Obstetrics

SAN FRANCISCO — To optimize maternal and neonatal outcomes in pregnancies complicated by placenta previa, administer antenatal steroids at 35 weeks' and 5 days' gestation, and follow with delivery at 36 weeks, Dr. Marya Zlatnik said at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates conducted a decision analysis modeling study to weigh the risks to mothers and babies at various times of delivery in the setting of placenta previa. In general, earlier deliveries would benefit mothers by minimizing the risk of bleeding, but later deliveries allow fetuses to increase gestational age and avoid potential complications of preterm births.

A typical recommendation used in clinical practice calls for amniocentesis to check for fetal lung maturity followed by delivery at 26–37 weeks' gestation, yet there are no randomized controlled trial data to support that, noted Dr. Zlatnik, of the University of California, San Francisco. A randomized study would need 10,000 women in each arm and is unlikely to be conducted.

The present study compared total maternal and neonatal quality-adjusted life years after delivery at gestational ages ranging from 34 to 38 weeks.

The model looked at four delivery strategies. The first entailed amniocentesis for fetal lung maturity, with expectant management if results were negative. The second scenario used amniocentesis for lung maturity plus administration of antenatal steroids if results were negative, followed by delivery in 48 hours. The third strategy involved giving steroids to all women followed by delivery in 48 hours. The fourth option skipped amniocentesis and steroids and called for immediate delivery at the gestational age being studied.

The investigators assumed a risk of emergent bleeding ranging from 5% at 35 weeks to 29% at 38 weeks, and a risk for hysterectomy ranging from 2% with scheduled deliveries to 6% for delivery after emergent bleeding.

Total quality-adjusted life years peaked for women with delivery at 36 weeks with or without use of steroids. Adding antenatal steroids improved fetal outcomes. The modeling did not incorporate potential long-term effects from use of steroids.

“For situations in which administration of steroids at term is considered unsafe, or steroids were administered early in pregnancy, delivery at 36 weeks” without further steroids was the best option, she said.

The results remained the same unless the risk for maternal bleeding was more than four times higher than estimates used, or the risk for adverse neonatal outcomes (respiratory distress syndrome or cerebral palsy) were more than 160% of estimates used.

The modeling did not control for the effects of diabetes, which could affect the conclusions, Dr. Zlatnik said. She hoped to stratify maternal risks for women with a history of bleeding in a future analysis.

For every 100,000 women with placenta previa delivered at 36 weeks under the current study's modeling, 15,040 would have emergent bleeds, 2,225 would have hysterectomies, and 31 would die. For neonates, 3,290 would have respiratory distress syndrome. “Most of the strategies achieved fairly similar results, with the absolute differences being minimal, especially between the 36-week options, so there is some room for obstetric practices to determine the optimal time for delivery for each patient,” she said.

Decision analysis study techniques are useful but simplify the clinical situation, and some data on probabilities of risk come from small sample sizes, Dr. Zlatnik commented. Choosing strategies that maximize quality-adjusted life years may not coincide with individual preferences, she added.

Approximately 3 per 1,000 pregnant women with singletons have placenta previa at term, with higher risk levels in some subgroups. Placenta previa caused 7% of maternal deaths between 1979 and 2002, Dr. Zlatnik said.

Placenta previa is known to have caused 7% of maternal deaths between 1979 and 2002. DR. ZLATNIK

SAN FRANCISCO — To optimize maternal and neonatal outcomes in pregnancies complicated by placenta previa, administer antenatal steroids at 35 weeks' and 5 days' gestation, and follow with delivery at 36 weeks, Dr. Marya Zlatnik said at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates conducted a decision analysis modeling study to weigh the risks to mothers and babies at various times of delivery in the setting of placenta previa. In general, earlier deliveries would benefit mothers by minimizing the risk of bleeding, but later deliveries allow fetuses to increase gestational age and avoid potential complications of preterm births.

A typical recommendation used in clinical practice calls for amniocentesis to check for fetal lung maturity followed by delivery at 26–37 weeks' gestation, yet there are no randomized controlled trial data to support that, noted Dr. Zlatnik, of the University of California, San Francisco. A randomized study would need 10,000 women in each arm and is unlikely to be conducted.

The present study compared total maternal and neonatal quality-adjusted life years after delivery at gestational ages ranging from 34 to 38 weeks.

The model looked at four delivery strategies. The first entailed amniocentesis for fetal lung maturity, with expectant management if results were negative. The second scenario used amniocentesis for lung maturity plus administration of antenatal steroids if results were negative, followed by delivery in 48 hours. The third strategy involved giving steroids to all women followed by delivery in 48 hours. The fourth option skipped amniocentesis and steroids and called for immediate delivery at the gestational age being studied.

The investigators assumed a risk of emergent bleeding ranging from 5% at 35 weeks to 29% at 38 weeks, and a risk for hysterectomy ranging from 2% with scheduled deliveries to 6% for delivery after emergent bleeding.

Total quality-adjusted life years peaked for women with delivery at 36 weeks with or without use of steroids. Adding antenatal steroids improved fetal outcomes. The modeling did not incorporate potential long-term effects from use of steroids.

“For situations in which administration of steroids at term is considered unsafe, or steroids were administered early in pregnancy, delivery at 36 weeks” without further steroids was the best option, she said.

The results remained the same unless the risk for maternal bleeding was more than four times higher than estimates used, or the risk for adverse neonatal outcomes (respiratory distress syndrome or cerebral palsy) were more than 160% of estimates used.

The modeling did not control for the effects of diabetes, which could affect the conclusions, Dr. Zlatnik said. She hoped to stratify maternal risks for women with a history of bleeding in a future analysis.

For every 100,000 women with placenta previa delivered at 36 weeks under the current study's modeling, 15,040 would have emergent bleeds, 2,225 would have hysterectomies, and 31 would die. For neonates, 3,290 would have respiratory distress syndrome. “Most of the strategies achieved fairly similar results, with the absolute differences being minimal, especially between the 36-week options, so there is some room for obstetric practices to determine the optimal time for delivery for each patient,” she said.

Decision analysis study techniques are useful but simplify the clinical situation, and some data on probabilities of risk come from small sample sizes, Dr. Zlatnik commented. Choosing strategies that maximize quality-adjusted life years may not coincide with individual preferences, she added.

Approximately 3 per 1,000 pregnant women with singletons have placenta previa at term, with higher risk levels in some subgroups. Placenta previa caused 7% of maternal deaths between 1979 and 2002, Dr. Zlatnik said.

Placenta previa is known to have caused 7% of maternal deaths between 1979 and 2002. DR. ZLATNIK

SAN FRANCISCO — To optimize maternal and neonatal outcomes in pregnancies complicated by placenta previa, administer antenatal steroids at 35 weeks' and 5 days' gestation, and follow with delivery at 36 weeks, Dr. Marya Zlatnik said at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates conducted a decision analysis modeling study to weigh the risks to mothers and babies at various times of delivery in the setting of placenta previa. In general, earlier deliveries would benefit mothers by minimizing the risk of bleeding, but later deliveries allow fetuses to increase gestational age and avoid potential complications of preterm births.

A typical recommendation used in clinical practice calls for amniocentesis to check for fetal lung maturity followed by delivery at 26–37 weeks' gestation, yet there are no randomized controlled trial data to support that, noted Dr. Zlatnik, of the University of California, San Francisco. A randomized study would need 10,000 women in each arm and is unlikely to be conducted.

The present study compared total maternal and neonatal quality-adjusted life years after delivery at gestational ages ranging from 34 to 38 weeks.

The model looked at four delivery strategies. The first entailed amniocentesis for fetal lung maturity, with expectant management if results were negative. The second scenario used amniocentesis for lung maturity plus administration of antenatal steroids if results were negative, followed by delivery in 48 hours. The third strategy involved giving steroids to all women followed by delivery in 48 hours. The fourth option skipped amniocentesis and steroids and called for immediate delivery at the gestational age being studied.

The investigators assumed a risk of emergent bleeding ranging from 5% at 35 weeks to 29% at 38 weeks, and a risk for hysterectomy ranging from 2% with scheduled deliveries to 6% for delivery after emergent bleeding.

Total quality-adjusted life years peaked for women with delivery at 36 weeks with or without use of steroids. Adding antenatal steroids improved fetal outcomes. The modeling did not incorporate potential long-term effects from use of steroids.

“For situations in which administration of steroids at term is considered unsafe, or steroids were administered early in pregnancy, delivery at 36 weeks” without further steroids was the best option, she said.

The results remained the same unless the risk for maternal bleeding was more than four times higher than estimates used, or the risk for adverse neonatal outcomes (respiratory distress syndrome or cerebral palsy) were more than 160% of estimates used.

The modeling did not control for the effects of diabetes, which could affect the conclusions, Dr. Zlatnik said. She hoped to stratify maternal risks for women with a history of bleeding in a future analysis.

For every 100,000 women with placenta previa delivered at 36 weeks under the current study's modeling, 15,040 would have emergent bleeds, 2,225 would have hysterectomies, and 31 would die. For neonates, 3,290 would have respiratory distress syndrome. “Most of the strategies achieved fairly similar results, with the absolute differences being minimal, especially between the 36-week options, so there is some room for obstetric practices to determine the optimal time for delivery for each patient,” she said.

Decision analysis study techniques are useful but simplify the clinical situation, and some data on probabilities of risk come from small sample sizes, Dr. Zlatnik commented. Choosing strategies that maximize quality-adjusted life years may not coincide with individual preferences, she added.

Approximately 3 per 1,000 pregnant women with singletons have placenta previa at term, with higher risk levels in some subgroups. Placenta previa caused 7% of maternal deaths between 1979 and 2002, Dr. Zlatnik said.

Placenta previa is known to have caused 7% of maternal deaths between 1979 and 2002. DR. ZLATNIK

SAN FRANCISCO — Urinary excretion of podocytes appears to be a highly sensitive and specific marker for preeclampsia, Dr. Brian Brost said at the annual meeting of the Society for Maternal-Fetal Medicine.

Podocytes are highly differentiated epithelial cells that line the urinary surface of the glomerular capillary tuft. As part of the glomerular filtration barrier, “they play a central role in glomerular function,” according to Dr. Brost, an ob.gyn. at the Mayo Clinic in Rochester, Minn.

Because podocyturia is thought to occur earlier in the course of glomerular disease than does proteinuria, the detection of this marker may enable clinicians to identify women at risk for preeclampsia earlier than is currently possible, he said.

Preeclampsia has long been associated with pathologic renal changes, and recently published studies have linked the urinary shedding of podocytes with active glomerular disease.

“We hypothesized that viable podocytes would be present in urinary samples from women with clinically confirmed preeclampsia and would not be present in samples from normotensive pregnant women,” Dr. Brost said.

To test this hypothesis, the investigators analyzed clean-catch urine samples from 15 preeclamptic women and 16 normotensive women for podocyturia. Preeclampsia was diagnosed based on the American College of Obstetricians and Gynecologists' criteria for new-onset hypertension and proteinuria in previously normotensive pregnant women.

“We also evaluated serum concentrations of circulating angiogenic factors [thought to be predictive of preeclampsia] in order to compare the diagnostic accuracy of both tests,” Dr. Brost said.

In terms of patient characteristics, “maternal age in the preeclamptic group was higher than in the control group, as would be expected,” Dr. Brost said.

Additionally, by design, there was a statistically significant difference in gestational age at time of analysis.

“We had done some preliminary studies looking at the degree of podocyturia based on gestational age and there was no difference in those values, so for this investigation we picked term controls to try to ensure that these women would not develop preeclampsia along the way,” he commented.

For the podocyte assay, urine sediments were cultured on collagen-coated slides and incubated overnight. Urinary podocytes were identified and quantified based on their expression of the podocyte-specific protein, podocin. “Each sample was reviewed by a single renal pathologist, blinded to the diagnosis, to determine the number and percentage of cells that stained for podocin,” Dr. Brost said.

The assay results showed that podocytes were present in all of the samples collected from preeclamptic women and were not present in any of the control samples, indicating “the sensitivity and specificity of the assay were both 100%,” Dr. Brost reported.

Because the value of a diagnostic test depends on the pretest probability of the disease, “we estimated the diagnostic accuracy of both [the podocyte and the angiogenic factor] tests using pretest probabilities of 5% and 25%, which are the most commonly cited for low-risk and high-risk populations, respectively” Dr. Brost noted.

With use of the low pretest probability, “the negative predictive value did not differ between podocyturia and the angiogenic factor test,” he said. “For patients with a pretest probability of 25%, the negative predictive value was higher with podocyturia.”

In both the low and high pretest probability groups, the positive-predictive value was higher for podocyturia, he said.

Among the study's limitations is its small sample size, Dr. Brost said. “The numbers are low because this was meant to be a preliminary pilot study, but it has yielded exciting results. Our next step is to evaluate podocyturia in pregnancy with other renal processes to see what the effects would be.”

Future studies are needed both to confirm the study findings “and to test the hypothesis that podocyturia predates proteinuria and would thus provide a useful screening test for preeclampsia,” Dr. Brost concluded.

SAN FRANCISCO — Urinary excretion of podocytes appears to be a highly sensitive and specific marker for preeclampsia, Dr. Brian Brost said at the annual meeting of the Society for Maternal-Fetal Medicine.

Podocytes are highly differentiated epithelial cells that line the urinary surface of the glomerular capillary tuft. As part of the glomerular filtration barrier, “they play a central role in glomerular function,” according to Dr. Brost, an ob.gyn. at the Mayo Clinic in Rochester, Minn.

Because podocyturia is thought to occur earlier in the course of glomerular disease than does proteinuria, the detection of this marker may enable clinicians to identify women at risk for preeclampsia earlier than is currently possible, he said.

Preeclampsia has long been associated with pathologic renal changes, and recently published studies have linked the urinary shedding of podocytes with active glomerular disease.

“We hypothesized that viable podocytes would be present in urinary samples from women with clinically confirmed preeclampsia and would not be present in samples from normotensive pregnant women,” Dr. Brost said.

To test this hypothesis, the investigators analyzed clean-catch urine samples from 15 preeclamptic women and 16 normotensive women for podocyturia. Preeclampsia was diagnosed based on the American College of Obstetricians and Gynecologists' criteria for new-onset hypertension and proteinuria in previously normotensive pregnant women.

“We also evaluated serum concentrations of circulating angiogenic factors [thought to be predictive of preeclampsia] in order to compare the diagnostic accuracy of both tests,” Dr. Brost said.

In terms of patient characteristics, “maternal age in the preeclamptic group was higher than in the control group, as would be expected,” Dr. Brost said.

Additionally, by design, there was a statistically significant difference in gestational age at time of analysis.

“We had done some preliminary studies looking at the degree of podocyturia based on gestational age and there was no difference in those values, so for this investigation we picked term controls to try to ensure that these women would not develop preeclampsia along the way,” he commented.

For the podocyte assay, urine sediments were cultured on collagen-coated slides and incubated overnight. Urinary podocytes were identified and quantified based on their expression of the podocyte-specific protein, podocin. “Each sample was reviewed by a single renal pathologist, blinded to the diagnosis, to determine the number and percentage of cells that stained for podocin,” Dr. Brost said.

The assay results showed that podocytes were present in all of the samples collected from preeclamptic women and were not present in any of the control samples, indicating “the sensitivity and specificity of the assay were both 100%,” Dr. Brost reported.

Because the value of a diagnostic test depends on the pretest probability of the disease, “we estimated the diagnostic accuracy of both [the podocyte and the angiogenic factor] tests using pretest probabilities of 5% and 25%, which are the most commonly cited for low-risk and high-risk populations, respectively” Dr. Brost noted.

With use of the low pretest probability, “the negative predictive value did not differ between podocyturia and the angiogenic factor test,” he said. “For patients with a pretest probability of 25%, the negative predictive value was higher with podocyturia.”

In both the low and high pretest probability groups, the positive-predictive value was higher for podocyturia, he said.

Among the study's limitations is its small sample size, Dr. Brost said. “The numbers are low because this was meant to be a preliminary pilot study, but it has yielded exciting results. Our next step is to evaluate podocyturia in pregnancy with other renal processes to see what the effects would be.”

Future studies are needed both to confirm the study findings “and to test the hypothesis that podocyturia predates proteinuria and would thus provide a useful screening test for preeclampsia,” Dr. Brost concluded.

SAN FRANCISCO — Urinary excretion of podocytes appears to be a highly sensitive and specific marker for preeclampsia, Dr. Brian Brost said at the annual meeting of the Society for Maternal-Fetal Medicine.

Podocytes are highly differentiated epithelial cells that line the urinary surface of the glomerular capillary tuft. As part of the glomerular filtration barrier, “they play a central role in glomerular function,” according to Dr. Brost, an ob.gyn. at the Mayo Clinic in Rochester, Minn.

Because podocyturia is thought to occur earlier in the course of glomerular disease than does proteinuria, the detection of this marker may enable clinicians to identify women at risk for preeclampsia earlier than is currently possible, he said.

Preeclampsia has long been associated with pathologic renal changes, and recently published studies have linked the urinary shedding of podocytes with active glomerular disease.

“We hypothesized that viable podocytes would be present in urinary samples from women with clinically confirmed preeclampsia and would not be present in samples from normotensive pregnant women,” Dr. Brost said.

To test this hypothesis, the investigators analyzed clean-catch urine samples from 15 preeclamptic women and 16 normotensive women for podocyturia. Preeclampsia was diagnosed based on the American College of Obstetricians and Gynecologists' criteria for new-onset hypertension and proteinuria in previously normotensive pregnant women.

“We also evaluated serum concentrations of circulating angiogenic factors [thought to be predictive of preeclampsia] in order to compare the diagnostic accuracy of both tests,” Dr. Brost said.

In terms of patient characteristics, “maternal age in the preeclamptic group was higher than in the control group, as would be expected,” Dr. Brost said.

Additionally, by design, there was a statistically significant difference in gestational age at time of analysis.

“We had done some preliminary studies looking at the degree of podocyturia based on gestational age and there was no difference in those values, so for this investigation we picked term controls to try to ensure that these women would not develop preeclampsia along the way,” he commented.

For the podocyte assay, urine sediments were cultured on collagen-coated slides and incubated overnight. Urinary podocytes were identified and quantified based on their expression of the podocyte-specific protein, podocin. “Each sample was reviewed by a single renal pathologist, blinded to the diagnosis, to determine the number and percentage of cells that stained for podocin,” Dr. Brost said.

The assay results showed that podocytes were present in all of the samples collected from preeclamptic women and were not present in any of the control samples, indicating “the sensitivity and specificity of the assay were both 100%,” Dr. Brost reported.

Because the value of a diagnostic test depends on the pretest probability of the disease, “we estimated the diagnostic accuracy of both [the podocyte and the angiogenic factor] tests using pretest probabilities of 5% and 25%, which are the most commonly cited for low-risk and high-risk populations, respectively” Dr. Brost noted.

With use of the low pretest probability, “the negative predictive value did not differ between podocyturia and the angiogenic factor test,” he said. “For patients with a pretest probability of 25%, the negative predictive value was higher with podocyturia.”

In both the low and high pretest probability groups, the positive-predictive value was higher for podocyturia, he said.

Among the study's limitations is its small sample size, Dr. Brost said. “The numbers are low because this was meant to be a preliminary pilot study, but it has yielded exciting results. Our next step is to evaluate podocyturia in pregnancy with other renal processes to see what the effects would be.”

Future studies are needed both to confirm the study findings “and to test the hypothesis that podocyturia predates proteinuria and would thus provide a useful screening test for preeclampsia,” Dr. Brost concluded.

SAN FRANCISCO — Two oral medications deserve further investigation as alternative therapies for gestational diabetes, results of separate small studies suggest.

Acarbose or metformin might be helpful additions to the therapeutic armamentarium if additional research supports these preliminary findings, investigators said in separate poster presentations at the annual meeting of the Society for Maternal-Fetal Medicine.

Neither drug is approved for the treatment of gestational diabetes. Both are Food and Drug Administration pregnancy category B. Injected insulin or oral glyburide are approved to treat gestational diabetes.

Having an oral option other than glyburide might allow patients to be managed on one or potentially two oral agents before resorting to injections of insulin, Dr. Jacquelyn Cortez said in an interview at one of the posters.

She and associates conducted a prospective, double-blind trial that randomized 59 women who were diagnosed with gestational diabetes in their second or third trimester, prior to 34 weeks' gestation, to 50 mg acarbose t.i.d. or identical placebo pills taken with meals. All patients had failed diet therapy.

At regular follow-ups, if more than half of the patient's fasting glucose values were above 95 mg/dL, or more than half of her postprandial glucose values were above 135 mg/dL, the dosage was increased to 100 mg t.i.d.

If this did not control blood glucose levels, the patient was considered to have failed single-agent therapy and was started on a second agent.

Fewer patients in the acarbose group failed monotherapy and required a second agent, compared with the placebo group, but the difference did not quite reach statistical significance in this small study.

Women in the acarbose group gained significantly less weight (19 pounds) than did women on placebo (27 pounds), said Dr. Cortez of the department of reproductive medicine at the University of California, San Diego.

Postprandial blood glucose levels were significantly lower on acarbose therapy (122 mg/dL), compared with placebo (130 mg/dL).

There were no differences between groups in perinatal outcomes, including gestational age at delivery, mode of delivery, or rate of macrosomia.

The failure rate with acarbose in this study and failure rates with glyburide in other studies both are high, but women on acarbose in the present study did not develop the hypoglycemia sometimes seen with glyburide, Dr. Cortez noted.

Acarbose is a glycosidase inhibitor that prevents intestinal breakdown of starches to glucose in the upper small bowel.

Metformin, an insulin sensitizer, was the subject of a separate review of data from two randomized trials in which 67 women with gestational diabetes took the drug. Of these patients, 59 met glycemic goals of fasting glucose values lower than 105 mg/dL and 2-hour postprandial glucose values lower than 120 mg/dL, reported Dr. Lisa E. Moore and associates.

The eight women who did not meet glycemic goals started insulin therapy, said Dr. Moore of the University of New Mexico, Albuquerque.

Macrosomia occurred in four infants (6%), and all were delivered vaginally.

The primary cesarean delivery rate (excluding elective repeat C-sections) was 15% (10 patients).

There were no cases of fetal anomalies or maternal or fetal hypoglycemia. Eight neonates had hyperbilirubinemia and two had 5-minute Apgar scores that were lower than 5.

The efficacy rate with metformin appeared to be similar to success rates with glyburide in other studies, Dr. Moore commented.

“[Metformin] is certainly better at controlling the fasting blood sugar than glyburide,” she added.

Failure of metformin was not predicted by maternal body mass index or by the value of the 1-hour glucose challenge test.

Although metformin is not approved in the United States for this indication, there is a wealth of data from other countries on its use in gestational diabetes, she noted.

Dr. Cortez and Dr. Moore have no financial relationships with the companies that make the medications studied.

SAN FRANCISCO — Two oral medications deserve further investigation as alternative therapies for gestational diabetes, results of separate small studies suggest.

Acarbose or metformin might be helpful additions to the therapeutic armamentarium if additional research supports these preliminary findings, investigators said in separate poster presentations at the annual meeting of the Society for Maternal-Fetal Medicine.

Neither drug is approved for the treatment of gestational diabetes. Both are Food and Drug Administration pregnancy category B. Injected insulin or oral glyburide are approved to treat gestational diabetes.

Having an oral option other than glyburide might allow patients to be managed on one or potentially two oral agents before resorting to injections of insulin, Dr. Jacquelyn Cortez said in an interview at one of the posters.

She and associates conducted a prospective, double-blind trial that randomized 59 women who were diagnosed with gestational diabetes in their second or third trimester, prior to 34 weeks' gestation, to 50 mg acarbose t.i.d. or identical placebo pills taken with meals. All patients had failed diet therapy.

At regular follow-ups, if more than half of the patient's fasting glucose values were above 95 mg/dL, or more than half of her postprandial glucose values were above 135 mg/dL, the dosage was increased to 100 mg t.i.d.

If this did not control blood glucose levels, the patient was considered to have failed single-agent therapy and was started on a second agent.

Fewer patients in the acarbose group failed monotherapy and required a second agent, compared with the placebo group, but the difference did not quite reach statistical significance in this small study.

Women in the acarbose group gained significantly less weight (19 pounds) than did women on placebo (27 pounds), said Dr. Cortez of the department of reproductive medicine at the University of California, San Diego.

Postprandial blood glucose levels were significantly lower on acarbose therapy (122 mg/dL), compared with placebo (130 mg/dL).

There were no differences between groups in perinatal outcomes, including gestational age at delivery, mode of delivery, or rate of macrosomia.

The failure rate with acarbose in this study and failure rates with glyburide in other studies both are high, but women on acarbose in the present study did not develop the hypoglycemia sometimes seen with glyburide, Dr. Cortez noted.

Acarbose is a glycosidase inhibitor that prevents intestinal breakdown of starches to glucose in the upper small bowel.

Metformin, an insulin sensitizer, was the subject of a separate review of data from two randomized trials in which 67 women with gestational diabetes took the drug. Of these patients, 59 met glycemic goals of fasting glucose values lower than 105 mg/dL and 2-hour postprandial glucose values lower than 120 mg/dL, reported Dr. Lisa E. Moore and associates.

The eight women who did not meet glycemic goals started insulin therapy, said Dr. Moore of the University of New Mexico, Albuquerque.

Macrosomia occurred in four infants (6%), and all were delivered vaginally.

The primary cesarean delivery rate (excluding elective repeat C-sections) was 15% (10 patients).

There were no cases of fetal anomalies or maternal or fetal hypoglycemia. Eight neonates had hyperbilirubinemia and two had 5-minute Apgar scores that were lower than 5.

The efficacy rate with metformin appeared to be similar to success rates with glyburide in other studies, Dr. Moore commented.

“[Metformin] is certainly better at controlling the fasting blood sugar than glyburide,” she added.

Failure of metformin was not predicted by maternal body mass index or by the value of the 1-hour glucose challenge test.

Although metformin is not approved in the United States for this indication, there is a wealth of data from other countries on its use in gestational diabetes, she noted.

Dr. Cortez and Dr. Moore have no financial relationships with the companies that make the medications studied.

SAN FRANCISCO — Two oral medications deserve further investigation as alternative therapies for gestational diabetes, results of separate small studies suggest.

Acarbose or metformin might be helpful additions to the therapeutic armamentarium if additional research supports these preliminary findings, investigators said in separate poster presentations at the annual meeting of the Society for Maternal-Fetal Medicine.

Neither drug is approved for the treatment of gestational diabetes. Both are Food and Drug Administration pregnancy category B. Injected insulin or oral glyburide are approved to treat gestational diabetes.

Having an oral option other than glyburide might allow patients to be managed on one or potentially two oral agents before resorting to injections of insulin, Dr. Jacquelyn Cortez said in an interview at one of the posters.

She and associates conducted a prospective, double-blind trial that randomized 59 women who were diagnosed with gestational diabetes in their second or third trimester, prior to 34 weeks' gestation, to 50 mg acarbose t.i.d. or identical placebo pills taken with meals. All patients had failed diet therapy.

At regular follow-ups, if more than half of the patient's fasting glucose values were above 95 mg/dL, or more than half of her postprandial glucose values were above 135 mg/dL, the dosage was increased to 100 mg t.i.d.

If this did not control blood glucose levels, the patient was considered to have failed single-agent therapy and was started on a second agent.

Fewer patients in the acarbose group failed monotherapy and required a second agent, compared with the placebo group, but the difference did not quite reach statistical significance in this small study.

Women in the acarbose group gained significantly less weight (19 pounds) than did women on placebo (27 pounds), said Dr. Cortez of the department of reproductive medicine at the University of California, San Diego.

Postprandial blood glucose levels were significantly lower on acarbose therapy (122 mg/dL), compared with placebo (130 mg/dL).

There were no differences between groups in perinatal outcomes, including gestational age at delivery, mode of delivery, or rate of macrosomia.

The failure rate with acarbose in this study and failure rates with glyburide in other studies both are high, but women on acarbose in the present study did not develop the hypoglycemia sometimes seen with glyburide, Dr. Cortez noted.

Acarbose is a glycosidase inhibitor that prevents intestinal breakdown of starches to glucose in the upper small bowel.

Metformin, an insulin sensitizer, was the subject of a separate review of data from two randomized trials in which 67 women with gestational diabetes took the drug. Of these patients, 59 met glycemic goals of fasting glucose values lower than 105 mg/dL and 2-hour postprandial glucose values lower than 120 mg/dL, reported Dr. Lisa E. Moore and associates.

The eight women who did not meet glycemic goals started insulin therapy, said Dr. Moore of the University of New Mexico, Albuquerque.

Macrosomia occurred in four infants (6%), and all were delivered vaginally.

The primary cesarean delivery rate (excluding elective repeat C-sections) was 15% (10 patients).

There were no cases of fetal anomalies or maternal or fetal hypoglycemia. Eight neonates had hyperbilirubinemia and two had 5-minute Apgar scores that were lower than 5.

The efficacy rate with metformin appeared to be similar to success rates with glyburide in other studies, Dr. Moore commented.

“[Metformin] is certainly better at controlling the fasting blood sugar than glyburide,” she added.

Failure of metformin was not predicted by maternal body mass index or by the value of the 1-hour glucose challenge test.

Although metformin is not approved in the United States for this indication, there is a wealth of data from other countries on its use in gestational diabetes, she noted.

Dr. Cortez and Dr. Moore have no financial relationships with the companies that make the medications studied.

SAN FRANCISCO — Adjustments made to maternal serum alpha fetoprotein values in pregnant diabetics may be inadequate to screen for neural tube defects or Down syndrome, Dr. Loralei L. Thornburg reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates studied data on 77 pregnant women with type 1 diabetes, 75 with type 2 diabetes, and 304 nondiabetic pregnant women with normal glucose levels who had maternal serum alpha fetoprotein (MSAFP) levels drawn between July 2001 and August 2003 at the same institution. MSAFP levels are used in prenatal screening for neural tube defects and Down syndrome. Previous studies have shown that MSAFP values are lower in type 1 diabetics than in nondiabetics, and MSAFP in type 2 diabetics is not well studied.

Usually clinicians apply a 20% upward adjustment of the MSAFP multiple-of-the-median value for pregnant type 1 diabetics, and they use a lower cut-off for normal to improve the sensitivity of screening for neural tube defects.

In the study population, a 10% correction factor appeared to be a more appropriate adjustment to MSAFP values in both type 1 and type 2 diabetics. In addition, correction for both diabetes and weight were needed to normalize MSAFP values, said Dr. Thornburg of the University of Rochester (N.Y.).

With the 20% correction factor, the MSAFP multiple-of-the-median value was significantly higher in both diabetic groups than in control patients. After the correction factor was decreased to 10% in the diabetes groups, the MSAFP multiple-of-the-median value did not differ significantly between the three groups. All medians were specific to gestational age and race. Fifty-five (73%) of patients with type 2 diabetes were on insulin therapy.

The MSAFP multiple-of-the-median values before correction for diabetes differed between patients with type 1 and type 2 diabetes until correction for weight.

Correction for weight and the 10% correction for diabetes were needed to control for significant differences between the control group and either diabetes group in MSAFP multiple-of-the-median values.

The retrospective study excluded patients with an MSAFP multiple-of-the-median value greater than 2.0, patients whose serum samples were drawn too early or redrawn, patients who underwent early chorionic villi sampling, and patients with fetal anomalies, aneuploidy, multiple gestations, or no information on diabetes type.

SAN FRANCISCO — Adjustments made to maternal serum alpha fetoprotein values in pregnant diabetics may be inadequate to screen for neural tube defects or Down syndrome, Dr. Loralei L. Thornburg reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates studied data on 77 pregnant women with type 1 diabetes, 75 with type 2 diabetes, and 304 nondiabetic pregnant women with normal glucose levels who had maternal serum alpha fetoprotein (MSAFP) levels drawn between July 2001 and August 2003 at the same institution. MSAFP levels are used in prenatal screening for neural tube defects and Down syndrome. Previous studies have shown that MSAFP values are lower in type 1 diabetics than in nondiabetics, and MSAFP in type 2 diabetics is not well studied.

Usually clinicians apply a 20% upward adjustment of the MSAFP multiple-of-the-median value for pregnant type 1 diabetics, and they use a lower cut-off for normal to improve the sensitivity of screening for neural tube defects.

In the study population, a 10% correction factor appeared to be a more appropriate adjustment to MSAFP values in both type 1 and type 2 diabetics. In addition, correction for both diabetes and weight were needed to normalize MSAFP values, said Dr. Thornburg of the University of Rochester (N.Y.).

With the 20% correction factor, the MSAFP multiple-of-the-median value was significantly higher in both diabetic groups than in control patients. After the correction factor was decreased to 10% in the diabetes groups, the MSAFP multiple-of-the-median value did not differ significantly between the three groups. All medians were specific to gestational age and race. Fifty-five (73%) of patients with type 2 diabetes were on insulin therapy.

The MSAFP multiple-of-the-median values before correction for diabetes differed between patients with type 1 and type 2 diabetes until correction for weight.

Correction for weight and the 10% correction for diabetes were needed to control for significant differences between the control group and either diabetes group in MSAFP multiple-of-the-median values.

The retrospective study excluded patients with an MSAFP multiple-of-the-median value greater than 2.0, patients whose serum samples were drawn too early or redrawn, patients who underwent early chorionic villi sampling, and patients with fetal anomalies, aneuploidy, multiple gestations, or no information on diabetes type.

SAN FRANCISCO — Adjustments made to maternal serum alpha fetoprotein values in pregnant diabetics may be inadequate to screen for neural tube defects or Down syndrome, Dr. Loralei L. Thornburg reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her associates studied data on 77 pregnant women with type 1 diabetes, 75 with type 2 diabetes, and 304 nondiabetic pregnant women with normal glucose levels who had maternal serum alpha fetoprotein (MSAFP) levels drawn between July 2001 and August 2003 at the same institution. MSAFP levels are used in prenatal screening for neural tube defects and Down syndrome. Previous studies have shown that MSAFP values are lower in type 1 diabetics than in nondiabetics, and MSAFP in type 2 diabetics is not well studied.

Usually clinicians apply a 20% upward adjustment of the MSAFP multiple-of-the-median value for pregnant type 1 diabetics, and they use a lower cut-off for normal to improve the sensitivity of screening for neural tube defects.

In the study population, a 10% correction factor appeared to be a more appropriate adjustment to MSAFP values in both type 1 and type 2 diabetics. In addition, correction for both diabetes and weight were needed to normalize MSAFP values, said Dr. Thornburg of the University of Rochester (N.Y.).

With the 20% correction factor, the MSAFP multiple-of-the-median value was significantly higher in both diabetic groups than in control patients. After the correction factor was decreased to 10% in the diabetes groups, the MSAFP multiple-of-the-median value did not differ significantly between the three groups. All medians were specific to gestational age and race. Fifty-five (73%) of patients with type 2 diabetes were on insulin therapy.

The MSAFP multiple-of-the-median values before correction for diabetes differed between patients with type 1 and type 2 diabetes until correction for weight.

Correction for weight and the 10% correction for diabetes were needed to control for significant differences between the control group and either diabetes group in MSAFP multiple-of-the-median values.

The retrospective study excluded patients with an MSAFP multiple-of-the-median value greater than 2.0, patients whose serum samples were drawn too early or redrawn, patients who underwent early chorionic villi sampling, and patients with fetal anomalies, aneuploidy, multiple gestations, or no information on diabetes type.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

SAN FRANCISCO — Accelerated fetal growth in the midtrimester, as assessed by individualized growth potentials and ultrasound imaging, helped predict macrosomia in a study of 70 women who developed gestational diabetes.

“Early suggestion of accelerated fetal growth offers a window of opportunity to optimize glycemic management” of the mother and potentially prevent macrosomic stillbirth and perinatal morbidity, Dr. Anita Manogura reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her colleagues prospectively followed 70 women who went on to develop gestational diabetes. The women underwent serial assessments, including standardized ultrasound exams for nuchal translucency screening (11–14 weeks' gestation), detailed evaluation of anatomy (18–20 weeks' gestation), and formal fetal echocardiogram (22–24 weeks' gestation and then every 4 weeks thereafter), wrote Dr. Manogura of the University of Maryland, Baltimore, and her associates.

They used the Gardosi method to predict individual fetal growth potentials based on fetal gender and the mother's height, weight, parity, ethnicity, and other characteristics. Estimated fetal weights from imaging were converted to percentiles, with large for gestational age (LGA) defined as above the 90th percentile.

Early differences were seen between the 27 LGA infants and infants born at normal weights. By 24 weeks' gestation, LGA infants had a median estimated fetal weight in the 54th percentile, significantly higher than the 48th percentile for normal-weight neonates. At 24 weeks, an estimated weight that was above the 58th percentile predicted an LGA baby with a sensitivity of 30% and specificity of 84%.

If this trend continued at 28 weeks, then the odds of having an LGA baby were four times higher. At 28 weeks, future LGA babies were at a median 72nd percentile of estimated fetal weight, compared with the 51st percentile for normal-weight infants. An estimated fetal weight of greater than the 58th percentile at 28 weeks increased the sensitivity of predicting macrosomia to 63%, with a specificity of 87%.

“The potential to interrupt this progression by intensive midtrimester glycemic management deserves further study,” the investigators concluded.

Elevated estimated fetal weight percentiles on ultrasound did not predict adverse perinatal outcomes such as shoulder dystocia, cesarean delivery, or neonatal complications.

SAN FRANCISCO — Accelerated fetal growth in the midtrimester, as assessed by individualized growth potentials and ultrasound imaging, helped predict macrosomia in a study of 70 women who developed gestational diabetes.

“Early suggestion of accelerated fetal growth offers a window of opportunity to optimize glycemic management” of the mother and potentially prevent macrosomic stillbirth and perinatal morbidity, Dr. Anita Manogura reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her colleagues prospectively followed 70 women who went on to develop gestational diabetes. The women underwent serial assessments, including standardized ultrasound exams for nuchal translucency screening (11–14 weeks' gestation), detailed evaluation of anatomy (18–20 weeks' gestation), and formal fetal echocardiogram (22–24 weeks' gestation and then every 4 weeks thereafter), wrote Dr. Manogura of the University of Maryland, Baltimore, and her associates.

They used the Gardosi method to predict individual fetal growth potentials based on fetal gender and the mother's height, weight, parity, ethnicity, and other characteristics. Estimated fetal weights from imaging were converted to percentiles, with large for gestational age (LGA) defined as above the 90th percentile.

Early differences were seen between the 27 LGA infants and infants born at normal weights. By 24 weeks' gestation, LGA infants had a median estimated fetal weight in the 54th percentile, significantly higher than the 48th percentile for normal-weight neonates. At 24 weeks, an estimated weight that was above the 58th percentile predicted an LGA baby with a sensitivity of 30% and specificity of 84%.

If this trend continued at 28 weeks, then the odds of having an LGA baby were four times higher. At 28 weeks, future LGA babies were at a median 72nd percentile of estimated fetal weight, compared with the 51st percentile for normal-weight infants. An estimated fetal weight of greater than the 58th percentile at 28 weeks increased the sensitivity of predicting macrosomia to 63%, with a specificity of 87%.

“The potential to interrupt this progression by intensive midtrimester glycemic management deserves further study,” the investigators concluded.

Elevated estimated fetal weight percentiles on ultrasound did not predict adverse perinatal outcomes such as shoulder dystocia, cesarean delivery, or neonatal complications.

SAN FRANCISCO — Accelerated fetal growth in the midtrimester, as assessed by individualized growth potentials and ultrasound imaging, helped predict macrosomia in a study of 70 women who developed gestational diabetes.

“Early suggestion of accelerated fetal growth offers a window of opportunity to optimize glycemic management” of the mother and potentially prevent macrosomic stillbirth and perinatal morbidity, Dr. Anita Manogura reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

She and her colleagues prospectively followed 70 women who went on to develop gestational diabetes. The women underwent serial assessments, including standardized ultrasound exams for nuchal translucency screening (11–14 weeks' gestation), detailed evaluation of anatomy (18–20 weeks' gestation), and formal fetal echocardiogram (22–24 weeks' gestation and then every 4 weeks thereafter), wrote Dr. Manogura of the University of Maryland, Baltimore, and her associates.

They used the Gardosi method to predict individual fetal growth potentials based on fetal gender and the mother's height, weight, parity, ethnicity, and other characteristics. Estimated fetal weights from imaging were converted to percentiles, with large for gestational age (LGA) defined as above the 90th percentile.

Early differences were seen between the 27 LGA infants and infants born at normal weights. By 24 weeks' gestation, LGA infants had a median estimated fetal weight in the 54th percentile, significantly higher than the 48th percentile for normal-weight neonates. At 24 weeks, an estimated weight that was above the 58th percentile predicted an LGA baby with a sensitivity of 30% and specificity of 84%.

If this trend continued at 28 weeks, then the odds of having an LGA baby were four times higher. At 28 weeks, future LGA babies were at a median 72nd percentile of estimated fetal weight, compared with the 51st percentile for normal-weight infants. An estimated fetal weight of greater than the 58th percentile at 28 weeks increased the sensitivity of predicting macrosomia to 63%, with a specificity of 87%.

“The potential to interrupt this progression by intensive midtrimester glycemic management deserves further study,” the investigators concluded.

Elevated estimated fetal weight percentiles on ultrasound did not predict adverse perinatal outcomes such as shoulder dystocia, cesarean delivery, or neonatal complications.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

Among women with type 1 diabetes whose pregnancies were managed at one clinic in Finland, those who had a history of preeclampsia went on to have a higher rate of diabetic nephropathy in the following years than did those with normotensive pregnancies.

In the report, researcher Daniel Gordin and colleagues at Helsinki University Central Hospital reported findings for 203 women with type 1 diabetes who had been pregnant between 1988 and 1996 and who were followed an average of 11 years within the nationwide, multicenter Finnish Diabetic Nephropathy Study.

For purposes of the study, diabetic nephropathy was defined as microalbuminuria, macroalbuminuria, or end-stage renal disease.

Among the women with history of preeclampsia, the rate of diabetic nephropathy at follow-up was 42%, versus 9% for those without such history (Diabetologia 2007 [Epub ahead of print doi 10.1007/s00125-006-0544-5

Women with pregnancy-induced hypertension, however, were not at significantly increased risk of microvascular disease, compared with normotensive women (10.3% vs. 8.9%).

Diabetic nephropathy at follow-up was also predicted by poor glycemic control during pregnancy. Hemoglobin A_1c levels in each trimester significantly correlated with kidney disease.

These results warrant more intensive monitoring of women with type 1 diabetes and a history of preeclampsia, as well as special emphasis on early detection of microalbuminuria, the investigators concluded.

In addition, “an early start to renoprotective medication in type 1 diabetic women with prior preeclampsia could be beneficial,” they suggested.

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at [email protected]

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at [email protected]

WASHINGTON — Preliminary data suggest no increased risk for adverse pregnancy outcomes in women exposed to either etanercept or adalimumab during the first trimester, Christina Chambers, Ph.D., reported in two posters at the annual meeting of the American Academy of Dermatology.

Although the numbers are small thus far, no worrisome pattern has emerged. “Based on preliminary data at the present time, we don't see any big red flags,” said Dr. Chambers, a perinatal epidemiologist at the University of California, San Diego, who specializes in drug safety during pregnancy.

The prospective cohort data come from the Organization of Teratology Information Specialists (OTIS), a network of telephone-based teratology counseling services based at hospitals and universities throughout the United States and Canada. Since 1999, network members have collaborated on the OTIS Autoimmune Diseases in Pregnancy Project, a registry study focused on the safety of medications used to treat a variety of autoimmune diseases. The project is sponsored in part by research grants from several pharmaceutical companies, including Amgen Inc., the manufacturer of etanercept (Enbrel), and Abbott Laboratories, maker of adalimumab (Humira).

Both etanercept and adalimumab are self-injectable anti-tumor necrosis factor-α monoclonal antibody medications approved in the United States for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis.

Etanercept is also approved for treating psoriasis and ankylosing spondylitis. Dr. Chambers presented early data from ongoing studies of both drugs.

A total of 82 women were enrolled in the etanercept study between March 2005 and October 2006. Of those, 48 were exposed to etanercept: 28 for RA, 14 for psoriasis or psoriatic arthritis, and 6 for ankylosing spondylitis.

Another 34 women who did not take etanercept were also enrolled: 18 with RA, 14 with psoriasis or psoriatic arthritis, and 2 with ankylosing spondylitis. Mean age was about 33 years in both groups, and mean gestational age at enrollment was 11.4 weeks for the etanercept-exposed group and 12.2 weeks for the disease-matched comparison group.

Outcome was known for 42 pregnancies as of October 2006. No stillbirths occurred in either group. There was one spontaneous abortion among the 22 in the etanercept group (4.5%), far below both the 3 of 20 (15%) in the disease-matched comparison group and the 10%–15% pregnancy loss rate in the general population, Dr. Chambers noted.

Gestational age was 37.5 weeks for the etanercept group, which was not significantly different from the 37.8 weeks for the disease-matched controls.

Gestational age in both groups, however, was about a week earlier than normal, a phenomenon that has been documented previously in patients with RA. Similarly, birth weights—3,323 g for the etanercept group and 3,317 g for the nonexposed disease-matched women—were slightly lower than the 3,400–3,500 g average birth weight in the general population, but were not increased in those with etanercept exposure, she said.

Of the 21 infants born alive in the etanercept group, three had major defects: One infant, a twin, was born with malrotation of the stomach, which required surgery; a preterm infant had a unilateral inguinal hernia that required surgery; and a third, whose mother had Hashimoto's thyroiditis, was born with congenital hypothyroidism.

In the comparison group, one pregnancy was terminated following a prenatal diagnosis of Down syndrome.

The adalimumab data set comprised a total of 130 women who were enrolled in the prospective cohort study: 23 exposed to adalimumab for the treatment of RA, 48 with disease who did not take adalimumab, and 26 without disease.

Another 33 women who did not meet the study cohort criteria were also enrolled in the adalimumab pregnancy registry. These included five women treated for Crohn's disease, two treated for psoriasis or psoriatic arthritis, and two others treated for nonspecific autoimmune disorders.

Rates of spontaneous abortion among the pregnancies with known outcome were higher among all the groups with RA or other autoimmune disease: 2 (11.8%) of the 17 in the adalimumab study cohort, 5 (20.0%) of the 25 from the registry, and 3 (7.1%) of the 42 in the diseased comparison group, versus 0 of 15 pregnancies with known outcomes among healthy women who were not exposed to adalimumab. The only stillbirth occurred in the healthy nonexposed group.

As with etanercept, no increased risks for preterm delivery or malformations were seen with adalimumab exposure. There was one preterm delivery among the 15 live births in the study cohort (7%), compared with 4 of the 14 in the registry (29%), 7 of the 37 in the disease comparison group (19%), and 0 of the 14 in the nondisease comparison group.

Malformations occurred in none of the 17 total known outcomes in the study (0%), in 1 of 14 in the registry (7%), in 1 of 42 disease comparison patients (2%), and in 1 of 15 of the healthy controls (7%).

In both of these drug studies, all of the infants will be evaluated up to 1 year of age for major and minor anomalies by pediatric specialists, Dr. Chambers said.

Final results for preterm delivery, birth weight, and congenital malformations should be available in 1–2 years. In the meantime, even these small preliminary numbers are reassuring because they don't show any particular pattern.

“All the major teratogens are associated with very specific patterns of abnormal outcomes. When you don't see a pattern and you just see one of this and one of that, it makes you a little more confident that this is not an Accutane,” Dr. Chambers said.

Physicians who prescribe etanercept and adalimumab to women of childbearing age are encouraged to enroll patients in OTIS. For more information, call 877-311-8972 or e-mail Dr. Chambers at [email protected]

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, hematologic disorders, and death during pregnancy, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide.

Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with systemic lupus erythematosus (SLE), according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4), and diabetes (odds ratio 1.6), according to Dr. Clowse.

They were also more likely to experience complications during pregnancy (see table).

More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed in only a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems during pregnancy. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more were African American (20%) than in the general pregnancy population (14%).

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in women of reproductive age by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” Dr. Clowse observed.

Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all pregnant SLE patients to have prophylaxis with low-dose aspirin, she noted.

Dr. Clowse disclosed that she had no conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, hematologic disorders, and death during pregnancy, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide.

Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with systemic lupus erythematosus (SLE), according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4), and diabetes (odds ratio 1.6), according to Dr. Clowse.

They were also more likely to experience complications during pregnancy (see table).

More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed in only a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems during pregnancy. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more were African American (20%) than in the general pregnancy population (14%).

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in women of reproductive age by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” Dr. Clowse observed.

Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all pregnant SLE patients to have prophylaxis with low-dose aspirin, she noted.

Dr. Clowse disclosed that she had no conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, hematologic disorders, and death during pregnancy, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide.

Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with systemic lupus erythematosus (SLE), according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4), and diabetes (odds ratio 1.6), according to Dr. Clowse.

They were also more likely to experience complications during pregnancy (see table).

More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed in only a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems during pregnancy. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more were African American (20%) than in the general pregnancy population (14%).

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in women of reproductive age by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” Dr. Clowse observed.

Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all pregnant SLE patients to have prophylaxis with low-dose aspirin, she noted.

Dr. Clowse disclosed that she had no conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS