Obstetrics

Major Finding: The combination of elevated second-trimester levels of inhibin A and MSAFP had a positive likelihood ratio of 15.77 for the prediction of stillbirth. 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.

Data Source: A population-based, case-control study of 157 women with a stillbirth and 626 women with a live birth.

Disclosures: Dr. Saade did not report any relevant conflicts of interest.

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 meeting o “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.

Major Finding: The combination of elevated second-trimester levels of inhibin A and MSAFP had a positive likelihood ratio of 15.77 for the prediction of stillbirth. 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.

Data Source: A population-based, case-control study of 157 women with a stillbirth and 626 women with a live birth.

Disclosures: Dr. Saade did not report any relevant conflicts of interest.

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 meeting o “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.

Major Finding: The combination of elevated second-trimester levels of inhibin A and MSAFP had a positive likelihood ratio of 15.77 for the prediction of stillbirth. 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.

Data Source: A population-based, case-control study of 157 women with a stillbirth and 626 women with a live birth.

Disclosures: Dr. Saade did not report any relevant conflicts of interest.

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 meeting o “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.

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

A Cat-I tracing is characterized by:

• baseline rate of 110–160 beats/min
• moderate variability
• no late or variable decelerations
• early decelerations being present or absent
• accelerations being present or absent.

For laboring women who exhibit a Cat-I FHR tracing, FHR monitoring during labor may either be continuous or intermittent.

Category III—highly troubling and damaging

Conversely, the Cat-III tracing is an OB’s nightmare. It is clearly abnormal and is associated with increased risk of fetal acidemia, neonatal encephalopathy, and cerebral palsy.

A Cat-III tracing is characterized by absent variability plus any one of the following:

• recurrent late decelerations
• recurrent variable decelerations
• bradycardia.

Recurrent late or variable decelerations are defined as those decelerations that occur with 50% or more of contractions. A sinusoidal pattern—characterized by a smooth, sine wave-like, undulating pattern with a cycle frequency of 3–5 waves/min that persists for 20 minutes or longer—is also classified as a Cat-III tracing.

Delivery is often warranted if a Cat-III tracing cannot be resolved, promptly, by means of obstetrical interventions.

The great gray zone—Category II

The label of “Cat-II tracing” is given to all FHR patterns that cannot be assigned to Cat I or Cat III.

A Cat-II tracing is neither normal nor definitively abnormal. Namely:

• If FHR accelerations or moderate variability are detected, the fetus is unlikely to be currently acidemic.
• If fetal heart accelerations are absent and variability is absent or minimal, the risk of fetal acidemia increases.

Cat-II tracings should be monitored closely and evaluated carefully.

Sometimes, when an OB nurse, an OB, or a midwife assigns a tracing to Cat II, she (or he) decides to take no action to improve fetal status. Why not? Because she is temporarily paralyzed with the hope that the tracing will improve. A common rationalization is that a Cat-II tracing is caused by a fetal sleep cycle, and that (again—it’s hoped) the tracing will improve once the fetus awakens.

There is an alternative to such hopeful watching and waiting: you cando something to improve the fetal status so that the FHR tracing converts to Category I.

Suggestions for moving to a better category

In 2010, ACOG offered a number of recommendations for obstetrical maneuvers that might improve Cat-II and Cat-III FHR tracings.² These include advice to:

• change the position of the mother³ (see below)
• give her an intravenous bolus of 500–1,000 mL of lactated Ringer’s solution over 20 minutes⁴
• administer O₂ to her⁴
• decrease or stop oxytocin infusion (especially if tachysystole is present)
• discontinue cervical ripening agents
• consider administering a tocolytic, such as terbutaline, if tachysystole is present or if uterine contractions are prolonged or coupled⁵
• consider amnio-infusion if variable decelerations are present.⁶

Cervical examination and digital scalp stimulation.These two interventions are not discussed in the 2010 ACOG recommendations, but they are often useful for assessing the progression of labor and fetal status. After digital scalp stimulation, acceleration in the FHR is evidence that the fetus is unlikely to be acidemic.^7,8

If you prefer not to perform a vaginal examination, an alternative method of fetal stimulation is to use vibro-acoustic stimulation to assess fetal status.⁹

Last, when the mother has a regional anesthetic, such as an epidural, and her blood pressure is lower than it was at baseline, interventions to increase blood pressure, such as an IV bolus of ephedrine and fluids, may be effective.¹⁰

Changing maternal position may be pivotal

In the case example with which I began this discussion, the Cat-II tracing was occurring while the mother was lying flat on her back. Consider this finding: In a study of more than 900 laboring patients, 14% had an FHR tracing characterized by late decelerations.³ Of that subset of subjects, the late decelerations resolved in approximately 20% when they were moved from a supine to a lateral position. Furthermore, late decelerations recurred in some of those women when they were returned to a supine position.

In that same study, laboring in the supine, as opposed to the lateral, position was associated with lower femoral arterial blood pressure, lower toe capillary pulse pressure, and lower fetal scalp capillary pH. Other studies^11,12 have also reported a decrease in fetal oxygen saturation when the mother labors supine.

CASE: Delivery accomplished

The OB snapped out of her reverie and instructed the labor nurse to change the patient’s position, administer a fluid bolus and O₂, and recheck the blood pressure to assess for hypotension.

Twenty minutes after these interventions, the FHR tracing became Category I.

Later that night, the patient delivered a girl—Apgar scores, 8/9.

Value of a checklist

Long used in the aviation industry, checklists are thought to help practitioners remember what interventions are available when it’s necessary to respond to evolving, and potentially risky, situations. Checklists also help to build a joint vision of management options among providers on a clinical team.

I’ve provided a checklist for you on page 8 that lists the interventions available for responding to a Cat-II tracing—so that you don’t find yourself staring at it….

In utero resuscitation for Category-II and Category-III FHR tracings

Make a check mark alongside the interventions that you plan to execute. Recheck the fetal heart rate pattern 15 to 20 minutes after each intervention.
	Change maternal position—preferably, to a lateral position
	Fluid bolus: Administer 500–1,000 mL lactated Ringer’s solution IV over 20 min
	Maternal oxygen: Administer 10 L/min of O2 by nonrebreather face mask for at least 15 min
	Decrease or stop infusion of oxytocin
	Discontinue cervical ripening agent
	Consider amnio-infusion if recurrent deep, variable decelerations are present (For transcervical amnio-infusion, place an intrauterine pressure catheter and administer 1) a bolus of 250–1,000 mL of lactated Ringer’s solution at 10 to 15 mL/min and then 2) continuous infusion at 100–200 mL/h by infusion pump or gravity.)
	If clinically appropriate, consider 1) a cervical check to assess the progress of labor and 2) fetal scalp stimulation to assess for FHR acceleration (Digital scalp stimulation is performed by vigorously rubbing the fetal scalp for 15 sec using an examining finger. Following stimulation, acceleration in the FHR >15 beats/min above baseline, lasting longer than 15 sec, is associated with a low prevalence of fetal acidemia.)
	Consider vibro-acoustic stimulation as an alternative method of fetal stimulation that does not require vaginal examination (Apply a vibro-acoustic stimulator to the abdominal wall for 5 sec to assess fetal status. After the stimulus, acceleration in the fetal heart >15 beats/min above baseline, lasting longer than 15 sec, is associated with a low prevalence of fetal acidemia.)
	If the mother is relatively hypotensive, which may occur in association with an epidural anesthetic, consider ephedrine, in a 5-mg IV bolus (Note: Ephedrine may increase FHR.)
	Consider administering terbutaline, 0.25 mg subcutaneously, if tachysystole is present
	Consider placing a fetal scalp electrode if the FHR tracing is of suboptimal quality

Copyright © 2011 Quadrant HealthCom, Inc. Clinicians may copy and use this checklist without permission of the publisher to provide care. All other copying and uses require explicit permission from the publisher.

To print a copy of the checklist, upload the PDF of this article

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A Cat-I tracing is characterized by:

• baseline rate of 110–160 beats/min
• moderate variability
• no late or variable decelerations
• early decelerations being present or absent
• accelerations being present or absent.

For laboring women who exhibit a Cat-I FHR tracing, FHR monitoring during labor may either be continuous or intermittent.

Category III—highly troubling and damaging

Conversely, the Cat-III tracing is an OB’s nightmare. It is clearly abnormal and is associated with increased risk of fetal acidemia, neonatal encephalopathy, and cerebral palsy.

A Cat-III tracing is characterized by absent variability plus any one of the following:

• recurrent late decelerations
• recurrent variable decelerations
• bradycardia.

Recurrent late or variable decelerations are defined as those decelerations that occur with 50% or more of contractions. A sinusoidal pattern—characterized by a smooth, sine wave-like, undulating pattern with a cycle frequency of 3–5 waves/min that persists for 20 minutes or longer—is also classified as a Cat-III tracing.

Delivery is often warranted if a Cat-III tracing cannot be resolved, promptly, by means of obstetrical interventions.

The great gray zone—Category II

The label of “Cat-II tracing” is given to all FHR patterns that cannot be assigned to Cat I or Cat III.

A Cat-II tracing is neither normal nor definitively abnormal. Namely:

• If FHR accelerations or moderate variability are detected, the fetus is unlikely to be currently acidemic.
• If fetal heart accelerations are absent and variability is absent or minimal, the risk of fetal acidemia increases.

Cat-II tracings should be monitored closely and evaluated carefully.

Sometimes, when an OB nurse, an OB, or a midwife assigns a tracing to Cat II, she (or he) decides to take no action to improve fetal status. Why not? Because she is temporarily paralyzed with the hope that the tracing will improve. A common rationalization is that a Cat-II tracing is caused by a fetal sleep cycle, and that (again—it’s hoped) the tracing will improve once the fetus awakens.

There is an alternative to such hopeful watching and waiting: you cando something to improve the fetal status so that the FHR tracing converts to Category I.

Suggestions for moving to a better category

In 2010, ACOG offered a number of recommendations for obstetrical maneuvers that might improve Cat-II and Cat-III FHR tracings.² These include advice to:

• change the position of the mother³ (see below)
• give her an intravenous bolus of 500–1,000 mL of lactated Ringer’s solution over 20 minutes⁴
• administer O₂ to her⁴
• decrease or stop oxytocin infusion (especially if tachysystole is present)
• discontinue cervical ripening agents
• consider administering a tocolytic, such as terbutaline, if tachysystole is present or if uterine contractions are prolonged or coupled⁵
• consider amnio-infusion if variable decelerations are present.⁶

Cervical examination and digital scalp stimulation.These two interventions are not discussed in the 2010 ACOG recommendations, but they are often useful for assessing the progression of labor and fetal status. After digital scalp stimulation, acceleration in the FHR is evidence that the fetus is unlikely to be acidemic.^7,8

If you prefer not to perform a vaginal examination, an alternative method of fetal stimulation is to use vibro-acoustic stimulation to assess fetal status.⁹

Last, when the mother has a regional anesthetic, such as an epidural, and her blood pressure is lower than it was at baseline, interventions to increase blood pressure, such as an IV bolus of ephedrine and fluids, may be effective.¹⁰

Changing maternal position may be pivotal

In the case example with which I began this discussion, the Cat-II tracing was occurring while the mother was lying flat on her back. Consider this finding: In a study of more than 900 laboring patients, 14% had an FHR tracing characterized by late decelerations.³ Of that subset of subjects, the late decelerations resolved in approximately 20% when they were moved from a supine to a lateral position. Furthermore, late decelerations recurred in some of those women when they were returned to a supine position.

In that same study, laboring in the supine, as opposed to the lateral, position was associated with lower femoral arterial blood pressure, lower toe capillary pulse pressure, and lower fetal scalp capillary pH. Other studies^11,12 have also reported a decrease in fetal oxygen saturation when the mother labors supine.

CASE: Delivery accomplished

The OB snapped out of her reverie and instructed the labor nurse to change the patient’s position, administer a fluid bolus and O₂, and recheck the blood pressure to assess for hypotension.

Twenty minutes after these interventions, the FHR tracing became Category I.

Later that night, the patient delivered a girl—Apgar scores, 8/9.

Value of a checklist

Long used in the aviation industry, checklists are thought to help practitioners remember what interventions are available when it’s necessary to respond to evolving, and potentially risky, situations. Checklists also help to build a joint vision of management options among providers on a clinical team.

I’ve provided a checklist for you on page 8 that lists the interventions available for responding to a Cat-II tracing—so that you don’t find yourself staring at it….

In utero resuscitation for Category-II and Category-III FHR tracings

Make a check mark alongside the interventions that you plan to execute. Recheck the fetal heart rate pattern 15 to 20 minutes after each intervention.
	Change maternal position—preferably, to a lateral position
	Fluid bolus: Administer 500–1,000 mL lactated Ringer’s solution IV over 20 min
	Maternal oxygen: Administer 10 L/min of O2 by nonrebreather face mask for at least 15 min
	Decrease or stop infusion of oxytocin
	Discontinue cervical ripening agent
	Consider amnio-infusion if recurrent deep, variable decelerations are present (For transcervical amnio-infusion, place an intrauterine pressure catheter and administer 1) a bolus of 250–1,000 mL of lactated Ringer’s solution at 10 to 15 mL/min and then 2) continuous infusion at 100–200 mL/h by infusion pump or gravity.)
	If clinically appropriate, consider 1) a cervical check to assess the progress of labor and 2) fetal scalp stimulation to assess for FHR acceleration (Digital scalp stimulation is performed by vigorously rubbing the fetal scalp for 15 sec using an examining finger. Following stimulation, acceleration in the FHR >15 beats/min above baseline, lasting longer than 15 sec, is associated with a low prevalence of fetal acidemia.)
	Consider vibro-acoustic stimulation as an alternative method of fetal stimulation that does not require vaginal examination (Apply a vibro-acoustic stimulator to the abdominal wall for 5 sec to assess fetal status. After the stimulus, acceleration in the fetal heart >15 beats/min above baseline, lasting longer than 15 sec, is associated with a low prevalence of fetal acidemia.)
	If the mother is relatively hypotensive, which may occur in association with an epidural anesthetic, consider ephedrine, in a 5-mg IV bolus (Note: Ephedrine may increase FHR.)
	Consider administering terbutaline, 0.25 mg subcutaneously, if tachysystole is present
	Consider placing a fetal scalp electrode if the FHR tracing is of suboptimal quality

Copyright © 2011 Quadrant HealthCom, Inc. Clinicians may copy and use this checklist without permission of the publisher to provide care. All other copying and uses require explicit permission from the publisher.

To print a copy of the checklist, upload the PDF of this article

We want to hear from you!  Tell us what you think.

A Cat-I tracing is characterized by:

• baseline rate of 110–160 beats/min
• moderate variability
• no late or variable decelerations
• early decelerations being present or absent
• accelerations being present or absent.

For laboring women who exhibit a Cat-I FHR tracing, FHR monitoring during labor may either be continuous or intermittent.

Category III—highly troubling and damaging

Conversely, the Cat-III tracing is an OB’s nightmare. It is clearly abnormal and is associated with increased risk of fetal acidemia, neonatal encephalopathy, and cerebral palsy.

A Cat-III tracing is characterized by absent variability plus any one of the following:

• recurrent late decelerations
• recurrent variable decelerations
• bradycardia.

Recurrent late or variable decelerations are defined as those decelerations that occur with 50% or more of contractions. A sinusoidal pattern—characterized by a smooth, sine wave-like, undulating pattern with a cycle frequency of 3–5 waves/min that persists for 20 minutes or longer—is also classified as a Cat-III tracing.

Delivery is often warranted if a Cat-III tracing cannot be resolved, promptly, by means of obstetrical interventions.

The great gray zone—Category II

The label of “Cat-II tracing” is given to all FHR patterns that cannot be assigned to Cat I or Cat III.

A Cat-II tracing is neither normal nor definitively abnormal. Namely:

• If FHR accelerations or moderate variability are detected, the fetus is unlikely to be currently acidemic.
• If fetal heart accelerations are absent and variability is absent or minimal, the risk of fetal acidemia increases.

Cat-II tracings should be monitored closely and evaluated carefully.

Sometimes, when an OB nurse, an OB, or a midwife assigns a tracing to Cat II, she (or he) decides to take no action to improve fetal status. Why not? Because she is temporarily paralyzed with the hope that the tracing will improve. A common rationalization is that a Cat-II tracing is caused by a fetal sleep cycle, and that (again—it’s hoped) the tracing will improve once the fetus awakens.

There is an alternative to such hopeful watching and waiting: you cando something to improve the fetal status so that the FHR tracing converts to Category I.

Suggestions for moving to a better category

In 2010, ACOG offered a number of recommendations for obstetrical maneuvers that might improve Cat-II and Cat-III FHR tracings.² These include advice to:

• change the position of the mother³ (see below)
• give her an intravenous bolus of 500–1,000 mL of lactated Ringer’s solution over 20 minutes⁴
• administer O₂ to her⁴
• decrease or stop oxytocin infusion (especially if tachysystole is present)
• discontinue cervical ripening agents
• consider administering a tocolytic, such as terbutaline, if tachysystole is present or if uterine contractions are prolonged or coupled⁵
• consider amnio-infusion if variable decelerations are present.⁶

Cervical examination and digital scalp stimulation.These two interventions are not discussed in the 2010 ACOG recommendations, but they are often useful for assessing the progression of labor and fetal status. After digital scalp stimulation, acceleration in the FHR is evidence that the fetus is unlikely to be acidemic.^7,8

If you prefer not to perform a vaginal examination, an alternative method of fetal stimulation is to use vibro-acoustic stimulation to assess fetal status.⁹

Last, when the mother has a regional anesthetic, such as an epidural, and her blood pressure is lower than it was at baseline, interventions to increase blood pressure, such as an IV bolus of ephedrine and fluids, may be effective.¹⁰

Changing maternal position may be pivotal

In the case example with which I began this discussion, the Cat-II tracing was occurring while the mother was lying flat on her back. Consider this finding: In a study of more than 900 laboring patients, 14% had an FHR tracing characterized by late decelerations.³ Of that subset of subjects, the late decelerations resolved in approximately 20% when they were moved from a supine to a lateral position. Furthermore, late decelerations recurred in some of those women when they were returned to a supine position.

In that same study, laboring in the supine, as opposed to the lateral, position was associated with lower femoral arterial blood pressure, lower toe capillary pulse pressure, and lower fetal scalp capillary pH. Other studies^11,12 have also reported a decrease in fetal oxygen saturation when the mother labors supine.

CASE: Delivery accomplished

The OB snapped out of her reverie and instructed the labor nurse to change the patient’s position, administer a fluid bolus and O₂, and recheck the blood pressure to assess for hypotension.

Twenty minutes after these interventions, the FHR tracing became Category I.

Later that night, the patient delivered a girl—Apgar scores, 8/9.

Value of a checklist

Long used in the aviation industry, checklists are thought to help practitioners remember what interventions are available when it’s necessary to respond to evolving, and potentially risky, situations. Checklists also help to build a joint vision of management options among providers on a clinical team.

I’ve provided a checklist for you on page 8 that lists the interventions available for responding to a Cat-II tracing—so that you don’t find yourself staring at it….

To print a copy of the checklist, upload the PDF of this article

We want to hear from you!  Tell us what you think.

Although placenta previa is relatively rare—affecting one in every 200 to 300 singleton gestations—it is associated with significant maternal morbidity and death. Between 1979 and 1992, for example, 6.6% of maternal deaths were caused by bleeding associated with placenta previa. Perinatal mortality is also high—occurring at a rate that is three to four times higher than in normal pregnancies.^1,2

Zlatnick and colleagues have tackled a difficult issue in obstetrics, one that continues to spark debate among obstetricians—namely, when to optimally time the delivery of a patient who has placenta previa. They use a mathematical model that yields specific results based on very specific assumptions.Change the assumptions and the conclusions change, too. Although Zlatnick and colleagues have attempted to remain as fair and unbiased in their assumptions as possible, the reader must interpret their conclusions with caution.

Not all placenta previas are created equal

The mathematical model presented in this study is most relevant for truly uncomplicated placenta previa in an otherwise healthy gravida. Not all placenta previas are alike.

Despite this decision analysis, the role of amniocentesis remains unclear. The risk of respiratory distress syndrome (RDS) in an infant who has mature chemical indices is not much different than the a priori risk of RDS at 36 weeks’ gestation.

Another fact to consider: The role of maternal steroid administration to accelerate fetal lung maturity has not been firmly established beyond the 34th week of gestation.

Mathematical model is innovative but incomplete

Use of the “quality-adjusted life-year model” in this study is innovative. However, in my opinion, this decision analysis, although helpful, is incomplete.

The model has been used by two of the authors in a different decision analysis of optimal timing of delivery of women who have a prior classical cesarean section. Interestingly, in their conclusion, these authors arrived at exactly the same gestational age as the current study of placenta previa.³ That is surprising, given the entirely different biologies of placenta previa and rupture of a prior classical incision.

We want to hear from you!  Tell us what you think.

Although placenta previa is relatively rare—affecting one in every 200 to 300 singleton gestations—it is associated with significant maternal morbidity and death. Between 1979 and 1992, for example, 6.6% of maternal deaths were caused by bleeding associated with placenta previa. Perinatal mortality is also high—occurring at a rate that is three to four times higher than in normal pregnancies.^1,2

Zlatnick and colleagues have tackled a difficult issue in obstetrics, one that continues to spark debate among obstetricians—namely, when to optimally time the delivery of a patient who has placenta previa. They use a mathematical model that yields specific results based on very specific assumptions.Change the assumptions and the conclusions change, too. Although Zlatnick and colleagues have attempted to remain as fair and unbiased in their assumptions as possible, the reader must interpret their conclusions with caution.

Not all placenta previas are created equal

The mathematical model presented in this study is most relevant for truly uncomplicated placenta previa in an otherwise healthy gravida. Not all placenta previas are alike.

Despite this decision analysis, the role of amniocentesis remains unclear. The risk of respiratory distress syndrome (RDS) in an infant who has mature chemical indices is not much different than the a priori risk of RDS at 36 weeks’ gestation.

Another fact to consider: The role of maternal steroid administration to accelerate fetal lung maturity has not been firmly established beyond the 34th week of gestation.

Mathematical model is innovative but incomplete

Use of the “quality-adjusted life-year model” in this study is innovative. However, in my opinion, this decision analysis, although helpful, is incomplete.

The model has been used by two of the authors in a different decision analysis of optimal timing of delivery of women who have a prior classical cesarean section. Interestingly, in their conclusion, these authors arrived at exactly the same gestational age as the current study of placenta previa.³ That is surprising, given the entirely different biologies of placenta previa and rupture of a prior classical incision.

We want to hear from you!  Tell us what you think.

Although placenta previa is relatively rare—affecting one in every 200 to 300 singleton gestations—it is associated with significant maternal morbidity and death. Between 1979 and 1992, for example, 6.6% of maternal deaths were caused by bleeding associated with placenta previa. Perinatal mortality is also high—occurring at a rate that is three to four times higher than in normal pregnancies.^1,2

Zlatnick and colleagues have tackled a difficult issue in obstetrics, one that continues to spark debate among obstetricians—namely, when to optimally time the delivery of a patient who has placenta previa. They use a mathematical model that yields specific results based on very specific assumptions.Change the assumptions and the conclusions change, too. Although Zlatnick and colleagues have attempted to remain as fair and unbiased in their assumptions as possible, the reader must interpret their conclusions with caution.

Not all placenta previas are created equal

The mathematical model presented in this study is most relevant for truly uncomplicated placenta previa in an otherwise healthy gravida. Not all placenta previas are alike.

Despite this decision analysis, the role of amniocentesis remains unclear. The risk of respiratory distress syndrome (RDS) in an infant who has mature chemical indices is not much different than the a priori risk of RDS at 36 weeks’ gestation.

Another fact to consider: The role of maternal steroid administration to accelerate fetal lung maturity has not been firmly established beyond the 34th week of gestation.

Mathematical model is innovative but incomplete

Use of the “quality-adjusted life-year model” in this study is innovative. However, in my opinion, this decision analysis, although helpful, is incomplete.

The model has been used by two of the authors in a different decision analysis of optimal timing of delivery of women who have a prior classical cesarean section. Interestingly, in their conclusion, these authors arrived at exactly the same gestational age as the current study of placenta previa.³ That is surprising, given the entirely different biologies of placenta previa and rupture of a prior classical incision.

We want to hear from you!  Tell us what you think.

Major Finding: A prior term birth was independently protective among women who had just one previous spontaneous preterm delivery (OR, 0.83), but not among those who had more than one.

Data Source: Retrospective study of 7,319 women with a singleton pregnancy who received 17 alpha-hydroxyprogesterone caproate because they had previously experienced spontaneous preterm delivery.

Disclosures: 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 meeting. 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 said.

Major Finding: A prior term birth was independently protective among women who had just one previous spontaneous preterm delivery (OR, 0.83), but not among those who had more than one.

Data Source: Retrospective study of 7,319 women with a singleton pregnancy who received 17 alpha-hydroxyprogesterone caproate because they had previously experienced spontaneous preterm delivery.

Disclosures: 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 meeting. 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 said.

Major Finding: A prior term birth was independently protective among women who had just one previous spontaneous preterm delivery (OR, 0.83), but not among those who had more than one.

Data Source: Retrospective study of 7,319 women with a singleton pregnancy who received 17 alpha-hydroxyprogesterone caproate because they had previously experienced spontaneous preterm delivery.

Disclosures: 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 meeting. 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 said.

Major Finding: Scans revealed 43% more monamine oxidase across all brain regions in women during postpartum days 4-6, compared with those in controls.

Data Source: A case-control study of 15 postpartum women and 15 matched controls at a tertiary care academic psychiatric hospital.

Disclosures: The initial study was funded by the Canadian Institutes of Health Research and other national Canadian health alliances. Dr. Meyer said he has no financial conflicts.

MADRID – Beefing up a pregnant woman's diet with tryptophan and tyrosine might one day help avoid the “baby blues”– or even a downward slide into postpartum depression.

The proteins – found naturally in eggs, poultry, milk products, and some nuts and seeds – are important precursors of the mood-regulating brain monoamines dopamine, serotonin, and norepinephrine. Boosting them before giving birth could provide just enough cushion to counteract the effects of increased monoamine oxidase A (MAO-A). MAO-A rises sharply in the week after childbirth, metabolizing these neurotransmitters at a highly increased rate, which probably plays a key role in the emotional dysregulation many women experience, Dr. Jeffrey Meyer said at the conference.

“What we are emphasizing now in our research is trying to compensate for this increased MAO-A metabolism of serotonin, norepinephrine, and dopamine,” he said. “Giving these precursor proteins might be a potential strategy to lower the intensity of the postpartum 'blues' and possibly lead to a treatment for postpartum depression.”

Recent work in humans shows that MAO-A in postpartum women is inversely related to estrogen. This relationship, in which estrogen declines as MAO-A rises, could underlie the feelings of sadness that affect up to 75% of women around postpartum days 3-6, said Dr. Meyer, an associate professor in the psychiatry department at the University of Toronto.

Since he and his colleagues published their initial work on the MAO-A/estrogen connection last May (Arch. Gen. Psychiatry 2010;67:468-74), Dr. Meyer has begun to investigate whether nutritional supplementation with the precursor proteins could boost a woman's mood-regulating neurotransmitters enough to ward off the enzyme's postpartum effects.

The first step of that research is to examine how tyrosine and tryptophan – the proteins under investigation – affect breast milk. “If we see that there is a negligible level in milk relative to plasma, our next step will be to investigate whether their administration could attenuate postpartum blues,” he said.

The ultimate goal, however, would not be yet another prenatal supplement. “Ideally, instead of giving a powder as we're doing now [during research], we could offer some specific dietary recommendations – maybe recommending that a pregnant woman should have a diet rich in tryptophan and tyrosine.”

Such an intervention would probably be more acceptable than a medication, because it would circumvent concerns about drug excretion into breast milk, he added.

Dr. Meyer's research is based on previous animal studies – including his own – that show a precipitous drop in plasma estrogen within 48 hours of birth. Almost simultaneously and nearly in concert, Dr. Meyer said, MAO-A levels begin to rise. Plasma estrogen reaches its nadir around day 3, while MAO-A peaks around day 4. “Coincidentally, this is the typical time of postpartum sadness – this period of low mood, irritability, and sleeplessness,” Dr. Meyer said. He also said that his work represents the only MAO-A/estrogen investigation in humans.

That study looked at 15 immediately postpartum women and 15 age-matched controls, all of whom underwent positron-emission tomography with the radiotracer carbon 11–labeled harmine. The compound is extremely reliable for identifying brain levels of MAO-A, and has a 20-minute half-life, making it a good choice for lactating women, he noted. To further allay safety concerns, breastfeeding was delayed for 12 half-lives of the radiotracer, with a test sample confirming that the milk was clear. Geiger counters placed on the mothers' chests also ensured that background radiation was normal.

The new mothers all were scanned on postpartum days 4-6 – the most common time for symptoms of postpartum sadness to appear. The scans revealed 43% more MAO-A bound to the radiotracer in the postpartum group than in the controls, with significant differences seen in all the brain regions measured (prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain).

The findings mesh with a wealth of literature confirming the relationship between depression, low neurotransmitter levels, and MAO-A levels, Dr. Meyer noted, as well as with an entire class of antidepressants aimed at inhibiting the enzyme.

“I'm not saying this is the only mechanism” underlying postpartum mood changes, he noted. “But this is an important one, because there is a strong magnitude of effect, and MAO-A is a target that directly affects mood. This is something we should be looking at.

“We give women all kinds of recommendations during pregnancy,” such as iron to prevent anemia and folate to prevent neural tube defects. “But no one has ever said to a woman, 'Look, there is a biological underpinning for the sadness you might feel after delivery, and here is something we might be able to do about it.'”

Major Finding: Scans revealed 43% more monamine oxidase across all brain regions in women during postpartum days 4-6, compared with those in controls.

Data Source: A case-control study of 15 postpartum women and 15 matched controls at a tertiary care academic psychiatric hospital.

Disclosures: The initial study was funded by the Canadian Institutes of Health Research and other national Canadian health alliances. Dr. Meyer said he has no financial conflicts.

MADRID – Beefing up a pregnant woman's diet with tryptophan and tyrosine might one day help avoid the “baby blues”– or even a downward slide into postpartum depression.

The proteins – found naturally in eggs, poultry, milk products, and some nuts and seeds – are important precursors of the mood-regulating brain monoamines dopamine, serotonin, and norepinephrine. Boosting them before giving birth could provide just enough cushion to counteract the effects of increased monoamine oxidase A (MAO-A). MAO-A rises sharply in the week after childbirth, metabolizing these neurotransmitters at a highly increased rate, which probably plays a key role in the emotional dysregulation many women experience, Dr. Jeffrey Meyer said at the conference.

“What we are emphasizing now in our research is trying to compensate for this increased MAO-A metabolism of serotonin, norepinephrine, and dopamine,” he said. “Giving these precursor proteins might be a potential strategy to lower the intensity of the postpartum 'blues' and possibly lead to a treatment for postpartum depression.”

Recent work in humans shows that MAO-A in postpartum women is inversely related to estrogen. This relationship, in which estrogen declines as MAO-A rises, could underlie the feelings of sadness that affect up to 75% of women around postpartum days 3-6, said Dr. Meyer, an associate professor in the psychiatry department at the University of Toronto.

Since he and his colleagues published their initial work on the MAO-A/estrogen connection last May (Arch. Gen. Psychiatry 2010;67:468-74), Dr. Meyer has begun to investigate whether nutritional supplementation with the precursor proteins could boost a woman's mood-regulating neurotransmitters enough to ward off the enzyme's postpartum effects.

The first step of that research is to examine how tyrosine and tryptophan – the proteins under investigation – affect breast milk. “If we see that there is a negligible level in milk relative to plasma, our next step will be to investigate whether their administration could attenuate postpartum blues,” he said.

The ultimate goal, however, would not be yet another prenatal supplement. “Ideally, instead of giving a powder as we're doing now [during research], we could offer some specific dietary recommendations – maybe recommending that a pregnant woman should have a diet rich in tryptophan and tyrosine.”

Such an intervention would probably be more acceptable than a medication, because it would circumvent concerns about drug excretion into breast milk, he added.

Dr. Meyer's research is based on previous animal studies – including his own – that show a precipitous drop in plasma estrogen within 48 hours of birth. Almost simultaneously and nearly in concert, Dr. Meyer said, MAO-A levels begin to rise. Plasma estrogen reaches its nadir around day 3, while MAO-A peaks around day 4. “Coincidentally, this is the typical time of postpartum sadness – this period of low mood, irritability, and sleeplessness,” Dr. Meyer said. He also said that his work represents the only MAO-A/estrogen investigation in humans.

That study looked at 15 immediately postpartum women and 15 age-matched controls, all of whom underwent positron-emission tomography with the radiotracer carbon 11–labeled harmine. The compound is extremely reliable for identifying brain levels of MAO-A, and has a 20-minute half-life, making it a good choice for lactating women, he noted. To further allay safety concerns, breastfeeding was delayed for 12 half-lives of the radiotracer, with a test sample confirming that the milk was clear. Geiger counters placed on the mothers' chests also ensured that background radiation was normal.

The new mothers all were scanned on postpartum days 4-6 – the most common time for symptoms of postpartum sadness to appear. The scans revealed 43% more MAO-A bound to the radiotracer in the postpartum group than in the controls, with significant differences seen in all the brain regions measured (prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain).

The findings mesh with a wealth of literature confirming the relationship between depression, low neurotransmitter levels, and MAO-A levels, Dr. Meyer noted, as well as with an entire class of antidepressants aimed at inhibiting the enzyme.

“I'm not saying this is the only mechanism” underlying postpartum mood changes, he noted. “But this is an important one, because there is a strong magnitude of effect, and MAO-A is a target that directly affects mood. This is something we should be looking at.

“We give women all kinds of recommendations during pregnancy,” such as iron to prevent anemia and folate to prevent neural tube defects. “But no one has ever said to a woman, 'Look, there is a biological underpinning for the sadness you might feel after delivery, and here is something we might be able to do about it.'”

Major Finding: Scans revealed 43% more monamine oxidase across all brain regions in women during postpartum days 4-6, compared with those in controls.

Data Source: A case-control study of 15 postpartum women and 15 matched controls at a tertiary care academic psychiatric hospital.

Disclosures: The initial study was funded by the Canadian Institutes of Health Research and other national Canadian health alliances. Dr. Meyer said he has no financial conflicts.

MADRID – Beefing up a pregnant woman's diet with tryptophan and tyrosine might one day help avoid the “baby blues”– or even a downward slide into postpartum depression.

The proteins – found naturally in eggs, poultry, milk products, and some nuts and seeds – are important precursors of the mood-regulating brain monoamines dopamine, serotonin, and norepinephrine. Boosting them before giving birth could provide just enough cushion to counteract the effects of increased monoamine oxidase A (MAO-A). MAO-A rises sharply in the week after childbirth, metabolizing these neurotransmitters at a highly increased rate, which probably plays a key role in the emotional dysregulation many women experience, Dr. Jeffrey Meyer said at the conference.

“What we are emphasizing now in our research is trying to compensate for this increased MAO-A metabolism of serotonin, norepinephrine, and dopamine,” he said. “Giving these precursor proteins might be a potential strategy to lower the intensity of the postpartum 'blues' and possibly lead to a treatment for postpartum depression.”

Recent work in humans shows that MAO-A in postpartum women is inversely related to estrogen. This relationship, in which estrogen declines as MAO-A rises, could underlie the feelings of sadness that affect up to 75% of women around postpartum days 3-6, said Dr. Meyer, an associate professor in the psychiatry department at the University of Toronto.

Since he and his colleagues published their initial work on the MAO-A/estrogen connection last May (Arch. Gen. Psychiatry 2010;67:468-74), Dr. Meyer has begun to investigate whether nutritional supplementation with the precursor proteins could boost a woman's mood-regulating neurotransmitters enough to ward off the enzyme's postpartum effects.

The first step of that research is to examine how tyrosine and tryptophan – the proteins under investigation – affect breast milk. “If we see that there is a negligible level in milk relative to plasma, our next step will be to investigate whether their administration could attenuate postpartum blues,” he said.

The ultimate goal, however, would not be yet another prenatal supplement. “Ideally, instead of giving a powder as we're doing now [during research], we could offer some specific dietary recommendations – maybe recommending that a pregnant woman should have a diet rich in tryptophan and tyrosine.”

Such an intervention would probably be more acceptable than a medication, because it would circumvent concerns about drug excretion into breast milk, he added.

Dr. Meyer's research is based on previous animal studies – including his own – that show a precipitous drop in plasma estrogen within 48 hours of birth. Almost simultaneously and nearly in concert, Dr. Meyer said, MAO-A levels begin to rise. Plasma estrogen reaches its nadir around day 3, while MAO-A peaks around day 4. “Coincidentally, this is the typical time of postpartum sadness – this period of low mood, irritability, and sleeplessness,” Dr. Meyer said. He also said that his work represents the only MAO-A/estrogen investigation in humans.

That study looked at 15 immediately postpartum women and 15 age-matched controls, all of whom underwent positron-emission tomography with the radiotracer carbon 11–labeled harmine. The compound is extremely reliable for identifying brain levels of MAO-A, and has a 20-minute half-life, making it a good choice for lactating women, he noted. To further allay safety concerns, breastfeeding was delayed for 12 half-lives of the radiotracer, with a test sample confirming that the milk was clear. Geiger counters placed on the mothers' chests also ensured that background radiation was normal.

The new mothers all were scanned on postpartum days 4-6 – the most common time for symptoms of postpartum sadness to appear. The scans revealed 43% more MAO-A bound to the radiotracer in the postpartum group than in the controls, with significant differences seen in all the brain regions measured (prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain).

The findings mesh with a wealth of literature confirming the relationship between depression, low neurotransmitter levels, and MAO-A levels, Dr. Meyer noted, as well as with an entire class of antidepressants aimed at inhibiting the enzyme.

“I'm not saying this is the only mechanism” underlying postpartum mood changes, he noted. “But this is an important one, because there is a strong magnitude of effect, and MAO-A is a target that directly affects mood. This is something we should be looking at.

“We give women all kinds of recommendations during pregnancy,” such as iron to prevent anemia and folate to prevent neural tube defects. “But no one has ever said to a woman, 'Look, there is a biological underpinning for the sadness you might feel after delivery, and here is something we might be able to do about it.'”

Women who have lost a baby in a miscarriage or stillbirth can experience persistent depression during a later pregnancy that continues even after the birth of a healthy baby.

In a study of 13,133 women who gave birth in the early 1990s in southwest England and 21% had experienced miscarriages or stillbirths, “previous prenatal loss showed a persisting prediction of depressive and anxiety symptoms well after what would conventionally be defined as the postnatal period,” reported Emma Robertson Blackmore, Ph.D., of the University of Rochester Medical Center, New York, and her associates (Br. J. Psychiatry 2011 March 7 [doi:10.1192/bjp.bp.110.083105]).

The study builds on previous findings about increased anxiety and depression in pregnant women who had previously lost a baby in a miscarriage or stillbirth “by showing that the impact persists well past the subsequent pregnancy and despite the birth of a healthy child.” Because depression is very treatable, Dr. Blackmore emphasized in an interview the need for a heightened focus on identifying women with a previous prenatal loss and routinely screening them for depression.

The study, which drew its large sample from the Avon Longitudinal Study of Parents and Children (ALSPAC), measured data from six assessments, two prenatal (at 18 and 32 weeks) and four post partum (at 8 weeks and 8, 21, and 33 months). In the first assessment, the women self-reported any previous miscarriages and stillbirths. At each assessment stage, the women self-reported maternal anxiety using the Crown–Crisp Experiential Index (CCEI) and depression using the Edinburgh Postnatal Depression Scale (EPDS).

Covariates included “maternal age at initial interview, currently living with husband or partner, number of living children, education level, ethnicity, and use of tobacco and alcohol during the first 3 months of pregnancy,” previous depressive episodes, birth weight and gestational age, and a household crowding index. The investigators combined stillbirths and miscarriages after finding no significant difference in results.

Dr. Blackmore, who is in the department of psychiatry, said that she has done extensive work in postpartum depression, but she “was actually quite surprised by the findings” because it never crossed her mind before to ask women about previous loss. She had focused instead on factors such as any history of depression.

She explained how women who had a previous loss can “get incredibly anxious leading up to the gestational point” during which they lost the baby, which is when an ob.gyn. can step in and alleviate anxiety about physical symptoms.

The investigators did not report any relevant financial disclosures. The U.K. Medical Research Council, the Wellcome Trust, and the University of Bristol currently provide core support for ALSPAC. This particular study received funding from the National Institutes of Health.

View on the News

Miscarriages Require More Sensitivity

Dr. Nada Stotland sees this study as an important reminder for physicians not to trivialize miscarriages. “Sometimes medical professionals don't know what to say,” she said, and they may unintentionally hurt the patient by saying “You didn't even know the baby” or “Have another one.”

Because miscarriage is so common, Dr. Stotland thinks that physicians should be screening every woman for depression, whether or not she has risk factors.

The absence of cultural rituals for miscarriages can prevent the patient from getting closure in a time of grief. Dr. Stotland noted how Americans place importance on retrieving the bodies of fallen soldiers, but “we have nothing for miscarriage.” A physician's sensitivity to a patient's desire to name the child or hold a memorial service can help formalize this loss.

“It's just a matter of not saying something dismissive,” she said in an interview.

DR. STOTLAND is a professor of psychiatry and obstetrics and gynecology at Rush Medical College in Chicago. She did not report any relevant financial disclosures.

Women who have lost a baby in a miscarriage or stillbirth can experience persistent depression during a later pregnancy that continues even after the birth of a healthy baby.

In a study of 13,133 women who gave birth in the early 1990s in southwest England and 21% had experienced miscarriages or stillbirths, “previous prenatal loss showed a persisting prediction of depressive and anxiety symptoms well after what would conventionally be defined as the postnatal period,” reported Emma Robertson Blackmore, Ph.D., of the University of Rochester Medical Center, New York, and her associates (Br. J. Psychiatry 2011 March 7 [doi:10.1192/bjp.bp.110.083105]).

The study builds on previous findings about increased anxiety and depression in pregnant women who had previously lost a baby in a miscarriage or stillbirth “by showing that the impact persists well past the subsequent pregnancy and despite the birth of a healthy child.” Because depression is very treatable, Dr. Blackmore emphasized in an interview the need for a heightened focus on identifying women with a previous prenatal loss and routinely screening them for depression.

The study, which drew its large sample from the Avon Longitudinal Study of Parents and Children (ALSPAC), measured data from six assessments, two prenatal (at 18 and 32 weeks) and four post partum (at 8 weeks and 8, 21, and 33 months). In the first assessment, the women self-reported any previous miscarriages and stillbirths. At each assessment stage, the women self-reported maternal anxiety using the Crown–Crisp Experiential Index (CCEI) and depression using the Edinburgh Postnatal Depression Scale (EPDS).

Covariates included “maternal age at initial interview, currently living with husband or partner, number of living children, education level, ethnicity, and use of tobacco and alcohol during the first 3 months of pregnancy,” previous depressive episodes, birth weight and gestational age, and a household crowding index. The investigators combined stillbirths and miscarriages after finding no significant difference in results.

Dr. Blackmore, who is in the department of psychiatry, said that she has done extensive work in postpartum depression, but she “was actually quite surprised by the findings” because it never crossed her mind before to ask women about previous loss. She had focused instead on factors such as any history of depression.

She explained how women who had a previous loss can “get incredibly anxious leading up to the gestational point” during which they lost the baby, which is when an ob.gyn. can step in and alleviate anxiety about physical symptoms.

The investigators did not report any relevant financial disclosures. The U.K. Medical Research Council, the Wellcome Trust, and the University of Bristol currently provide core support for ALSPAC. This particular study received funding from the National Institutes of Health.

View on the News

Miscarriages Require More Sensitivity

Dr. Nada Stotland sees this study as an important reminder for physicians not to trivialize miscarriages. “Sometimes medical professionals don't know what to say,” she said, and they may unintentionally hurt the patient by saying “You didn't even know the baby” or “Have another one.”

Because miscarriage is so common, Dr. Stotland thinks that physicians should be screening every woman for depression, whether or not she has risk factors.

The absence of cultural rituals for miscarriages can prevent the patient from getting closure in a time of grief. Dr. Stotland noted how Americans place importance on retrieving the bodies of fallen soldiers, but “we have nothing for miscarriage.” A physician's sensitivity to a patient's desire to name the child or hold a memorial service can help formalize this loss.

“It's just a matter of not saying something dismissive,” she said in an interview.

DR. STOTLAND is a professor of psychiatry and obstetrics and gynecology at Rush Medical College in Chicago. She did not report any relevant financial disclosures.

Women who have lost a baby in a miscarriage or stillbirth can experience persistent depression during a later pregnancy that continues even after the birth of a healthy baby.

In a study of 13,133 women who gave birth in the early 1990s in southwest England and 21% had experienced miscarriages or stillbirths, “previous prenatal loss showed a persisting prediction of depressive and anxiety symptoms well after what would conventionally be defined as the postnatal period,” reported Emma Robertson Blackmore, Ph.D., of the University of Rochester Medical Center, New York, and her associates (Br. J. Psychiatry 2011 March 7 [doi:10.1192/bjp.bp.110.083105]).

The study builds on previous findings about increased anxiety and depression in pregnant women who had previously lost a baby in a miscarriage or stillbirth “by showing that the impact persists well past the subsequent pregnancy and despite the birth of a healthy child.” Because depression is very treatable, Dr. Blackmore emphasized in an interview the need for a heightened focus on identifying women with a previous prenatal loss and routinely screening them for depression.

The study, which drew its large sample from the Avon Longitudinal Study of Parents and Children (ALSPAC), measured data from six assessments, two prenatal (at 18 and 32 weeks) and four post partum (at 8 weeks and 8, 21, and 33 months). In the first assessment, the women self-reported any previous miscarriages and stillbirths. At each assessment stage, the women self-reported maternal anxiety using the Crown–Crisp Experiential Index (CCEI) and depression using the Edinburgh Postnatal Depression Scale (EPDS).

Covariates included “maternal age at initial interview, currently living with husband or partner, number of living children, education level, ethnicity, and use of tobacco and alcohol during the first 3 months of pregnancy,” previous depressive episodes, birth weight and gestational age, and a household crowding index. The investigators combined stillbirths and miscarriages after finding no significant difference in results.

Dr. Blackmore, who is in the department of psychiatry, said that she has done extensive work in postpartum depression, but she “was actually quite surprised by the findings” because it never crossed her mind before to ask women about previous loss. She had focused instead on factors such as any history of depression.

She explained how women who had a previous loss can “get incredibly anxious leading up to the gestational point” during which they lost the baby, which is when an ob.gyn. can step in and alleviate anxiety about physical symptoms.

The investigators did not report any relevant financial disclosures. The U.K. Medical Research Council, the Wellcome Trust, and the University of Bristol currently provide core support for ALSPAC. This particular study received funding from the National Institutes of Health.

View on the News

Miscarriages Require More Sensitivity

Dr. Nada Stotland sees this study as an important reminder for physicians not to trivialize miscarriages. “Sometimes medical professionals don't know what to say,” she said, and they may unintentionally hurt the patient by saying “You didn't even know the baby” or “Have another one.”

Because miscarriage is so common, Dr. Stotland thinks that physicians should be screening every woman for depression, whether or not she has risk factors.

The absence of cultural rituals for miscarriages can prevent the patient from getting closure in a time of grief. Dr. Stotland noted how Americans place importance on retrieving the bodies of fallen soldiers, but “we have nothing for miscarriage.” A physician's sensitivity to a patient's desire to name the child or hold a memorial service can help formalize this loss.

“It's just a matter of not saying something dismissive,” she said in an interview.

DR. STOTLAND is a professor of psychiatry and obstetrics and gynecology at Rush Medical College in Chicago. She did not report any relevant financial disclosures.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.

Although some still believe that GDM is a diagnosis looking for a disease, we have excellent evidence that the treatment of even mild forms of insulin resistance leads to improved maternal and neonatal outcomes.^1,2 (See, for example, the article on GDM by E. Albert Reece, MD, PhD, MBA.) Treatment typically involves dietary modification, exercise, and, if necessary, injectable insulin. The most recent ACOG Practice Bulletin on GDM recommends that further studies be conducted before widespread use of oral hypoglycemic agents is initiated.³

The meta-analysis by Dhulkotia and colleagues compares “any” oral hypoglycemic agent (glyburide or metformin) with insulin and concludes that there is no difference between the two types of treatment. However, this conclusion can’t be drawn from the existing literature, and it is certainly nonsensical to conduct a meta-analysis in which both types of oral agents are combined. Studies that lump different medications with distinct mechanisms of action into the same category are unlikely to produce a coherent conclusion. In this meta-analysis, clinical heterogeneity likely exists because glyburide and metformin have entirely different modes of action.

When viewed in isolation, glyburide looks less promising

Let’s consider the literature on glyburide and metformin separately. All three studies comparing glyburide and insulin demonstrated a higher incidence of neonatal hypoglycemia among women taking glyburide, with one of those studies demonstrating a statistically significant effect. In contrast, the single large randomized, controlled study comparing metformin and insulin showed a non-significant reduction in the rate of neonatal hypoglycemia for women taking metformin. The combined effect of the oral agents in the meta-analysis is a nonsignificant increase in neonatal hypoglycemia, but the odds ratio is 1.59, which certainly has some clinical meaning. A similar clinical heterogeneity of the effect on birth weight is seen when the different oral agents are compared with insulin.

Overall, data on glyburide are confusing. Most studies find glyburide and insulin to be essentially equivalent for glycemic control, but insulin leads to better outcomes (although this effect is not significant, probably owing to insufficient power).⁴ The bias among many researchers exploring the use of glyburide for GDM is obvious. One study observed that glyburide was associated with a greater likelihood of neonatal hypoglycemia and higher birth weight than insulin, but still concluded that glyburide is a reasonable first-line therapy for GDM.⁵

Data on metformin are more promising.⁶ In the large prospective trial of metformin, the great majority of outcomes were essentially the same for both metformin and insulin. However, two findings give pause:

• Approximately half the patients randomized to metformin eventually needed insulin to achieve adequate glucose control
• There was a higher incidence of preterm birth (<37 weeks) in the metformin arm. Although neonatal complications did not occur at a statistically higher rate in the metformin group, the risk of preterm birth should certainly be mentioned to the patient before she is started on the medication.

Ease of use shouldn’t trump safety concerns

Over the past decade, it has become increasingly common for health-care providers to prescribe an oral agent instead of insulin for glycemic control—even though insulin remains the standard of care. I note a prevailing perception that oral agents are easier to use than insulin, thereby improving compliance. Oral agents are easier to prescribe and do not require extensive teaching, which does save time, including nonreimbursable office time. As a result, it makes economic sense to prescribe a pill.

In my experience, however, most pregnant women are adherent with insulin therapy, and insulin injection can be reliably taught and appropriately performed regardless of the patient’s socioeconomic status, education, or language. In terms of efficacy and safety, then, insulin remains our best option.

INSTANT POLL: How would you treat this woman with gestational diabetes?
To read the entire question, enter your response, and see how others have answered, click on the blue title.

Although some still believe that GDM is a diagnosis looking for a disease, we have excellent evidence that the treatment of even mild forms of insulin resistance leads to improved maternal and neonatal outcomes.^1,2 (See, for example, the article on GDM by E. Albert Reece, MD, PhD, MBA.) Treatment typically involves dietary modification, exercise, and, if necessary, injectable insulin. The most recent ACOG Practice Bulletin on GDM recommends that further studies be conducted before widespread use of oral hypoglycemic agents is initiated.³

The meta-analysis by Dhulkotia and colleagues compares “any” oral hypoglycemic agent (glyburide or metformin) with insulin and concludes that there is no difference between the two types of treatment. However, this conclusion can’t be drawn from the existing literature, and it is certainly nonsensical to conduct a meta-analysis in which both types of oral agents are combined. Studies that lump different medications with distinct mechanisms of action into the same category are unlikely to produce a coherent conclusion. In this meta-analysis, clinical heterogeneity likely exists because glyburide and metformin have entirely different modes of action.

When viewed in isolation, glyburide looks less promising

Let’s consider the literature on glyburide and metformin separately. All three studies comparing glyburide and insulin demonstrated a higher incidence of neonatal hypoglycemia among women taking glyburide, with one of those studies demonstrating a statistically significant effect. In contrast, the single large randomized, controlled study comparing metformin and insulin showed a non-significant reduction in the rate of neonatal hypoglycemia for women taking metformin. The combined effect of the oral agents in the meta-analysis is a nonsignificant increase in neonatal hypoglycemia, but the odds ratio is 1.59, which certainly has some clinical meaning. A similar clinical heterogeneity of the effect on birth weight is seen when the different oral agents are compared with insulin.

Overall, data on glyburide are confusing. Most studies find glyburide and insulin to be essentially equivalent for glycemic control, but insulin leads to better outcomes (although this effect is not significant, probably owing to insufficient power).⁴ The bias among many researchers exploring the use of glyburide for GDM is obvious. One study observed that glyburide was associated with a greater likelihood of neonatal hypoglycemia and higher birth weight than insulin, but still concluded that glyburide is a reasonable first-line therapy for GDM.⁵

Data on metformin are more promising.⁶ In the large prospective trial of metformin, the great majority of outcomes were essentially the same for both metformin and insulin. However, two findings give pause:

• Approximately half the patients randomized to metformin eventually needed insulin to achieve adequate glucose control
• There was a higher incidence of preterm birth (<37 weeks) in the metformin arm. Although neonatal complications did not occur at a statistically higher rate in the metformin group, the risk of preterm birth should certainly be mentioned to the patient before she is started on the medication.

Ease of use shouldn’t trump safety concerns

Over the past decade, it has become increasingly common for health-care providers to prescribe an oral agent instead of insulin for glycemic control—even though insulin remains the standard of care. I note a prevailing perception that oral agents are easier to use than insulin, thereby improving compliance. Oral agents are easier to prescribe and do not require extensive teaching, which does save time, including nonreimbursable office time. As a result, it makes economic sense to prescribe a pill.

In my experience, however, most pregnant women are adherent with insulin therapy, and insulin injection can be reliably taught and appropriately performed regardless of the patient’s socioeconomic status, education, or language. In terms of efficacy and safety, then, insulin remains our best option.

INSTANT POLL: How would you treat this woman with gestational diabetes?
To read the entire question, enter your response, and see how others have answered, click on the blue title.

Although some still believe that GDM is a diagnosis looking for a disease, we have excellent evidence that the treatment of even mild forms of insulin resistance leads to improved maternal and neonatal outcomes.^1,2 (See, for example, the article on GDM by E. Albert Reece, MD, PhD, MBA.) Treatment typically involves dietary modification, exercise, and, if necessary, injectable insulin. The most recent ACOG Practice Bulletin on GDM recommends that further studies be conducted before widespread use of oral hypoglycemic agents is initiated.³

The meta-analysis by Dhulkotia and colleagues compares “any” oral hypoglycemic agent (glyburide or metformin) with insulin and concludes that there is no difference between the two types of treatment. However, this conclusion can’t be drawn from the existing literature, and it is certainly nonsensical to conduct a meta-analysis in which both types of oral agents are combined. Studies that lump different medications with distinct mechanisms of action into the same category are unlikely to produce a coherent conclusion. In this meta-analysis, clinical heterogeneity likely exists because glyburide and metformin have entirely different modes of action.

When viewed in isolation, glyburide looks less promising

Let’s consider the literature on glyburide and metformin separately. All three studies comparing glyburide and insulin demonstrated a higher incidence of neonatal hypoglycemia among women taking glyburide, with one of those studies demonstrating a statistically significant effect. In contrast, the single large randomized, controlled study comparing metformin and insulin showed a non-significant reduction in the rate of neonatal hypoglycemia for women taking metformin. The combined effect of the oral agents in the meta-analysis is a nonsignificant increase in neonatal hypoglycemia, but the odds ratio is 1.59, which certainly has some clinical meaning. A similar clinical heterogeneity of the effect on birth weight is seen when the different oral agents are compared with insulin.

Overall, data on glyburide are confusing. Most studies find glyburide and insulin to be essentially equivalent for glycemic control, but insulin leads to better outcomes (although this effect is not significant, probably owing to insufficient power).⁴ The bias among many researchers exploring the use of glyburide for GDM is obvious. One study observed that glyburide was associated with a greater likelihood of neonatal hypoglycemia and higher birth weight than insulin, but still concluded that glyburide is a reasonable first-line therapy for GDM.⁵

Data on metformin are more promising.⁶ In the large prospective trial of metformin, the great majority of outcomes were essentially the same for both metformin and insulin. However, two findings give pause:

• Approximately half the patients randomized to metformin eventually needed insulin to achieve adequate glucose control
• There was a higher incidence of preterm birth (<37 weeks) in the metformin arm. Although neonatal complications did not occur at a statistically higher rate in the metformin group, the risk of preterm birth should certainly be mentioned to the patient before she is started on the medication.

Ease of use shouldn’t trump safety concerns

Over the past decade, it has become increasingly common for health-care providers to prescribe an oral agent instead of insulin for glycemic control—even though insulin remains the standard of care. I note a prevailing perception that oral agents are easier to use than insulin, thereby improving compliance. Oral agents are easier to prescribe and do not require extensive teaching, which does save time, including nonreimbursable office time. As a result, it makes economic sense to prescribe a pill.

In my experience, however, most pregnant women are adherent with insulin therapy, and insulin injection can be reliably taught and appropriately performed regardless of the patient’s socioeconomic status, education, or language. In terms of efficacy and safety, then, insulin remains our best option.

INSTANT POLL: How would you treat this woman with gestational diabetes?
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