Obstetrics

WASHINGTON — Digoxin Immune Fab (DIF), a polyclonal fragmented antibody marketed for the treatment of digoxin toxicity, appears to improve renal function in women with severe preeclampsia, based on results of the first known study to show pharmacologic benefit for a drug that protects end-organ function in preeclamptic patients.

And DIF appeared to have no ill effects on the newborn, Dr. Garrett Lam said at the annual congress of the International Society for the Study of Hypertension in Pregnancy.

He and his colleagues collaborated on a randomized controlled trial of DIF vs. placebo that examined two primary end points—change in creatinine clearance and the use of antihypertensive medication. The study, known as the Digibind Efficacy Evaluation in Preeclampsia (DEEP) study, was supported in part by Protherics PLC, whose DIF product (marketed in the United States as Digifab) is an alternative to the GlaxoSmithKline's (marketed in the United States as Digibind).

In all, 51 women who met criteria for severe preeclampsia were randomized to receive either DIF or placebo intravenously every 6 hours for 48 hours. Candidates were selected based on the American College of Obstetricians and Gynecologists' criteria for severe preeclampsia, or by the presence of preeclampsia so severe that delivery was expected within 72 hours of admission. The gestational ages ranged from 23 weeks and 5 days to 34 weeks, and no patient had a family history of chronic hypertension, autoimmune disease, liver disease, or renal disease.

Overall, creatinine clearance was essentially preserved in the DIF-treated group, while the placebo group showed a statistically significant change. By the end of the 48-hour treatment phase, the placebo group had a drop in creatinine clearance of 34 mL/min from baseline vs. a change of only 3 mL/min from baseline in the DIF group. Once DIF was stopped, the creatinine clearance of the treatment group began to drop. “When DIF is discontinued, renal function deteriorates,” said Dr. Lam, who is in private practice in Phoenix.

While there is strong evidence for DIF's beneficial effect, Dr. Lam emphasized that larger studies are needed, both to assess the clinical implications of treating preeclamptic women with DIF and to evaluate neonatal outcomes.

Fewer patients in the DIF group needed antihypertensive medication vs. the placebo group, although this difference was not significant (46% vs. 52%). However, the study did not dictate a protocol for when antihypertensives were initiated or increased, which may have contributed to the null result for this end point, Dr. Lam said. Adverse events were reported in 8% of the DIF group and in 22% of the placebo group, but none of these was determined to be related to the study drug, he said.

The researchers also examined DIF's impact on newborns weighing 1,250 grams or less as a secondary outcome. They found fewer instances of both intraventricular hemorrhage and necrotizing enterocolitis (trending toward a significant difference) among low-birth-weight babies in the DIF group than among their same-sized counterparts in the placebo group. “The interpretation can be made that DIF has a possible protective effect in these very low-birth-weight infants,” Dr. Lam said.

Previous studies have shown increased levels of endogenous digoxinlike factors (EDLFs) in patients with preeclampsia, Dr. Lam said. EDLFs impair sodium/potassium ATPase pump activity, which is crucial in transporting calcium and in maintaining the action potential across cell membranes. The impairment of calcium clearance thus can cause contraction of vascular smooth muscle, resulting in hypertension. Three other presentations at the meeting showed evidence of the direct influence of DIF on the sodium/potassium ATPase pump. DIF binds EDLF, and it may improve outcomes in preeclamptic patients, he said.

Dr. Lam stated that he had no financial conflicts to disclose.

WASHINGTON — Digoxin Immune Fab (DIF), a polyclonal fragmented antibody marketed for the treatment of digoxin toxicity, appears to improve renal function in women with severe preeclampsia, based on results of the first known study to show pharmacologic benefit for a drug that protects end-organ function in preeclamptic patients.

And DIF appeared to have no ill effects on the newborn, Dr. Garrett Lam said at the annual congress of the International Society for the Study of Hypertension in Pregnancy.

He and his colleagues collaborated on a randomized controlled trial of DIF vs. placebo that examined two primary end points—change in creatinine clearance and the use of antihypertensive medication. The study, known as the Digibind Efficacy Evaluation in Preeclampsia (DEEP) study, was supported in part by Protherics PLC, whose DIF product (marketed in the United States as Digifab) is an alternative to the GlaxoSmithKline's (marketed in the United States as Digibind).

In all, 51 women who met criteria for severe preeclampsia were randomized to receive either DIF or placebo intravenously every 6 hours for 48 hours. Candidates were selected based on the American College of Obstetricians and Gynecologists' criteria for severe preeclampsia, or by the presence of preeclampsia so severe that delivery was expected within 72 hours of admission. The gestational ages ranged from 23 weeks and 5 days to 34 weeks, and no patient had a family history of chronic hypertension, autoimmune disease, liver disease, or renal disease.

Overall, creatinine clearance was essentially preserved in the DIF-treated group, while the placebo group showed a statistically significant change. By the end of the 48-hour treatment phase, the placebo group had a drop in creatinine clearance of 34 mL/min from baseline vs. a change of only 3 mL/min from baseline in the DIF group. Once DIF was stopped, the creatinine clearance of the treatment group began to drop. “When DIF is discontinued, renal function deteriorates,” said Dr. Lam, who is in private practice in Phoenix.

While there is strong evidence for DIF's beneficial effect, Dr. Lam emphasized that larger studies are needed, both to assess the clinical implications of treating preeclamptic women with DIF and to evaluate neonatal outcomes.

Fewer patients in the DIF group needed antihypertensive medication vs. the placebo group, although this difference was not significant (46% vs. 52%). However, the study did not dictate a protocol for when antihypertensives were initiated or increased, which may have contributed to the null result for this end point, Dr. Lam said. Adverse events were reported in 8% of the DIF group and in 22% of the placebo group, but none of these was determined to be related to the study drug, he said.

The researchers also examined DIF's impact on newborns weighing 1,250 grams or less as a secondary outcome. They found fewer instances of both intraventricular hemorrhage and necrotizing enterocolitis (trending toward a significant difference) among low-birth-weight babies in the DIF group than among their same-sized counterparts in the placebo group. “The interpretation can be made that DIF has a possible protective effect in these very low-birth-weight infants,” Dr. Lam said.

Previous studies have shown increased levels of endogenous digoxinlike factors (EDLFs) in patients with preeclampsia, Dr. Lam said. EDLFs impair sodium/potassium ATPase pump activity, which is crucial in transporting calcium and in maintaining the action potential across cell membranes. The impairment of calcium clearance thus can cause contraction of vascular smooth muscle, resulting in hypertension. Three other presentations at the meeting showed evidence of the direct influence of DIF on the sodium/potassium ATPase pump. DIF binds EDLF, and it may improve outcomes in preeclamptic patients, he said.

Dr. Lam stated that he had no financial conflicts to disclose.

WASHINGTON — Digoxin Immune Fab (DIF), a polyclonal fragmented antibody marketed for the treatment of digoxin toxicity, appears to improve renal function in women with severe preeclampsia, based on results of the first known study to show pharmacologic benefit for a drug that protects end-organ function in preeclamptic patients.

And DIF appeared to have no ill effects on the newborn, Dr. Garrett Lam said at the annual congress of the International Society for the Study of Hypertension in Pregnancy.

He and his colleagues collaborated on a randomized controlled trial of DIF vs. placebo that examined two primary end points—change in creatinine clearance and the use of antihypertensive medication. The study, known as the Digibind Efficacy Evaluation in Preeclampsia (DEEP) study, was supported in part by Protherics PLC, whose DIF product (marketed in the United States as Digifab) is an alternative to the GlaxoSmithKline's (marketed in the United States as Digibind).

In all, 51 women who met criteria for severe preeclampsia were randomized to receive either DIF or placebo intravenously every 6 hours for 48 hours. Candidates were selected based on the American College of Obstetricians and Gynecologists' criteria for severe preeclampsia, or by the presence of preeclampsia so severe that delivery was expected within 72 hours of admission. The gestational ages ranged from 23 weeks and 5 days to 34 weeks, and no patient had a family history of chronic hypertension, autoimmune disease, liver disease, or renal disease.

Overall, creatinine clearance was essentially preserved in the DIF-treated group, while the placebo group showed a statistically significant change. By the end of the 48-hour treatment phase, the placebo group had a drop in creatinine clearance of 34 mL/min from baseline vs. a change of only 3 mL/min from baseline in the DIF group. Once DIF was stopped, the creatinine clearance of the treatment group began to drop. “When DIF is discontinued, renal function deteriorates,” said Dr. Lam, who is in private practice in Phoenix.

While there is strong evidence for DIF's beneficial effect, Dr. Lam emphasized that larger studies are needed, both to assess the clinical implications of treating preeclamptic women with DIF and to evaluate neonatal outcomes.

Fewer patients in the DIF group needed antihypertensive medication vs. the placebo group, although this difference was not significant (46% vs. 52%). However, the study did not dictate a protocol for when antihypertensives were initiated or increased, which may have contributed to the null result for this end point, Dr. Lam said. Adverse events were reported in 8% of the DIF group and in 22% of the placebo group, but none of these was determined to be related to the study drug, he said.

The researchers also examined DIF's impact on newborns weighing 1,250 grams or less as a secondary outcome. They found fewer instances of both intraventricular hemorrhage and necrotizing enterocolitis (trending toward a significant difference) among low-birth-weight babies in the DIF group than among their same-sized counterparts in the placebo group. “The interpretation can be made that DIF has a possible protective effect in these very low-birth-weight infants,” Dr. Lam said.

Previous studies have shown increased levels of endogenous digoxinlike factors (EDLFs) in patients with preeclampsia, Dr. Lam said. EDLFs impair sodium/potassium ATPase pump activity, which is crucial in transporting calcium and in maintaining the action potential across cell membranes. The impairment of calcium clearance thus can cause contraction of vascular smooth muscle, resulting in hypertension. Three other presentations at the meeting showed evidence of the direct influence of DIF on the sodium/potassium ATPase pump. DIF binds EDLF, and it may improve outcomes in preeclamptic patients, he said.

Dr. Lam stated that he had no financial conflicts to disclose.

Dozens of times, every week, obstetricians are guided by the results of electronic fetal heart rate (FHR) monitoring when they make labor management decisions. Now, The National Institute of Child Health and Human Development (NICHD), along with ACOG and the Society for Maternal–Fetal Medicine, have revisited the nomenclature for interpreting FHR patterns.¹ I’ll explain how the changes may affect your management of labor.

Does FHR monitoring have clinical value?

FHR is, of course, a proxy for fetal acid–base status, oxygenation, and blood volume. Despite some modest scientific evidence that electronic FHR monitoring improves the outcome of labor for mother or newborn (compared with outcomes with intermittent auscultation), that conclusion is not what most studies reach; instead, in low-risk pregnancies, electronic FHR monitoring does not decrease the rate of perinatal complications and death, compared with intermittent auscultation, and does increase the rate of cesarean delivery.

The US Preventive Services Task Force² and the Canadian Task Force on Preventive Health Care³ therefore recommend against routine electronic FHR monitoring for low-risk women in labor. Furthermore, both task forces have concluded that evidence is insufficient to recommend for, or against, electronic FHR monitoring in high-risk women in labor.

In contrast, a 2005 ACOG bulletin recommends continuous FHR monitoring for high-risk women during labor and intermittent FHR monitoring, by auscultation or electronic means, during labor in uncomplicated pregnancies.⁴ The bulletin notes that it may be logistically difficult on most labor units to adequately execute a plan to provide intermittent auscultation because the team does not have time to assess FHR frequently by auscultation.

From a practical viewpoint, medicolegal precedent and the opinion of OB experts has led to FHR monitoring of most laboring women in US hospitals.

“Normal,” “abnormal,” and “indeterminate” categories

New NICHD guidelines¹ divide all FHR patterns into three categories:

Category I: Normal A Category I FHR pattern has the following four characteristics:

• baseline rate, 110–160 bpm
• moderate variability (6–25 bpm)
• absence of late or variable decelerations
• absence or presence of early decelerations or accelerations.

Patterns in Category I are almost always associated with normal fetal acid–base status. No specific obstetric intervention is necessary when a Category I FHR pattern is observed.

Category II: Indeterminate Category II comprises all FHR patterns not in Category I or III. Category II tracings are not predictive of abnormal fetal acid–base status. When a Category II tracing is identified, a fetal scalp stimulation test may help identify fetuses in which acid–base status is normal.

Category III: Abnormal The new NICHD guidelines label four FHR patterns as abnormal. One of the abnormal patterns is a sinusoidal heart rate, defined as a pattern of regular variability resembling a sine wave, with fixed periodicity of 3–5 cycles/ min and amplitude of 5–40 bpm. A sinusoidal pattern may indicate fetal anemia caused by fetomaternal hemorrhage or alloimmunization.

The other three abnormal FHR patterns in Category III are diagnosed when baseline FHR variability is absent and any one of the following is present:

• recurrent late decelerations
• recurrent variable deceleration
• bradycardia.

These patterns are predictive of abnormal fetal acid–base status.

NICHD categories and practical matters

Management of labor is complex. When a Category I tracing is observed, obstetric issues, independent of the FHR tracing, occupy center stage in management.

When a Category II FHR tracing is observed, a fetal scalp stimulation test may help define fetal acid–base status. When gentle stroking of the fetal scalp for 15 seconds during a vaginal examination elicits an acceleration of 15 bpm for 15 seconds, fetal acid–base status is very likely normal.⁵

(Note: Fetal scalp stimulation is a diagnostic test, not a therapeutic intervention. The test should not be performed during a deceleration because the information gained in that setting doesn’t predict the acid–base status of the fetus.)

When a Category III tracing is observed, the presence of a responsible clinician at the bedside—one who is authorized to make decisions regarding timing and route of delivery—is of paramount importance. Efforts should be made to identify the cause of the nonreassuring FHR pattern and initiate a plan to improve fetal status. Standard interventions that may help to resolve the abnormal pattern (and that may also be warranted for some Category II tracings) include:

• supplemental oxygen to the mother
• a change in maternal position
• discontinuation of oxytocin
• resolution of maternal hypotension.

In most situations, expeditious delivery is likely warranted if an abnormal pattern persists.

Neutralizing a critical inconsistency—the observer

A major problem in the use of FHR tracings is significant interclinician variability in how they are interpreted.⁶ When clinicians disagree on the interpretation of a particular FHR pattern, it often becomes difficult to develop and execute a unified plan for managing the mother’s labor.

To improve communication among nurses and physicians, it helps for each labor unit to accept a uniform approach to how FHR tracings are interpreted. Focusing on FHR variability and accurate identification of late and variable decelerations is of particular importance (see “2 keys to interpreting FHR tracings,”).

This tool offers welcome uniformity

For practical reasons, obstetricians in the United States have accepted FHR monitoring as a standard component of labor management. Given that we have accepted this technology, we can improve the consistency of our approach to interpreting FHR patterns by adopting a uniform set of definitions of what is normal and what is abnormal. Focusing on FHR variability and correctly identifying the type of deceleration that is present are the two best ways to achieve a unified approach to using FHR patterns to guide management of labor.

Dozens of times, every week, obstetricians are guided by the results of electronic fetal heart rate (FHR) monitoring when they make labor management decisions. Now, The National Institute of Child Health and Human Development (NICHD), along with ACOG and the Society for Maternal–Fetal Medicine, have revisited the nomenclature for interpreting FHR patterns.¹ I’ll explain how the changes may affect your management of labor.

Does FHR monitoring have clinical value?

FHR is, of course, a proxy for fetal acid–base status, oxygenation, and blood volume. Despite some modest scientific evidence that electronic FHR monitoring improves the outcome of labor for mother or newborn (compared with outcomes with intermittent auscultation), that conclusion is not what most studies reach; instead, in low-risk pregnancies, electronic FHR monitoring does not decrease the rate of perinatal complications and death, compared with intermittent auscultation, and does increase the rate of cesarean delivery.

The US Preventive Services Task Force² and the Canadian Task Force on Preventive Health Care³ therefore recommend against routine electronic FHR monitoring for low-risk women in labor. Furthermore, both task forces have concluded that evidence is insufficient to recommend for, or against, electronic FHR monitoring in high-risk women in labor.

In contrast, a 2005 ACOG bulletin recommends continuous FHR monitoring for high-risk women during labor and intermittent FHR monitoring, by auscultation or electronic means, during labor in uncomplicated pregnancies.⁴ The bulletin notes that it may be logistically difficult on most labor units to adequately execute a plan to provide intermittent auscultation because the team does not have time to assess FHR frequently by auscultation.

From a practical viewpoint, medicolegal precedent and the opinion of OB experts has led to FHR monitoring of most laboring women in US hospitals.

“Normal,” “abnormal,” and “indeterminate” categories

New NICHD guidelines¹ divide all FHR patterns into three categories:

Category I: Normal A Category I FHR pattern has the following four characteristics:

• baseline rate, 110–160 bpm
• moderate variability (6–25 bpm)
• absence of late or variable decelerations
• absence or presence of early decelerations or accelerations.

Patterns in Category I are almost always associated with normal fetal acid–base status. No specific obstetric intervention is necessary when a Category I FHR pattern is observed.

Category II: Indeterminate Category II comprises all FHR patterns not in Category I or III. Category II tracings are not predictive of abnormal fetal acid–base status. When a Category II tracing is identified, a fetal scalp stimulation test may help identify fetuses in which acid–base status is normal.

Category III: Abnormal The new NICHD guidelines label four FHR patterns as abnormal. One of the abnormal patterns is a sinusoidal heart rate, defined as a pattern of regular variability resembling a sine wave, with fixed periodicity of 3–5 cycles/ min and amplitude of 5–40 bpm. A sinusoidal pattern may indicate fetal anemia caused by fetomaternal hemorrhage or alloimmunization.

The other three abnormal FHR patterns in Category III are diagnosed when baseline FHR variability is absent and any one of the following is present:

• recurrent late decelerations
• recurrent variable deceleration
• bradycardia.

These patterns are predictive of abnormal fetal acid–base status.

NICHD categories and practical matters

Management of labor is complex. When a Category I tracing is observed, obstetric issues, independent of the FHR tracing, occupy center stage in management.

When a Category II FHR tracing is observed, a fetal scalp stimulation test may help define fetal acid–base status. When gentle stroking of the fetal scalp for 15 seconds during a vaginal examination elicits an acceleration of 15 bpm for 15 seconds, fetal acid–base status is very likely normal.⁵

(Note: Fetal scalp stimulation is a diagnostic test, not a therapeutic intervention. The test should not be performed during a deceleration because the information gained in that setting doesn’t predict the acid–base status of the fetus.)

When a Category III tracing is observed, the presence of a responsible clinician at the bedside—one who is authorized to make decisions regarding timing and route of delivery—is of paramount importance. Efforts should be made to identify the cause of the nonreassuring FHR pattern and initiate a plan to improve fetal status. Standard interventions that may help to resolve the abnormal pattern (and that may also be warranted for some Category II tracings) include:

• supplemental oxygen to the mother
• a change in maternal position
• discontinuation of oxytocin
• resolution of maternal hypotension.

In most situations, expeditious delivery is likely warranted if an abnormal pattern persists.

Neutralizing a critical inconsistency—the observer

A major problem in the use of FHR tracings is significant interclinician variability in how they are interpreted.⁶ When clinicians disagree on the interpretation of a particular FHR pattern, it often becomes difficult to develop and execute a unified plan for managing the mother’s labor.

To improve communication among nurses and physicians, it helps for each labor unit to accept a uniform approach to how FHR tracings are interpreted. Focusing on FHR variability and accurate identification of late and variable decelerations is of particular importance (see “2 keys to interpreting FHR tracings,”).

This tool offers welcome uniformity

For practical reasons, obstetricians in the United States have accepted FHR monitoring as a standard component of labor management. Given that we have accepted this technology, we can improve the consistency of our approach to interpreting FHR patterns by adopting a uniform set of definitions of what is normal and what is abnormal. Focusing on FHR variability and correctly identifying the type of deceleration that is present are the two best ways to achieve a unified approach to using FHR patterns to guide management of labor.

Dozens of times, every week, obstetricians are guided by the results of electronic fetal heart rate (FHR) monitoring when they make labor management decisions. Now, The National Institute of Child Health and Human Development (NICHD), along with ACOG and the Society for Maternal–Fetal Medicine, have revisited the nomenclature for interpreting FHR patterns.¹ I’ll explain how the changes may affect your management of labor.

Does FHR monitoring have clinical value?

FHR is, of course, a proxy for fetal acid–base status, oxygenation, and blood volume. Despite some modest scientific evidence that electronic FHR monitoring improves the outcome of labor for mother or newborn (compared with outcomes with intermittent auscultation), that conclusion is not what most studies reach; instead, in low-risk pregnancies, electronic FHR monitoring does not decrease the rate of perinatal complications and death, compared with intermittent auscultation, and does increase the rate of cesarean delivery.

The US Preventive Services Task Force² and the Canadian Task Force on Preventive Health Care³ therefore recommend against routine electronic FHR monitoring for low-risk women in labor. Furthermore, both task forces have concluded that evidence is insufficient to recommend for, or against, electronic FHR monitoring in high-risk women in labor.

In contrast, a 2005 ACOG bulletin recommends continuous FHR monitoring for high-risk women during labor and intermittent FHR monitoring, by auscultation or electronic means, during labor in uncomplicated pregnancies.⁴ The bulletin notes that it may be logistically difficult on most labor units to adequately execute a plan to provide intermittent auscultation because the team does not have time to assess FHR frequently by auscultation.

From a practical viewpoint, medicolegal precedent and the opinion of OB experts has led to FHR monitoring of most laboring women in US hospitals.

“Normal,” “abnormal,” and “indeterminate” categories

New NICHD guidelines¹ divide all FHR patterns into three categories:

Category I: Normal A Category I FHR pattern has the following four characteristics:

• baseline rate, 110–160 bpm
• moderate variability (6–25 bpm)
• absence of late or variable decelerations
• absence or presence of early decelerations or accelerations.

Patterns in Category I are almost always associated with normal fetal acid–base status. No specific obstetric intervention is necessary when a Category I FHR pattern is observed.

Category II: Indeterminate Category II comprises all FHR patterns not in Category I or III. Category II tracings are not predictive of abnormal fetal acid–base status. When a Category II tracing is identified, a fetal scalp stimulation test may help identify fetuses in which acid–base status is normal.

Category III: Abnormal The new NICHD guidelines label four FHR patterns as abnormal. One of the abnormal patterns is a sinusoidal heart rate, defined as a pattern of regular variability resembling a sine wave, with fixed periodicity of 3–5 cycles/ min and amplitude of 5–40 bpm. A sinusoidal pattern may indicate fetal anemia caused by fetomaternal hemorrhage or alloimmunization.

The other three abnormal FHR patterns in Category III are diagnosed when baseline FHR variability is absent and any one of the following is present:

• recurrent late decelerations
• recurrent variable deceleration
• bradycardia.

These patterns are predictive of abnormal fetal acid–base status.

NICHD categories and practical matters

Management of labor is complex. When a Category I tracing is observed, obstetric issues, independent of the FHR tracing, occupy center stage in management.

When a Category II FHR tracing is observed, a fetal scalp stimulation test may help define fetal acid–base status. When gentle stroking of the fetal scalp for 15 seconds during a vaginal examination elicits an acceleration of 15 bpm for 15 seconds, fetal acid–base status is very likely normal.⁵

(Note: Fetal scalp stimulation is a diagnostic test, not a therapeutic intervention. The test should not be performed during a deceleration because the information gained in that setting doesn’t predict the acid–base status of the fetus.)

When a Category III tracing is observed, the presence of a responsible clinician at the bedside—one who is authorized to make decisions regarding timing and route of delivery—is of paramount importance. Efforts should be made to identify the cause of the nonreassuring FHR pattern and initiate a plan to improve fetal status. Standard interventions that may help to resolve the abnormal pattern (and that may also be warranted for some Category II tracings) include:

• supplemental oxygen to the mother
• a change in maternal position
• discontinuation of oxytocin
• resolution of maternal hypotension.

In most situations, expeditious delivery is likely warranted if an abnormal pattern persists.

Neutralizing a critical inconsistency—the observer

A major problem in the use of FHR tracings is significant interclinician variability in how they are interpreted.⁶ When clinicians disagree on the interpretation of a particular FHR pattern, it often becomes difficult to develop and execute a unified plan for managing the mother’s labor.

To improve communication among nurses and physicians, it helps for each labor unit to accept a uniform approach to how FHR tracings are interpreted. Focusing on FHR variability and accurate identification of late and variable decelerations is of particular importance (see “2 keys to interpreting FHR tracings,”).

This tool offers welcome uniformity

For practical reasons, obstetricians in the United States have accepted FHR monitoring as a standard component of labor management. Given that we have accepted this technology, we can improve the consistency of our approach to interpreting FHR patterns by adopting a uniform set of definitions of what is normal and what is abnormal. Focusing on FHR variability and correctly identifying the type of deceleration that is present are the two best ways to achieve a unified approach to using FHR patterns to guide management of labor.

Obese women who undergo bariatric surgery before pregnancy have significantly better perinatal outcomes, according to findings from a retrospective study of 808 deliveries.

When 507 deliveries after bariatric surgery were compared with 301 deliveries prior to such surgery, lower rates of diabetes mellitus and hypertensive disorders (11% vs. 17% and 11% vs. 24%, respectively) were seen in those who had prepregnancy surgery, investigators said in the International Journal of Gynecology and Obstetrics (doi:10.1016/j.ijgo.2008.07.008

As for fetal outcomes, macrosomia occurred in 3% of postsurgery deliveries and 8% of presurgery deliveries, Dr. Adi Y. Weintraub of Ben-Gurion University of the Negev in Beer-Sheva, Israel, and associates wrote.

All differences were statistically significant. After controlling for potential confounders, the researchers found bariatric surgery to be independently associated with a reduction in the incidence of each of these outcomes (odds ratios of 0.42 for diabetes mellitus, 0.38 for hypertensive disorders, and 0.45 for fetal macrosomia).

The findings are important given the increasing incidence of obesity—and a concomitant increase in adverse perinatal outcomes and comorbidities—in many nations throughout the world. In the United States and Israel, about a third of women of childbearing age were classified as obese between 1999 and 2002, for example. In the United Kingdom, about 40% of women in one study were classified as moderately or very obese.

“Weight loss before conception is the optimum way to decrease the risk for medical and obstetric complications in obese women of reproductive age,” according to the authors, who note that bariatric surgery has become an increasingly popular alternative to medical therapy and lifestyle changes, which have had limited success for maintaining long-term weight loss.

Previous studies have shown that pregnancies after bariatric surgery are uncomplicated and well tolerated by the mothers, despite the presence of gestational diabetes, and these findings are corroborated by those from the current study.

Women included in the current study delivered at a tertiary medical center from 1988 to 2006, and in those who delivered after bariatric surgery there was a significant reduction in the obesity rate (10% vs. 20%; odds ratio 0.43). Such a reduction indicates the surgical intervention was relatively successful, the researchers wrote.

No significant differences were seen between post- and prebariatric surgery patients in this study in the rates of recurrent abortion (6% vs. 4%), placental abruption (0.8% vs. 0.3%), premature rupture of the membranes (11% vs. 8%), intrauterine growth restriction (4% vs. 2%), or anemia (62% vs. 71%). Cesarean deliveries, however, were significantly more common in those who underwent bariatric surgery (30% vs. 18%).

Women who had bariatric surgery before delivery also had higher rates of previous Cesarean deliveries, and prior Cesarean delivery was the most common indication for Cesarean delivery among postsurgery patients. After controlling for previous Cesarean delivery, the difference in Cesarean rates between the post- and presurgery patients was no longer statistically significant. Fetal macrosomia, however, was the indication for Cesarean delivery in only 4% of postsurgery cases, compared with 15% of presurgery patients.

Limitations of the study include the fact that all forms of bariatric surgery were included and grouped together (including restrictive and malabsorptive procedures and procedures performed using open and laparoscopic techniques). There also was a lack of information regarding body mass index and weight gain during pregnancy.

Based on their findings, the researchers concluded that bariatric surgery reduces maternal complications and fetal macrosomia, and that it is not an independent risk factor for adverse perinatal outcomes.

Obese women who undergo bariatric surgery before pregnancy have significantly better perinatal outcomes, according to findings from a retrospective study of 808 deliveries.

When 507 deliveries after bariatric surgery were compared with 301 deliveries prior to such surgery, lower rates of diabetes mellitus and hypertensive disorders (11% vs. 17% and 11% vs. 24%, respectively) were seen in those who had prepregnancy surgery, investigators said in the International Journal of Gynecology and Obstetrics (doi:10.1016/j.ijgo.2008.07.008

As for fetal outcomes, macrosomia occurred in 3% of postsurgery deliveries and 8% of presurgery deliveries, Dr. Adi Y. Weintraub of Ben-Gurion University of the Negev in Beer-Sheva, Israel, and associates wrote.

All differences were statistically significant. After controlling for potential confounders, the researchers found bariatric surgery to be independently associated with a reduction in the incidence of each of these outcomes (odds ratios of 0.42 for diabetes mellitus, 0.38 for hypertensive disorders, and 0.45 for fetal macrosomia).

The findings are important given the increasing incidence of obesity—and a concomitant increase in adverse perinatal outcomes and comorbidities—in many nations throughout the world. In the United States and Israel, about a third of women of childbearing age were classified as obese between 1999 and 2002, for example. In the United Kingdom, about 40% of women in one study were classified as moderately or very obese.

“Weight loss before conception is the optimum way to decrease the risk for medical and obstetric complications in obese women of reproductive age,” according to the authors, who note that bariatric surgery has become an increasingly popular alternative to medical therapy and lifestyle changes, which have had limited success for maintaining long-term weight loss.

Previous studies have shown that pregnancies after bariatric surgery are uncomplicated and well tolerated by the mothers, despite the presence of gestational diabetes, and these findings are corroborated by those from the current study.

Women included in the current study delivered at a tertiary medical center from 1988 to 2006, and in those who delivered after bariatric surgery there was a significant reduction in the obesity rate (10% vs. 20%; odds ratio 0.43). Such a reduction indicates the surgical intervention was relatively successful, the researchers wrote.

No significant differences were seen between post- and prebariatric surgery patients in this study in the rates of recurrent abortion (6% vs. 4%), placental abruption (0.8% vs. 0.3%), premature rupture of the membranes (11% vs. 8%), intrauterine growth restriction (4% vs. 2%), or anemia (62% vs. 71%). Cesarean deliveries, however, were significantly more common in those who underwent bariatric surgery (30% vs. 18%).

Women who had bariatric surgery before delivery also had higher rates of previous Cesarean deliveries, and prior Cesarean delivery was the most common indication for Cesarean delivery among postsurgery patients. After controlling for previous Cesarean delivery, the difference in Cesarean rates between the post- and presurgery patients was no longer statistically significant. Fetal macrosomia, however, was the indication for Cesarean delivery in only 4% of postsurgery cases, compared with 15% of presurgery patients.

Limitations of the study include the fact that all forms of bariatric surgery were included and grouped together (including restrictive and malabsorptive procedures and procedures performed using open and laparoscopic techniques). There also was a lack of information regarding body mass index and weight gain during pregnancy.

Based on their findings, the researchers concluded that bariatric surgery reduces maternal complications and fetal macrosomia, and that it is not an independent risk factor for adverse perinatal outcomes.

Obese women who undergo bariatric surgery before pregnancy have significantly better perinatal outcomes, according to findings from a retrospective study of 808 deliveries.

When 507 deliveries after bariatric surgery were compared with 301 deliveries prior to such surgery, lower rates of diabetes mellitus and hypertensive disorders (11% vs. 17% and 11% vs. 24%, respectively) were seen in those who had prepregnancy surgery, investigators said in the International Journal of Gynecology and Obstetrics (doi:10.1016/j.ijgo.2008.07.008

As for fetal outcomes, macrosomia occurred in 3% of postsurgery deliveries and 8% of presurgery deliveries, Dr. Adi Y. Weintraub of Ben-Gurion University of the Negev in Beer-Sheva, Israel, and associates wrote.

All differences were statistically significant. After controlling for potential confounders, the researchers found bariatric surgery to be independently associated with a reduction in the incidence of each of these outcomes (odds ratios of 0.42 for diabetes mellitus, 0.38 for hypertensive disorders, and 0.45 for fetal macrosomia).

The findings are important given the increasing incidence of obesity—and a concomitant increase in adverse perinatal outcomes and comorbidities—in many nations throughout the world. In the United States and Israel, about a third of women of childbearing age were classified as obese between 1999 and 2002, for example. In the United Kingdom, about 40% of women in one study were classified as moderately or very obese.

“Weight loss before conception is the optimum way to decrease the risk for medical and obstetric complications in obese women of reproductive age,” according to the authors, who note that bariatric surgery has become an increasingly popular alternative to medical therapy and lifestyle changes, which have had limited success for maintaining long-term weight loss.

Previous studies have shown that pregnancies after bariatric surgery are uncomplicated and well tolerated by the mothers, despite the presence of gestational diabetes, and these findings are corroborated by those from the current study.

Women included in the current study delivered at a tertiary medical center from 1988 to 2006, and in those who delivered after bariatric surgery there was a significant reduction in the obesity rate (10% vs. 20%; odds ratio 0.43). Such a reduction indicates the surgical intervention was relatively successful, the researchers wrote.

No significant differences were seen between post- and prebariatric surgery patients in this study in the rates of recurrent abortion (6% vs. 4%), placental abruption (0.8% vs. 0.3%), premature rupture of the membranes (11% vs. 8%), intrauterine growth restriction (4% vs. 2%), or anemia (62% vs. 71%). Cesarean deliveries, however, were significantly more common in those who underwent bariatric surgery (30% vs. 18%).

Women who had bariatric surgery before delivery also had higher rates of previous Cesarean deliveries, and prior Cesarean delivery was the most common indication for Cesarean delivery among postsurgery patients. After controlling for previous Cesarean delivery, the difference in Cesarean rates between the post- and presurgery patients was no longer statistically significant. Fetal macrosomia, however, was the indication for Cesarean delivery in only 4% of postsurgery cases, compared with 15% of presurgery patients.

Limitations of the study include the fact that all forms of bariatric surgery were included and grouped together (including restrictive and malabsorptive procedures and procedures performed using open and laparoscopic techniques). There also was a lack of information regarding body mass index and weight gain during pregnancy.

Based on their findings, the researchers concluded that bariatric surgery reduces maternal complications and fetal macrosomia, and that it is not an independent risk factor for adverse perinatal outcomes.

CHICAGO — High maternal body mass index decreases the ability to detect fetal abnormalities with standard or targeted second-trimester ultrasound, a retrospective study of more than 10,000 examinations has shown.

The study found a significant decrease in detection of anomalous fetuses with increasing body mass index (BMI) with standard ultrasound and also when standard and targeted ultrasound were combined.

“Counseling may need to be modified to reflect the limitations of sonography in the setting of obesity,” Dr. Jodi S. Dashe of the University of Texas at Dallas reported at the World Congress on Ultrasound in Obstetrics and Gynecology.

“It may be harder to identify fetal anomalies in obese women because the ultrasound transducer is farther from the fetus, which limits the image resolution,” Dr. Dashe commented in an interview.

In the present study, researchers reviewed pregnancies that received standard or targeted ultrasound between 18 and 24 weeks of gestation and were delivered at the University of Texas Southwestern Medical Center between 2003 and 2007.

Standard ultrasound had been done in keeping with the criteria of the American Institute of Ultrasound in Medicine. Targeted ultrasound was performed for specific high-risk indications.

The researchers included all potentially life-threatening structural abnormalities in their analysis as well as those requiring surgery, even if detection of the anomaly would not be expected with ultrasound. Researchers used a prospectively kept database of birth defects to verify ultrasound-detected anomalies.

An anomalous fetus was considered detected if an abnormality of the relevant organ system was identified. The researchers used patients' BMIs at first prenatal visit in their analysis, categorizing BMI according to National Institutes of Health criteria: normal (less than 25 kg/m

Of 10,112 standard and 1,023 targeted ultrasound examinations, anomalies were verified in 181 infants (1.6%).

Standard ultrasound detected 66% of anomalous fetuses in women with a normal BMI, but only 49%, 48%, 42%, and 25% of anomalous fetuses in women in the overweight and class I, II, and III obesity categories, respectively.

The combined detection of anomalous fetuses was 68% in women with a normal BMI but only 55%, 49%, 47%, and 43% in women in the overweight and class I, II, and III obesity categories.

Previous research on fetal cardiac visualization and BMI also found significantly higher rates of persistent suboptimal ultrasonographic visualization (SUV) on a repeated ultrasound examination in obese women, compared with nonobese women.

SUV rates increased with increasing BMI in obese patients (J. Ultrasound Med. 2005;24:1205-9).

Dr. Dashe said she and her colleagues hope to do further research in this area. She had no financial conflicts of interest to report.

CHICAGO — High maternal body mass index decreases the ability to detect fetal abnormalities with standard or targeted second-trimester ultrasound, a retrospective study of more than 10,000 examinations has shown.

The study found a significant decrease in detection of anomalous fetuses with increasing body mass index (BMI) with standard ultrasound and also when standard and targeted ultrasound were combined.

“Counseling may need to be modified to reflect the limitations of sonography in the setting of obesity,” Dr. Jodi S. Dashe of the University of Texas at Dallas reported at the World Congress on Ultrasound in Obstetrics and Gynecology.

“It may be harder to identify fetal anomalies in obese women because the ultrasound transducer is farther from the fetus, which limits the image resolution,” Dr. Dashe commented in an interview.

In the present study, researchers reviewed pregnancies that received standard or targeted ultrasound between 18 and 24 weeks of gestation and were delivered at the University of Texas Southwestern Medical Center between 2003 and 2007.

Standard ultrasound had been done in keeping with the criteria of the American Institute of Ultrasound in Medicine. Targeted ultrasound was performed for specific high-risk indications.

The researchers included all potentially life-threatening structural abnormalities in their analysis as well as those requiring surgery, even if detection of the anomaly would not be expected with ultrasound. Researchers used a prospectively kept database of birth defects to verify ultrasound-detected anomalies.

An anomalous fetus was considered detected if an abnormality of the relevant organ system was identified. The researchers used patients' BMIs at first prenatal visit in their analysis, categorizing BMI according to National Institutes of Health criteria: normal (less than 25 kg/m

Of 10,112 standard and 1,023 targeted ultrasound examinations, anomalies were verified in 181 infants (1.6%).

Standard ultrasound detected 66% of anomalous fetuses in women with a normal BMI, but only 49%, 48%, 42%, and 25% of anomalous fetuses in women in the overweight and class I, II, and III obesity categories, respectively.

The combined detection of anomalous fetuses was 68% in women with a normal BMI but only 55%, 49%, 47%, and 43% in women in the overweight and class I, II, and III obesity categories.

Previous research on fetal cardiac visualization and BMI also found significantly higher rates of persistent suboptimal ultrasonographic visualization (SUV) on a repeated ultrasound examination in obese women, compared with nonobese women.

SUV rates increased with increasing BMI in obese patients (J. Ultrasound Med. 2005;24:1205-9).

Dr. Dashe said she and her colleagues hope to do further research in this area. She had no financial conflicts of interest to report.

CHICAGO — High maternal body mass index decreases the ability to detect fetal abnormalities with standard or targeted second-trimester ultrasound, a retrospective study of more than 10,000 examinations has shown.

The study found a significant decrease in detection of anomalous fetuses with increasing body mass index (BMI) with standard ultrasound and also when standard and targeted ultrasound were combined.

“Counseling may need to be modified to reflect the limitations of sonography in the setting of obesity,” Dr. Jodi S. Dashe of the University of Texas at Dallas reported at the World Congress on Ultrasound in Obstetrics and Gynecology.

“It may be harder to identify fetal anomalies in obese women because the ultrasound transducer is farther from the fetus, which limits the image resolution,” Dr. Dashe commented in an interview.

In the present study, researchers reviewed pregnancies that received standard or targeted ultrasound between 18 and 24 weeks of gestation and were delivered at the University of Texas Southwestern Medical Center between 2003 and 2007.

Standard ultrasound had been done in keeping with the criteria of the American Institute of Ultrasound in Medicine. Targeted ultrasound was performed for specific high-risk indications.

The researchers included all potentially life-threatening structural abnormalities in their analysis as well as those requiring surgery, even if detection of the anomaly would not be expected with ultrasound. Researchers used a prospectively kept database of birth defects to verify ultrasound-detected anomalies.

An anomalous fetus was considered detected if an abnormality of the relevant organ system was identified. The researchers used patients' BMIs at first prenatal visit in their analysis, categorizing BMI according to National Institutes of Health criteria: normal (less than 25 kg/m

Of 10,112 standard and 1,023 targeted ultrasound examinations, anomalies were verified in 181 infants (1.6%).

Standard ultrasound detected 66% of anomalous fetuses in women with a normal BMI, but only 49%, 48%, 42%, and 25% of anomalous fetuses in women in the overweight and class I, II, and III obesity categories, respectively.

The combined detection of anomalous fetuses was 68% in women with a normal BMI but only 55%, 49%, 47%, and 43% in women in the overweight and class I, II, and III obesity categories.

Previous research on fetal cardiac visualization and BMI also found significantly higher rates of persistent suboptimal ultrasonographic visualization (SUV) on a repeated ultrasound examination in obese women, compared with nonobese women.

SUV rates increased with increasing BMI in obese patients (J. Ultrasound Med. 2005;24:1205-9).

Dr. Dashe said she and her colleagues hope to do further research in this area. She had no financial conflicts of interest to report.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

Gestational impaired glucose tolerance, defined by a single abnormal value at 1 hour during the oral glucose tolerance test, is associated with many of the same adverse outcomes as gestational diabetes mellitus, including postpartum glycemia, insulin resistance, and β-cell dysfunction, according to the results of a recent study.

Investigators evaluated metabolic function and outcomes in a cohort of more than 360 women stratified by glucose tolerance status during pregnancy. The participants underwent an antepartum glucose challenge test (GCT) and a 3-hour oral glucose tolerance test (OGTT), an assessment of obstetric outcome at delivery, and a metabolic characterization by OGTT at 3 months post partum.

The investigators identified five study groups: those with gestational diabetes mellitus (GDM), 1-hour gestational impaired glucose tolerance (GIGT), 2- or 3-hour GIGT, abnormal glucose challenge test (GCT) with normal glucose tolerance (NGT), and normal GCT with NGT (Diabetes Care 2008;31:1275–81). There were no significant differences among the groups with respect to mean age, smoking status, and parity.

The researchers noted the 1-hour GIGT group had adverse outcomes similar to the group with gestational diabetes mellitus, although the GIGT group did not have increased infant birth weight. The “Caesarian section rate was highest in the 1-hour GIGT group; there were no significant differences [among] the four non-GDM groups,” wrote Dr. Ravi Retnakaran of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, and his colleagues.

In addition, there were no significant differences among the four non-GDM groups with respect to length of gestation, infant sex, or Apgar scores.

At 3 months post partum, glycemic parameters progressively increased from normal glucose challenge test with normal glucose tolerance to abnormal glucose challenge test with normal glucose tolerance to 2- or 3-hour gestational impaired glucose tolerance to 1-hour GIGT to gestational diabetes mellitus. Insulin sensitivity and β-cell function progressively decreased across the groups in the same manner.

Participants in the normal GCT NGT group underwent the 3-hour oral glucose tolerance test at a median of 32 weeks' gestation, compared with a median of 29 weeks' gestation for the other four groups.

Gestational diabetes mellitus is a metabolically heterogeneous disorder, which could lead to a higher risk of developing type 2 diabetes in the years following pregnancy.

Short term, there is an increased risk of adverse obstetric outcomes related to fetal overgrowth and higher birth weight. Long term, women with a history of GDM have chronic insulin resistance and β-cell dysfunction.

One limitation of the current study is the relatively modest number of participants with GIGT (28), wrote Dr. Retnakaran and his colleagues. Still, they said the issue warrants further investigation, including long-term follow-up to determine the risk of type 2 diabetes and appropriate cost-benefit evaluation of postpartum care strategies.

Dr. Retnakaran also is in the division of endocrinology and metabolism at the University of Toronto.

The study was supported by a grant from the Canadian Institutes of Health Research.

Gestational impaired glucose tolerance, defined by a single abnormal value at 1 hour during the oral glucose tolerance test, is associated with many of the same adverse outcomes as gestational diabetes mellitus, including postpartum glycemia, insulin resistance, and β-cell dysfunction, according to the results of a recent study.

Investigators evaluated metabolic function and outcomes in a cohort of more than 360 women stratified by glucose tolerance status during pregnancy. The participants underwent an antepartum glucose challenge test (GCT) and a 3-hour oral glucose tolerance test (OGTT), an assessment of obstetric outcome at delivery, and a metabolic characterization by OGTT at 3 months post partum.

The investigators identified five study groups: those with gestational diabetes mellitus (GDM), 1-hour gestational impaired glucose tolerance (GIGT), 2- or 3-hour GIGT, abnormal glucose challenge test (GCT) with normal glucose tolerance (NGT), and normal GCT with NGT (Diabetes Care 2008;31:1275–81). There were no significant differences among the groups with respect to mean age, smoking status, and parity.

The researchers noted the 1-hour GIGT group had adverse outcomes similar to the group with gestational diabetes mellitus, although the GIGT group did not have increased infant birth weight. The “Caesarian section rate was highest in the 1-hour GIGT group; there were no significant differences [among] the four non-GDM groups,” wrote Dr. Ravi Retnakaran of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, and his colleagues.

In addition, there were no significant differences among the four non-GDM groups with respect to length of gestation, infant sex, or Apgar scores.

At 3 months post partum, glycemic parameters progressively increased from normal glucose challenge test with normal glucose tolerance to abnormal glucose challenge test with normal glucose tolerance to 2- or 3-hour gestational impaired glucose tolerance to 1-hour GIGT to gestational diabetes mellitus. Insulin sensitivity and β-cell function progressively decreased across the groups in the same manner.

Participants in the normal GCT NGT group underwent the 3-hour oral glucose tolerance test at a median of 32 weeks' gestation, compared with a median of 29 weeks' gestation for the other four groups.

Gestational diabetes mellitus is a metabolically heterogeneous disorder, which could lead to a higher risk of developing type 2 diabetes in the years following pregnancy.

Short term, there is an increased risk of adverse obstetric outcomes related to fetal overgrowth and higher birth weight. Long term, women with a history of GDM have chronic insulin resistance and β-cell dysfunction.

One limitation of the current study is the relatively modest number of participants with GIGT (28), wrote Dr. Retnakaran and his colleagues. Still, they said the issue warrants further investigation, including long-term follow-up to determine the risk of type 2 diabetes and appropriate cost-benefit evaluation of postpartum care strategies.

Dr. Retnakaran also is in the division of endocrinology and metabolism at the University of Toronto.

The study was supported by a grant from the Canadian Institutes of Health Research.

Gestational impaired glucose tolerance, defined by a single abnormal value at 1 hour during the oral glucose tolerance test, is associated with many of the same adverse outcomes as gestational diabetes mellitus, including postpartum glycemia, insulin resistance, and β-cell dysfunction, according to the results of a recent study.

Investigators evaluated metabolic function and outcomes in a cohort of more than 360 women stratified by glucose tolerance status during pregnancy. The participants underwent an antepartum glucose challenge test (GCT) and a 3-hour oral glucose tolerance test (OGTT), an assessment of obstetric outcome at delivery, and a metabolic characterization by OGTT at 3 months post partum.

The investigators identified five study groups: those with gestational diabetes mellitus (GDM), 1-hour gestational impaired glucose tolerance (GIGT), 2- or 3-hour GIGT, abnormal glucose challenge test (GCT) with normal glucose tolerance (NGT), and normal GCT with NGT (Diabetes Care 2008;31:1275–81). There were no significant differences among the groups with respect to mean age, smoking status, and parity.

The researchers noted the 1-hour GIGT group had adverse outcomes similar to the group with gestational diabetes mellitus, although the GIGT group did not have increased infant birth weight. The “Caesarian section rate was highest in the 1-hour GIGT group; there were no significant differences [among] the four non-GDM groups,” wrote Dr. Ravi Retnakaran of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, and his colleagues.

In addition, there were no significant differences among the four non-GDM groups with respect to length of gestation, infant sex, or Apgar scores.

At 3 months post partum, glycemic parameters progressively increased from normal glucose challenge test with normal glucose tolerance to abnormal glucose challenge test with normal glucose tolerance to 2- or 3-hour gestational impaired glucose tolerance to 1-hour GIGT to gestational diabetes mellitus. Insulin sensitivity and β-cell function progressively decreased across the groups in the same manner.

Participants in the normal GCT NGT group underwent the 3-hour oral glucose tolerance test at a median of 32 weeks' gestation, compared with a median of 29 weeks' gestation for the other four groups.

Gestational diabetes mellitus is a metabolically heterogeneous disorder, which could lead to a higher risk of developing type 2 diabetes in the years following pregnancy.

Short term, there is an increased risk of adverse obstetric outcomes related to fetal overgrowth and higher birth weight. Long term, women with a history of GDM have chronic insulin resistance and β-cell dysfunction.

One limitation of the current study is the relatively modest number of participants with GIGT (28), wrote Dr. Retnakaran and his colleagues. Still, they said the issue warrants further investigation, including long-term follow-up to determine the risk of type 2 diabetes and appropriate cost-benefit evaluation of postpartum care strategies.

Dr. Retnakaran also is in the division of endocrinology and metabolism at the University of Toronto.

The study was supported by a grant from the Canadian Institutes of Health Research.

MONTEREY, CALIF. — Women with thyroid disease are 50% more likely to have a child with left ventricular outflow tract obstruction than women without thyroid disease, according to a study that compared about 6,000 women in each of the two groups.

In particular, the risk of aortic valve stenosis and/or coarctation of the aorta appeared to be elevated, Marilyn L. Browne of the New York State Department of Health and her colleagues wrote in a poster presentation at the annual meeting of the Teratology Society.

There were no other statistically significant associations between maternal thyroid disease and congenital cardiovascular malformations.

The multicenter case control study was part of the National Birth Defects Prevention Study (NBDPS), which collects data from 10 regions in the United States. The investigators identified 6,068 women with a thyroid disease whose babies were born between October 1997 and December 2004 and compared them with 5,875 controls.

There were no significant demographic differences between the case and control groups, they reported.

The odds ratios were adjusted for potential confounders, including maternal age, race/ethnicity, education, prepregnancy BMI, gestational diabetes, smoking, alcohol use, and the state of residence at time of delivery.

The investigators acknowledged that their study did not identify the women's underlying thyroid conditions. They recommended that additional studies should evaluate the risks of antithyroid medication and should examine risk by type of thyroid disorder.

Ms. Browne stated she had no conflicts of interest to disclose related to her presentation.

MONTEREY, CALIF. — Women with thyroid disease are 50% more likely to have a child with left ventricular outflow tract obstruction than women without thyroid disease, according to a study that compared about 6,000 women in each of the two groups.

In particular, the risk of aortic valve stenosis and/or coarctation of the aorta appeared to be elevated, Marilyn L. Browne of the New York State Department of Health and her colleagues wrote in a poster presentation at the annual meeting of the Teratology Society.

There were no other statistically significant associations between maternal thyroid disease and congenital cardiovascular malformations.

The multicenter case control study was part of the National Birth Defects Prevention Study (NBDPS), which collects data from 10 regions in the United States. The investigators identified 6,068 women with a thyroid disease whose babies were born between October 1997 and December 2004 and compared them with 5,875 controls.

There were no significant demographic differences between the case and control groups, they reported.

The odds ratios were adjusted for potential confounders, including maternal age, race/ethnicity, education, prepregnancy BMI, gestational diabetes, smoking, alcohol use, and the state of residence at time of delivery.

The investigators acknowledged that their study did not identify the women's underlying thyroid conditions. They recommended that additional studies should evaluate the risks of antithyroid medication and should examine risk by type of thyroid disorder.

Ms. Browne stated she had no conflicts of interest to disclose related to her presentation.

MONTEREY, CALIF. — Women with thyroid disease are 50% more likely to have a child with left ventricular outflow tract obstruction than women without thyroid disease, according to a study that compared about 6,000 women in each of the two groups.

In particular, the risk of aortic valve stenosis and/or coarctation of the aorta appeared to be elevated, Marilyn L. Browne of the New York State Department of Health and her colleagues wrote in a poster presentation at the annual meeting of the Teratology Society.

There were no other statistically significant associations between maternal thyroid disease and congenital cardiovascular malformations.

The multicenter case control study was part of the National Birth Defects Prevention Study (NBDPS), which collects data from 10 regions in the United States. The investigators identified 6,068 women with a thyroid disease whose babies were born between October 1997 and December 2004 and compared them with 5,875 controls.

There were no significant demographic differences between the case and control groups, they reported.

The odds ratios were adjusted for potential confounders, including maternal age, race/ethnicity, education, prepregnancy BMI, gestational diabetes, smoking, alcohol use, and the state of residence at time of delivery.

The investigators acknowledged that their study did not identify the women's underlying thyroid conditions. They recommended that additional studies should evaluate the risks of antithyroid medication and should examine risk by type of thyroid disorder.

Ms. Browne stated she had no conflicts of interest to disclose related to her presentation.

CHICAGO — Anticipated pain, anxiety, and sensitivity to standardized audio tones can predict a woman's pain experience and narcotic requirements following cesarean section, according to a study of 118 recipients of elective C-sections.

“These findings indicate that simple questions prior to cesarean section can help providers identify patients who may be at risk for inadequate pain control and subsequent development of persistent pain and depression,” Dr. Ashley M. Tonidandel of Wake Forest University, Winston-Salem, N.C., reported at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Previous research presented at last year's meeting indicated that pain severity following delivery is a stronger predictor of persistent pain and postpartum depression than is method of delivery.

The link between acute pain and postpartum depression, which can impair the mother's ability to attach to the infant, underscores the need for an easy method of identifying at-risk patients, Dr. Tonidandel commented.

“The Joint Commission suggests that it's both a hospital standard and a patient right to have a goal for pain scores of less than four,” she said.

To date, Dr. Tonidandel and her colleagues have collected data on 118 parturients who underwent elective C-section with subarachnoid anesthesia and spinal morphine.

Most of the patients were undergoing repeat C-sections, and the rest were undergoing primary sections for breech and other reasons.

During the preoperative anesthetic consultation, patients were asked a set of questions regarding their level of anticipated pain and anxiety.

They also rated the loudness of a series of tones with a visual analog scale.

Chart reviews provided data on actual narcotic usage in the postanesthesia care unit and 24 hours after surgery.

Assessments of resting pain, evoked pain, and satisfaction with pain control also were conducted 24 hours after surgery using the same visual analog scale.

Patient scores on anticipated pain, anxiety, and sensitivity to sound predicted levels of narcotic usage in the postanesthesia care unit and at 24 hours post surgery, as well as degree of resting and evoked pain.

Satisfaction with pain control was generally high and was not associated with patient scores.

Anticipated pain surfaced as the most significant predictor of postsurgical pain and analgesic requirements; however, audio sensitivity was an important and unique predictor of narcotic usage in the postanesthesia care unit as well.

Previous research has shown that sensitivity to heat can help predict narcotic requirements after cesarean delivery (Anesthesiology 2006;104:417–25). However, the use of audio stimuli, which were shown to be predictive in this study, provides “a nice way to get around having to use heat on parturients before C-section,” Dr. Tonidandel said.

“By asking patients [a few questions] preoperatively, I'm much less surprised by what happens later,” she added.

As more data are collected, Dr. Tonidandel and her colleagues plan to develop threshold scores to identify patients who might benefit from early intervention and the initiation of customized, multimodal pain management.

The model used in this study also may have potential applications for patients undergoing other types of surgery, they said.

CHICAGO — Anticipated pain, anxiety, and sensitivity to standardized audio tones can predict a woman's pain experience and narcotic requirements following cesarean section, according to a study of 118 recipients of elective C-sections.

“These findings indicate that simple questions prior to cesarean section can help providers identify patients who may be at risk for inadequate pain control and subsequent development of persistent pain and depression,” Dr. Ashley M. Tonidandel of Wake Forest University, Winston-Salem, N.C., reported at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Previous research presented at last year's meeting indicated that pain severity following delivery is a stronger predictor of persistent pain and postpartum depression than is method of delivery.

The link between acute pain and postpartum depression, which can impair the mother's ability to attach to the infant, underscores the need for an easy method of identifying at-risk patients, Dr. Tonidandel commented.

“The Joint Commission suggests that it's both a hospital standard and a patient right to have a goal for pain scores of less than four,” she said.

To date, Dr. Tonidandel and her colleagues have collected data on 118 parturients who underwent elective C-section with subarachnoid anesthesia and spinal morphine.

Most of the patients were undergoing repeat C-sections, and the rest were undergoing primary sections for breech and other reasons.

During the preoperative anesthetic consultation, patients were asked a set of questions regarding their level of anticipated pain and anxiety.

They also rated the loudness of a series of tones with a visual analog scale.

Chart reviews provided data on actual narcotic usage in the postanesthesia care unit and 24 hours after surgery.

Assessments of resting pain, evoked pain, and satisfaction with pain control also were conducted 24 hours after surgery using the same visual analog scale.

Patient scores on anticipated pain, anxiety, and sensitivity to sound predicted levels of narcotic usage in the postanesthesia care unit and at 24 hours post surgery, as well as degree of resting and evoked pain.

Satisfaction with pain control was generally high and was not associated with patient scores.

Anticipated pain surfaced as the most significant predictor of postsurgical pain and analgesic requirements; however, audio sensitivity was an important and unique predictor of narcotic usage in the postanesthesia care unit as well.

Previous research has shown that sensitivity to heat can help predict narcotic requirements after cesarean delivery (Anesthesiology 2006;104:417–25). However, the use of audio stimuli, which were shown to be predictive in this study, provides “a nice way to get around having to use heat on parturients before C-section,” Dr. Tonidandel said.

“By asking patients [a few questions] preoperatively, I'm much less surprised by what happens later,” she added.

As more data are collected, Dr. Tonidandel and her colleagues plan to develop threshold scores to identify patients who might benefit from early intervention and the initiation of customized, multimodal pain management.

The model used in this study also may have potential applications for patients undergoing other types of surgery, they said.

CHICAGO — Anticipated pain, anxiety, and sensitivity to standardized audio tones can predict a woman's pain experience and narcotic requirements following cesarean section, according to a study of 118 recipients of elective C-sections.

“These findings indicate that simple questions prior to cesarean section can help providers identify patients who may be at risk for inadequate pain control and subsequent development of persistent pain and depression,” Dr. Ashley M. Tonidandel of Wake Forest University, Winston-Salem, N.C., reported at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Previous research presented at last year's meeting indicated that pain severity following delivery is a stronger predictor of persistent pain and postpartum depression than is method of delivery.

The link between acute pain and postpartum depression, which can impair the mother's ability to attach to the infant, underscores the need for an easy method of identifying at-risk patients, Dr. Tonidandel commented.

“The Joint Commission suggests that it's both a hospital standard and a patient right to have a goal for pain scores of less than four,” she said.

To date, Dr. Tonidandel and her colleagues have collected data on 118 parturients who underwent elective C-section with subarachnoid anesthesia and spinal morphine.

Most of the patients were undergoing repeat C-sections, and the rest were undergoing primary sections for breech and other reasons.

During the preoperative anesthetic consultation, patients were asked a set of questions regarding their level of anticipated pain and anxiety.

They also rated the loudness of a series of tones with a visual analog scale.

Chart reviews provided data on actual narcotic usage in the postanesthesia care unit and 24 hours after surgery.

Assessments of resting pain, evoked pain, and satisfaction with pain control also were conducted 24 hours after surgery using the same visual analog scale.

Patient scores on anticipated pain, anxiety, and sensitivity to sound predicted levels of narcotic usage in the postanesthesia care unit and at 24 hours post surgery, as well as degree of resting and evoked pain.

Satisfaction with pain control was generally high and was not associated with patient scores.

Anticipated pain surfaced as the most significant predictor of postsurgical pain and analgesic requirements; however, audio sensitivity was an important and unique predictor of narcotic usage in the postanesthesia care unit as well.

Previous research has shown that sensitivity to heat can help predict narcotic requirements after cesarean delivery (Anesthesiology 2006;104:417–25). However, the use of audio stimuli, which were shown to be predictive in this study, provides “a nice way to get around having to use heat on parturients before C-section,” Dr. Tonidandel said.

“By asking patients [a few questions] preoperatively, I'm much less surprised by what happens later,” she added.

As more data are collected, Dr. Tonidandel and her colleagues plan to develop threshold scores to identify patients who might benefit from early intervention and the initiation of customized, multimodal pain management.

The model used in this study also may have potential applications for patients undergoing other types of surgery, they said.

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

CHICAGO — A recent multivariate analysis found that low birth weight is the single most significant risk factor for having a hemangioma of infancy.

These findings come at a time when the rates of preterm and low-birth-weight infants continue to rise in the United States, mainly because of assisted reproductive technologies, Dr. Ilona J. Frieden said at the American Academy of Dermatology's Academy 2008 meeting.

In 2005, 8.2% of infants born in the United States weighed 2,500 g or less—the highest percentage since 1968. Physicians can expect to see more hemangioma patients, and should use anatomic location and growth patterns to assess risk and management options, she said.

If one assumes a 15% incidence in preterm infants, 50,000 infants in 2005 in the United States would have one or more infantile hemangiomas, compared with 20,000 in 1985, said Dr. Frieden, director of pediatric dermatology at the University of California, San Francisco.

The new findings are based on research by the Hemangioma Investigator Group (HIG) that compared 420 infants with hemangiomas with 353 patients without hemangiomas seen for other skin problems. With use of multivariate logistic regression analysis, low birth weight was identified as the single most significant risk factor for having a hemangioma.

For each 500-g decrease in weight from a control group of 3,000-g to 3,500-g infants, there was a 29% increase in risk, Dr. Frieden said.

The current study whittles down a list of significant risk factors identified by an earlier HIG study that included female gender; white, non-Hispanic race; prematurity; low birth weight; multiple gestation; and advanced maternal age (J. Pediatr. 2007;150:291–4).

Dr. Frieden said traditional descriptions of infantile hemangiomas as superficial, deep, or mixed fail to capture essential differences in these benign tumors, and that a better classification schema is needed.

Most hemangiomas of infancy can be classified as “segmental” or “localized,” she postulated. Segmental hemangiomas cover a broad anatomic region or recognized developmental unit such as the entire ear, while localized hemangiomas are confined spatially and often appear to arise from a central focal point.

Prior research has shown that segmental lesions are larger, require more intensive and prolonged therapy, and are more frequently associated with developmental abnormalities, complications, and a poorer overall outcome (Arch. Dermatol. 2002;138:1567–76).

More recent data from the HIG, an international consortium of researchers, confirmed these findings. Infants with segmental hemangiomas were found to be 11 times more likely to experience complications and 8 times more likely to receive treatment than were those with localized hemangiomas (Pediatrics 2006;118:882–7). The effect persists, even when controlled for size, Dr. Frieden said.

In addition to distribution, hemangiomas have distinct growth patterns, suggesting a critical period of intervention in the first few weeks to months of life. HIG findings to be published in an upcoming issue of Pediatrics indicate that hemangiomas reach 80% of their maximum size at a mean age of 3 months. By 5 months of age, 80% of hemangiomas have completed their growth, she said. Segmental hemangiomas were found to present 1 month earlier, yet were 10 times larger than were localized hemangiomas.

Intervention, when necessary, is best during this early period because treatments such as systemic corticosteroids work better at preventing growth than shrinking established lesions, Dr. Frieden said.

She proceeded to highlight a pilot study in France that showed rapid improvement with the use of propranolol in nine infants with severe infantile hemangiomas (N. Engl. J. Med. 2008;358:2649–51).

Dr. Frieden characterized the findings as very exciting, but cautioned that the drug's use in infants is off label and that there is no consensus on how to monitor for side effects in very young children. Potential side effects include hypoglycemia, bradycardia, hypotension, and exacerbation of asthma, she noted.

Dr. Frieden said in an interview that she has started two children with complicated segmental hemangiomas on propranolol, but after just 4 weeks, it is too early to say if it is helping.

Dr. Frieden is a consultant for Pierre-Fabre Dermo-Cosmétique and is planning drug studies with propranolol.

The risk of developing diabetes after a history of gestational diabetes increased over time and reached nearly 20% by 9 years post partum, according to results from a large, population-based study involving Canadian women.

The finding confirms those from the United States and elsewhere regarding the rise in both gestational diabetes and type 2 diabetes, as well as the highly elevated risk for the development of subsequent diabetes among women who have gestational diabetes. “This estimate should be used by clinicians to assist in their counseling of pregnant women and by policy makers to target these women for screening and prevention,” said Dr. Denice S. Feig of the University of Toronto and her associates (CMAJ;2008:179:229-34).

They utilized data from two sources: a database of hospital discharges for deliveries that occurred in Ontario from April 1, 1995, to March 31, 2002; and a database of all Ontario residents diagnosed with diabetes through March 31, 2004. Of 659,164 women aged 16-49 years without pre-existing diabetes who delivered a baby between 1995 and 2002, a total of 21,823 were diagnosed with gestational diabetes. The overall incidence of gestational diabetes in Ontario rose from 3.2% in 1995 to 3.6% in 2001.

The incidence of having gestational diabetes was higher among women with higher Charlson Comorbidity Index scores (an estimate of the risk of death from comorbid disease), those with lower incomes, and those living in urban areas, compared with rural. Women who had 10 or fewer primary care visits in the 2 years prior to the index delivery were less likely to be diagnosed with gestational diabetes than were women with more than 10 visits (2.7% vs. 3.7%), and those without a usual care provider were less likely to be diagnosed with gestational diabetes than were those who did have one (3.0% vs. 3.4%).

Following delivery, the probability of developing diabetes among the women with gestational diabetes during pregnancy rose rapidly during the first 9 months post partum, and remained more or less constant thereafter over the 9-year follow-up period of the study.

At 9 months, 3.7% of the women had been diagnosed with diabetes. Most of these women probably had pre-existing type 2 diabetes that was only discovered via screening for gestational diabetes. The database doesn't distinguish between type 1 and type 2 diabetes, but most were probably type 2, Dr. Feig and her associates noted.

The probability of developing diabetes among those with a history of gestational diabetes was 5% at the end of 15 months and 13% at 5 years. By the end of the 9-year follow-up, 19% had developed diabetes, compared with just 2% of those without gestational diabetes. The women with gestational diabetes who delivered during 1999-2001 had a higher risk of subsequent diabetes than did those who delivered during 1995-1996. Among the women in the later group, diabetes had developed in 16% by 5 years, whereas it took 9 years for the earlier group to reach a rate of 16%, they said.

Other factors increasing the risk of diabetes following gestational diabetes included Charlson index, greater age, a higher number of primary care visits prepregnancy, and the development of hypertension after delivery. On the other hand, living in a rural area, having a higher income, and having a prior pregnancy within 4 years of the index pregnancy decreased the risk. However, previous gestational diabetes was a more significant predictive factor than all the others were, the investigators said.

In an accompanying editorial, Dr. David Simmons of the Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, England, called the study “timely, allowing renewal of attention to an important condition where we could do better.” Among the areas needing improvement, he said, are increased efforts to prevent progression to diabetes in these women, particularly those who might become pregnant again, and to improve the diagnosis of type 2 diabetes prior to pregnancy.

“Even if there were no primary prevention programs in place, there should be secondary prevention programs to detect diabetes as near to its development as possible. Such programs would allow control of hyperglycemia before a subsequent pregnancy, something clearly of benefit to any future fetus,” he commented.

The risk of developing diabetes after a history of gestational diabetes increased over time and reached nearly 20% by 9 years post partum, according to results from a large, population-based study involving Canadian women.

The finding confirms those from the United States and elsewhere regarding the rise in both gestational diabetes and type 2 diabetes, as well as the highly elevated risk for the development of subsequent diabetes among women who have gestational diabetes. “This estimate should be used by clinicians to assist in their counseling of pregnant women and by policy makers to target these women for screening and prevention,” said Dr. Denice S. Feig of the University of Toronto and her associates (CMAJ;2008:179:229-34).

They utilized data from two sources: a database of hospital discharges for deliveries that occurred in Ontario from April 1, 1995, to March 31, 2002; and a database of all Ontario residents diagnosed with diabetes through March 31, 2004. Of 659,164 women aged 16-49 years without pre-existing diabetes who delivered a baby between 1995 and 2002, a total of 21,823 were diagnosed with gestational diabetes. The overall incidence of gestational diabetes in Ontario rose from 3.2% in 1995 to 3.6% in 2001.

The incidence of having gestational diabetes was higher among women with higher Charlson Comorbidity Index scores (an estimate of the risk of death from comorbid disease), those with lower incomes, and those living in urban areas, compared with rural. Women who had 10 or fewer primary care visits in the 2 years prior to the index delivery were less likely to be diagnosed with gestational diabetes than were women with more than 10 visits (2.7% vs. 3.7%), and those without a usual care provider were less likely to be diagnosed with gestational diabetes than were those who did have one (3.0% vs. 3.4%).

Following delivery, the probability of developing diabetes among the women with gestational diabetes during pregnancy rose rapidly during the first 9 months post partum, and remained more or less constant thereafter over the 9-year follow-up period of the study.

At 9 months, 3.7% of the women had been diagnosed with diabetes. Most of these women probably had pre-existing type 2 diabetes that was only discovered via screening for gestational diabetes. The database doesn't distinguish between type 1 and type 2 diabetes, but most were probably type 2, Dr. Feig and her associates noted.

The probability of developing diabetes among those with a history of gestational diabetes was 5% at the end of 15 months and 13% at 5 years. By the end of the 9-year follow-up, 19% had developed diabetes, compared with just 2% of those without gestational diabetes. The women with gestational diabetes who delivered during 1999-2001 had a higher risk of subsequent diabetes than did those who delivered during 1995-1996. Among the women in the later group, diabetes had developed in 16% by 5 years, whereas it took 9 years for the earlier group to reach a rate of 16%, they said.

Other factors increasing the risk of diabetes following gestational diabetes included Charlson index, greater age, a higher number of primary care visits prepregnancy, and the development of hypertension after delivery. On the other hand, living in a rural area, having a higher income, and having a prior pregnancy within 4 years of the index pregnancy decreased the risk. However, previous gestational diabetes was a more significant predictive factor than all the others were, the investigators said.

In an accompanying editorial, Dr. David Simmons of the Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, England, called the study “timely, allowing renewal of attention to an important condition where we could do better.” Among the areas needing improvement, he said, are increased efforts to prevent progression to diabetes in these women, particularly those who might become pregnant again, and to improve the diagnosis of type 2 diabetes prior to pregnancy.

“Even if there were no primary prevention programs in place, there should be secondary prevention programs to detect diabetes as near to its development as possible. Such programs would allow control of hyperglycemia before a subsequent pregnancy, something clearly of benefit to any future fetus,” he commented.

The risk of developing diabetes after a history of gestational diabetes increased over time and reached nearly 20% by 9 years post partum, according to results from a large, population-based study involving Canadian women.

The finding confirms those from the United States and elsewhere regarding the rise in both gestational diabetes and type 2 diabetes, as well as the highly elevated risk for the development of subsequent diabetes among women who have gestational diabetes. “This estimate should be used by clinicians to assist in their counseling of pregnant women and by policy makers to target these women for screening and prevention,” said Dr. Denice S. Feig of the University of Toronto and her associates (CMAJ;2008:179:229-34).

They utilized data from two sources: a database of hospital discharges for deliveries that occurred in Ontario from April 1, 1995, to March 31, 2002; and a database of all Ontario residents diagnosed with diabetes through March 31, 2004. Of 659,164 women aged 16-49 years without pre-existing diabetes who delivered a baby between 1995 and 2002, a total of 21,823 were diagnosed with gestational diabetes. The overall incidence of gestational diabetes in Ontario rose from 3.2% in 1995 to 3.6% in 2001.

The incidence of having gestational diabetes was higher among women with higher Charlson Comorbidity Index scores (an estimate of the risk of death from comorbid disease), those with lower incomes, and those living in urban areas, compared with rural. Women who had 10 or fewer primary care visits in the 2 years prior to the index delivery were less likely to be diagnosed with gestational diabetes than were women with more than 10 visits (2.7% vs. 3.7%), and those without a usual care provider were less likely to be diagnosed with gestational diabetes than were those who did have one (3.0% vs. 3.4%).

Following delivery, the probability of developing diabetes among the women with gestational diabetes during pregnancy rose rapidly during the first 9 months post partum, and remained more or less constant thereafter over the 9-year follow-up period of the study.

At 9 months, 3.7% of the women had been diagnosed with diabetes. Most of these women probably had pre-existing type 2 diabetes that was only discovered via screening for gestational diabetes. The database doesn't distinguish between type 1 and type 2 diabetes, but most were probably type 2, Dr. Feig and her associates noted.

The probability of developing diabetes among those with a history of gestational diabetes was 5% at the end of 15 months and 13% at 5 years. By the end of the 9-year follow-up, 19% had developed diabetes, compared with just 2% of those without gestational diabetes. The women with gestational diabetes who delivered during 1999-2001 had a higher risk of subsequent diabetes than did those who delivered during 1995-1996. Among the women in the later group, diabetes had developed in 16% by 5 years, whereas it took 9 years for the earlier group to reach a rate of 16%, they said.

Other factors increasing the risk of diabetes following gestational diabetes included Charlson index, greater age, a higher number of primary care visits prepregnancy, and the development of hypertension after delivery. On the other hand, living in a rural area, having a higher income, and having a prior pregnancy within 4 years of the index pregnancy decreased the risk. However, previous gestational diabetes was a more significant predictive factor than all the others were, the investigators said.

In an accompanying editorial, Dr. David Simmons of the Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, England, called the study “timely, allowing renewal of attention to an important condition where we could do better.” Among the areas needing improvement, he said, are increased efforts to prevent progression to diabetes in these women, particularly those who might become pregnant again, and to improve the diagnosis of type 2 diabetes prior to pregnancy.

“Even if there were no primary prevention programs in place, there should be secondary prevention programs to detect diabetes as near to its development as possible. Such programs would allow control of hyperglycemia before a subsequent pregnancy, something clearly of benefit to any future fetus,” he commented.