Susan London

SAN FRANCISCO – Obstetric history may influence how much benefit pregnant women obtain from 17 alpha-hydroxyprogesterone caproate that is taken to prevent a recurrence of preterm delivery, according to results of a retrospective study.

All of the 7,319 pregnant women in the retrospective study were receiving 17 alpha-hydroxyprogesterone caproate (17P) because they had experienced at least one spontaneous preterm delivery (SPTD).

The group who had just a single SPTD was 17% less likely to have a recurrence if they had also experienced a prior term birth. There was a trend toward a benefit of a prior term birth only in the group who had had multiple SPTDs.

These findings raise the possibility that a prior term birth may modify the effectiveness of 17P, according to Dr. John R. Barton.

Still, "current information would suggest that 17P be offered to all women with a history of prior SPTD in a current singleton pregnancy, even if they have experienced a term gestation, especially now with the Food and Drug Administration’s approval of 17P," he said at the annual meeting of the Society for Maternal-Fetal Medicine. The FDA said that it had approved 17P for the prevention of recurrent preterm birth in women with singleton pregnancies.

Investigators have noted a lack of direct data on the benefit of 17P in women with a prior term birth followed by SPTD, Dr. Barton observed. Additionally, some have expressed concern that this treatment may increase fetal loss.

He and his colleagues studied women with a singleton pregnancy who received weekly 250-mg intramuscular injections of 17P through a home administration program because of previous SPTD. Treatment began before 25 weeks’ gestation and continued until 36 completed weeks or preterm delivery.

About 70% of the women had previously experienced just one SPTD, while the other 30% had experienced more than one, reported Dr. Barton, who is director of maternal-fetal medicine at Central Baptist Hospital in Lexington, Ky.

In the group who had just one SPTD, women with a prior term birth were significantly less likely than those without a prior term birth to have a recurrent SPTD before 37 weeks’ gestation (odds ratio, 0.83), and also before 35 weeks (OR, 0.73) and before 32 weeks (OR, 0.74).

In a multivariate logistic regression analysis, a prior term birth still significantly protected against recurrent SPTD before 37 weeks (OR, 0.83; P = .01).

In the group who had more than one SPTD, women with a prior term birth were significantly less likely to have a recurrent SPTD before 37 weeks’ gestation (OR, 0.79) but not before 35 or 32 weeks. And in a multivariate logistic regression analysis, there was a trend toward a lower risk of recurrent SPTD only before 37 weeks (OR, 0.83; P = .06).

Comparing results across singleton progestin studies, Dr. Barton noted that the rate of fetal death in the study cohort was just 0.37%, or much lower than the 1.3% observed in the placebo arms of two randomized trials (N. Engl. J. Med. 2003;348:2379-85; Ultrasound Obstet. Gynecol. 2007;30:687-96).

Moreover, those two trials were much smaller. Therefore, "I think we can conclude that our stillbirth rate was not increased above those in the placebo cohorts."

The study had its limitations, acknowledged Dr. Barton. It was retrospective, did not have data on cervical length, and lacked a control group not given 17P.

But there also were some noteworthy strengths. "This is the largest cohort of women with a prior SPTD evaluating 17P therapy in a community setting," he elaborated. "It’s also the first to evaluate the impact of a prior term delivery as a modifier of the risk of recurrent SPTD at less than 37, less than 35, and less than 32 weeks’ gestation."

Dr. Barton reported receiving support from Alere San Diego Inc. for preeclampsia research.

SAN FRANCISCO – Obstetric history may influence how much benefit pregnant women obtain from 17 alpha-hydroxyprogesterone caproate that is taken to prevent a recurrence of preterm delivery, according to results of a retrospective study.

All of the 7,319 pregnant women in the retrospective study were receiving 17 alpha-hydroxyprogesterone caproate (17P) because they had experienced at least one spontaneous preterm delivery (SPTD).

The group who had just a single SPTD was 17% less likely to have a recurrence if they had also experienced a prior term birth. There was a trend toward a benefit of a prior term birth only in the group who had had multiple SPTDs.

These findings raise the possibility that a prior term birth may modify the effectiveness of 17P, according to Dr. John R. Barton.

Still, "current information would suggest that 17P be offered to all women with a history of prior SPTD in a current singleton pregnancy, even if they have experienced a term gestation, especially now with the Food and Drug Administration’s approval of 17P," he said at the annual meeting of the Society for Maternal-Fetal Medicine. The FDA said that it had approved 17P for the prevention of recurrent preterm birth in women with singleton pregnancies.

Investigators have noted a lack of direct data on the benefit of 17P in women with a prior term birth followed by SPTD, Dr. Barton observed. Additionally, some have expressed concern that this treatment may increase fetal loss.

He and his colleagues studied women with a singleton pregnancy who received weekly 250-mg intramuscular injections of 17P through a home administration program because of previous SPTD. Treatment began before 25 weeks’ gestation and continued until 36 completed weeks or preterm delivery.

About 70% of the women had previously experienced just one SPTD, while the other 30% had experienced more than one, reported Dr. Barton, who is director of maternal-fetal medicine at Central Baptist Hospital in Lexington, Ky.

In the group who had just one SPTD, women with a prior term birth were significantly less likely than those without a prior term birth to have a recurrent SPTD before 37 weeks’ gestation (odds ratio, 0.83), and also before 35 weeks (OR, 0.73) and before 32 weeks (OR, 0.74).

In a multivariate logistic regression analysis, a prior term birth still significantly protected against recurrent SPTD before 37 weeks (OR, 0.83; P = .01).

In the group who had more than one SPTD, women with a prior term birth were significantly less likely to have a recurrent SPTD before 37 weeks’ gestation (OR, 0.79) but not before 35 or 32 weeks. And in a multivariate logistic regression analysis, there was a trend toward a lower risk of recurrent SPTD only before 37 weeks (OR, 0.83; P = .06).

Comparing results across singleton progestin studies, Dr. Barton noted that the rate of fetal death in the study cohort was just 0.37%, or much lower than the 1.3% observed in the placebo arms of two randomized trials (N. Engl. J. Med. 2003;348:2379-85; Ultrasound Obstet. Gynecol. 2007;30:687-96).

Moreover, those two trials were much smaller. Therefore, "I think we can conclude that our stillbirth rate was not increased above those in the placebo cohorts."

The study had its limitations, acknowledged Dr. Barton. It was retrospective, did not have data on cervical length, and lacked a control group not given 17P.

But there also were some noteworthy strengths. "This is the largest cohort of women with a prior SPTD evaluating 17P therapy in a community setting," he elaborated. "It’s also the first to evaluate the impact of a prior term delivery as a modifier of the risk of recurrent SPTD at less than 37, less than 35, and less than 32 weeks’ gestation."

Dr. Barton reported receiving support from Alere San Diego Inc. for preeclampsia research.

SAN FRANCISCO – Obstetric history may influence how much benefit pregnant women obtain from 17 alpha-hydroxyprogesterone caproate that is taken to prevent a recurrence of preterm delivery, according to results of a retrospective study.

All of the 7,319 pregnant women in the retrospective study were receiving 17 alpha-hydroxyprogesterone caproate (17P) because they had experienced at least one spontaneous preterm delivery (SPTD).

The group who had just a single SPTD was 17% less likely to have a recurrence if they had also experienced a prior term birth. There was a trend toward a benefit of a prior term birth only in the group who had had multiple SPTDs.

These findings raise the possibility that a prior term birth may modify the effectiveness of 17P, according to Dr. John R. Barton.

Still, "current information would suggest that 17P be offered to all women with a history of prior SPTD in a current singleton pregnancy, even if they have experienced a term gestation, especially now with the Food and Drug Administration’s approval of 17P," he said at the annual meeting of the Society for Maternal-Fetal Medicine. The FDA said that it had approved 17P for the prevention of recurrent preterm birth in women with singleton pregnancies.

Investigators have noted a lack of direct data on the benefit of 17P in women with a prior term birth followed by SPTD, Dr. Barton observed. Additionally, some have expressed concern that this treatment may increase fetal loss.

He and his colleagues studied women with a singleton pregnancy who received weekly 250-mg intramuscular injections of 17P through a home administration program because of previous SPTD. Treatment began before 25 weeks’ gestation and continued until 36 completed weeks or preterm delivery.

About 70% of the women had previously experienced just one SPTD, while the other 30% had experienced more than one, reported Dr. Barton, who is director of maternal-fetal medicine at Central Baptist Hospital in Lexington, Ky.

In the group who had just one SPTD, women with a prior term birth were significantly less likely than those without a prior term birth to have a recurrent SPTD before 37 weeks’ gestation (odds ratio, 0.83), and also before 35 weeks (OR, 0.73) and before 32 weeks (OR, 0.74).

In a multivariate logistic regression analysis, a prior term birth still significantly protected against recurrent SPTD before 37 weeks (OR, 0.83; P = .01).

In the group who had more than one SPTD, women with a prior term birth were significantly less likely to have a recurrent SPTD before 37 weeks’ gestation (OR, 0.79) but not before 35 or 32 weeks. And in a multivariate logistic regression analysis, there was a trend toward a lower risk of recurrent SPTD only before 37 weeks (OR, 0.83; P = .06).

Comparing results across singleton progestin studies, Dr. Barton noted that the rate of fetal death in the study cohort was just 0.37%, or much lower than the 1.3% observed in the placebo arms of two randomized trials (N. Engl. J. Med. 2003;348:2379-85; Ultrasound Obstet. Gynecol. 2007;30:687-96).

Moreover, those two trials were much smaller. Therefore, "I think we can conclude that our stillbirth rate was not increased above those in the placebo cohorts."

The study had its limitations, acknowledged Dr. Barton. It was retrospective, did not have data on cervical length, and lacked a control group not given 17P.

But there also were some noteworthy strengths. "This is the largest cohort of women with a prior SPTD evaluating 17P therapy in a community setting," he elaborated. "It’s also the first to evaluate the impact of a prior term delivery as a modifier of the risk of recurrent SPTD at less than 37, less than 35, and less than 32 weeks’ gestation."

Dr. Barton reported receiving support from Alere San Diego Inc. for preeclampsia research.

SAN FRANCISCO – Allowing women to control their own epidural analgesia during labor dramatically reduces the amount of anesthetic they use, according to a randomized double-blind trial.

Among the 254 laboring nulliparous women studied, those given patient-controlled epidural analgesia (PCEA) used nearly one-third less bupivacaine and fentanyl than did their counterparts given conventional continuous infusion epidural analgesia.

Women in the PCEA group had more pain during pushing, but their satisfaction with pain relief during labor overall was similar, Dr. Michael L. Haydon, an ob.gyn. at Long Beach (Calif.) Memorial Medical Center, reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"Overall satisfaction in the [PCEA] group may possibly be due to our higher volume of bolus resulting in more uniform epidural spread of anesthetic, as well as the benefit of the patient controlling her own analgesia needs in labor," he commented.

The investigators also found that there was no increase with PCEA in adverse outcomes such as longer labor, motor weakness in the legs, or neonatal complications.

Dr. Haydon noted that, although PCEA gives women autonomy in managing their labor pain and has other benefits, conventional continuous infusion epidural analgesia remains the most commonly used method.

One reservation when it comes to using PCEA among nulliparous women has been the relatively higher rate of breakthrough pain (Anesth. Analg. 2008;107:1968-72). Also, questions remain regarding the optimal concentration of anesthetic, lockout interval (the time required before the next bolus of anesthetic becomes available), and volume of the bolus.

The investigators recruited women who had a singleton pregnancy, a gestational age of at least 37 weeks, a cephalic presentation, and spontaneous labor. Those with any contraindications to epidural analgesia, a fetus with malformations, or a category II or III fetal tracing were excluded.

All of the women were given initial pain relief with combined spinal-epidural analgesia and had an epidural catheter placed.

They were then randomly assigned in equal numbers to three groups: continuous epidural infusion only (bupivacaine 0.1% and fentanyl 2 mcg/mL at a rate of 10 mL per hour); PCEA only (bupivacaine 0.1% and fentanyl 2 mcg/mL in a 10-mL bolus on patient request with a 20-minute lockout), or the combination.

"Previous studies were not all completely blinded; specifically, the continuous epidural groups did not all have working PCEA bolus buttons," Dr. Haydon noted. "In our study, all three groups were identical in that each had an epidural catheter placed and a patient-controlled button to push at the patient request. Subjects, nurses, and physicians were unaware of patient assignment."

Women who did not obtain adequate pain relief from their assigned analgesia were given up to two boluses (10 mL of 0.25% bupivacaine per bolus) by the anesthesia staff.

The women rated their pain hourly verbally on a 10-point scale and had hourly assessments of motor weakness. They also rated their satisfaction with their analgesia on a 100-point scale post partum, within 12 hours of delivery.

On average, the 254 women studied were 24 years old and had a gestational age of 39.4 weeks. Mean cervical dilation at baseline was 3.6 cm, and the mean pain score was nearly 10 out of 10 (most pain) before the initial combined spinal-epidural analgesia.

Study results showed that the average amount of bupivacaine used differed across groups (P less than .001). The PCEA-only group used 30% less than the continuous infusion–only group and 46% less than did the combination group.

Similarly, the average amount of fentanyl used differed across groups (P less than .001). Here, the PCEA-only group used 26% less than the continuous infusion–only group and 44% less than the combination group.

The percentage of women getting boluses from anesthesia staff was lowest in the combination group (6%) and similar in the continuous infusion–only group (12%) and PCEA-only group (15%) (P less than .001 for difference across three groups).

The groups did not differ significantly with respect to the duration of labor. Although the study was not powered to detect differences in rates of cesarean section and vacuum-assisted delivery, both were lowest with PCEA alone, Dr. Haydon noted. Neonatal outcomes did not differ.

Satisfaction with pain relief while pushing was lowest in the PCEA-only group, intermediate in the continuous infusion–only group, and highest in the combination group (P = .001).

"This aspect of labor has many influential factors, including whether the pump was turned off to push, whether laboring down was employed, and whether the subjects had a vaginal or cesarean delivery," he commented. "All of these are potential confounders."

Additionally, the relatively long lockout period of 20 minutes with PCEA might have played a role, speculated Dr. Haydon.

However, overall maternal satisfaction with pain relief was similarly high in all three groups, and hourly pain scores did not differ.

An attendee noted that it is difficult to get anesthesiologists to change their practice and asked Dr. Haydon whether PCEA would be "a hard sell" given that the main benefit was simply reduced anesthetic use.

"The dollars aren’t going to be worth it in terms of the medication cost," he acknowledged, but if there were any reduction in cesarean section rate that would certainly be compelling.

Dr. Haydon did not report any relevant financial disclosures.

SAN FRANCISCO – Allowing women to control their own epidural analgesia during labor dramatically reduces the amount of anesthetic they use, according to a randomized double-blind trial.

Among the 254 laboring nulliparous women studied, those given patient-controlled epidural analgesia (PCEA) used nearly one-third less bupivacaine and fentanyl than did their counterparts given conventional continuous infusion epidural analgesia.

Women in the PCEA group had more pain during pushing, but their satisfaction with pain relief during labor overall was similar, Dr. Michael L. Haydon, an ob.gyn. at Long Beach (Calif.) Memorial Medical Center, reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"Overall satisfaction in the [PCEA] group may possibly be due to our higher volume of bolus resulting in more uniform epidural spread of anesthetic, as well as the benefit of the patient controlling her own analgesia needs in labor," he commented.

The investigators also found that there was no increase with PCEA in adverse outcomes such as longer labor, motor weakness in the legs, or neonatal complications.

Dr. Haydon noted that, although PCEA gives women autonomy in managing their labor pain and has other benefits, conventional continuous infusion epidural analgesia remains the most commonly used method.

One reservation when it comes to using PCEA among nulliparous women has been the relatively higher rate of breakthrough pain (Anesth. Analg. 2008;107:1968-72). Also, questions remain regarding the optimal concentration of anesthetic, lockout interval (the time required before the next bolus of anesthetic becomes available), and volume of the bolus.

The investigators recruited women who had a singleton pregnancy, a gestational age of at least 37 weeks, a cephalic presentation, and spontaneous labor. Those with any contraindications to epidural analgesia, a fetus with malformations, or a category II or III fetal tracing were excluded.

All of the women were given initial pain relief with combined spinal-epidural analgesia and had an epidural catheter placed.

They were then randomly assigned in equal numbers to three groups: continuous epidural infusion only (bupivacaine 0.1% and fentanyl 2 mcg/mL at a rate of 10 mL per hour); PCEA only (bupivacaine 0.1% and fentanyl 2 mcg/mL in a 10-mL bolus on patient request with a 20-minute lockout), or the combination.

"Previous studies were not all completely blinded; specifically, the continuous epidural groups did not all have working PCEA bolus buttons," Dr. Haydon noted. "In our study, all three groups were identical in that each had an epidural catheter placed and a patient-controlled button to push at the patient request. Subjects, nurses, and physicians were unaware of patient assignment."

Women who did not obtain adequate pain relief from their assigned analgesia were given up to two boluses (10 mL of 0.25% bupivacaine per bolus) by the anesthesia staff.

The women rated their pain hourly verbally on a 10-point scale and had hourly assessments of motor weakness. They also rated their satisfaction with their analgesia on a 100-point scale post partum, within 12 hours of delivery.

On average, the 254 women studied were 24 years old and had a gestational age of 39.4 weeks. Mean cervical dilation at baseline was 3.6 cm, and the mean pain score was nearly 10 out of 10 (most pain) before the initial combined spinal-epidural analgesia.

Study results showed that the average amount of bupivacaine used differed across groups (P less than .001). The PCEA-only group used 30% less than the continuous infusion–only group and 46% less than did the combination group.

Similarly, the average amount of fentanyl used differed across groups (P less than .001). Here, the PCEA-only group used 26% less than the continuous infusion–only group and 44% less than the combination group.

The percentage of women getting boluses from anesthesia staff was lowest in the combination group (6%) and similar in the continuous infusion–only group (12%) and PCEA-only group (15%) (P less than .001 for difference across three groups).

The groups did not differ significantly with respect to the duration of labor. Although the study was not powered to detect differences in rates of cesarean section and vacuum-assisted delivery, both were lowest with PCEA alone, Dr. Haydon noted. Neonatal outcomes did not differ.

Satisfaction with pain relief while pushing was lowest in the PCEA-only group, intermediate in the continuous infusion–only group, and highest in the combination group (P = .001).

"This aspect of labor has many influential factors, including whether the pump was turned off to push, whether laboring down was employed, and whether the subjects had a vaginal or cesarean delivery," he commented. "All of these are potential confounders."

Additionally, the relatively long lockout period of 20 minutes with PCEA might have played a role, speculated Dr. Haydon.

However, overall maternal satisfaction with pain relief was similarly high in all three groups, and hourly pain scores did not differ.

An attendee noted that it is difficult to get anesthesiologists to change their practice and asked Dr. Haydon whether PCEA would be "a hard sell" given that the main benefit was simply reduced anesthetic use.

"The dollars aren’t going to be worth it in terms of the medication cost," he acknowledged, but if there were any reduction in cesarean section rate that would certainly be compelling.

Dr. Haydon did not report any relevant financial disclosures.

SAN FRANCISCO – Allowing women to control their own epidural analgesia during labor dramatically reduces the amount of anesthetic they use, according to a randomized double-blind trial.

Among the 254 laboring nulliparous women studied, those given patient-controlled epidural analgesia (PCEA) used nearly one-third less bupivacaine and fentanyl than did their counterparts given conventional continuous infusion epidural analgesia.

Women in the PCEA group had more pain during pushing, but their satisfaction with pain relief during labor overall was similar, Dr. Michael L. Haydon, an ob.gyn. at Long Beach (Calif.) Memorial Medical Center, reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"Overall satisfaction in the [PCEA] group may possibly be due to our higher volume of bolus resulting in more uniform epidural spread of anesthetic, as well as the benefit of the patient controlling her own analgesia needs in labor," he commented.

The investigators also found that there was no increase with PCEA in adverse outcomes such as longer labor, motor weakness in the legs, or neonatal complications.

Dr. Haydon noted that, although PCEA gives women autonomy in managing their labor pain and has other benefits, conventional continuous infusion epidural analgesia remains the most commonly used method.

One reservation when it comes to using PCEA among nulliparous women has been the relatively higher rate of breakthrough pain (Anesth. Analg. 2008;107:1968-72). Also, questions remain regarding the optimal concentration of anesthetic, lockout interval (the time required before the next bolus of anesthetic becomes available), and volume of the bolus.

The investigators recruited women who had a singleton pregnancy, a gestational age of at least 37 weeks, a cephalic presentation, and spontaneous labor. Those with any contraindications to epidural analgesia, a fetus with malformations, or a category II or III fetal tracing were excluded.

All of the women were given initial pain relief with combined spinal-epidural analgesia and had an epidural catheter placed.

They were then randomly assigned in equal numbers to three groups: continuous epidural infusion only (bupivacaine 0.1% and fentanyl 2 mcg/mL at a rate of 10 mL per hour); PCEA only (bupivacaine 0.1% and fentanyl 2 mcg/mL in a 10-mL bolus on patient request with a 20-minute lockout), or the combination.

"Previous studies were not all completely blinded; specifically, the continuous epidural groups did not all have working PCEA bolus buttons," Dr. Haydon noted. "In our study, all three groups were identical in that each had an epidural catheter placed and a patient-controlled button to push at the patient request. Subjects, nurses, and physicians were unaware of patient assignment."

Women who did not obtain adequate pain relief from their assigned analgesia were given up to two boluses (10 mL of 0.25% bupivacaine per bolus) by the anesthesia staff.

The women rated their pain hourly verbally on a 10-point scale and had hourly assessments of motor weakness. They also rated their satisfaction with their analgesia on a 100-point scale post partum, within 12 hours of delivery.

On average, the 254 women studied were 24 years old and had a gestational age of 39.4 weeks. Mean cervical dilation at baseline was 3.6 cm, and the mean pain score was nearly 10 out of 10 (most pain) before the initial combined spinal-epidural analgesia.

Study results showed that the average amount of bupivacaine used differed across groups (P less than .001). The PCEA-only group used 30% less than the continuous infusion–only group and 46% less than did the combination group.

Similarly, the average amount of fentanyl used differed across groups (P less than .001). Here, the PCEA-only group used 26% less than the continuous infusion–only group and 44% less than the combination group.

The percentage of women getting boluses from anesthesia staff was lowest in the combination group (6%) and similar in the continuous infusion–only group (12%) and PCEA-only group (15%) (P less than .001 for difference across three groups).

The groups did not differ significantly with respect to the duration of labor. Although the study was not powered to detect differences in rates of cesarean section and vacuum-assisted delivery, both were lowest with PCEA alone, Dr. Haydon noted. Neonatal outcomes did not differ.

Satisfaction with pain relief while pushing was lowest in the PCEA-only group, intermediate in the continuous infusion–only group, and highest in the combination group (P = .001).

"This aspect of labor has many influential factors, including whether the pump was turned off to push, whether laboring down was employed, and whether the subjects had a vaginal or cesarean delivery," he commented. "All of these are potential confounders."

Additionally, the relatively long lockout period of 20 minutes with PCEA might have played a role, speculated Dr. Haydon.

However, overall maternal satisfaction with pain relief was similarly high in all three groups, and hourly pain scores did not differ.

An attendee noted that it is difficult to get anesthesiologists to change their practice and asked Dr. Haydon whether PCEA would be "a hard sell" given that the main benefit was simply reduced anesthetic use.

"The dollars aren’t going to be worth it in terms of the medication cost," he acknowledged, but if there were any reduction in cesarean section rate that would certainly be compelling.

Dr. Haydon did not report any relevant financial disclosures.

SAN FRANCISCO – A simple blood test may improve on systems conventionally used to estimate prognosis in patients with hepatocellular carcinoma, new data suggest.

In a study of nearly 300 patients mainly with advanced hepatocellular carcinoma (HCC), baseline plasma levels of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) significantly refined the risk stratification seen with the Barcelona Clinic Liver Cancer system, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

As a whole, patients with stage C disease had a median overall survival of 11 months. But when levels of both growth factors were also considered, the population split into four groups having widely differing overall survival, ranging from 3 to 14 months.

"Baseline assessment of both markers – IGF-1 and VEGF – significantly improved the prediction of survival and prognostic stratification of HCC patients," reported lead investigator Dr. Ahmed O. Kaseb. "If the results of forthcoming, large collaborative studies confirm our results, this approach will really be beneficial in stratification of patients in clinical trials, ... guiding therapy decisions, and ultimately improving HCC outcome."

Patients with advanced HCC usually have two pathologic processes going on, he observed. "Really, the hallmark of this disease in the majority of patients is the presence of angiogenesis-driven tumor in addition to liver that is affected by underlying liver condition, specifically cirrhosis."

As both processes affect survival, there is marked heterogeneity among patients whose cancer is of similar stage. "So the challenge that prompted our study was the heterogeneity of patients with advanced HCC," he said.

Systems currently used to stratify the HCC population are limited because they do not capture this heterogeneity well, often fail to incorporate liver reserve, and require biopsies in patients having coagulopathy and thrombocytopenia.

"Therefore, integration of noninvasive biomarkers that would reflect [both] the tumor and the liver condition is really needed," commented Dr. Kaseb, a gastrointestinal oncologist at the University of Texas M.D. Anderson Cancer Center in Houston.

The investigators focused on VEGF, because it is a main mediator of angiogenesis, and IGF-1, because it is synthesized primarily in the liver and circulating levels are lower in chronic liver disease. Hence, high levels of the former might be associated with a more advanced tumor, and low levels of the latter might be associated with more severe cirrhosis.

The 288 patients with HCC studied were participants in an ongoing case-control study at the center that began in 2001 and is the largest in this patient population in the United States. Plasma samples were prospectively collected.

The investigators assessed the impact of adding growth factor levels to the Barcelona Clinic Liver Cancer (BCLC) system and the Cancer of the Liver Italian Program (CLIP) system, the two HCC risk stratification systems most commonly used in Western countries.

About 62% of the patients were aged 60 years or older, and 69% were men. Most had cirrhosis (60%) and a Child-Pugh class of A (72%).

The BCLC staging system stratified the patients into groups having significantly different median overall survival (P less than .0001). It classified two-thirds as having stage C disease, the group that is usually the focus of clinical trials, Dr. Kaseb noted.

This group had a median overall survival of 11 months. But their heterogeneity became apparent when they were stratified according to levels of both IGF-1 (up to 26 pg/mL vs. greater than 26 pg/mL) and VEGF (up to 450 vs. greater than 450 pg/mL).

Median overall survival was 14 months for patients with high levels of both growth factors, 12 months for patients with high IGF-1 and low VEGF levels, 6 months for patients with low levels of both growth factors, and 3 months for patients with low IGF-1 and high VEGF levels (P less than .0006).

Adding the two growth factors to the BCLC system improved on its predictive ability: The concordance index was 0.65 with the system alone vs. 0.68 with system plus growth factors.

In a multivariate analysis with the factors used in the CLIP system, levels of both growth factors independently predicted the risk of death. However, they did not significantly improve on the risk stratification seen with this system.

"I hope I was able to make a strong case for the important role of these two biomarkers in HCC, which will be a step forward toward personalizing therapy for HCC, which is really a cornerstone in improving HCC outcome," concluded Dr. Kaseb.

He reported being a consultant and adviser to Bayer/Onyx, which manufactures sorafenib (Nexavar), currently approved by the Food and Drug Administration for the treatment of unresectable HCC.

SAN FRANCISCO – A simple blood test may improve on systems conventionally used to estimate prognosis in patients with hepatocellular carcinoma, new data suggest.

In a study of nearly 300 patients mainly with advanced hepatocellular carcinoma (HCC), baseline plasma levels of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) significantly refined the risk stratification seen with the Barcelona Clinic Liver Cancer system, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

As a whole, patients with stage C disease had a median overall survival of 11 months. But when levels of both growth factors were also considered, the population split into four groups having widely differing overall survival, ranging from 3 to 14 months.

"Baseline assessment of both markers – IGF-1 and VEGF – significantly improved the prediction of survival and prognostic stratification of HCC patients," reported lead investigator Dr. Ahmed O. Kaseb. "If the results of forthcoming, large collaborative studies confirm our results, this approach will really be beneficial in stratification of patients in clinical trials, ... guiding therapy decisions, and ultimately improving HCC outcome."

Patients with advanced HCC usually have two pathologic processes going on, he observed. "Really, the hallmark of this disease in the majority of patients is the presence of angiogenesis-driven tumor in addition to liver that is affected by underlying liver condition, specifically cirrhosis."

As both processes affect survival, there is marked heterogeneity among patients whose cancer is of similar stage. "So the challenge that prompted our study was the heterogeneity of patients with advanced HCC," he said.

Systems currently used to stratify the HCC population are limited because they do not capture this heterogeneity well, often fail to incorporate liver reserve, and require biopsies in patients having coagulopathy and thrombocytopenia.

"Therefore, integration of noninvasive biomarkers that would reflect [both] the tumor and the liver condition is really needed," commented Dr. Kaseb, a gastrointestinal oncologist at the University of Texas M.D. Anderson Cancer Center in Houston.

The investigators focused on VEGF, because it is a main mediator of angiogenesis, and IGF-1, because it is synthesized primarily in the liver and circulating levels are lower in chronic liver disease. Hence, high levels of the former might be associated with a more advanced tumor, and low levels of the latter might be associated with more severe cirrhosis.

The 288 patients with HCC studied were participants in an ongoing case-control study at the center that began in 2001 and is the largest in this patient population in the United States. Plasma samples were prospectively collected.

The investigators assessed the impact of adding growth factor levels to the Barcelona Clinic Liver Cancer (BCLC) system and the Cancer of the Liver Italian Program (CLIP) system, the two HCC risk stratification systems most commonly used in Western countries.

About 62% of the patients were aged 60 years or older, and 69% were men. Most had cirrhosis (60%) and a Child-Pugh class of A (72%).

The BCLC staging system stratified the patients into groups having significantly different median overall survival (P less than .0001). It classified two-thirds as having stage C disease, the group that is usually the focus of clinical trials, Dr. Kaseb noted.

This group had a median overall survival of 11 months. But their heterogeneity became apparent when they were stratified according to levels of both IGF-1 (up to 26 pg/mL vs. greater than 26 pg/mL) and VEGF (up to 450 vs. greater than 450 pg/mL).

Median overall survival was 14 months for patients with high levels of both growth factors, 12 months for patients with high IGF-1 and low VEGF levels, 6 months for patients with low levels of both growth factors, and 3 months for patients with low IGF-1 and high VEGF levels (P less than .0006).

Adding the two growth factors to the BCLC system improved on its predictive ability: The concordance index was 0.65 with the system alone vs. 0.68 with system plus growth factors.

In a multivariate analysis with the factors used in the CLIP system, levels of both growth factors independently predicted the risk of death. However, they did not significantly improve on the risk stratification seen with this system.

"I hope I was able to make a strong case for the important role of these two biomarkers in HCC, which will be a step forward toward personalizing therapy for HCC, which is really a cornerstone in improving HCC outcome," concluded Dr. Kaseb.

He reported being a consultant and adviser to Bayer/Onyx, which manufactures sorafenib (Nexavar), currently approved by the Food and Drug Administration for the treatment of unresectable HCC.

SAN FRANCISCO – A simple blood test may improve on systems conventionally used to estimate prognosis in patients with hepatocellular carcinoma, new data suggest.

In a study of nearly 300 patients mainly with advanced hepatocellular carcinoma (HCC), baseline plasma levels of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) significantly refined the risk stratification seen with the Barcelona Clinic Liver Cancer system, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

As a whole, patients with stage C disease had a median overall survival of 11 months. But when levels of both growth factors were also considered, the population split into four groups having widely differing overall survival, ranging from 3 to 14 months.

"Baseline assessment of both markers – IGF-1 and VEGF – significantly improved the prediction of survival and prognostic stratification of HCC patients," reported lead investigator Dr. Ahmed O. Kaseb. "If the results of forthcoming, large collaborative studies confirm our results, this approach will really be beneficial in stratification of patients in clinical trials, ... guiding therapy decisions, and ultimately improving HCC outcome."

Patients with advanced HCC usually have two pathologic processes going on, he observed. "Really, the hallmark of this disease in the majority of patients is the presence of angiogenesis-driven tumor in addition to liver that is affected by underlying liver condition, specifically cirrhosis."

As both processes affect survival, there is marked heterogeneity among patients whose cancer is of similar stage. "So the challenge that prompted our study was the heterogeneity of patients with advanced HCC," he said.

Systems currently used to stratify the HCC population are limited because they do not capture this heterogeneity well, often fail to incorporate liver reserve, and require biopsies in patients having coagulopathy and thrombocytopenia.

"Therefore, integration of noninvasive biomarkers that would reflect [both] the tumor and the liver condition is really needed," commented Dr. Kaseb, a gastrointestinal oncologist at the University of Texas M.D. Anderson Cancer Center in Houston.

The investigators focused on VEGF, because it is a main mediator of angiogenesis, and IGF-1, because it is synthesized primarily in the liver and circulating levels are lower in chronic liver disease. Hence, high levels of the former might be associated with a more advanced tumor, and low levels of the latter might be associated with more severe cirrhosis.

The 288 patients with HCC studied were participants in an ongoing case-control study at the center that began in 2001 and is the largest in this patient population in the United States. Plasma samples were prospectively collected.

The investigators assessed the impact of adding growth factor levels to the Barcelona Clinic Liver Cancer (BCLC) system and the Cancer of the Liver Italian Program (CLIP) system, the two HCC risk stratification systems most commonly used in Western countries.

About 62% of the patients were aged 60 years or older, and 69% were men. Most had cirrhosis (60%) and a Child-Pugh class of A (72%).

The BCLC staging system stratified the patients into groups having significantly different median overall survival (P less than .0001). It classified two-thirds as having stage C disease, the group that is usually the focus of clinical trials, Dr. Kaseb noted.

This group had a median overall survival of 11 months. But their heterogeneity became apparent when they were stratified according to levels of both IGF-1 (up to 26 pg/mL vs. greater than 26 pg/mL) and VEGF (up to 450 vs. greater than 450 pg/mL).

Median overall survival was 14 months for patients with high levels of both growth factors, 12 months for patients with high IGF-1 and low VEGF levels, 6 months for patients with low levels of both growth factors, and 3 months for patients with low IGF-1 and high VEGF levels (P less than .0006).

Adding the two growth factors to the BCLC system improved on its predictive ability: The concordance index was 0.65 with the system alone vs. 0.68 with system plus growth factors.

In a multivariate analysis with the factors used in the CLIP system, levels of both growth factors independently predicted the risk of death. However, they did not significantly improve on the risk stratification seen with this system.

"I hope I was able to make a strong case for the important role of these two biomarkers in HCC, which will be a step forward toward personalizing therapy for HCC, which is really a cornerstone in improving HCC outcome," concluded Dr. Kaseb.

He reported being a consultant and adviser to Bayer/Onyx, which manufactures sorafenib (Nexavar), currently approved by the Food and Drug Administration for the treatment of unresectable HCC.

SAN FRANCISCO – A simple, standardized protocol for managing shoulder dystocia, called Code D, reduced the incidence of obstetric brachial plexus injury, according to a study reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Investigators retrospectively assessed the impact of the protocol – which entails mobilization of experienced staff, a hands-off pause for assessment, and varied maneuvers – in a cohort of nearly 12,000 vaginal deliveries.

Study results showed that with use of the protocol, the rate of obstetric brachial plexus injury (Erb’s palsy) among cases of shoulder dystocia fell by nearly three-fourths, from 40% before the protocol’s implementation to 14% afterward.

"A standardized and simple protocol to manage shoulder dystocia appears to reduce the risk of Erb’s palsy," commented lead investigator Dr. Steven R. Inglis.

"We were unable to tell which part of the protocol really was helping us," he added, so further research is needed to determine the responsible components and maneuvers.

Rates of both shoulder dystocia and brachial plexus injury appear to be on the rise, in part because of increasing maternal obesity and diabetes, as well as increasing fetal macrosomia, according to Dr. Inglis, chairman of the department of ob.gyn. at the Jamaica (N.Y.) Hospital Medical Center.

These complications not only can be associated with long-term morbidity, but also account for a substantial share of obstetricians’ liability payouts, he noted.

Many strategies for managing shoulder dystocia have been introduced, but few of them have been studied to assess their impact on important neonatal outcomes, he said.

Dr. Inglis and his colleagues determined the rate of brachial plexus injury at Jamaica Hospital Medical Center before and after implementation of the Code D shoulder dystocia protocol. The protocol emphasized a stepwise team approach to management, conducted in a calm and relaxed environment.

Code D training was provided to all labor and delivery staff including attending and resident physicians, midwives, and nurses. "I don’t think anybody else has really included nurses," he commented. "I think they were a key part of it."

Training included didactic presentations followed by hands-on practice with a manikin. "Everybody had to go through shoulder dystocia once or twice and get it done right according to our protocol," Dr. Inglis explained.

When the staff diagnosed dystocia (tight or difficult shoulders, or the so-called turtle sign requiring additional maneuvers to achieve delivery), they activated the Code D protocol, which summoned to the room the most experienced available obstetrician, and also an anesthesiologist, a neonatologist, and a nurse.

Staff were taught, first, to assess – using a hands-off pause during which there was no maternal pushing, application of fundal pressure, or head traction –the orientation of the infant’s back and shoulders, and to announce it to the delivery team.

This hands-off period lasted just a few seconds, according to Dr. Inglis. "You basically want to stop, take a deep breath, collect yourself, make sure you are following the protocol, and then go on."

Staff then began one of several maneuvers performed in an order of their choice, including rotating the shoulders to the oblique position, changing maternal position, implementing the corkscrew maneuver, and delivering the posterior arm.

"Each should last no longer than 30 seconds, and you could go back to a maneuver if it didn’t work the first time," Dr. Inglis said. Suprapubic pressure also could be used.

To assess the impact of the Code D protocol, the investigators retrospectively reviewed medical records for mothers and their singleton, live born, nonbreech infants delivered vaginally between August 2003 and December 2009.

Analyses were based on 6,269 deliveries in the pretraining period before September 2006, and 5,593 deliveries in the posttraining period.

Study results showed that the rate of shoulder dystocia did not differ significantly between periods: This complication occurred in 83 or 1.32% of deliveries in the former period, and in 75 or 1.34% of deliveries in the latter period.

However, the percentage of cases of shoulder dystocia that resulted in brachial plexus injury was 40% in the pretraining period, compared with just 14% in the posttraining period (P less than .01).

Among the cases of shoulder dystocia, those in the pretraining period had a higher maternal body mass index (33.4 vs. 30.3 kg/m²; P less than .01) and infant birth weight (3,825 g vs. 3643 g; P = .02), both of which are potential confounders, Dr. Inglis noted.

But in a logistic regression analysis, use of the shoulder dystocia protocol was still associated with a reduced risk of obstetric brachial plexus injury (P = .02).

The interval between delivery of the infant’s head and body in cases of shoulder dystocia was longer in the posttraining period than in the pretraining period (2.0 minutes vs. 1.5 minutes; P = .03).

"We wanted everyone to go slowly, so we were actually happy to see that the head-body interval went up," commented Dr. Inglis. "That certainly didn’t seem to worsen the risk of Erb’s palsy."

Study results also showed that staff were more likely to use the Rubin maneuver (P = .02) and posterior arm delivery (P = .03) in the posttraining vs. pretraining period, and were less likely to use the McRoberts maneuver (P less than .01).

Dr. Inglis did not report any relevant financial disclosures.

SAN FRANCISCO – A simple, standardized protocol for managing shoulder dystocia, called Code D, reduced the incidence of obstetric brachial plexus injury, according to a study reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Investigators retrospectively assessed the impact of the protocol – which entails mobilization of experienced staff, a hands-off pause for assessment, and varied maneuvers – in a cohort of nearly 12,000 vaginal deliveries.

Study results showed that with use of the protocol, the rate of obstetric brachial plexus injury (Erb’s palsy) among cases of shoulder dystocia fell by nearly three-fourths, from 40% before the protocol’s implementation to 14% afterward.

"A standardized and simple protocol to manage shoulder dystocia appears to reduce the risk of Erb’s palsy," commented lead investigator Dr. Steven R. Inglis.

"We were unable to tell which part of the protocol really was helping us," he added, so further research is needed to determine the responsible components and maneuvers.

Rates of both shoulder dystocia and brachial plexus injury appear to be on the rise, in part because of increasing maternal obesity and diabetes, as well as increasing fetal macrosomia, according to Dr. Inglis, chairman of the department of ob.gyn. at the Jamaica (N.Y.) Hospital Medical Center.

These complications not only can be associated with long-term morbidity, but also account for a substantial share of obstetricians’ liability payouts, he noted.

Many strategies for managing shoulder dystocia have been introduced, but few of them have been studied to assess their impact on important neonatal outcomes, he said.

Dr. Inglis and his colleagues determined the rate of brachial plexus injury at Jamaica Hospital Medical Center before and after implementation of the Code D shoulder dystocia protocol. The protocol emphasized a stepwise team approach to management, conducted in a calm and relaxed environment.

Code D training was provided to all labor and delivery staff including attending and resident physicians, midwives, and nurses. "I don’t think anybody else has really included nurses," he commented. "I think they were a key part of it."

Training included didactic presentations followed by hands-on practice with a manikin. "Everybody had to go through shoulder dystocia once or twice and get it done right according to our protocol," Dr. Inglis explained.

When the staff diagnosed dystocia (tight or difficult shoulders, or the so-called turtle sign requiring additional maneuvers to achieve delivery), they activated the Code D protocol, which summoned to the room the most experienced available obstetrician, and also an anesthesiologist, a neonatologist, and a nurse.

Staff were taught, first, to assess – using a hands-off pause during which there was no maternal pushing, application of fundal pressure, or head traction –the orientation of the infant’s back and shoulders, and to announce it to the delivery team.

This hands-off period lasted just a few seconds, according to Dr. Inglis. "You basically want to stop, take a deep breath, collect yourself, make sure you are following the protocol, and then go on."

Staff then began one of several maneuvers performed in an order of their choice, including rotating the shoulders to the oblique position, changing maternal position, implementing the corkscrew maneuver, and delivering the posterior arm.

"Each should last no longer than 30 seconds, and you could go back to a maneuver if it didn’t work the first time," Dr. Inglis said. Suprapubic pressure also could be used.

To assess the impact of the Code D protocol, the investigators retrospectively reviewed medical records for mothers and their singleton, live born, nonbreech infants delivered vaginally between August 2003 and December 2009.

Analyses were based on 6,269 deliveries in the pretraining period before September 2006, and 5,593 deliveries in the posttraining period.

Study results showed that the rate of shoulder dystocia did not differ significantly between periods: This complication occurred in 83 or 1.32% of deliveries in the former period, and in 75 or 1.34% of deliveries in the latter period.

However, the percentage of cases of shoulder dystocia that resulted in brachial plexus injury was 40% in the pretraining period, compared with just 14% in the posttraining period (P less than .01).

Among the cases of shoulder dystocia, those in the pretraining period had a higher maternal body mass index (33.4 vs. 30.3 kg/m²; P less than .01) and infant birth weight (3,825 g vs. 3643 g; P = .02), both of which are potential confounders, Dr. Inglis noted.

But in a logistic regression analysis, use of the shoulder dystocia protocol was still associated with a reduced risk of obstetric brachial plexus injury (P = .02).

The interval between delivery of the infant’s head and body in cases of shoulder dystocia was longer in the posttraining period than in the pretraining period (2.0 minutes vs. 1.5 minutes; P = .03).

"We wanted everyone to go slowly, so we were actually happy to see that the head-body interval went up," commented Dr. Inglis. "That certainly didn’t seem to worsen the risk of Erb’s palsy."

Study results also showed that staff were more likely to use the Rubin maneuver (P = .02) and posterior arm delivery (P = .03) in the posttraining vs. pretraining period, and were less likely to use the McRoberts maneuver (P less than .01).

Dr. Inglis did not report any relevant financial disclosures.

SAN FRANCISCO – A simple, standardized protocol for managing shoulder dystocia, called Code D, reduced the incidence of obstetric brachial plexus injury, according to a study reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Investigators retrospectively assessed the impact of the protocol – which entails mobilization of experienced staff, a hands-off pause for assessment, and varied maneuvers – in a cohort of nearly 12,000 vaginal deliveries.

Study results showed that with use of the protocol, the rate of obstetric brachial plexus injury (Erb’s palsy) among cases of shoulder dystocia fell by nearly three-fourths, from 40% before the protocol’s implementation to 14% afterward.

"A standardized and simple protocol to manage shoulder dystocia appears to reduce the risk of Erb’s palsy," commented lead investigator Dr. Steven R. Inglis.

"We were unable to tell which part of the protocol really was helping us," he added, so further research is needed to determine the responsible components and maneuvers.

Rates of both shoulder dystocia and brachial plexus injury appear to be on the rise, in part because of increasing maternal obesity and diabetes, as well as increasing fetal macrosomia, according to Dr. Inglis, chairman of the department of ob.gyn. at the Jamaica (N.Y.) Hospital Medical Center.

These complications not only can be associated with long-term morbidity, but also account for a substantial share of obstetricians’ liability payouts, he noted.

Many strategies for managing shoulder dystocia have been introduced, but few of them have been studied to assess their impact on important neonatal outcomes, he said.

Dr. Inglis and his colleagues determined the rate of brachial plexus injury at Jamaica Hospital Medical Center before and after implementation of the Code D shoulder dystocia protocol. The protocol emphasized a stepwise team approach to management, conducted in a calm and relaxed environment.

Code D training was provided to all labor and delivery staff including attending and resident physicians, midwives, and nurses. "I don’t think anybody else has really included nurses," he commented. "I think they were a key part of it."

Training included didactic presentations followed by hands-on practice with a manikin. "Everybody had to go through shoulder dystocia once or twice and get it done right according to our protocol," Dr. Inglis explained.

When the staff diagnosed dystocia (tight or difficult shoulders, or the so-called turtle sign requiring additional maneuvers to achieve delivery), they activated the Code D protocol, which summoned to the room the most experienced available obstetrician, and also an anesthesiologist, a neonatologist, and a nurse.

Staff were taught, first, to assess – using a hands-off pause during which there was no maternal pushing, application of fundal pressure, or head traction –the orientation of the infant’s back and shoulders, and to announce it to the delivery team.

This hands-off period lasted just a few seconds, according to Dr. Inglis. "You basically want to stop, take a deep breath, collect yourself, make sure you are following the protocol, and then go on."

Staff then began one of several maneuvers performed in an order of their choice, including rotating the shoulders to the oblique position, changing maternal position, implementing the corkscrew maneuver, and delivering the posterior arm.

"Each should last no longer than 30 seconds, and you could go back to a maneuver if it didn’t work the first time," Dr. Inglis said. Suprapubic pressure also could be used.

To assess the impact of the Code D protocol, the investigators retrospectively reviewed medical records for mothers and their singleton, live born, nonbreech infants delivered vaginally between August 2003 and December 2009.

Analyses were based on 6,269 deliveries in the pretraining period before September 2006, and 5,593 deliveries in the posttraining period.

Study results showed that the rate of shoulder dystocia did not differ significantly between periods: This complication occurred in 83 or 1.32% of deliveries in the former period, and in 75 or 1.34% of deliveries in the latter period.

However, the percentage of cases of shoulder dystocia that resulted in brachial plexus injury was 40% in the pretraining period, compared with just 14% in the posttraining period (P less than .01).

Among the cases of shoulder dystocia, those in the pretraining period had a higher maternal body mass index (33.4 vs. 30.3 kg/m²; P less than .01) and infant birth weight (3,825 g vs. 3643 g; P = .02), both of which are potential confounders, Dr. Inglis noted.

But in a logistic regression analysis, use of the shoulder dystocia protocol was still associated with a reduced risk of obstetric brachial plexus injury (P = .02).

The interval between delivery of the infant’s head and body in cases of shoulder dystocia was longer in the posttraining period than in the pretraining period (2.0 minutes vs. 1.5 minutes; P = .03).

"We wanted everyone to go slowly, so we were actually happy to see that the head-body interval went up," commented Dr. Inglis. "That certainly didn’t seem to worsen the risk of Erb’s palsy."

Study results also showed that staff were more likely to use the Rubin maneuver (P = .02) and posterior arm delivery (P = .03) in the posttraining vs. pretraining period, and were less likely to use the McRoberts maneuver (P less than .01).

Dr. Inglis did not report any relevant financial disclosures.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Levels of serum markers measured early in the second trimester of pregnancy may help identify women who are likely to develop severe preeclampsia, the results of a nested case-control study indicated.

In the study, there was no association between the level of vitamin D and levels of two angiogenic factors that have been previously implicated in the development of preeclampsia, soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF).

But both the level of vitamin D and the ratio of sFlt-1 to PlGF predicted the development of severe preeclampsia after other risk factors were taken into account. And in ROC (receiver operating characteristic) curve analysis, the combination outperformed either measure individually.

"These results suggest that 25-hydroxyvitamin D and angiogenic factors play independent roles in the pathogenesis of preeclampsia," lead investigator Dr. Padmashree Chaudhury Woodham told attendees at the annual meeting of the Society for Maternal-Fetal Medicine.

"Our findings suggest that the combination of 25-hydroxyvitamin D level and sFlt-1:PlGF ratio is a better predictor of preeclampsia in midgestation than either marker alone," she added.

A low 25-hydroxyvitamin D level has previously been shown to be a risk factor for severe preeclampsia, according to Dr. Woodham, who is a fellow in ob.gyn. at the University of North Carolina at Chapel Hill. But its association with angiogenic factors is unclear.

"In vitro and animal studies have found that its active form regulates [vascular endothelial growth factor] production through vitamin D response elements in the VEGF promoter," she explained. "The clinical significance of these findings remains to be determined."

The investigators drew their study patients from a large cohort of pregnant women who gave blood for routine prenatal screening early in the second trimester (gestational age, 15-20 weeks). They restricted analyses to women with a singleton pregnancy who did not have chronic medical illnesses and whose fetuses did not have congenital abnormalities.

Each woman who developed severe preeclampsia (n = 41) was matched by race/ethnicity with three control women who had uncomplicated births at term (n = 123).

Banked frozen serum samples were assayed to determine levels of vitamin D (total 25-hydroxyvitamin D) and the angiogenic markers sFlt-1, PlGF, and VEGF.

The severe preeclampsia and control groups were similar in terms of age, parity, and body mass index, Dr. Woodham reported. Overall, 39% were black, 29% were white, 27% were Hispanic, and 5% were Asian.

The season and the median gestational age at the time blood was drawn were also similar. But the median gestational age at delivery was younger in the preeclampsia group (32.6 vs. 39.6 weeks; P less than .001).

Relative to their control counterparts, the women who developed preeclampsia had lower levels of vitamin D (P less than .001), VEGF (P less than .001), and PlGF (P = .03), and a higher ratio of sFlt-1 to PlGF (P = .02).

Levels of vitamin D were not correlated with levels of any of the angiogenic factors or with the sFlt-1:PlGF ratio, contrary to the findings of in vitro and animal studies, according to Dr. Woodham.

However, in a multivariate model, each 1-nmol/L increase in total vitamin D level was associated with a 5% reduction in the odds of preeclampsia, whereas each 1-unit increase in the sFlt-1:PlGF ratio was associated with an 11% increase in the odds.

ROC curve analysis showed that for predicting preeclampsia, the area under the curve was 0.745 for vitamin D alone and 0.669 for the sFlt-1:PlGF ratio alone. But it was higher with their combination (0.834).

There was also a small further improvement when VEGF level was added to the mix, with an area under the curve of 0.851.

"Clinical trials targeting risk factors such as we have identified in this study will be needed to establish whether these associations are causal," she concluded.

Dr. Woodham did not report any relevant conflicts of interest.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Maternal levels of several proinflammatory cytokines are elevated shortly before the onset of spontaneous labor, and thus may help pinpoint the timing of this event, new data suggest.

In a nested, case-control study reported at the annual meeting of the Society for Maternal-Fetal Medicine, women at term whose labor began within 48 hours had significantly higher levels of interleukin-1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor–alpha (TNF-alpha) than did their counterparts whose labor did not begin for at least 14 days.

"This finding supports the hypothesis that inflammatory activation is present shortly prior to clinically recognizable labor," said Dr. Elizabeth Ramsey Unal of the Medical University of South Carolina, Charleston.

The investigators were also able to determine cutoff values for the cytokines that had high negative predictive values for labor onset and, in some cases, good sensitivity.

Clinically, information from this and related studies "could be of great value in identifying maternal biomarkers to select women who are either very good vs. very poor candidates for induction of labor, or could potentially also be used for labor triage in specific cases," Dr. Unal noted.

Previous research has found elevated levels of proinflammatory markers during labor. "What is unclear, however, is the timing of this involvement: Is inflammation solely a result of the labor process, or is inflammation actually involved in the steps that initiate labor?" she said, explaining the study’s rationale.

The investigators drew their study sample from a cohort of healthy, nulliparous women with a singleton pregnancy who enrolled in a related study during a routine office visit at term (defined as greater than or equal to 37 weeks’ gestation) and gave a blood sample at that time.

They were excluded if they had any signs or symptoms of latent labor, had an autoimmune disease, had any infection in the third trimester, or used anti-inflammatory medications during pregnancy.

Analyses were based on 20 women who had spontaneous onset of labor within 48 hours (cases) and 80 women who did not have spontaneous onset of labor for at least 14 days (controls).

The investigators measured serum levels of seven cytokines (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-alpha, and interferon-gamma) that "were selected to encompass the signature cytokines for the Th1 and Th2 and Treg pathways," Dr. Unal explained.

The women studied were 22 years old, on average; 44% were Hispanic, 31% were white, and 25% were black.

Compared with their counterparts whose labor did not begin for at least 14 days, those whose labor began within 48 hours had an older mean gestational age (39.2 vs. 37.3 weeks) and greater mean cervical dilatation (2 cm vs. 1 cm) at enrollment. But the groups were similar with respect to group B streptococcus positivity and the rate of infections in the first and second trimester.

The women whose labor started within 48 hours had a younger gestational age at delivery (39.2 weeks vs. 40.4 weeks) and smaller infants (3,205 g vs. 3,485 g). However, the groups were similar with respect to mode of delivery, white blood cell count on admission, and fever during labor.

Study results showed that none of the levels of the seven cytokines was correlated either with gestational age at enrollment or maternal body mass index, Dr. Unal reported.

Compared with their counterparts whose labor did not begin for at least 14 days, the women whose labor began within 48 hours had higher levels of IL-1B (P less than .01), IL-6 (P = .03), and TNF-alpha (P = .02). Levels of the other cytokines did not differ between the two groups.

In ROC (receiver operating characteristic) curve analyses, TNF-alpha was the best predictor of labor onset within 48 hours, with an area under the curve of 0.703.

Using these curves, the investigators selected cutoff values for each cytokine to optimize the negative predictive value, according to Dr. Unal.

By this process, high levels of IL-1B (greater than 0.5 pg/mL), IL-6 (greater than 4.0 pg/mL), and TNF-alpha (greater than 0.6 pg/mL) had negative predictive values of 89%, 84%, and 92%, respectively. Or, stated another way, "in our data, labor was very unlikely to occur within 48 hours in the presence of low levels" of IL-1B, IL-6, and TNF-alpha.

Also, at these cutoff values, IL-1B and TNF-alpha had good sensitivity for predicting labor onset within 48 hours, with values of 70% and 80%, respectively.

In a regression analysis, cervical dilatation at enrollment was a better predictor of labor onset, according to Dr. Unal. But it is possible that adding cytokines to cervical dilatation could improve prediction.

She acknowledged that a larger study would have enabled more precise determination of the timing of the rise in proinflammatory cytokines. Also, serial blood sampling before and throughout pregnancy would be necessary to rule out baseline differences between groups in inflammatory reactivity.

"Since our study design cannot delineate whether inflammation is the primary stimulus for labor or instead a signal downstream of some other primary trigger or triggers, future research will focus on exploring the temporal sequence of events leading to the initiation of labor at term," Dr. Unal concluded. "We are also very interested in investigating whether or not maternal inflammatory markers influence or predict labor performance and outcome."

Dr. Unal did not report any relevant financial disclosures.

SAN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

SAN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

SAN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.