risk of preterm delivery in nulliparous women with a cervix length less than the 10th percentile, findings from a randomized placebo-controlled study involving 657 women have shown.

Based on findings from prior studies, 17P is indicated in women with a cervical length of 10-20 mm, which represents only a very small proportion of patients. The objective of the current study was to determine if the benefits of 17P might extend to those with a "longer short cervix," Dr. William Grobman said at the annual meeting of the Society for Maternal-Fetal Medicine.

"Using a cervical length cutoff of the 10th percentile potentially expands the benefits of progesterone to a larger proportion of the population," said Dr. Grobman of the department of obstetrics and gynecology at Northwestern University, Chicago, who was speaking on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

Between 16 and 22 weeks’ gestation, when routine anatomic surveys are performed, the 10th percentile for cervical length is 30 mm, he explained.

Of 15,436 women screened at the 14 centers that are part of the Maternal-Fetal Medicine Units Network, 1,588 had a cervical length of less than 30 mm, and 657 consented to randomization. The frequency of preterm birth, defined as delivery prior to 37 weeks’ gestation, was 25.1% in 327 women randomized to receive 17P, and 24.5% in the 330 who received placebo.

There also were no differences in the rates of preterm birth at less than 32 weeks and less than 28 weeks, and no difference in the survival curve – defined as the number of days the women remained pregnant following 17P injection, Dr. Grobman said.

Based on these findings, enrollment in the study was stopped at the third interim analysis, he noted.

As for neonatal outcomes, no difference was seen between the treatment and placebo groups in regard to a composite outcome including, but not limited to, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, retinopathy of prematurity, and perinatal death.

When neonatal outcomes were analyzed individually, a significant difference was seen between the treatment and placebo groups with regard to sepsis; those in the 17P group had a lower risk of developing sepsis, Dr. Grobman noted.

Women in this study had a singleton pregnancy, and were screened between 16 and 22³/₇ weeks by a certified sonographer. They had no major fetal anomalies, no increased probability of indicated preterm birth, and no prior loop electrosurgical excision procedure or müllerian anomalies.

Those who consented to participate received an injection of 1 mL of placebo, and those who returned at least 3 days later but before 23 weeks’ gestation were randomized to receive 250 mg of intramuscular 17P weekly, or identically appearing placebo. All received weekly injections until delivery or 37 weeks.

Those in the treatment group were slightly, but significantly older. All other characteristics, including body mass index, race/ethnicity, and estimated gestational age at randomization were similar in the treatment and placebo groups.

The mean cervical length was 24 mm in both groups; less than 10% had a cervical length less than 15 mm, and less than 20% of those had the cervical funnel visualized, Dr. Grobman said.

"Based on these data, we do conclude that weekly intramuscular 17P does not reduce the frequency of preterm birth in nulliparous women with a cervix less than 30 mm," he concluded.

"This is really a study more than anything of women with a longer short cervix," he added, explaining during a question and answer session that the study isn’t powered to look at outcomes for those with other cervical lengths, for example, less than 20 mm or less than 15 mm. About 85% of women in this study had a cervical length between 25 and 30 mm.

Dr. Grobman said he had no relevant financial disclosures.

DALLAS – The drug 17-hydroxyprogesterone caproate, or 17P, is not effective for reducing the risk of preterm delivery in nulliparous women with a cervix length less than the 10th percentile, findings from a randomized placebo-controlled study involving 657 women have shown.

Based on findings from prior studies, 17P is indicated in women with a cervical length of 10-20 mm, which represents only a very small proportion of patients. The objective of the current study was to determine if the benefits of 17P might extend to those with a "longer short cervix," Dr. William Grobman said at the annual meeting of the Society for Maternal-Fetal Medicine.

"Using a cervical length cutoff of the 10th percentile potentially expands the benefits of progesterone to a larger proportion of the population," said Dr. Grobman of the department of obstetrics and gynecology at Northwestern University, Chicago, who was speaking on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

Between 16 and 22 weeks’ gestation, when routine anatomic surveys are performed, the 10th percentile for cervical length is 30 mm, he explained.

Of 15,436 women screened at the 14 centers that are part of the Maternal-Fetal Medicine Units Network, 1,588 had a cervical length of less than 30 mm, and 657 consented to randomization. The frequency of preterm birth, defined as delivery prior to 37 weeks’ gestation, was 25.1% in 327 women randomized to receive 17P, and 24.5% in the 330 who received placebo.

There also were no differences in the rates of preterm birth at less than 32 weeks and less than 28 weeks, and no difference in the survival curve – defined as the number of days the women remained pregnant following 17P injection, Dr. Grobman said.

Based on these findings, enrollment in the study was stopped at the third interim analysis, he noted.

As for neonatal outcomes, no difference was seen between the treatment and placebo groups in regard to a composite outcome including, but not limited to, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, retinopathy of prematurity, and perinatal death.

When neonatal outcomes were analyzed individually, a significant difference was seen between the treatment and placebo groups with regard to sepsis; those in the 17P group had a lower risk of developing sepsis, Dr. Grobman noted.

Women in this study had a singleton pregnancy, and were screened between 16 and 22³/₇ weeks by a certified sonographer. They had no major fetal anomalies, no increased probability of indicated preterm birth, and no prior loop electrosurgical excision procedure or müllerian anomalies.

Those who consented to participate received an injection of 1 mL of placebo, and those who returned at least 3 days later but before 23 weeks’ gestation were randomized to receive 250 mg of intramuscular 17P weekly, or identically appearing placebo. All received weekly injections until delivery or 37 weeks.

Those in the treatment group were slightly, but significantly older. All other characteristics, including body mass index, race/ethnicity, and estimated gestational age at randomization were similar in the treatment and placebo groups.

The mean cervical length was 24 mm in both groups; less than 10% had a cervical length less than 15 mm, and less than 20% of those had the cervical funnel visualized, Dr. Grobman said.

"Based on these data, we do conclude that weekly intramuscular 17P does not reduce the frequency of preterm birth in nulliparous women with a cervix less than 30 mm," he concluded.

"This is really a study more than anything of women with a longer short cervix," he added, explaining during a question and answer session that the study isn’t powered to look at outcomes for those with other cervical lengths, for example, less than 20 mm or less than 15 mm. About 85% of women in this study had a cervical length between 25 and 30 mm.

Dr. Grobman said he had no relevant financial disclosures.

DALLAS – Preterm birth may be related in part to potentially preventable environmental factors, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2006 suggest.

Survey responses from 2,441 Hispanic women with a prior live birth show that the rate of births prior to 36 weeks’ gestation in Hispanic immigrants who resided in the United States for less than 10 years was 3.1%, which was significantly lower than the 7.4% rate among those who lived in the United States for more than 10 years, and the 10.1% rate among Hispanic women born in the United States (age adjusted odds ratios, 2.1 and 3.1, respectively), Dr. Radek Bukowski reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings were similar after further adjustment for numerous factors that might affect preterm birth risk, such as age, body mass index, education, nutrition, marital status, sexual behaviors, toxic exposures, income, smoking status, diabetes, and hypertension (fully adjusted odds ratios, 2.1 and 3.5), said Dr. Bukowski of the University of Texas Medical Branch at Galveston.

One factor – language spoken at home – did appear to have a modifying effect on the association between length of residence in the United States and the risk of preterm birth, however.

"Compared with women who lived in the United States less than 10 years, those who lived here 10 years or longer and those who were born in the United States had the highest risk if they predominantly or exclusively spoke Spanish at home," Dr. Bukowski said.

Also, body mass index was negatively associated with preterm birth, and hypertension was positively associated with preterm birth, but these were not found to be independent risk factors in the fully adjusted model, he said.

Although nongenetic environmental factors have been thought to play a role in preterm birth risk, it has not been clear whether risk is predominantly related to genetic or environmental factors. However, many immigrants are known to have a lower risk, which could be related to better diet and health status, he said.

Although limited by the study’s cross-sectional design, the current findings suggest that risk is acquired with residence in the United States. Given this, as well as the fact that preterm birth was not associated with a number of other risk factors in this study, it is possible that the level of risk is modifiable, Dr. Bukowski concluded.

Dr. Bukowski said he had no relevant financial disclosures.

DALLAS – Preterm birth may be related in part to potentially preventable environmental factors, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2006 suggest.

Survey responses from 2,441 Hispanic women with a prior live birth show that the rate of births prior to 36 weeks’ gestation in Hispanic immigrants who resided in the United States for less than 10 years was 3.1%, which was significantly lower than the 7.4% rate among those who lived in the United States for more than 10 years, and the 10.1% rate among Hispanic women born in the United States (age adjusted odds ratios, 2.1 and 3.1, respectively), Dr. Radek Bukowski reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings were similar after further adjustment for numerous factors that might affect preterm birth risk, such as age, body mass index, education, nutrition, marital status, sexual behaviors, toxic exposures, income, smoking status, diabetes, and hypertension (fully adjusted odds ratios, 2.1 and 3.5), said Dr. Bukowski of the University of Texas Medical Branch at Galveston.

One factor – language spoken at home – did appear to have a modifying effect on the association between length of residence in the United States and the risk of preterm birth, however.

"Compared with women who lived in the United States less than 10 years, those who lived here 10 years or longer and those who were born in the United States had the highest risk if they predominantly or exclusively spoke Spanish at home," Dr. Bukowski said.

Also, body mass index was negatively associated with preterm birth, and hypertension was positively associated with preterm birth, but these were not found to be independent risk factors in the fully adjusted model, he said.

Although nongenetic environmental factors have been thought to play a role in preterm birth risk, it has not been clear whether risk is predominantly related to genetic or environmental factors. However, many immigrants are known to have a lower risk, which could be related to better diet and health status, he said.

Although limited by the study’s cross-sectional design, the current findings suggest that risk is acquired with residence in the United States. Given this, as well as the fact that preterm birth was not associated with a number of other risk factors in this study, it is possible that the level of risk is modifiable, Dr. Bukowski concluded.

Dr. Bukowski said he had no relevant financial disclosures.

DALLAS – Preterm birth may be related in part to potentially preventable environmental factors, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2006 suggest.

Survey responses from 2,441 Hispanic women with a prior live birth show that the rate of births prior to 36 weeks’ gestation in Hispanic immigrants who resided in the United States for less than 10 years was 3.1%, which was significantly lower than the 7.4% rate among those who lived in the United States for more than 10 years, and the 10.1% rate among Hispanic women born in the United States (age adjusted odds ratios, 2.1 and 3.1, respectively), Dr. Radek Bukowski reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings were similar after further adjustment for numerous factors that might affect preterm birth risk, such as age, body mass index, education, nutrition, marital status, sexual behaviors, toxic exposures, income, smoking status, diabetes, and hypertension (fully adjusted odds ratios, 2.1 and 3.5), said Dr. Bukowski of the University of Texas Medical Branch at Galveston.

One factor – language spoken at home – did appear to have a modifying effect on the association between length of residence in the United States and the risk of preterm birth, however.

"Compared with women who lived in the United States less than 10 years, those who lived here 10 years or longer and those who were born in the United States had the highest risk if they predominantly or exclusively spoke Spanish at home," Dr. Bukowski said.

Also, body mass index was negatively associated with preterm birth, and hypertension was positively associated with preterm birth, but these were not found to be independent risk factors in the fully adjusted model, he said.

Although nongenetic environmental factors have been thought to play a role in preterm birth risk, it has not been clear whether risk is predominantly related to genetic or environmental factors. However, many immigrants are known to have a lower risk, which could be related to better diet and health status, he said.

Although limited by the study’s cross-sectional design, the current findings suggest that risk is acquired with residence in the United States. Given this, as well as the fact that preterm birth was not associated with a number of other risk factors in this study, it is possible that the level of risk is modifiable, Dr. Bukowski concluded.

Dr. Bukowski said he had no relevant financial disclosures.

DALLAS – The risk of autism is significantly increased in both very small and very large for gestational age infants, compared with average for gestational age infants, according to findings from a large retrospective population-based cohort study.

The findings, which indicate that the risk for autism is increased by 10% for very small for gestational age (SGA) and 12% for very large for gestational age (LGA) infants confirm similar findings from prior smaller studies, and also provide new information about the influence of birth weight on the risk, Dr. Gaea Moore reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Of the nearly 6 million infants from the 1991-2001 California birth cohort, 21,717 who were eventually diagnosed with autism were included in the study. When stratified based on birth weight, the likelihood of autism in the SGA group was significant only in the preterm very SGA infants (those above the 95th percentile), said Dr. Moore of the University of Colorado at Denver, Aurora.

In the LGA group, the pattern was more complex. A significantly increased risk for autism was found only in very LGA infants (above the 95th percentile) born at term (greater than 39 weeks’ gestation).

"Interestingly, we found a protective effect in the LGA birth weight group, which was significant in the preterm period at less than 32 weeks," Dr. Moore said, noting that the finding was significant for both LGA and very LGA infants.

The findings confirm the results of multiple smaller analyses, but also provide a "new piece of the puzzle," she said.

"That is the finding that very SGA children born in the preterm setting have an increased risk of autism," she said, adding, "We suspect that the association might be the result of a combination of neurologic insults at a key window of development – likely, whatever contributed to the restricted growth in the intrauterine environment, combined with the typical neurological insults of prematurity."

As for the dichotomous pattern of risk in the LGA infants, the finding may explain why LGA birth weight has not been associated with autism in the past, she said, explaining that the protection afforded in the preterm period likely cancelled out the increased risk at term.

The increased risk in the term setting may reflect maternal abnormalities such as obesity and diabetes, which are risk factors both for delivery of an LGA child, and for delivery of a child with autism, she noted.

"The decreased risk in the preterm period (for LGA infants), is interesting. We know that LGA preterm infants have a higher rate of survival and a higher rate of survival without major morbidity. Thus, these larger preterm infants may simply survive prematurity with a lesser degree of neurologic insult," she suggested.

Alternately, the finding may reflect incorrect dating, which would explain both larger infants and infants less likely to sustain perinatal or neurological injury, she said.

The findings have implications for heightened screening for SGA and LGA during pregnancy, as well as for encouraging appropriate weight gain during pregnancy, she concluded.

Dr. Moore said she had no relevant financial disclosures.

DALLAS – The risk of autism is significantly increased in both very small and very large for gestational age infants, compared with average for gestational age infants, according to findings from a large retrospective population-based cohort study.

The findings, which indicate that the risk for autism is increased by 10% for very small for gestational age (SGA) and 12% for very large for gestational age (LGA) infants confirm similar findings from prior smaller studies, and also provide new information about the influence of birth weight on the risk, Dr. Gaea Moore reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Of the nearly 6 million infants from the 1991-2001 California birth cohort, 21,717 who were eventually diagnosed with autism were included in the study. When stratified based on birth weight, the likelihood of autism in the SGA group was significant only in the preterm very SGA infants (those above the 95th percentile), said Dr. Moore of the University of Colorado at Denver, Aurora.

In the LGA group, the pattern was more complex. A significantly increased risk for autism was found only in very LGA infants (above the 95th percentile) born at term (greater than 39 weeks’ gestation).

"Interestingly, we found a protective effect in the LGA birth weight group, which was significant in the preterm period at less than 32 weeks," Dr. Moore said, noting that the finding was significant for both LGA and very LGA infants.

The findings confirm the results of multiple smaller analyses, but also provide a "new piece of the puzzle," she said.

"That is the finding that very SGA children born in the preterm setting have an increased risk of autism," she said, adding, "We suspect that the association might be the result of a combination of neurologic insults at a key window of development – likely, whatever contributed to the restricted growth in the intrauterine environment, combined with the typical neurological insults of prematurity."

As for the dichotomous pattern of risk in the LGA infants, the finding may explain why LGA birth weight has not been associated with autism in the past, she said, explaining that the protection afforded in the preterm period likely cancelled out the increased risk at term.

The increased risk in the term setting may reflect maternal abnormalities such as obesity and diabetes, which are risk factors both for delivery of an LGA child, and for delivery of a child with autism, she noted.

"The decreased risk in the preterm period (for LGA infants), is interesting. We know that LGA preterm infants have a higher rate of survival and a higher rate of survival without major morbidity. Thus, these larger preterm infants may simply survive prematurity with a lesser degree of neurologic insult," she suggested.

Alternately, the finding may reflect incorrect dating, which would explain both larger infants and infants less likely to sustain perinatal or neurological injury, she said.

The findings have implications for heightened screening for SGA and LGA during pregnancy, as well as for encouraging appropriate weight gain during pregnancy, she concluded.

Dr. Moore said she had no relevant financial disclosures.

DALLAS – The risk of autism is significantly increased in both very small and very large for gestational age infants, compared with average for gestational age infants, according to findings from a large retrospective population-based cohort study.

The findings, which indicate that the risk for autism is increased by 10% for very small for gestational age (SGA) and 12% for very large for gestational age (LGA) infants confirm similar findings from prior smaller studies, and also provide new information about the influence of birth weight on the risk, Dr. Gaea Moore reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Of the nearly 6 million infants from the 1991-2001 California birth cohort, 21,717 who were eventually diagnosed with autism were included in the study. When stratified based on birth weight, the likelihood of autism in the SGA group was significant only in the preterm very SGA infants (those above the 95th percentile), said Dr. Moore of the University of Colorado at Denver, Aurora.

In the LGA group, the pattern was more complex. A significantly increased risk for autism was found only in very LGA infants (above the 95th percentile) born at term (greater than 39 weeks’ gestation).

"Interestingly, we found a protective effect in the LGA birth weight group, which was significant in the preterm period at less than 32 weeks," Dr. Moore said, noting that the finding was significant for both LGA and very LGA infants.

The findings confirm the results of multiple smaller analyses, but also provide a "new piece of the puzzle," she said.

"That is the finding that very SGA children born in the preterm setting have an increased risk of autism," she said, adding, "We suspect that the association might be the result of a combination of neurologic insults at a key window of development – likely, whatever contributed to the restricted growth in the intrauterine environment, combined with the typical neurological insults of prematurity."

As for the dichotomous pattern of risk in the LGA infants, the finding may explain why LGA birth weight has not been associated with autism in the past, she said, explaining that the protection afforded in the preterm period likely cancelled out the increased risk at term.

The increased risk in the term setting may reflect maternal abnormalities such as obesity and diabetes, which are risk factors both for delivery of an LGA child, and for delivery of a child with autism, she noted.

"The decreased risk in the preterm period (for LGA infants), is interesting. We know that LGA preterm infants have a higher rate of survival and a higher rate of survival without major morbidity. Thus, these larger preterm infants may simply survive prematurity with a lesser degree of neurologic insult," she suggested.

Alternately, the finding may reflect incorrect dating, which would explain both larger infants and infants less likely to sustain perinatal or neurological injury, she said.

The findings have implications for heightened screening for SGA and LGA during pregnancy, as well as for encouraging appropriate weight gain during pregnancy, she concluded.

Dr. Moore said she had no relevant financial disclosures.

DALLAS – Chromosomal microarray, or CMA, is as effective as karyotyping for identifying common aneuploidies during routine and high-risk prenatal screening, and it also provides clinically significant and relevant information in patients with a normal karyotype, according to findings from a prospective study involving more than 4,400 women.

The findings support a transition from the use of karyotyping to the use of CMA as the first tier test for invasive cytogenetic testing, Dr. Ronald Wapner said at the annual meeting of the Society for Maternal-Fetal Medicine.

Reporting on behalf of the Prenatal Microarray Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Dr. Wapner noted that the analyses were performed on 4,391 samples, of which about half were obtained by chorionic villus sampling and about half by amniocentesis. DNA extraction or microarray failed in 51 samples, for a CMA success rate of nearly 99%.

He reported the findings from 4,282 samples with nonmosaic karyotype results.

Indications for enrollment among the 4,401 women who participated in the study included advanced maternal age in about half of the patients, a positive first or second trimester screen in about 20%, and an abnormal ultrasound in about 25%, with "other" indications accounting for the remaining participants.

Of all cases with common autosomal or sex chromosome aneuploidy identified by karyotyping, 100% were confirmed by microarray testing, said Dr. Wapner, chief of maternal fetal medicine at Columbia University Medical Center, New York.

Eight of the samples were identified as mosaic by microarray testing, but none of those led to an incorrect diagnosis; interestingly, all eight were from chorionic villus samples, Dr. Wapner noted. "Therefore, we can say very comfortably that CMA is a 100% comparison with karyotyping for common autosomal and sex chromosome aneuploidies."

Consistent with what is known about the technique of microarray testing; however, none of the triploidy pregnancies were identified, but 15 of 17 were correctly called using maternal cell contamination results, he noted.

Among participants with normal karyotypes, 35 (0.9%) had a CMA finding included on a predetermined pathogenic list. Of 94 (2.5%) with another finding not on the list, about two-thirds were determined by a clinical advisory committee to be clinically relevant. Thus, 96 samples (2.5%) were found to have clinically relevant material beyond what was seen on the karyotype, Dr. Wapner said.

A break-down based on participant’s indication for testing showed that of cases with an ultrasound abnormality, 6% had additional clinically significant results on CMA despite a normal karyotype, and of those with advanced maternal age or a positive screen, 1.6%-1.7% had additional clinically significant results on CMA despite a normal karyotype.

The findings indicate that a transition from karyotyping to CMA for prenatal cytogenetic diagnosis is warranted, Dr. Wapner said. "But if we are going to use CMA in prenatal care, particularly, we will have to have an additional approach that will allow the detection of triploidy pregnancy, and there are many that are available," he added.

Also, the transition will require a very methodical, well-thought-out approach including development of standardized pre- and post-test counseling, and discussion of how to manage some of the unusual findings identified using CMA, he noted.

Dr. Wapner said he had no relevant financial disclosures.

DALLAS – Chromosomal microarray, or CMA, is as effective as karyotyping for identifying common aneuploidies during routine and high-risk prenatal screening, and it also provides clinically significant and relevant information in patients with a normal karyotype, according to findings from a prospective study involving more than 4,400 women.

The findings support a transition from the use of karyotyping to the use of CMA as the first tier test for invasive cytogenetic testing, Dr. Ronald Wapner said at the annual meeting of the Society for Maternal-Fetal Medicine.

Reporting on behalf of the Prenatal Microarray Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Dr. Wapner noted that the analyses were performed on 4,391 samples, of which about half were obtained by chorionic villus sampling and about half by amniocentesis. DNA extraction or microarray failed in 51 samples, for a CMA success rate of nearly 99%.

He reported the findings from 4,282 samples with nonmosaic karyotype results.

Indications for enrollment among the 4,401 women who participated in the study included advanced maternal age in about half of the patients, a positive first or second trimester screen in about 20%, and an abnormal ultrasound in about 25%, with "other" indications accounting for the remaining participants.

Of all cases with common autosomal or sex chromosome aneuploidy identified by karyotyping, 100% were confirmed by microarray testing, said Dr. Wapner, chief of maternal fetal medicine at Columbia University Medical Center, New York.

Eight of the samples were identified as mosaic by microarray testing, but none of those led to an incorrect diagnosis; interestingly, all eight were from chorionic villus samples, Dr. Wapner noted. "Therefore, we can say very comfortably that CMA is a 100% comparison with karyotyping for common autosomal and sex chromosome aneuploidies."

Consistent with what is known about the technique of microarray testing; however, none of the triploidy pregnancies were identified, but 15 of 17 were correctly called using maternal cell contamination results, he noted.

Among participants with normal karyotypes, 35 (0.9%) had a CMA finding included on a predetermined pathogenic list. Of 94 (2.5%) with another finding not on the list, about two-thirds were determined by a clinical advisory committee to be clinically relevant. Thus, 96 samples (2.5%) were found to have clinically relevant material beyond what was seen on the karyotype, Dr. Wapner said.

A break-down based on participant’s indication for testing showed that of cases with an ultrasound abnormality, 6% had additional clinically significant results on CMA despite a normal karyotype, and of those with advanced maternal age or a positive screen, 1.6%-1.7% had additional clinically significant results on CMA despite a normal karyotype.

The findings indicate that a transition from karyotyping to CMA for prenatal cytogenetic diagnosis is warranted, Dr. Wapner said. "But if we are going to use CMA in prenatal care, particularly, we will have to have an additional approach that will allow the detection of triploidy pregnancy, and there are many that are available," he added.

Also, the transition will require a very methodical, well-thought-out approach including development of standardized pre- and post-test counseling, and discussion of how to manage some of the unusual findings identified using CMA, he noted.

Dr. Wapner said he had no relevant financial disclosures.

DALLAS – Chromosomal microarray, or CMA, is as effective as karyotyping for identifying common aneuploidies during routine and high-risk prenatal screening, and it also provides clinically significant and relevant information in patients with a normal karyotype, according to findings from a prospective study involving more than 4,400 women.

The findings support a transition from the use of karyotyping to the use of CMA as the first tier test for invasive cytogenetic testing, Dr. Ronald Wapner said at the annual meeting of the Society for Maternal-Fetal Medicine.

Reporting on behalf of the Prenatal Microarray Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Dr. Wapner noted that the analyses were performed on 4,391 samples, of which about half were obtained by chorionic villus sampling and about half by amniocentesis. DNA extraction or microarray failed in 51 samples, for a CMA success rate of nearly 99%.

He reported the findings from 4,282 samples with nonmosaic karyotype results.

Indications for enrollment among the 4,401 women who participated in the study included advanced maternal age in about half of the patients, a positive first or second trimester screen in about 20%, and an abnormal ultrasound in about 25%, with "other" indications accounting for the remaining participants.

Of all cases with common autosomal or sex chromosome aneuploidy identified by karyotyping, 100% were confirmed by microarray testing, said Dr. Wapner, chief of maternal fetal medicine at Columbia University Medical Center, New York.

Eight of the samples were identified as mosaic by microarray testing, but none of those led to an incorrect diagnosis; interestingly, all eight were from chorionic villus samples, Dr. Wapner noted. "Therefore, we can say very comfortably that CMA is a 100% comparison with karyotyping for common autosomal and sex chromosome aneuploidies."

Consistent with what is known about the technique of microarray testing; however, none of the triploidy pregnancies were identified, but 15 of 17 were correctly called using maternal cell contamination results, he noted.

Among participants with normal karyotypes, 35 (0.9%) had a CMA finding included on a predetermined pathogenic list. Of 94 (2.5%) with another finding not on the list, about two-thirds were determined by a clinical advisory committee to be clinically relevant. Thus, 96 samples (2.5%) were found to have clinically relevant material beyond what was seen on the karyotype, Dr. Wapner said.

A break-down based on participant’s indication for testing showed that of cases with an ultrasound abnormality, 6% had additional clinically significant results on CMA despite a normal karyotype, and of those with advanced maternal age or a positive screen, 1.6%-1.7% had additional clinically significant results on CMA despite a normal karyotype.

The findings indicate that a transition from karyotyping to CMA for prenatal cytogenetic diagnosis is warranted, Dr. Wapner said. "But if we are going to use CMA in prenatal care, particularly, we will have to have an additional approach that will allow the detection of triploidy pregnancy, and there are many that are available," he added.

Also, the transition will require a very methodical, well-thought-out approach including development of standardized pre- and post-test counseling, and discussion of how to manage some of the unusual findings identified using CMA, he noted.

Dr. Wapner said he had no relevant financial disclosures.