Obstetrics

CHICAGO — The infants of mothers taking antiepileptic drugs showed no adverse cognitive effects as a result of breast-feeding, judging from the findings of a small, preliminary study.

“Concerns have been raised, but there are no prior formal studies examining the effect of breast-feeding in women taking antiepileptic drugs,” the study's lead author, Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville, where he serves as director of the epilepsy program and of the clinical Alzheimer program, said in an interview. Findings from “our study suggest that it is safe.”

Dr. Meador and his colleagues looked at 187 children of mothers enrolled in the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. The NEAD study is a multicenter, prospective, parallel-group, observational study that is ongoing at 25 centers in the United States and the United Kingdom. Pregnant mothers with partial or primary generalized epilepsy taking pharmacologic monotherapy (including valproate, carbamazepine, phenytoin, or lamotrigine) were eligible to enroll. In this study, a blinded cognitive assessment of the children was conducted at 2 years old; follow-up assessments will be conducted at years 3, 4.5, and 6.

Compared with their non-breast-fed counterparts, the breast-fed children in this cohort (41%) actually had higher cognition, 98.1 vs. 89.5 on the Bayley Mental Developmental Index. However, Dr. Meador said that when investigators controlled for the mother's IQ, there was no significant difference between groups.

“The NEAD study is not randomized and was not specifically designed to examine the effects of breast-feeding,” he said, listing some of its limitations. Also, “there are only four drugs in the study.” However, “breast-feeding during antiepilepsy drug treatment doesn't appear to have a negative impact on a child's cognitive abilities.”

Speaking at the annual meeting of the American Academy of Neurology, Dr. Meador added that the 3-year follow-up data analysis is just being completed and that the final child in the study will reach age 6—the last follow-up point—in 2010.

Dr. Meador has received research support from GlaxoSmithKline Inc., UCB SA, Eisai Co., Myriad Genetics Inc., NeuroPace Inc., and SAM Technology Inc. His fellow researchers also disclosed financial or other relationships to drug companies.

CHICAGO — The infants of mothers taking antiepileptic drugs showed no adverse cognitive effects as a result of breast-feeding, judging from the findings of a small, preliminary study.

“Concerns have been raised, but there are no prior formal studies examining the effect of breast-feeding in women taking antiepileptic drugs,” the study's lead author, Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville, where he serves as director of the epilepsy program and of the clinical Alzheimer program, said in an interview. Findings from “our study suggest that it is safe.”

Dr. Meador and his colleagues looked at 187 children of mothers enrolled in the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. The NEAD study is a multicenter, prospective, parallel-group, observational study that is ongoing at 25 centers in the United States and the United Kingdom. Pregnant mothers with partial or primary generalized epilepsy taking pharmacologic monotherapy (including valproate, carbamazepine, phenytoin, or lamotrigine) were eligible to enroll. In this study, a blinded cognitive assessment of the children was conducted at 2 years old; follow-up assessments will be conducted at years 3, 4.5, and 6.

Compared with their non-breast-fed counterparts, the breast-fed children in this cohort (41%) actually had higher cognition, 98.1 vs. 89.5 on the Bayley Mental Developmental Index. However, Dr. Meador said that when investigators controlled for the mother's IQ, there was no significant difference between groups.

“The NEAD study is not randomized and was not specifically designed to examine the effects of breast-feeding,” he said, listing some of its limitations. Also, “there are only four drugs in the study.” However, “breast-feeding during antiepilepsy drug treatment doesn't appear to have a negative impact on a child's cognitive abilities.”

Speaking at the annual meeting of the American Academy of Neurology, Dr. Meador added that the 3-year follow-up data analysis is just being completed and that the final child in the study will reach age 6—the last follow-up point—in 2010.

Dr. Meador has received research support from GlaxoSmithKline Inc., UCB SA, Eisai Co., Myriad Genetics Inc., NeuroPace Inc., and SAM Technology Inc. His fellow researchers also disclosed financial or other relationships to drug companies.

CHICAGO — The infants of mothers taking antiepileptic drugs showed no adverse cognitive effects as a result of breast-feeding, judging from the findings of a small, preliminary study.

“Concerns have been raised, but there are no prior formal studies examining the effect of breast-feeding in women taking antiepileptic drugs,” the study's lead author, Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville, where he serves as director of the epilepsy program and of the clinical Alzheimer program, said in an interview. Findings from “our study suggest that it is safe.”

Dr. Meador and his colleagues looked at 187 children of mothers enrolled in the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. The NEAD study is a multicenter, prospective, parallel-group, observational study that is ongoing at 25 centers in the United States and the United Kingdom. Pregnant mothers with partial or primary generalized epilepsy taking pharmacologic monotherapy (including valproate, carbamazepine, phenytoin, or lamotrigine) were eligible to enroll. In this study, a blinded cognitive assessment of the children was conducted at 2 years old; follow-up assessments will be conducted at years 3, 4.5, and 6.

Compared with their non-breast-fed counterparts, the breast-fed children in this cohort (41%) actually had higher cognition, 98.1 vs. 89.5 on the Bayley Mental Developmental Index. However, Dr. Meador said that when investigators controlled for the mother's IQ, there was no significant difference between groups.

“The NEAD study is not randomized and was not specifically designed to examine the effects of breast-feeding,” he said, listing some of its limitations. Also, “there are only four drugs in the study.” However, “breast-feeding during antiepilepsy drug treatment doesn't appear to have a negative impact on a child's cognitive abilities.”

Speaking at the annual meeting of the American Academy of Neurology, Dr. Meador added that the 3-year follow-up data analysis is just being completed and that the final child in the study will reach age 6—the last follow-up point—in 2010.

Dr. Meador has received research support from GlaxoSmithKline Inc., UCB SA, Eisai Co., Myriad Genetics Inc., NeuroPace Inc., and SAM Technology Inc. His fellow researchers also disclosed financial or other relationships to drug companies.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in an international study of 23,316 pregnant women.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes and a host of neonatal problems: hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia, investigators reported in the New England Journal of Medicine.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” reported Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study (N. Engl. J. Med. 2008;358:1991–2002).

The researchers assessed the 23,316 gravid women “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.” The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems increased as plasma glucose levels increased.

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes. A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

In a separate study of gestational diabetes published in the same issue, Dr. Janet A. Rowan of Auckland City (New Zealand) Hospital and her associates in the Metformin in Gestational Diabetes trial found that metformin was “noninferior” to insulin in safety and efficacy, and was preferred by patients with overt disease.

In that open-label study, Dr. Rowan and her associates compared oral metformin with insulin therapy in 733 women who had overt gestational diabetes and were followed at 10 New Zealand and Australian obstetric hospitals.

The composite outcome of numerous neonatal complications, including hypoglycemia in the infant, was no different between the metformin group and the insulin group, at 32% in both. There also were no differences between the two groups in neonatal anthropometric measures or in umbilical cord serum insulin concentrations.

The women preferred metformin to insulin. However, 46% of those who took metformin eventually required supplemental insulin as well, Dr. Rowan and her associates said (N. Engl. J. Med. 2008;358:2003–15).

Further follow-up data on the offspring are needed to determine the long-term safety of metformin use in pregnancy, they noted.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in an international study of 23,316 pregnant women.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes and a host of neonatal problems: hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia, investigators reported in the New England Journal of Medicine.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” reported Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study (N. Engl. J. Med. 2008;358:1991–2002).

The researchers assessed the 23,316 gravid women “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.” The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems increased as plasma glucose levels increased.

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes. A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

In a separate study of gestational diabetes published in the same issue, Dr. Janet A. Rowan of Auckland City (New Zealand) Hospital and her associates in the Metformin in Gestational Diabetes trial found that metformin was “noninferior” to insulin in safety and efficacy, and was preferred by patients with overt disease.

In that open-label study, Dr. Rowan and her associates compared oral metformin with insulin therapy in 733 women who had overt gestational diabetes and were followed at 10 New Zealand and Australian obstetric hospitals.

The composite outcome of numerous neonatal complications, including hypoglycemia in the infant, was no different between the metformin group and the insulin group, at 32% in both. There also were no differences between the two groups in neonatal anthropometric measures or in umbilical cord serum insulin concentrations.

The women preferred metformin to insulin. However, 46% of those who took metformin eventually required supplemental insulin as well, Dr. Rowan and her associates said (N. Engl. J. Med. 2008;358:2003–15).

Further follow-up data on the offspring are needed to determine the long-term safety of metformin use in pregnancy, they noted.

Maternal glucose levels that were high but below the diagnostic threshold for gestational diabetes were strongly associated with high fetal insulin levels and birth weights in an international study of 23,316 pregnant women.

There were also weaker—but still significant—associations between maternal hyperglycemia that fell short of overt gestational diabetes and a host of neonatal problems: hypoglycemia in the neonate, the need for cesarean delivery, premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia, investigators reported in the New England Journal of Medicine.

These findings “indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy,” reported Dr. Boyd E. Metzger of Northwestern University, Chicago, and his associates in the Hyperglycemia and Adverse Pregnancy Outcome study (N. Engl. J. Med. 2008;358:1991–2002).

The researchers assessed the 23,316 gravid women “to clarify the risk of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus.” The study subjects underwent standard oral glucose tolerance testing at 24–32 weeks' gestation at 15 medical centers in nine countries.

Cord blood specimens were obtained at delivery to assess serum C-peptide levels, an indicator of fetal β-cell function.

High levels of fasting, 1-hour, and 2-hour plasma glucose were strongly correlated with birth weight above the 90th percentile and C-peptide levels above the 90th percentile, and the rates of these problems increased as plasma glucose levels increased.

There were weaker but significant correlations between maternal hyperglycemia and two other primary outcomes of this study (cesarean delivery and clinical neonatal hyperglycemia), as well as five secondary outcomes. A similar dose-response relationship was seen between increasing maternal glucose level and rising rates of these problems, Dr. Metzger and his associates said.

In a separate study of gestational diabetes published in the same issue, Dr. Janet A. Rowan of Auckland City (New Zealand) Hospital and her associates in the Metformin in Gestational Diabetes trial found that metformin was “noninferior” to insulin in safety and efficacy, and was preferred by patients with overt disease.

In that open-label study, Dr. Rowan and her associates compared oral metformin with insulin therapy in 733 women who had overt gestational diabetes and were followed at 10 New Zealand and Australian obstetric hospitals.

The composite outcome of numerous neonatal complications, including hypoglycemia in the infant, was no different between the metformin group and the insulin group, at 32% in both. There also were no differences between the two groups in neonatal anthropometric measures or in umbilical cord serum insulin concentrations.

The women preferred metformin to insulin. However, 46% of those who took metformin eventually required supplemental insulin as well, Dr. Rowan and her associates said (N. Engl. J. Med. 2008;358:2003–15).

Further follow-up data on the offspring are needed to determine the long-term safety of metformin use in pregnancy, they noted.

SAN FRANCISCO — Check serum bile acid levels to determine if severe itching during pregnancy is the result of intrahepatic cholestasis of pregnancy, advises a dermatologic pathologist.

“Intrahepatic cholestasis of pregnancy is about the only dermatosis of pregnancy that has poor outcomes for the unborn,” Dr. Senait W. Dyson said at a meeting sponsored by Skin Disease Education Foundation.

An uncommon problem in the United States, intrahepatic cholestasis of pregnancy (also called prurigo gravidarum or obstetric cholestasis) is a reversible form of cholestasis that presents in late pregnancy and persists until delivery.

The disease increases the risk of intrauterine fetal distress and leads to a three- to fourfold increase in the risk of stillbirth.

It typically presents during the third trimester and resolves within days after delivery. Clinically, the problem is characterized by generalized, severe pruritus without primary skin lesions, said Dr. Dyson, director of dermatopathology at the University of California, Irvine. Involvement of the palms and soles is common. You'll seldom see jaundice with intrahepatic cholestasis of pregnancy.

The main diagnostic finding is increased serum bile acids in all cases, resulting from impaired bile flow. Elevated serum bile acid levels greater than 4.07 mcg/mL (10 micromol/L) in these patients can reach as high as 16 mcg/mL (40 micromol/L), she said.

Some patients will have abnormal liver function tests. Histology is nonspecific, and immunofluorescence tests will be negative.

Prolonged disease causes vitamin K deficiency and increases the risk for bleeding in the mother. It is not clear whether the bleeding risk increases in the infant. Check prothrombin times in women with intrahepatic cholestasis of pregnancy, Dr. Dyson advised. Women with increased prothrombin times should get vitamin K injections.

“Treatments that I use for other cholestasis diseases are not helpful in this condition,” she noted.

Antihistamines will help control the pruritus. Ursodeoxycholic acid (UDCA), the only approved medication to treat primary biliary cirrhosis, also helps improve pruritus in patients with intrahepatic cholestasis of pregnancy. Dr. Dyson said that most medical centers, including her institution, dose UDCA at 14 mg/kg per day t.i.d. to treat intrahepatic cholestasis of pregnancy from the time of diagnosis until delivery. Some clinicians suggest that dosages as high as 20–25 mg/kg per day t.i.d. might be better.

Delivery by 38 weeks' gestation is advisable, and some physicians suggest elective delivery by 37 weeks to decrease the risk of stillbirth, but it's not clear whether the potential benefits of delivering at 37 weeks outweigh the risks from preterm delivery, Dr. Dyson said.

“It's definitely agreed that patients should have frequent nonstress tests” and biophysical profiles to assess for fetal stress starting at 34 weeks' gestation, she said.

The incidence of intrahepatic cholestasis of pregnancy worldwide ranges from 10 to 760 cases per 10,000 pregnancies, with a higher incidence seen in Latin America (especially in Chile and Bolivia) and low rates in the United States and Europe.

Dr. Dyson reported having no conflicts of interest.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

SAN FRANCISCO — Check serum bile acid levels to determine if severe itching during pregnancy is the result of intrahepatic cholestasis of pregnancy, advises a dermatologic pathologist.

“Intrahepatic cholestasis of pregnancy is about the only dermatosis of pregnancy that has poor outcomes for the unborn,” Dr. Senait W. Dyson said at a meeting sponsored by Skin Disease Education Foundation.

An uncommon problem in the United States, intrahepatic cholestasis of pregnancy (also called prurigo gravidarum or obstetric cholestasis) is a reversible form of cholestasis that presents in late pregnancy and persists until delivery.

The disease increases the risk of intrauterine fetal distress and leads to a three- to fourfold increase in the risk of stillbirth.

It typically presents during the third trimester and resolves within days after delivery. Clinically, the problem is characterized by generalized, severe pruritus without primary skin lesions, said Dr. Dyson, director of dermatopathology at the University of California, Irvine. Involvement of the palms and soles is common. You'll seldom see jaundice with intrahepatic cholestasis of pregnancy.

The main diagnostic finding is increased serum bile acids in all cases, resulting from impaired bile flow. Elevated serum bile acid levels greater than 4.07 mcg/mL (10 micromol/L) in these patients can reach as high as 16 mcg/mL (40 micromol/L), she said.

Some patients will have abnormal liver function tests. Histology is nonspecific, and immunofluorescence tests will be negative.

Prolonged disease causes vitamin K deficiency and increases the risk for bleeding in the mother. It is not clear whether the bleeding risk increases in the infant. Check prothrombin times in women with intrahepatic cholestasis of pregnancy, Dr. Dyson advised. Women with increased prothrombin times should get vitamin K injections.

“Treatments that I use for other cholestasis diseases are not helpful in this condition,” she noted.

Antihistamines will help control the pruritus. Ursodeoxycholic acid (UDCA), the only approved medication to treat primary biliary cirrhosis, also helps improve pruritus in patients with intrahepatic cholestasis of pregnancy. Dr. Dyson said that most medical centers, including her institution, dose UDCA at 14 mg/kg per day t.i.d. to treat intrahepatic cholestasis of pregnancy from the time of diagnosis until delivery. Some clinicians suggest that dosages as high as 20–25 mg/kg per day t.i.d. might be better.

Delivery by 38 weeks' gestation is advisable, and some physicians suggest elective delivery by 37 weeks to decrease the risk of stillbirth, but it's not clear whether the potential benefits of delivering at 37 weeks outweigh the risks from preterm delivery, Dr. Dyson said.

“It's definitely agreed that patients should have frequent nonstress tests” and biophysical profiles to assess for fetal stress starting at 34 weeks' gestation, she said.

The incidence of intrahepatic cholestasis of pregnancy worldwide ranges from 10 to 760 cases per 10,000 pregnancies, with a higher incidence seen in Latin America (especially in Chile and Bolivia) and low rates in the United States and Europe.

Dr. Dyson reported having no conflicts of interest.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

SAN FRANCISCO — Check serum bile acid levels to determine if severe itching during pregnancy is the result of intrahepatic cholestasis of pregnancy, advises a dermatologic pathologist.

“Intrahepatic cholestasis of pregnancy is about the only dermatosis of pregnancy that has poor outcomes for the unborn,” Dr. Senait W. Dyson said at a meeting sponsored by Skin Disease Education Foundation.

An uncommon problem in the United States, intrahepatic cholestasis of pregnancy (also called prurigo gravidarum or obstetric cholestasis) is a reversible form of cholestasis that presents in late pregnancy and persists until delivery.

The disease increases the risk of intrauterine fetal distress and leads to a three- to fourfold increase in the risk of stillbirth.

It typically presents during the third trimester and resolves within days after delivery. Clinically, the problem is characterized by generalized, severe pruritus without primary skin lesions, said Dr. Dyson, director of dermatopathology at the University of California, Irvine. Involvement of the palms and soles is common. You'll seldom see jaundice with intrahepatic cholestasis of pregnancy.

The main diagnostic finding is increased serum bile acids in all cases, resulting from impaired bile flow. Elevated serum bile acid levels greater than 4.07 mcg/mL (10 micromol/L) in these patients can reach as high as 16 mcg/mL (40 micromol/L), she said.

Some patients will have abnormal liver function tests. Histology is nonspecific, and immunofluorescence tests will be negative.

Prolonged disease causes vitamin K deficiency and increases the risk for bleeding in the mother. It is not clear whether the bleeding risk increases in the infant. Check prothrombin times in women with intrahepatic cholestasis of pregnancy, Dr. Dyson advised. Women with increased prothrombin times should get vitamin K injections.

“Treatments that I use for other cholestasis diseases are not helpful in this condition,” she noted.

Antihistamines will help control the pruritus. Ursodeoxycholic acid (UDCA), the only approved medication to treat primary biliary cirrhosis, also helps improve pruritus in patients with intrahepatic cholestasis of pregnancy. Dr. Dyson said that most medical centers, including her institution, dose UDCA at 14 mg/kg per day t.i.d. to treat intrahepatic cholestasis of pregnancy from the time of diagnosis until delivery. Some clinicians suggest that dosages as high as 20–25 mg/kg per day t.i.d. might be better.

Delivery by 38 weeks' gestation is advisable, and some physicians suggest elective delivery by 37 weeks to decrease the risk of stillbirth, but it's not clear whether the potential benefits of delivering at 37 weeks outweigh the risks from preterm delivery, Dr. Dyson said.

“It's definitely agreed that patients should have frequent nonstress tests” and biophysical profiles to assess for fetal stress starting at 34 weeks' gestation, she said.

The incidence of intrahepatic cholestasis of pregnancy worldwide ranges from 10 to 760 cases per 10,000 pregnancies, with a higher incidence seen in Latin America (especially in Chile and Bolivia) and low rates in the United States and Europe.

Dr. Dyson reported having no conflicts of interest.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — Early administration of fresh-frozen plasma to address coagulopathy can potentially reduce mortality, according to a study of 97 patients who received massive transfusions.

Although hemorrhage is still a major cause of early mortality in trauma patients, it is commonly believed that patients are not coagulopathic when they arrive in the emergency department, and that coagulopathy develops over time, said Dr. Swaminatha Mahadevan, who is associate chief of emergency medicine at Stanford (Calif.) University.

However, recent studies suggest that patients are coagulopathic when they “hit the ED door,” Dr. Mahadevan said at a symposium on emergency medicine sponsored by Stanford University.

“Most massive-transfusion protocols don't address this,” he added.

In Stanford's massive-transfusion protocol, and in many such guidelines throughout the United States, fresh-frozen plasma (FFP) is not given until the patient has received 4–6 U of blood, Dr. Mahadevan said.

In his presentation, Dr. Mahadevan referred to findings from a published study done at the University of Texas, Houston, which pointed to the need for earlier administration of FFP (J. Trauma 2007;62:112–9).

The University of Texas investigators reviewed data on 97 severely injured patients who required a massive transfusion of at least 10 U of packed red blood cells during their first 24 hours in the university hospital. “These patients were sick enough that they eventually had to go to the operating room, or to interventional radiology, to stop the bleeding,” Dr. Mahadevan said.

All of the patients studied were found to have had severe coagulopathy on arrival at the ED, with international normalized ratios (INRs) of 1.8, plus or minus 0.2.

Nevertheless, Dr. Mahadevan noted, because of the way the massive-transfusion guidelines have been set up, none of the patients received FFP until after they received 6 U of packed red cells.

Upon arrival in the ICU following initial resuscitation in the ED, the patients' INRs were still high (1.6, plus or minus 0.1).

Finally, they would start receiving packed red cells and FFP in a 1:1 ratio, Dr. Mahadevan said.

The patients were still moderately coagulopathic 8 hours later, he noted, with a mean INR of 1.4, plus or minus 0.03.

The University of Texas study found that the severity of coagulopathy on ICU admission correlated with an increase in mortality, Dr. Mahadevan observed.

“If your INR was greater than 2, you had a 50% mortality, which, obviously, is significant,” he commented.

Learning from this study, Dr. Mahadevan stressed that “we should be assuming that these patients are coagulopathic, and [we should be] giving FFP right out of the gates,” with an initial transfusion in a 1:1 ratio with packed red blood cells.

Based on the study's findings, the University of Texas investigators influenced the hospital to revise its massive-transfusion protocol for severe bleeding, Dr. Mahadevan noted.

WAIKOLOA, HAWAII — Early administration of fresh-frozen plasma to address coagulopathy can potentially reduce mortality, according to a study of 97 patients who received massive transfusions.

Although hemorrhage is still a major cause of early mortality in trauma patients, it is commonly believed that patients are not coagulopathic when they arrive in the emergency department, and that coagulopathy develops over time, said Dr. Swaminatha Mahadevan, who is associate chief of emergency medicine at Stanford (Calif.) University.

However, recent studies suggest that patients are coagulopathic when they “hit the ED door,” Dr. Mahadevan said at a symposium on emergency medicine sponsored by Stanford University.

“Most massive-transfusion protocols don't address this,” he added.

In Stanford's massive-transfusion protocol, and in many such guidelines throughout the United States, fresh-frozen plasma (FFP) is not given until the patient has received 4–6 U of blood, Dr. Mahadevan said.

In his presentation, Dr. Mahadevan referred to findings from a published study done at the University of Texas, Houston, which pointed to the need for earlier administration of FFP (J. Trauma 2007;62:112–9).

The University of Texas investigators reviewed data on 97 severely injured patients who required a massive transfusion of at least 10 U of packed red blood cells during their first 24 hours in the university hospital. “These patients were sick enough that they eventually had to go to the operating room, or to interventional radiology, to stop the bleeding,” Dr. Mahadevan said.

All of the patients studied were found to have had severe coagulopathy on arrival at the ED, with international normalized ratios (INRs) of 1.8, plus or minus 0.2.

Nevertheless, Dr. Mahadevan noted, because of the way the massive-transfusion guidelines have been set up, none of the patients received FFP until after they received 6 U of packed red cells.

Upon arrival in the ICU following initial resuscitation in the ED, the patients' INRs were still high (1.6, plus or minus 0.1).

Finally, they would start receiving packed red cells and FFP in a 1:1 ratio, Dr. Mahadevan said.

The patients were still moderately coagulopathic 8 hours later, he noted, with a mean INR of 1.4, plus or minus 0.03.

The University of Texas study found that the severity of coagulopathy on ICU admission correlated with an increase in mortality, Dr. Mahadevan observed.

“If your INR was greater than 2, you had a 50% mortality, which, obviously, is significant,” he commented.

Learning from this study, Dr. Mahadevan stressed that “we should be assuming that these patients are coagulopathic, and [we should be] giving FFP right out of the gates,” with an initial transfusion in a 1:1 ratio with packed red blood cells.

Based on the study's findings, the University of Texas investigators influenced the hospital to revise its massive-transfusion protocol for severe bleeding, Dr. Mahadevan noted.

WAIKOLOA, HAWAII — Early administration of fresh-frozen plasma to address coagulopathy can potentially reduce mortality, according to a study of 97 patients who received massive transfusions.

Although hemorrhage is still a major cause of early mortality in trauma patients, it is commonly believed that patients are not coagulopathic when they arrive in the emergency department, and that coagulopathy develops over time, said Dr. Swaminatha Mahadevan, who is associate chief of emergency medicine at Stanford (Calif.) University.

However, recent studies suggest that patients are coagulopathic when they “hit the ED door,” Dr. Mahadevan said at a symposium on emergency medicine sponsored by Stanford University.

“Most massive-transfusion protocols don't address this,” he added.

In Stanford's massive-transfusion protocol, and in many such guidelines throughout the United States, fresh-frozen plasma (FFP) is not given until the patient has received 4–6 U of blood, Dr. Mahadevan said.

In his presentation, Dr. Mahadevan referred to findings from a published study done at the University of Texas, Houston, which pointed to the need for earlier administration of FFP (J. Trauma 2007;62:112–9).

The University of Texas investigators reviewed data on 97 severely injured patients who required a massive transfusion of at least 10 U of packed red blood cells during their first 24 hours in the university hospital. “These patients were sick enough that they eventually had to go to the operating room, or to interventional radiology, to stop the bleeding,” Dr. Mahadevan said.

All of the patients studied were found to have had severe coagulopathy on arrival at the ED, with international normalized ratios (INRs) of 1.8, plus or minus 0.2.

Nevertheless, Dr. Mahadevan noted, because of the way the massive-transfusion guidelines have been set up, none of the patients received FFP until after they received 6 U of packed red cells.

Upon arrival in the ICU following initial resuscitation in the ED, the patients' INRs were still high (1.6, plus or minus 0.1).

Finally, they would start receiving packed red cells and FFP in a 1:1 ratio, Dr. Mahadevan said.

The patients were still moderately coagulopathic 8 hours later, he noted, with a mean INR of 1.4, plus or minus 0.03.

The University of Texas study found that the severity of coagulopathy on ICU admission correlated with an increase in mortality, Dr. Mahadevan observed.

“If your INR was greater than 2, you had a 50% mortality, which, obviously, is significant,” he commented.

Learning from this study, Dr. Mahadevan stressed that “we should be assuming that these patients are coagulopathic, and [we should be] giving FFP right out of the gates,” with an initial transfusion in a 1:1 ratio with packed red blood cells.

Based on the study's findings, the University of Texas investigators influenced the hospital to revise its massive-transfusion protocol for severe bleeding, Dr. Mahadevan noted.

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can apparently exert a beneficial influence on the offspring's bone mineral density in later life, according to analysis of data from a longitudinal study of more than 17,000 Korean patients.

Peak bone mass contributes to bone strength in later life, and although the peak is reached in early adulthood it is influenced by factors in early life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology. For example, it has been shown that vitamin D supplementation during the first year of life is associated with higher bone mineral content in prepubertal children, she reported.

Antenatal factors such as maternal and fetal vitamin D exposure also appear to contribute. Most fetal skeletal calcium accumulation occurs in the third trimester of pregnancy, and placental calcium transport is influenced by maternal vitamin D, said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

It has not yet been determined, however, whether birth month—either influenced by antenatal or postnatal exposure to ultraviolet B (UVB) sunlight—affects the offspring's later life risk for low bone mineral density (BMD), she commented.

One study found that Korean babies born in winter had lower bone mineral concentration than did those born in summer (J. Pediatr. 1998;132:421–5), she noted.

“In the United Kingdom the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson.

This is in contrast to Canada and the United States, where milk is fortified with the vitamin, she noted.

To determine if variations in vitamin D levels resulting from either maternal exposure to sunlight during late pregnancy or neonatal exposure during the first 3 months of life could be associated with BMD in later life, birth records and dual energy x-ray absorptiometry (DXA) scan results for a large cohort of patients were examined.

All patients from the Morecambe Bay catchment district who had DXA scans between 1992 and 2004 were included in the study. The cohort included 15,042 women and 2,160 men whose mean age was 62 years.

At the latitude of this Korean district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life.

They were classified as having antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, explained Dr. Goodson.

Overall, 51% of patients had BMD in the normal range, and, as expected, women had lower mean T scores, at −1.7, than did men, at -0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said.

Those patients who had antenatal sunlight exposure also were less likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, again there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“These findings suggest that maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure, and this may be particularly important in the U.K., where vitamin D deficiency is very common,” Dr. Goodson said.

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can apparently exert a beneficial influence on the offspring's bone mineral density in later life, according to analysis of data from a longitudinal study of more than 17,000 Korean patients.

Peak bone mass contributes to bone strength in later life, and although the peak is reached in early adulthood it is influenced by factors in early life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology. For example, it has been shown that vitamin D supplementation during the first year of life is associated with higher bone mineral content in prepubertal children, she reported.

Antenatal factors such as maternal and fetal vitamin D exposure also appear to contribute. Most fetal skeletal calcium accumulation occurs in the third trimester of pregnancy, and placental calcium transport is influenced by maternal vitamin D, said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

It has not yet been determined, however, whether birth month—either influenced by antenatal or postnatal exposure to ultraviolet B (UVB) sunlight—affects the offspring's later life risk for low bone mineral density (BMD), she commented.

One study found that Korean babies born in winter had lower bone mineral concentration than did those born in summer (J. Pediatr. 1998;132:421–5), she noted.

“In the United Kingdom the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson.

This is in contrast to Canada and the United States, where milk is fortified with the vitamin, she noted.

To determine if variations in vitamin D levels resulting from either maternal exposure to sunlight during late pregnancy or neonatal exposure during the first 3 months of life could be associated with BMD in later life, birth records and dual energy x-ray absorptiometry (DXA) scan results for a large cohort of patients were examined.

All patients from the Morecambe Bay catchment district who had DXA scans between 1992 and 2004 were included in the study. The cohort included 15,042 women and 2,160 men whose mean age was 62 years.

At the latitude of this Korean district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life.

They were classified as having antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, explained Dr. Goodson.

Overall, 51% of patients had BMD in the normal range, and, as expected, women had lower mean T scores, at −1.7, than did men, at -0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said.

Those patients who had antenatal sunlight exposure also were less likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, again there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“These findings suggest that maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure, and this may be particularly important in the U.K., where vitamin D deficiency is very common,” Dr. Goodson said.

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can apparently exert a beneficial influence on the offspring's bone mineral density in later life, according to analysis of data from a longitudinal study of more than 17,000 Korean patients.

Peak bone mass contributes to bone strength in later life, and although the peak is reached in early adulthood it is influenced by factors in early life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology. For example, it has been shown that vitamin D supplementation during the first year of life is associated with higher bone mineral content in prepubertal children, she reported.

Antenatal factors such as maternal and fetal vitamin D exposure also appear to contribute. Most fetal skeletal calcium accumulation occurs in the third trimester of pregnancy, and placental calcium transport is influenced by maternal vitamin D, said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

It has not yet been determined, however, whether birth month—either influenced by antenatal or postnatal exposure to ultraviolet B (UVB) sunlight—affects the offspring's later life risk for low bone mineral density (BMD), she commented.

One study found that Korean babies born in winter had lower bone mineral concentration than did those born in summer (J. Pediatr. 1998;132:421–5), she noted.

“In the United Kingdom the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson.

This is in contrast to Canada and the United States, where milk is fortified with the vitamin, she noted.

To determine if variations in vitamin D levels resulting from either maternal exposure to sunlight during late pregnancy or neonatal exposure during the first 3 months of life could be associated with BMD in later life, birth records and dual energy x-ray absorptiometry (DXA) scan results for a large cohort of patients were examined.

All patients from the Morecambe Bay catchment district who had DXA scans between 1992 and 2004 were included in the study. The cohort included 15,042 women and 2,160 men whose mean age was 62 years.

At the latitude of this Korean district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life.

They were classified as having antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, explained Dr. Goodson.

Overall, 51% of patients had BMD in the normal range, and, as expected, women had lower mean T scores, at −1.7, than did men, at -0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said.

Those patients who had antenatal sunlight exposure also were less likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, again there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“These findings suggest that maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure, and this may be particularly important in the U.K., where vitamin D deficiency is very common,” Dr. Goodson said.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

DALLAS — Supplementation with vitamins C and E did not prevent preeclampsia, reduce its severity, or lower adverse neonatal outcomes in a World Health Organization randomized trial of 1,365 high-risk women.

The observed negative results are consistent with those of most previous antioxidant trials, although none of the previously reported adverse effects, such as earlier and more severe preeclampsia or reduced birth weight, were observed in the current trial, Dr. Mario Merialdi said at the annual meeting of the Society for Maternal-Fetal Medicine.

“We found no evidence of harm to either mother or fetus attributable to supplementation with vitamin C and E,” he said.

Still, lead investigator Dr. Jose Villar, a senior fellow in perinatal medicine at the University of Oxford (England), advised caution. “It is always of concern to give ineffective drugs to pregnant women, even if one study does not demonstrate harm,” he said in an interview.

The recent VIP (Vitamins in Preeclampsia) trial showed that concomitant vitamin C and E supplementation did not reduce preeclampsia among 2,395 women at risk, but did increase the rate of babies born with a low birth weight (Lancet 2006;367:1145–54).

The WHO trial parallels the VIP trial, but specifically targeted high-risk women with nutritional deficiencies who lived in India, Vietnam, South Africa, and Peru. Because previous failed antioxidant trials were conducted in women with adequate nutritional status, the investigators theorized that supplementing potentially vitamin-deficient women might produce beneficial results, explained Dr. Merialdi, a reproductive health specialist with WHO in Geneva.

In all, 687 women were randomized to daily vitamin C (1 g) and vitamin E (400 IU), and 678 women were randomized to placebo before gestational week 20. Their mean age was 27 years. Risk factors were similar between the intervention and control groups, including history of previous preeclampsia (217 vs. 205), chronic hypertension (163 vs. 170), and multiple pregnancies (81 vs. 100). Compliance was similar in both groups at about 87%.

Supplementation did not reduce the risk of preeclampsia (relative risk 1.0), eclampsia (RR 1.5), or severe gestational hypertension (RR 0.8). Adjustment for maternal age did not modify these results, he said. The incidence of preeclampsia was not significantly different between the intervention and placebo groups (24.5% vs. 23.3%).

The secondary outcomes of low birth weight (defined as less than 2,500 g, and found in 33% of the intervention group vs. 36% in controls), small size for gestational age (defined as less than 10th percentile, in 23% vs. 26%), and preterm delivery (defined as delivery before 37 weeks, in 21% vs. 24%) tended to be lower with supplementation, but were not statistically different (RR 0.9 for all three).

Perinatal death also tended to be lower with supplementation, but did not reach statistically significant levels (RR 0.8), and the trial was underpowered to test this outcome.

A stratified analysis of those women with a history of preeclampsia demonstrated similar rates of preeclampsia in the supplement and control groups (26% vs. 28%), said Dr. Merialdi, who reported no financial conflicts of interest.

DALLAS — Supplementation with vitamins C and E did not prevent preeclampsia, reduce its severity, or lower adverse neonatal outcomes in a World Health Organization randomized trial of 1,365 high-risk women.

The observed negative results are consistent with those of most previous antioxidant trials, although none of the previously reported adverse effects, such as earlier and more severe preeclampsia or reduced birth weight, were observed in the current trial, Dr. Mario Merialdi said at the annual meeting of the Society for Maternal-Fetal Medicine.

“We found no evidence of harm to either mother or fetus attributable to supplementation with vitamin C and E,” he said.

Still, lead investigator Dr. Jose Villar, a senior fellow in perinatal medicine at the University of Oxford (England), advised caution. “It is always of concern to give ineffective drugs to pregnant women, even if one study does not demonstrate harm,” he said in an interview.

The recent VIP (Vitamins in Preeclampsia) trial showed that concomitant vitamin C and E supplementation did not reduce preeclampsia among 2,395 women at risk, but did increase the rate of babies born with a low birth weight (Lancet 2006;367:1145–54).

The WHO trial parallels the VIP trial, but specifically targeted high-risk women with nutritional deficiencies who lived in India, Vietnam, South Africa, and Peru. Because previous failed antioxidant trials were conducted in women with adequate nutritional status, the investigators theorized that supplementing potentially vitamin-deficient women might produce beneficial results, explained Dr. Merialdi, a reproductive health specialist with WHO in Geneva.

In all, 687 women were randomized to daily vitamin C (1 g) and vitamin E (400 IU), and 678 women were randomized to placebo before gestational week 20. Their mean age was 27 years. Risk factors were similar between the intervention and control groups, including history of previous preeclampsia (217 vs. 205), chronic hypertension (163 vs. 170), and multiple pregnancies (81 vs. 100). Compliance was similar in both groups at about 87%.

Supplementation did not reduce the risk of preeclampsia (relative risk 1.0), eclampsia (RR 1.5), or severe gestational hypertension (RR 0.8). Adjustment for maternal age did not modify these results, he said. The incidence of preeclampsia was not significantly different between the intervention and placebo groups (24.5% vs. 23.3%).

The secondary outcomes of low birth weight (defined as less than 2,500 g, and found in 33% of the intervention group vs. 36% in controls), small size for gestational age (defined as less than 10th percentile, in 23% vs. 26%), and preterm delivery (defined as delivery before 37 weeks, in 21% vs. 24%) tended to be lower with supplementation, but were not statistically different (RR 0.9 for all three).

Perinatal death also tended to be lower with supplementation, but did not reach statistically significant levels (RR 0.8), and the trial was underpowered to test this outcome.

A stratified analysis of those women with a history of preeclampsia demonstrated similar rates of preeclampsia in the supplement and control groups (26% vs. 28%), said Dr. Merialdi, who reported no financial conflicts of interest.

DALLAS — Supplementation with vitamins C and E did not prevent preeclampsia, reduce its severity, or lower adverse neonatal outcomes in a World Health Organization randomized trial of 1,365 high-risk women.

The observed negative results are consistent with those of most previous antioxidant trials, although none of the previously reported adverse effects, such as earlier and more severe preeclampsia or reduced birth weight, were observed in the current trial, Dr. Mario Merialdi said at the annual meeting of the Society for Maternal-Fetal Medicine.

“We found no evidence of harm to either mother or fetus attributable to supplementation with vitamin C and E,” he said.

Still, lead investigator Dr. Jose Villar, a senior fellow in perinatal medicine at the University of Oxford (England), advised caution. “It is always of concern to give ineffective drugs to pregnant women, even if one study does not demonstrate harm,” he said in an interview.

The recent VIP (Vitamins in Preeclampsia) trial showed that concomitant vitamin C and E supplementation did not reduce preeclampsia among 2,395 women at risk, but did increase the rate of babies born with a low birth weight (Lancet 2006;367:1145–54).

The WHO trial parallels the VIP trial, but specifically targeted high-risk women with nutritional deficiencies who lived in India, Vietnam, South Africa, and Peru. Because previous failed antioxidant trials were conducted in women with adequate nutritional status, the investigators theorized that supplementing potentially vitamin-deficient women might produce beneficial results, explained Dr. Merialdi, a reproductive health specialist with WHO in Geneva.

In all, 687 women were randomized to daily vitamin C (1 g) and vitamin E (400 IU), and 678 women were randomized to placebo before gestational week 20. Their mean age was 27 years. Risk factors were similar between the intervention and control groups, including history of previous preeclampsia (217 vs. 205), chronic hypertension (163 vs. 170), and multiple pregnancies (81 vs. 100). Compliance was similar in both groups at about 87%.

Supplementation did not reduce the risk of preeclampsia (relative risk 1.0), eclampsia (RR 1.5), or severe gestational hypertension (RR 0.8). Adjustment for maternal age did not modify these results, he said. The incidence of preeclampsia was not significantly different between the intervention and placebo groups (24.5% vs. 23.3%).

The secondary outcomes of low birth weight (defined as less than 2,500 g, and found in 33% of the intervention group vs. 36% in controls), small size for gestational age (defined as less than 10th percentile, in 23% vs. 26%), and preterm delivery (defined as delivery before 37 weeks, in 21% vs. 24%) tended to be lower with supplementation, but were not statistically different (RR 0.9 for all three).

Perinatal death also tended to be lower with supplementation, but did not reach statistically significant levels (RR 0.8), and the trial was underpowered to test this outcome.

A stratified analysis of those women with a history of preeclampsia demonstrated similar rates of preeclampsia in the supplement and control groups (26% vs. 28%), said Dr. Merialdi, who reported no financial conflicts of interest.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.