Obstetrics

WASHINGTON — Complications were significantly more likely among pregnant women when their hyperemesis was managed with a peripherally inserted central catheter line than with either a Dobhoff tube or medication, Dr. Calla M. Holmgren reported in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Holmgren and her colleagues at the University of Utah, Salt Lake City, compared the three interventions in a prospective cohort study of 70 hyperemetic patients. Two of 24 patients whose mother's hyperemesis was managed with a PICC line developed sepsis and were admitted to the neonatal intensive care unit, and one fetus died as a direct result of PICC line use. Also, 7 of the 24 patients had thrombosis, 3 had skin infections, and 2 had bacteremia. One patient with bacteremia was admitted to the NICU.

By comparison, 1 of 13 women managed with a Dobhoff tube had tube displacement, and 2 of the 33 women managed with medication had adverse reactions.

WASHINGTON — Complications were significantly more likely among pregnant women when their hyperemesis was managed with a peripherally inserted central catheter line than with either a Dobhoff tube or medication, Dr. Calla M. Holmgren reported in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Holmgren and her colleagues at the University of Utah, Salt Lake City, compared the three interventions in a prospective cohort study of 70 hyperemetic patients. Two of 24 patients whose mother's hyperemesis was managed with a PICC line developed sepsis and were admitted to the neonatal intensive care unit, and one fetus died as a direct result of PICC line use. Also, 7 of the 24 patients had thrombosis, 3 had skin infections, and 2 had bacteremia. One patient with bacteremia was admitted to the NICU.

By comparison, 1 of 13 women managed with a Dobhoff tube had tube displacement, and 2 of the 33 women managed with medication had adverse reactions.

WASHINGTON — Complications were significantly more likely among pregnant women when their hyperemesis was managed with a peripherally inserted central catheter line than with either a Dobhoff tube or medication, Dr. Calla M. Holmgren reported in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Holmgren and her colleagues at the University of Utah, Salt Lake City, compared the three interventions in a prospective cohort study of 70 hyperemetic patients. Two of 24 patients whose mother's hyperemesis was managed with a PICC line developed sepsis and were admitted to the neonatal intensive care unit, and one fetus died as a direct result of PICC line use. Also, 7 of the 24 patients had thrombosis, 3 had skin infections, and 2 had bacteremia. One patient with bacteremia was admitted to the NICU.

By comparison, 1 of 13 women managed with a Dobhoff tube had tube displacement, and 2 of the 33 women managed with medication had adverse reactions.

TUCSON, ARIZ. — The use of carbamazepine, phenytoin, or phenobarbital as monotherapy by pregnant women was not associated with significant deficits in full-scale IQ in their offspring, a small study showed.

However, these data counter previous reports of lowered intellectual ability in children born to mothers who took anticonvulsant medications during pregnancy, Dr. Kenneth Lyons Jones said at the annual meeting of the Teratology Society.

“The results, then, should be considered in conjunction with previous studies when evaluating the risks associated with use of these medications during pregnancy,” cautioned Dr. Jones, chief of the division of dysmorphology and teratology in the department of pediatrics at the University of California, San Diego.

Despite the documented increased risk for certain major malformations following prenatal exposure to anticonvulsants, he said that “substantial controversy” exists regarding their impact on neurobehavioral outcomes.

“Compounding these concerns is the fact that in the United States, between 7.6 million and 12.7 million women have epilepsy, and 95% of them are being treated with anticonvulsant drugs,” Dr. Jones said. “In addition, 1 in every 200 pregnant women in the general population requires antiepileptic medication during her pregnancy.”

He and his associates studied 82 children aged 4–14 years whose mothers were on anticonvulsant monotherapy and contacted the California Teratogen Information Service (CTIS) during their pregnancy. Of the 82 children, 30 were exposed to carbamazepine, 23 were exposed to phenytoin, and 29 were exposed to phenobarbital.

The researchers randomly selected 50 matched controls born to women who contacted CTIS due to an exposure not deemed to be teratogenic.

All children underwent neuropsychiatric testing that included a measure of full-scale IQ (FSIQ). Testing was conducted at the Center for Behavioral Teratology at San Diego State University or in a location near the child's home.

Dr. Jones reported that 26% of children exposed to phenytoin were rated as affected with features of the anticonvulsant facies based on ratings of minor malformations, compared with 24% of those exposed to phenobarbital and only 3% of those exposed to carbamazepine. No one in the control group was considered affected.

In terms of the FSIQ, there were no statistically significant differences in scores between exposed children and controls, nor did any of the exposed children differ from each other, even after controlling for age and socioeconomic status.

Dr. Jones acknowledged certain limitations of the study, including the fact that the population studied was homogeneous, the sample size was small, and there was potential for selection bias.

TUCSON, ARIZ. — The use of carbamazepine, phenytoin, or phenobarbital as monotherapy by pregnant women was not associated with significant deficits in full-scale IQ in their offspring, a small study showed.

However, these data counter previous reports of lowered intellectual ability in children born to mothers who took anticonvulsant medications during pregnancy, Dr. Kenneth Lyons Jones said at the annual meeting of the Teratology Society.

“The results, then, should be considered in conjunction with previous studies when evaluating the risks associated with use of these medications during pregnancy,” cautioned Dr. Jones, chief of the division of dysmorphology and teratology in the department of pediatrics at the University of California, San Diego.

Despite the documented increased risk for certain major malformations following prenatal exposure to anticonvulsants, he said that “substantial controversy” exists regarding their impact on neurobehavioral outcomes.

“Compounding these concerns is the fact that in the United States, between 7.6 million and 12.7 million women have epilepsy, and 95% of them are being treated with anticonvulsant drugs,” Dr. Jones said. “In addition, 1 in every 200 pregnant women in the general population requires antiepileptic medication during her pregnancy.”

He and his associates studied 82 children aged 4–14 years whose mothers were on anticonvulsant monotherapy and contacted the California Teratogen Information Service (CTIS) during their pregnancy. Of the 82 children, 30 were exposed to carbamazepine, 23 were exposed to phenytoin, and 29 were exposed to phenobarbital.

The researchers randomly selected 50 matched controls born to women who contacted CTIS due to an exposure not deemed to be teratogenic.

All children underwent neuropsychiatric testing that included a measure of full-scale IQ (FSIQ). Testing was conducted at the Center for Behavioral Teratology at San Diego State University or in a location near the child's home.

Dr. Jones reported that 26% of children exposed to phenytoin were rated as affected with features of the anticonvulsant facies based on ratings of minor malformations, compared with 24% of those exposed to phenobarbital and only 3% of those exposed to carbamazepine. No one in the control group was considered affected.

In terms of the FSIQ, there were no statistically significant differences in scores between exposed children and controls, nor did any of the exposed children differ from each other, even after controlling for age and socioeconomic status.

Dr. Jones acknowledged certain limitations of the study, including the fact that the population studied was homogeneous, the sample size was small, and there was potential for selection bias.

TUCSON, ARIZ. — The use of carbamazepine, phenytoin, or phenobarbital as monotherapy by pregnant women was not associated with significant deficits in full-scale IQ in their offspring, a small study showed.

However, these data counter previous reports of lowered intellectual ability in children born to mothers who took anticonvulsant medications during pregnancy, Dr. Kenneth Lyons Jones said at the annual meeting of the Teratology Society.

“The results, then, should be considered in conjunction with previous studies when evaluating the risks associated with use of these medications during pregnancy,” cautioned Dr. Jones, chief of the division of dysmorphology and teratology in the department of pediatrics at the University of California, San Diego.

Despite the documented increased risk for certain major malformations following prenatal exposure to anticonvulsants, he said that “substantial controversy” exists regarding their impact on neurobehavioral outcomes.

“Compounding these concerns is the fact that in the United States, between 7.6 million and 12.7 million women have epilepsy, and 95% of them are being treated with anticonvulsant drugs,” Dr. Jones said. “In addition, 1 in every 200 pregnant women in the general population requires antiepileptic medication during her pregnancy.”

He and his associates studied 82 children aged 4–14 years whose mothers were on anticonvulsant monotherapy and contacted the California Teratogen Information Service (CTIS) during their pregnancy. Of the 82 children, 30 were exposed to carbamazepine, 23 were exposed to phenytoin, and 29 were exposed to phenobarbital.

The researchers randomly selected 50 matched controls born to women who contacted CTIS due to an exposure not deemed to be teratogenic.

All children underwent neuropsychiatric testing that included a measure of full-scale IQ (FSIQ). Testing was conducted at the Center for Behavioral Teratology at San Diego State University or in a location near the child's home.

Dr. Jones reported that 26% of children exposed to phenytoin were rated as affected with features of the anticonvulsant facies based on ratings of minor malformations, compared with 24% of those exposed to phenobarbital and only 3% of those exposed to carbamazepine. No one in the control group was considered affected.

In terms of the FSIQ, there were no statistically significant differences in scores between exposed children and controls, nor did any of the exposed children differ from each other, even after controlling for age and socioeconomic status.

Dr. Jones acknowledged certain limitations of the study, including the fact that the population studied was homogeneous, the sample size was small, and there was potential for selection bias.

SEATTLE — Preterm birth is the most frequent cause of infant mortality in the United States, accounting for one-third of infant deaths in 2002, according to data presented at a meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Prematurity remains a major cause of infant morbidity and mortality in the United States, and rates continue to rise. Across the board, the rate of premature births rose 13% between 1992 and 2002, with seven states showing increases of 30% or higher, according to the March of Dimes.

“As of yet we do not have good predictors and prevention for preterm birth,” Dr. William Callaghan said in an interview.

“We decided to reassess the contribution of preterm birth to infant mortality, in light of the strong connection between prematurity and infant death and the rising rates of preterm birth,” explained Dr. Callaghan, a senior scientist in the Maternal and Infant Health Branch, Division of Reproductive Health, at the CDC.

Although about two-thirds of infant deaths occur in those born at less than 37 weeks' gestation, fewer than 20% of infant deaths are classified as being due to preterm birth using the standard National Center for Health Statistics' classification of “leading cause of death.”

This seeming contradiction can be explained, Dr. Callaghan said. “Among all infants who died, 65% were born preterm. However, just because the association exists does not mean that being preterm was necessarily the cause of death.”

As an example, if a preterm infant with a lethal congenital anomaly dies, one cannot say with any certainty that the death was caused by preterm birth or by the congenital anomaly.

Dr. Callaghan explained that he and his coauthors took a very conservative strategy and looked only at the 20 leading causes of infant death. Of 27,970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22,273 or 80% of all infant deaths. Within this group, they assessed the contributing role of preterm birth for each of the causes of death that are embedded in the standard categories.

The methodology was broken down into three basic steps to determine whether the cause of death was actually related to prematurity. First, the cause of death had to be statistically associated with preterm birth. If preterm infants contributed to at least 75% of the mortality due to a specific cause, the death was considered as potentially due to preterm birth.

Second, information about the condition had to be sufficient in order to determine if preterm birth actually led to that condition, or if the condition designated as the cause of death led to preterm birth.

Finally, it had to be determined whether the infant who died from the proposed cause was actually preterm.

Not surprisingly, the earliest infants had the highest rate of mortality, said Dr. Callaghan. Infants born at less than 32 weeks' gestation and who weighed less than 1,500 g accounted for 88% of the total 9,596 deaths attributed to preterm birth.

“If you look at all infant deaths in total, preterm births account for 34% of them,” Dr. Callaghan said. “But if you look at infant deaths confined to the 20 leading causes, then that rate is 43%.”

The majority of the infants die within the first week of life, with two-thirds of these deaths occurring during the first 24 hours after birth. “Prevention of preterm birth, especially at the earliest gestations, is crucial if we are going to further reduce the infant mortality rate,” he said.

SEATTLE — Preterm birth is the most frequent cause of infant mortality in the United States, accounting for one-third of infant deaths in 2002, according to data presented at a meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Prematurity remains a major cause of infant morbidity and mortality in the United States, and rates continue to rise. Across the board, the rate of premature births rose 13% between 1992 and 2002, with seven states showing increases of 30% or higher, according to the March of Dimes.

“As of yet we do not have good predictors and prevention for preterm birth,” Dr. William Callaghan said in an interview.

“We decided to reassess the contribution of preterm birth to infant mortality, in light of the strong connection between prematurity and infant death and the rising rates of preterm birth,” explained Dr. Callaghan, a senior scientist in the Maternal and Infant Health Branch, Division of Reproductive Health, at the CDC.

Although about two-thirds of infant deaths occur in those born at less than 37 weeks' gestation, fewer than 20% of infant deaths are classified as being due to preterm birth using the standard National Center for Health Statistics' classification of “leading cause of death.”

This seeming contradiction can be explained, Dr. Callaghan said. “Among all infants who died, 65% were born preterm. However, just because the association exists does not mean that being preterm was necessarily the cause of death.”

As an example, if a preterm infant with a lethal congenital anomaly dies, one cannot say with any certainty that the death was caused by preterm birth or by the congenital anomaly.

Dr. Callaghan explained that he and his coauthors took a very conservative strategy and looked only at the 20 leading causes of infant death. Of 27,970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22,273 or 80% of all infant deaths. Within this group, they assessed the contributing role of preterm birth for each of the causes of death that are embedded in the standard categories.

The methodology was broken down into three basic steps to determine whether the cause of death was actually related to prematurity. First, the cause of death had to be statistically associated with preterm birth. If preterm infants contributed to at least 75% of the mortality due to a specific cause, the death was considered as potentially due to preterm birth.

Second, information about the condition had to be sufficient in order to determine if preterm birth actually led to that condition, or if the condition designated as the cause of death led to preterm birth.

Finally, it had to be determined whether the infant who died from the proposed cause was actually preterm.

Not surprisingly, the earliest infants had the highest rate of mortality, said Dr. Callaghan. Infants born at less than 32 weeks' gestation and who weighed less than 1,500 g accounted for 88% of the total 9,596 deaths attributed to preterm birth.

“If you look at all infant deaths in total, preterm births account for 34% of them,” Dr. Callaghan said. “But if you look at infant deaths confined to the 20 leading causes, then that rate is 43%.”

The majority of the infants die within the first week of life, with two-thirds of these deaths occurring during the first 24 hours after birth. “Prevention of preterm birth, especially at the earliest gestations, is crucial if we are going to further reduce the infant mortality rate,” he said.

SEATTLE — Preterm birth is the most frequent cause of infant mortality in the United States, accounting for one-third of infant deaths in 2002, according to data presented at a meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Prematurity remains a major cause of infant morbidity and mortality in the United States, and rates continue to rise. Across the board, the rate of premature births rose 13% between 1992 and 2002, with seven states showing increases of 30% or higher, according to the March of Dimes.

“As of yet we do not have good predictors and prevention for preterm birth,” Dr. William Callaghan said in an interview.

“We decided to reassess the contribution of preterm birth to infant mortality, in light of the strong connection between prematurity and infant death and the rising rates of preterm birth,” explained Dr. Callaghan, a senior scientist in the Maternal and Infant Health Branch, Division of Reproductive Health, at the CDC.

Although about two-thirds of infant deaths occur in those born at less than 37 weeks' gestation, fewer than 20% of infant deaths are classified as being due to preterm birth using the standard National Center for Health Statistics' classification of “leading cause of death.”

This seeming contradiction can be explained, Dr. Callaghan said. “Among all infants who died, 65% were born preterm. However, just because the association exists does not mean that being preterm was necessarily the cause of death.”

As an example, if a preterm infant with a lethal congenital anomaly dies, one cannot say with any certainty that the death was caused by preterm birth or by the congenital anomaly.

Dr. Callaghan explained that he and his coauthors took a very conservative strategy and looked only at the 20 leading causes of infant death. Of 27,970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22,273 or 80% of all infant deaths. Within this group, they assessed the contributing role of preterm birth for each of the causes of death that are embedded in the standard categories.

The methodology was broken down into three basic steps to determine whether the cause of death was actually related to prematurity. First, the cause of death had to be statistically associated with preterm birth. If preterm infants contributed to at least 75% of the mortality due to a specific cause, the death was considered as potentially due to preterm birth.

Second, information about the condition had to be sufficient in order to determine if preterm birth actually led to that condition, or if the condition designated as the cause of death led to preterm birth.

Finally, it had to be determined whether the infant who died from the proposed cause was actually preterm.

Not surprisingly, the earliest infants had the highest rate of mortality, said Dr. Callaghan. Infants born at less than 32 weeks' gestation and who weighed less than 1,500 g accounted for 88% of the total 9,596 deaths attributed to preterm birth.

“If you look at all infant deaths in total, preterm births account for 34% of them,” Dr. Callaghan said. “But if you look at infant deaths confined to the 20 leading causes, then that rate is 43%.”

The majority of the infants die within the first week of life, with two-thirds of these deaths occurring during the first 24 hours after birth. “Prevention of preterm birth, especially at the earliest gestations, is crucial if we are going to further reduce the infant mortality rate,” he said.

More than 500,000 infants or about 12.5% of infants born in 2004 in the United States were preterm and the rate of preterm births has risen by about 30% since 1981, according to a new report from the National Academy of Sciences' Institute of Medicine.

Preterm birth, defined as any birth that occurs at less than 37 completed weeks of gestation, disproportionately affects women in certain racial, ethnic, and socioeconomic groups. For example, in 2003, nearly 18% of African American women had preterm births, compared with 11.9% of Hispanic women and 11.5% of non-Hispanic white women, the Institute of Medicine (IOM) report said.

“This is a growing problem that can result in significant consequences for families and for society as a whole,” Dr. Richard E. Behrman, chair of the IOM committee that produced the report, said during a press conference. “Yet preterm birth is not receiving the attention and funding necessary to fully understand the causes and consequences and to identify ways to reduce the number of preterm deliveries.”

Infants delivered preterm are at greater risk for a variety of health and developmental problems than full-term infants but there are also significant economic costs associated with preterm births. The cost of medical care in infancy, maternal care, early intervention services, special education, and lost productivity from preterm birth added up to more than $26 billion in 2005, according to the IOM report. And this is likely to be a conservative estimate, said Dr. Behrman, who is executive chair of the Pediatric Education Steering Committee for the Federation of Pediatric Organizations Inc., in Menlo Park, Calif.

In addition to defining the scope of the problem, the IOM report outlines a multidisciplinary research agenda aimed at improving information on the causes and treatment of preterm birth. The report calls on the federal government and private institutions to do a better job on collecting preterm birth data and to increase research that will lead to better identification of women at risk for preterm labor.

Although there have been significant improvements in treating preterm infants, there has been comparatively little success in understanding and preventing preterm birth, Dr. Behrman said. In effort to address some of those gaps, the IOM committee made a series of recommendations for public and private researchers. Some of the recommendations include:

▸ Multidisciplinary research centers. The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers to focus on better understanding the causes of preterm birth and health outcomes for women and infants, the IOM committee recommended.

▸ Ultrasound use. Professional societies should encourage the use of ultrasound before 20 weeks' gestation and establish standards of practice for training personnel to improve the reliability of ultrasound data, the IOM committee recommended. These efforts are important to gain accurate measures of gestational age, according to the report.

▸ Infertility treatments. NIH, CDC, and other agencies should support research into how fertility treatments can increase the risk for preterm birth. The report also calls on professional societies to establish guidelines aimed at reducing the number of multiple gestations, such as single embryo transfer and restricted use of superovulation drugs. The Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine, which have already issued guidelines on the number of embryos that should be transferred per cycle, announced that upcoming revisions to their guidelines should help to further reduce the incidence of multiples and preterm births associated with assisted reproductive technology.

▸ Identification and treatment. Researchers should focus on ways to identify and treat women who have an increased risk of preterm labor, such as studying known markers of preterm labor and potential new genetic markers that could lead to the creation of an “individualized composite assessment of risk.” Better methods are needed to diagnose preterm labor, assess fetal health, and arrest labor, the report said.

▸ Perinatal data. National Center for Health Statistics, part of the Centers for Disease Control and Prevention, should collect and report national perinatal data, the IOM committee recommended.

▸ Etiologic and epidemiologic studies. Public and private funding agencies should support research into the etiologies of preterm birth, the report said. The IOM committee also urged agencies to promote research that would simultaneously examine multiple risk factors for preterm birth instead of looking at risk factors individually.

▸ Health disparities. NIH and other agencies should examine the causes of racial, ethnic, and socioeconomic disparities related to preterm birth and devote resources to developing prevention strategies, the IOM committee recommended.

The report is a “call to arms” for the federal government to devote significantly more resources to preterm birth, Dr. Charles Lockwood, professor and chair of the department of obstetrics and gynecology and reproductive sciences at Yale University, said in an interview. Dr. Lockwood, who was one of the reviewers of the IOM report, said a 10-fold increase in current government spending on preterm birth would be a good start.

The IOM report “elevates the seriousness of the problem,” Jennifer Howse, Ph.D., president of the March of Dimes said in an interview. The report, which was cosponsored by the March of Dimes, is a realistic assessment of prematurity in the United States, she said.

Although the March of Dimes endorsed the recommendations in the report, the group also called on Congress to pass pending federal legislation that would authorize more federal research into preterm birth. The Prematurity Research Expansion and Education for Mothers who deliver Infants Early Act or PREEMIE bill (S. 707/H.R. 2861) was introduced last year and was passed by the Senate in August.

Copies of the IOM report are available online at www.nap.edu

More than 500,000 infants or about 12.5% of infants born in 2004 in the United States were preterm and the rate of preterm births has risen by about 30% since 1981, according to a new report from the National Academy of Sciences' Institute of Medicine.

Preterm birth, defined as any birth that occurs at less than 37 completed weeks of gestation, disproportionately affects women in certain racial, ethnic, and socioeconomic groups. For example, in 2003, nearly 18% of African American women had preterm births, compared with 11.9% of Hispanic women and 11.5% of non-Hispanic white women, the Institute of Medicine (IOM) report said.

“This is a growing problem that can result in significant consequences for families and for society as a whole,” Dr. Richard E. Behrman, chair of the IOM committee that produced the report, said during a press conference. “Yet preterm birth is not receiving the attention and funding necessary to fully understand the causes and consequences and to identify ways to reduce the number of preterm deliveries.”

Infants delivered preterm are at greater risk for a variety of health and developmental problems than full-term infants but there are also significant economic costs associated with preterm births. The cost of medical care in infancy, maternal care, early intervention services, special education, and lost productivity from preterm birth added up to more than $26 billion in 2005, according to the IOM report. And this is likely to be a conservative estimate, said Dr. Behrman, who is executive chair of the Pediatric Education Steering Committee for the Federation of Pediatric Organizations Inc., in Menlo Park, Calif.

In addition to defining the scope of the problem, the IOM report outlines a multidisciplinary research agenda aimed at improving information on the causes and treatment of preterm birth. The report calls on the federal government and private institutions to do a better job on collecting preterm birth data and to increase research that will lead to better identification of women at risk for preterm labor.

Although there have been significant improvements in treating preterm infants, there has been comparatively little success in understanding and preventing preterm birth, Dr. Behrman said. In effort to address some of those gaps, the IOM committee made a series of recommendations for public and private researchers. Some of the recommendations include:

▸ Multidisciplinary research centers. The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers to focus on better understanding the causes of preterm birth and health outcomes for women and infants, the IOM committee recommended.

▸ Ultrasound use. Professional societies should encourage the use of ultrasound before 20 weeks' gestation and establish standards of practice for training personnel to improve the reliability of ultrasound data, the IOM committee recommended. These efforts are important to gain accurate measures of gestational age, according to the report.

▸ Infertility treatments. NIH, CDC, and other agencies should support research into how fertility treatments can increase the risk for preterm birth. The report also calls on professional societies to establish guidelines aimed at reducing the number of multiple gestations, such as single embryo transfer and restricted use of superovulation drugs. The Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine, which have already issued guidelines on the number of embryos that should be transferred per cycle, announced that upcoming revisions to their guidelines should help to further reduce the incidence of multiples and preterm births associated with assisted reproductive technology.

▸ Identification and treatment. Researchers should focus on ways to identify and treat women who have an increased risk of preterm labor, such as studying known markers of preterm labor and potential new genetic markers that could lead to the creation of an “individualized composite assessment of risk.” Better methods are needed to diagnose preterm labor, assess fetal health, and arrest labor, the report said.

▸ Perinatal data. National Center for Health Statistics, part of the Centers for Disease Control and Prevention, should collect and report national perinatal data, the IOM committee recommended.

▸ Etiologic and epidemiologic studies. Public and private funding agencies should support research into the etiologies of preterm birth, the report said. The IOM committee also urged agencies to promote research that would simultaneously examine multiple risk factors for preterm birth instead of looking at risk factors individually.

▸ Health disparities. NIH and other agencies should examine the causes of racial, ethnic, and socioeconomic disparities related to preterm birth and devote resources to developing prevention strategies, the IOM committee recommended.

The report is a “call to arms” for the federal government to devote significantly more resources to preterm birth, Dr. Charles Lockwood, professor and chair of the department of obstetrics and gynecology and reproductive sciences at Yale University, said in an interview. Dr. Lockwood, who was one of the reviewers of the IOM report, said a 10-fold increase in current government spending on preterm birth would be a good start.

The IOM report “elevates the seriousness of the problem,” Jennifer Howse, Ph.D., president of the March of Dimes said in an interview. The report, which was cosponsored by the March of Dimes, is a realistic assessment of prematurity in the United States, she said.

Although the March of Dimes endorsed the recommendations in the report, the group also called on Congress to pass pending federal legislation that would authorize more federal research into preterm birth. The Prematurity Research Expansion and Education for Mothers who deliver Infants Early Act or PREEMIE bill (S. 707/H.R. 2861) was introduced last year and was passed by the Senate in August.

Copies of the IOM report are available online at www.nap.edu

More than 500,000 infants or about 12.5% of infants born in 2004 in the United States were preterm and the rate of preterm births has risen by about 30% since 1981, according to a new report from the National Academy of Sciences' Institute of Medicine.

Preterm birth, defined as any birth that occurs at less than 37 completed weeks of gestation, disproportionately affects women in certain racial, ethnic, and socioeconomic groups. For example, in 2003, nearly 18% of African American women had preterm births, compared with 11.9% of Hispanic women and 11.5% of non-Hispanic white women, the Institute of Medicine (IOM) report said.

“This is a growing problem that can result in significant consequences for families and for society as a whole,” Dr. Richard E. Behrman, chair of the IOM committee that produced the report, said during a press conference. “Yet preterm birth is not receiving the attention and funding necessary to fully understand the causes and consequences and to identify ways to reduce the number of preterm deliveries.”

Infants delivered preterm are at greater risk for a variety of health and developmental problems than full-term infants but there are also significant economic costs associated with preterm births. The cost of medical care in infancy, maternal care, early intervention services, special education, and lost productivity from preterm birth added up to more than $26 billion in 2005, according to the IOM report. And this is likely to be a conservative estimate, said Dr. Behrman, who is executive chair of the Pediatric Education Steering Committee for the Federation of Pediatric Organizations Inc., in Menlo Park, Calif.

In addition to defining the scope of the problem, the IOM report outlines a multidisciplinary research agenda aimed at improving information on the causes and treatment of preterm birth. The report calls on the federal government and private institutions to do a better job on collecting preterm birth data and to increase research that will lead to better identification of women at risk for preterm labor.

Although there have been significant improvements in treating preterm infants, there has been comparatively little success in understanding and preventing preterm birth, Dr. Behrman said. In effort to address some of those gaps, the IOM committee made a series of recommendations for public and private researchers. Some of the recommendations include:

▸ Multidisciplinary research centers. The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers to focus on better understanding the causes of preterm birth and health outcomes for women and infants, the IOM committee recommended.

▸ Ultrasound use. Professional societies should encourage the use of ultrasound before 20 weeks' gestation and establish standards of practice for training personnel to improve the reliability of ultrasound data, the IOM committee recommended. These efforts are important to gain accurate measures of gestational age, according to the report.

▸ Infertility treatments. NIH, CDC, and other agencies should support research into how fertility treatments can increase the risk for preterm birth. The report also calls on professional societies to establish guidelines aimed at reducing the number of multiple gestations, such as single embryo transfer and restricted use of superovulation drugs. The Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine, which have already issued guidelines on the number of embryos that should be transferred per cycle, announced that upcoming revisions to their guidelines should help to further reduce the incidence of multiples and preterm births associated with assisted reproductive technology.

▸ Identification and treatment. Researchers should focus on ways to identify and treat women who have an increased risk of preterm labor, such as studying known markers of preterm labor and potential new genetic markers that could lead to the creation of an “individualized composite assessment of risk.” Better methods are needed to diagnose preterm labor, assess fetal health, and arrest labor, the report said.

▸ Perinatal data. National Center for Health Statistics, part of the Centers for Disease Control and Prevention, should collect and report national perinatal data, the IOM committee recommended.

▸ Etiologic and epidemiologic studies. Public and private funding agencies should support research into the etiologies of preterm birth, the report said. The IOM committee also urged agencies to promote research that would simultaneously examine multiple risk factors for preterm birth instead of looking at risk factors individually.

▸ Health disparities. NIH and other agencies should examine the causes of racial, ethnic, and socioeconomic disparities related to preterm birth and devote resources to developing prevention strategies, the IOM committee recommended.

The report is a “call to arms” for the federal government to devote significantly more resources to preterm birth, Dr. Charles Lockwood, professor and chair of the department of obstetrics and gynecology and reproductive sciences at Yale University, said in an interview. Dr. Lockwood, who was one of the reviewers of the IOM report, said a 10-fold increase in current government spending on preterm birth would be a good start.

The IOM report “elevates the seriousness of the problem,” Jennifer Howse, Ph.D., president of the March of Dimes said in an interview. The report, which was cosponsored by the March of Dimes, is a realistic assessment of prematurity in the United States, she said.

Although the March of Dimes endorsed the recommendations in the report, the group also called on Congress to pass pending federal legislation that would authorize more federal research into preterm birth. The Prematurity Research Expansion and Education for Mothers who deliver Infants Early Act or PREEMIE bill (S. 707/H.R. 2861) was introduced last year and was passed by the Senate in August.

Copies of the IOM report are available online at www.nap.edu

LISBON — The definition of severe preeclampsia that's been adopted by the U.S. National High Blood Pressure Education Program contains some criteria that did not lead to adverse maternal outcomes in an analysis of 657 patients.

Based on these findings, a narrower definition of severe preeclampsia is warranted, with a narrower list of criteria used to justify delivery for maternal indications, Dr. Peter von Dadelszen and his associates reported in a poster at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Three criteria that did not shake out as adverse-outcome predictors from the list of the National High Blood Pressure Education Program (NHBPEP) were proteinuria, persistent headache or other cerebral or visual disturbances, and persistent epigastric pain, reported the poster's authors, including Dr. Dadelszen, an ob.gyn. at the University of British Columbia, Vancouver. The NHBPEP Working Group on High Blood Pressure in Pregnancy published its revised recommendations in 2000.

The researchers found that the severe preeclampsia criteria of the Canadian Hypertension Society also included several diagnostic markers that weren't associated with adverse outcomes in the current study, including proteinuria, low serum albumin, severe nausea, intrauterine growth restriction, oligohydramnios, headache, and right upper quadrant pain.

The study was done at six hospitals in Canada, the United Kingdom, and New Zealand during September 2003 to May 2006. It included 657 women who were diagnosed with preeclampsia, superimposed preeclampsia, or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). For this study, preeclampsia was defined as a blood pressure of at least 140/90 mm Hg and proteinuria or hyperuricemia.

The researchers identified the clinical markers that were statistically significant predictors of adverse maternal outcomes in this group. The adverse outcomes included death, hepatic dysfunction, acute renal failure, eclampsia, pulmonary edema, and need for any transfusion.

The multivariate analysis identified these factors as independent predictors of adverse outcomes: blood pressure at or above 160/110 mm Hg, platelets less than 100 × 10

All of these conditions are diagnostic criteria in both the NHBPEP and Canadian Hypertension Society guidelines, except chest pain or dyspnea and placental abruption, which don't appear in the NHBPEP definition of severe preeclampsia, the researchers said. However, the researchers did not suggest that the NHBPEP needed to expand its criteria to match the Canadian guidelines.

LISBON — The definition of severe preeclampsia that's been adopted by the U.S. National High Blood Pressure Education Program contains some criteria that did not lead to adverse maternal outcomes in an analysis of 657 patients.

Based on these findings, a narrower definition of severe preeclampsia is warranted, with a narrower list of criteria used to justify delivery for maternal indications, Dr. Peter von Dadelszen and his associates reported in a poster at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Three criteria that did not shake out as adverse-outcome predictors from the list of the National High Blood Pressure Education Program (NHBPEP) were proteinuria, persistent headache or other cerebral or visual disturbances, and persistent epigastric pain, reported the poster's authors, including Dr. Dadelszen, an ob.gyn. at the University of British Columbia, Vancouver. The NHBPEP Working Group on High Blood Pressure in Pregnancy published its revised recommendations in 2000.

The researchers found that the severe preeclampsia criteria of the Canadian Hypertension Society also included several diagnostic markers that weren't associated with adverse outcomes in the current study, including proteinuria, low serum albumin, severe nausea, intrauterine growth restriction, oligohydramnios, headache, and right upper quadrant pain.

The study was done at six hospitals in Canada, the United Kingdom, and New Zealand during September 2003 to May 2006. It included 657 women who were diagnosed with preeclampsia, superimposed preeclampsia, or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). For this study, preeclampsia was defined as a blood pressure of at least 140/90 mm Hg and proteinuria or hyperuricemia.

The researchers identified the clinical markers that were statistically significant predictors of adverse maternal outcomes in this group. The adverse outcomes included death, hepatic dysfunction, acute renal failure, eclampsia, pulmonary edema, and need for any transfusion.

The multivariate analysis identified these factors as independent predictors of adverse outcomes: blood pressure at or above 160/110 mm Hg, platelets less than 100 × 10

All of these conditions are diagnostic criteria in both the NHBPEP and Canadian Hypertension Society guidelines, except chest pain or dyspnea and placental abruption, which don't appear in the NHBPEP definition of severe preeclampsia, the researchers said. However, the researchers did not suggest that the NHBPEP needed to expand its criteria to match the Canadian guidelines.

LISBON — The definition of severe preeclampsia that's been adopted by the U.S. National High Blood Pressure Education Program contains some criteria that did not lead to adverse maternal outcomes in an analysis of 657 patients.

Based on these findings, a narrower definition of severe preeclampsia is warranted, with a narrower list of criteria used to justify delivery for maternal indications, Dr. Peter von Dadelszen and his associates reported in a poster at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Three criteria that did not shake out as adverse-outcome predictors from the list of the National High Blood Pressure Education Program (NHBPEP) were proteinuria, persistent headache or other cerebral or visual disturbances, and persistent epigastric pain, reported the poster's authors, including Dr. Dadelszen, an ob.gyn. at the University of British Columbia, Vancouver. The NHBPEP Working Group on High Blood Pressure in Pregnancy published its revised recommendations in 2000.

The researchers found that the severe preeclampsia criteria of the Canadian Hypertension Society also included several diagnostic markers that weren't associated with adverse outcomes in the current study, including proteinuria, low serum albumin, severe nausea, intrauterine growth restriction, oligohydramnios, headache, and right upper quadrant pain.

The study was done at six hospitals in Canada, the United Kingdom, and New Zealand during September 2003 to May 2006. It included 657 women who were diagnosed with preeclampsia, superimposed preeclampsia, or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). For this study, preeclampsia was defined as a blood pressure of at least 140/90 mm Hg and proteinuria or hyperuricemia.

The researchers identified the clinical markers that were statistically significant predictors of adverse maternal outcomes in this group. The adverse outcomes included death, hepatic dysfunction, acute renal failure, eclampsia, pulmonary edema, and need for any transfusion.

The multivariate analysis identified these factors as independent predictors of adverse outcomes: blood pressure at or above 160/110 mm Hg, platelets less than 100 × 10

All of these conditions are diagnostic criteria in both the NHBPEP and Canadian Hypertension Society guidelines, except chest pain or dyspnea and placental abruption, which don't appear in the NHBPEP definition of severe preeclampsia, the researchers said. However, the researchers did not suggest that the NHBPEP needed to expand its criteria to match the Canadian guidelines.

LISBON — The high long-term death rates in women who have had one episode of severe preeclampsia suggest a strong link with cardiovascular disease in an analysis of more than 600,000 Norwegian women.

Integrating data from the Norwegian national registries for birth and for death showed that women who had one case of severe preeclampsia were nearly three times more likely to die in the long term and eight times more likely to die from cardiovascular disease, compared with women who had a term delivery and no preeclampsia, Dr. Rolv T. Lie reported at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The eightfold increased risk of cardiovascular disease death was “stunning,” said Dr. Lie, an epidemiologist at the University of Bergen (Norway). It suggests that both preeclampsia and cardiovascular disease occur because of a single underlying predisposition, or that serious preeclampsia results in long-term cardiovascular complications. “They're not independent. There has to be a common pathophysiology,” he said.

His initial analysis dealt with the 626,000 women who had their first delivery during 1967–1992. Subsequent mortality and cause of death were tracked through 1992.

During follow-up of up to 25 years, women who had a term delivery and no preeclampsia had a 0.8% mortality rate. Those who had preeclampsia and a preterm delivery (a marker for early and more severe preeclampsia) had a 2.3% mortality rate. When adjusted for the women's ages and the calendar year they gave birth, severe preeclampsia was linked with a statistically significant, 2.7-fold increased risk of death.

In addition to the much higher rate of cardiovascular death, women with severe preeclampsia also had a fivefold increased risk of death from stroke.

A more recent analysis used data collected through 2004, which allowed for up to 35 years of follow-up. It also allowed death rates to be analyzed for the first 10 years after delivery and for the subsequent 10 years, which gives some insight into the persistence of the mortality effect of severe preeclampsia.

The analysis showed that the women who had experienced serious preeclampsia had a lower mortality risk in the period 10–20 years after the episode, compared with during the initial 10 years following the pregnancy. This may mean that mortality risk from severe preeclampsia diminishes with time, or it may just mean that deaths due to other causes were diluting the effect, Dr. Lie said.

LISBON — The high long-term death rates in women who have had one episode of severe preeclampsia suggest a strong link with cardiovascular disease in an analysis of more than 600,000 Norwegian women.

Integrating data from the Norwegian national registries for birth and for death showed that women who had one case of severe preeclampsia were nearly three times more likely to die in the long term and eight times more likely to die from cardiovascular disease, compared with women who had a term delivery and no preeclampsia, Dr. Rolv T. Lie reported at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The eightfold increased risk of cardiovascular disease death was “stunning,” said Dr. Lie, an epidemiologist at the University of Bergen (Norway). It suggests that both preeclampsia and cardiovascular disease occur because of a single underlying predisposition, or that serious preeclampsia results in long-term cardiovascular complications. “They're not independent. There has to be a common pathophysiology,” he said.

His initial analysis dealt with the 626,000 women who had their first delivery during 1967–1992. Subsequent mortality and cause of death were tracked through 1992.

During follow-up of up to 25 years, women who had a term delivery and no preeclampsia had a 0.8% mortality rate. Those who had preeclampsia and a preterm delivery (a marker for early and more severe preeclampsia) had a 2.3% mortality rate. When adjusted for the women's ages and the calendar year they gave birth, severe preeclampsia was linked with a statistically significant, 2.7-fold increased risk of death.

In addition to the much higher rate of cardiovascular death, women with severe preeclampsia also had a fivefold increased risk of death from stroke.

A more recent analysis used data collected through 2004, which allowed for up to 35 years of follow-up. It also allowed death rates to be analyzed for the first 10 years after delivery and for the subsequent 10 years, which gives some insight into the persistence of the mortality effect of severe preeclampsia.

The analysis showed that the women who had experienced serious preeclampsia had a lower mortality risk in the period 10–20 years after the episode, compared with during the initial 10 years following the pregnancy. This may mean that mortality risk from severe preeclampsia diminishes with time, or it may just mean that deaths due to other causes were diluting the effect, Dr. Lie said.

LISBON — The high long-term death rates in women who have had one episode of severe preeclampsia suggest a strong link with cardiovascular disease in an analysis of more than 600,000 Norwegian women.

Integrating data from the Norwegian national registries for birth and for death showed that women who had one case of severe preeclampsia were nearly three times more likely to die in the long term and eight times more likely to die from cardiovascular disease, compared with women who had a term delivery and no preeclampsia, Dr. Rolv T. Lie reported at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The eightfold increased risk of cardiovascular disease death was “stunning,” said Dr. Lie, an epidemiologist at the University of Bergen (Norway). It suggests that both preeclampsia and cardiovascular disease occur because of a single underlying predisposition, or that serious preeclampsia results in long-term cardiovascular complications. “They're not independent. There has to be a common pathophysiology,” he said.

His initial analysis dealt with the 626,000 women who had their first delivery during 1967–1992. Subsequent mortality and cause of death were tracked through 1992.

During follow-up of up to 25 years, women who had a term delivery and no preeclampsia had a 0.8% mortality rate. Those who had preeclampsia and a preterm delivery (a marker for early and more severe preeclampsia) had a 2.3% mortality rate. When adjusted for the women's ages and the calendar year they gave birth, severe preeclampsia was linked with a statistically significant, 2.7-fold increased risk of death.

In addition to the much higher rate of cardiovascular death, women with severe preeclampsia also had a fivefold increased risk of death from stroke.

A more recent analysis used data collected through 2004, which allowed for up to 35 years of follow-up. It also allowed death rates to be analyzed for the first 10 years after delivery and for the subsequent 10 years, which gives some insight into the persistence of the mortality effect of severe preeclampsia.

The analysis showed that the women who had experienced serious preeclampsia had a lower mortality risk in the period 10–20 years after the episode, compared with during the initial 10 years following the pregnancy. This may mean that mortality risk from severe preeclampsia diminishes with time, or it may just mean that deaths due to other causes were diluting the effect, Dr. Lie said.

LISBON — Neutrophil infiltration and vascular inflammation were substantially more prevalent and severe in blood vessels from overweight and obese women than in vessels taken from normal-weight women in a study of 22 women.

“The data indicate that the vasculature of obese women is inflamed and susceptible to developing hypertension,” Scott W. Walsh, Ph.D., said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“We speculate that neutrophil infiltration and vascular inflammation puts obese women at risk for preeclampsia” through the release of reactive oxygen species and immunostimulants. This may explain why obesity is a risk factor for preeclampsia.

Until now, the pathophysiologic link between obesity and preeclampsia has been unclear, said Dr. Walsh, a professor of ob.gyn. at Virginia Commonwealth University in Richmond.

Dr. Walsh and his associates assessed neutrophil infiltration and vascular inflammation in the blood vessels of adipose tissue biopsies taken from volunteers. Participating women were divided into three groups based on their body mass index. Five normal-weight women had a BMI of less than 25 kg/m

Neutrophil infiltration was measured using a monoclonal-antibody stain against CD66b, a granulocyte membrane antigen (about 96% of granulocytes in blood vessels are neutrophils). Inflammation was measured with monoclonal-antibody stains against two markers of inflammation, nuclear factor (NF)-κB and cyclooxygenase (COX)-2. The extent of vessel staining with these reagents was gauged in fixed, adipose tissue specimens by two measures: a visual score scale of 0–3 and stained vessels as a percent of all vessels examined.

By both measurements, all three stains were significantly increased in both overweight and obese women, compared with the normal-weight controls. The greatest staining was in the vessels from obese women.

For example, for NF-κB staining, the visual score was about 0.3 in biopsies from normal-weight women, about 1.1 in overweight women, and about 2.6 in obese women. The percent of vessels stained was about 28%, 60%, and 90%, respectively. Similar results were obtained with the stains for neutrophils and for COX-2.

The patterns seen in adipose tissue are likely to be representative of the entire vasculature in each woman. In fact, inflammation may be even more extensive in certain other vascular beds in each woman, Dr. Walsh said.

The images show blood vessels in fixed, adipose-tissue biopsies that were stained for the cytokine NF-κB, a marker for vascular inflammation. The control specimen (left) is from a normal-weight woman and shows no NF-κB staining. The specimen on the right, from a woman with a BMI of at least 30 kg/m

LISBON — Neutrophil infiltration and vascular inflammation were substantially more prevalent and severe in blood vessels from overweight and obese women than in vessels taken from normal-weight women in a study of 22 women.

“The data indicate that the vasculature of obese women is inflamed and susceptible to developing hypertension,” Scott W. Walsh, Ph.D., said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“We speculate that neutrophil infiltration and vascular inflammation puts obese women at risk for preeclampsia” through the release of reactive oxygen species and immunostimulants. This may explain why obesity is a risk factor for preeclampsia.

Until now, the pathophysiologic link between obesity and preeclampsia has been unclear, said Dr. Walsh, a professor of ob.gyn. at Virginia Commonwealth University in Richmond.

Dr. Walsh and his associates assessed neutrophil infiltration and vascular inflammation in the blood vessels of adipose tissue biopsies taken from volunteers. Participating women were divided into three groups based on their body mass index. Five normal-weight women had a BMI of less than 25 kg/m

Neutrophil infiltration was measured using a monoclonal-antibody stain against CD66b, a granulocyte membrane antigen (about 96% of granulocytes in blood vessels are neutrophils). Inflammation was measured with monoclonal-antibody stains against two markers of inflammation, nuclear factor (NF)-κB and cyclooxygenase (COX)-2. The extent of vessel staining with these reagents was gauged in fixed, adipose tissue specimens by two measures: a visual score scale of 0–3 and stained vessels as a percent of all vessels examined.

By both measurements, all three stains were significantly increased in both overweight and obese women, compared with the normal-weight controls. The greatest staining was in the vessels from obese women.

For example, for NF-κB staining, the visual score was about 0.3 in biopsies from normal-weight women, about 1.1 in overweight women, and about 2.6 in obese women. The percent of vessels stained was about 28%, 60%, and 90%, respectively. Similar results were obtained with the stains for neutrophils and for COX-2.

The patterns seen in adipose tissue are likely to be representative of the entire vasculature in each woman. In fact, inflammation may be even more extensive in certain other vascular beds in each woman, Dr. Walsh said.

The images show blood vessels in fixed, adipose-tissue biopsies that were stained for the cytokine NF-κB, a marker for vascular inflammation. The control specimen (left) is from a normal-weight woman and shows no NF-κB staining. The specimen on the right, from a woman with a BMI of at least 30 kg/m

LISBON — Neutrophil infiltration and vascular inflammation were substantially more prevalent and severe in blood vessels from overweight and obese women than in vessels taken from normal-weight women in a study of 22 women.

“The data indicate that the vasculature of obese women is inflamed and susceptible to developing hypertension,” Scott W. Walsh, Ph.D., said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

“We speculate that neutrophil infiltration and vascular inflammation puts obese women at risk for preeclampsia” through the release of reactive oxygen species and immunostimulants. This may explain why obesity is a risk factor for preeclampsia.

Until now, the pathophysiologic link between obesity and preeclampsia has been unclear, said Dr. Walsh, a professor of ob.gyn. at Virginia Commonwealth University in Richmond.

Dr. Walsh and his associates assessed neutrophil infiltration and vascular inflammation in the blood vessels of adipose tissue biopsies taken from volunteers. Participating women were divided into three groups based on their body mass index. Five normal-weight women had a BMI of less than 25 kg/m

Neutrophil infiltration was measured using a monoclonal-antibody stain against CD66b, a granulocyte membrane antigen (about 96% of granulocytes in blood vessels are neutrophils). Inflammation was measured with monoclonal-antibody stains against two markers of inflammation, nuclear factor (NF)-κB and cyclooxygenase (COX)-2. The extent of vessel staining with these reagents was gauged in fixed, adipose tissue specimens by two measures: a visual score scale of 0–3 and stained vessels as a percent of all vessels examined.

By both measurements, all three stains were significantly increased in both overweight and obese women, compared with the normal-weight controls. The greatest staining was in the vessels from obese women.

For example, for NF-κB staining, the visual score was about 0.3 in biopsies from normal-weight women, about 1.1 in overweight women, and about 2.6 in obese women. The percent of vessels stained was about 28%, 60%, and 90%, respectively. Similar results were obtained with the stains for neutrophils and for COX-2.

The patterns seen in adipose tissue are likely to be representative of the entire vasculature in each woman. In fact, inflammation may be even more extensive in certain other vascular beds in each woman, Dr. Walsh said.

The images show blood vessels in fixed, adipose-tissue biopsies that were stained for the cytokine NF-κB, a marker for vascular inflammation. The control specimen (left) is from a normal-weight woman and shows no NF-κB staining. The specimen on the right, from a woman with a BMI of at least 30 kg/m

LISBON — Women who give birth prematurely have a markedly increased prevalence of placental Ureaplasma urealyticum infection, Dr. Leonard E. Weisman reported at the 12th International Congress on Infectious Diseases.

This novel observation raises the possibility that a significant fraction of preterm births might be preventable if a practical means of prospectively identifying women placentally colonized or infected with U. urealyticum can be developed. Their detection prior to labor would permit timely antimicrobial therapy aimed at clearing their placental infection—and deactivating their preterm birth trigger, Dr. Weisman explained in an interview.

This strategy would not provide a total answer to the enormous problem of preterm birth, which has a multitude of potential causes. But it would take a substantial bite out of the problem.

It has been estimated that reproductive tract infections play a role in up to 60% of all preterm births. Placental U. urealyticum probably figures in a substantial minority of those infections, said Dr. Weisman, professor of pediatrics at Baylor College of Medicine and director of the perinatal center at Texas Children's Hospital, Houston.

He presented a case-control study involving 58 women at three hospitals in the Texas Medical Center who gave birth at 30 weeks' gestation or earlier. The control group consisted of 194 randomly selected women who had a term birth. Twenty-seven women in the control group were classified as complicated controls, meaning they had a term delivery involving premature rupture of membranes, maternal fever, prolonged rupture of membranes lasting longer than 18 hours, and/or clinical endometritis or chorioamnionitis.

All study participants had their placental chorion cultured for U. urealyticum and group B streptococcus using sterile technique. The prevalence of U. urealyticum colonization/infection was significantly greater in women with preterm birth or a complicated term delivery than in those with an uncomplicated term birth (see box).

The medical literature describes numerous unsuccessful attempts to reduce the incidence of preterm birth via antibiotic therapy.

These past disappointments may have been due to reliance on easily assessable lower genital tract infection as the indication for treatment, when it's actually placental involvement that matters, Dr. Weisman said at the congress sponsored by the International Society for Infectious Diseases.

He and his Baylor coworkers recently launched a prospective trial to test their hypothesis that some identifiable aspect of vaginal colonization with U. urealyticum—one candidate is Ureaplasma biovar type—will correlate with placental colonization. If that indeed turns out to be the case, the next step will be a treatment study aimed at clearing placental infection in order to reduce the rate of preterm birth.

The best drug for use in this setting remains unclear. Erythromycin has often been used in trials aimed at eradicating vaginal infection; however, resistance of U. urealyticum to this antibiotic is a growing problem.

Tetracyclines show the best efficacy in vitro but are inappropriate for use in pregnancy. One of the quinolones may turn out to be the best choice, Dr. Weisman said.

LISBON — Women who give birth prematurely have a markedly increased prevalence of placental Ureaplasma urealyticum infection, Dr. Leonard E. Weisman reported at the 12th International Congress on Infectious Diseases.

This novel observation raises the possibility that a significant fraction of preterm births might be preventable if a practical means of prospectively identifying women placentally colonized or infected with U. urealyticum can be developed. Their detection prior to labor would permit timely antimicrobial therapy aimed at clearing their placental infection—and deactivating their preterm birth trigger, Dr. Weisman explained in an interview.

This strategy would not provide a total answer to the enormous problem of preterm birth, which has a multitude of potential causes. But it would take a substantial bite out of the problem.

It has been estimated that reproductive tract infections play a role in up to 60% of all preterm births. Placental U. urealyticum probably figures in a substantial minority of those infections, said Dr. Weisman, professor of pediatrics at Baylor College of Medicine and director of the perinatal center at Texas Children's Hospital, Houston.

He presented a case-control study involving 58 women at three hospitals in the Texas Medical Center who gave birth at 30 weeks' gestation or earlier. The control group consisted of 194 randomly selected women who had a term birth. Twenty-seven women in the control group were classified as complicated controls, meaning they had a term delivery involving premature rupture of membranes, maternal fever, prolonged rupture of membranes lasting longer than 18 hours, and/or clinical endometritis or chorioamnionitis.

All study participants had their placental chorion cultured for U. urealyticum and group B streptococcus using sterile technique. The prevalence of U. urealyticum colonization/infection was significantly greater in women with preterm birth or a complicated term delivery than in those with an uncomplicated term birth (see box).

The medical literature describes numerous unsuccessful attempts to reduce the incidence of preterm birth via antibiotic therapy.

These past disappointments may have been due to reliance on easily assessable lower genital tract infection as the indication for treatment, when it's actually placental involvement that matters, Dr. Weisman said at the congress sponsored by the International Society for Infectious Diseases.

He and his Baylor coworkers recently launched a prospective trial to test their hypothesis that some identifiable aspect of vaginal colonization with U. urealyticum—one candidate is Ureaplasma biovar type—will correlate with placental colonization. If that indeed turns out to be the case, the next step will be a treatment study aimed at clearing placental infection in order to reduce the rate of preterm birth.

The best drug for use in this setting remains unclear. Erythromycin has often been used in trials aimed at eradicating vaginal infection; however, resistance of U. urealyticum to this antibiotic is a growing problem.

Tetracyclines show the best efficacy in vitro but are inappropriate for use in pregnancy. One of the quinolones may turn out to be the best choice, Dr. Weisman said.

LISBON — Women who give birth prematurely have a markedly increased prevalence of placental Ureaplasma urealyticum infection, Dr. Leonard E. Weisman reported at the 12th International Congress on Infectious Diseases.

This novel observation raises the possibility that a significant fraction of preterm births might be preventable if a practical means of prospectively identifying women placentally colonized or infected with U. urealyticum can be developed. Their detection prior to labor would permit timely antimicrobial therapy aimed at clearing their placental infection—and deactivating their preterm birth trigger, Dr. Weisman explained in an interview.

This strategy would not provide a total answer to the enormous problem of preterm birth, which has a multitude of potential causes. But it would take a substantial bite out of the problem.

It has been estimated that reproductive tract infections play a role in up to 60% of all preterm births. Placental U. urealyticum probably figures in a substantial minority of those infections, said Dr. Weisman, professor of pediatrics at Baylor College of Medicine and director of the perinatal center at Texas Children's Hospital, Houston.

He presented a case-control study involving 58 women at three hospitals in the Texas Medical Center who gave birth at 30 weeks' gestation or earlier. The control group consisted of 194 randomly selected women who had a term birth. Twenty-seven women in the control group were classified as complicated controls, meaning they had a term delivery involving premature rupture of membranes, maternal fever, prolonged rupture of membranes lasting longer than 18 hours, and/or clinical endometritis or chorioamnionitis.

All study participants had their placental chorion cultured for U. urealyticum and group B streptococcus using sterile technique. The prevalence of U. urealyticum colonization/infection was significantly greater in women with preterm birth or a complicated term delivery than in those with an uncomplicated term birth (see box).

The medical literature describes numerous unsuccessful attempts to reduce the incidence of preterm birth via antibiotic therapy.

These past disappointments may have been due to reliance on easily assessable lower genital tract infection as the indication for treatment, when it's actually placental involvement that matters, Dr. Weisman said at the congress sponsored by the International Society for Infectious Diseases.

He and his Baylor coworkers recently launched a prospective trial to test their hypothesis that some identifiable aspect of vaginal colonization with U. urealyticum—one candidate is Ureaplasma biovar type—will correlate with placental colonization. If that indeed turns out to be the case, the next step will be a treatment study aimed at clearing placental infection in order to reduce the rate of preterm birth.

The best drug for use in this setting remains unclear. Erythromycin has often been used in trials aimed at eradicating vaginal infection; however, resistance of U. urealyticum to this antibiotic is a growing problem.

Tetracyclines show the best efficacy in vitro but are inappropriate for use in pregnancy. One of the quinolones may turn out to be the best choice, Dr. Weisman said.

LISBON — A metaanalysis of results from two major trials of prenatal supplementation with high dosages of vitamins C and E has raised concern about possible adverse effects, such as an increased risk of stillbirths and of gestational hypertension.

More stillbirths are “a worry, but it is an exploratory analysis. We'll need to look at the results from other studies” that are still in progress, Dr. Andrew H. Shennan said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Although results from the two recent trials—which together involved more than 4,000 women—showed that high dosages of vitamin C and E supplements had no benefit for preventing preeclampsia and may have caused harm, experts continued to endorse the underlying hypothesis that treatment with one or more antioxidant agents might prevent preeclampsia.

“There is a sound academic basis to think that oxidative stress plays a role in preeclampsia,” said Dr. Lucilla Poston, a professor in the maternal and fetal research unit at King's College London, and co-principle investigator for one of the trials.

“We don't want people to go away thinking that this is the end of oxidative stress in preeclampsia. Preeclampsia is a very rapid situation, with accelerated oxidative stress. We need to think about [intervening at] the etiology of oxidative stress and the enzymes that produce superoxides,” Dr. Poston said.

The Vitamins in Preeclampsia (VIP) trial enrolled about 2,400 pregnant women at week 14–21 gestational age who were at high risk for preeclampsia at 26 centers, 25 of them in the United Kingdom. The women were randomized to placebo or daily supplementation with 1 g vitamin C and 400 IU vitamin E daily through delivery. The high dosages of the two vitamins contrast with the content of a typical prenatal vitamin, which often contains 120 mg of vitamin C and 30 IU of vitamin E.

The primary end point was preeclampsia incidence. To qualify as high risk, women had to have at least one condition from a prespecified list that included a history of preeclampsia before 37 weeks in the preceding pregnancy, gestational hypertension, preconception diabetes, body mass index (kg/m

Preeclampsia occurred in 15% of women on the vitamin supplement and in 16% of those on placebo, a nonsignificant difference (Lancet 2006;367:1145–54).

The second trial reported in April was the Australian Collaborative Trial of Supplements (ACTS), which enrolled 1,877 pregnant women at 14–22 weeks gestational age who were at low risk for preeclampsia, at nine centers in Australia. The vitamin supplement dosages were the same as the dosages in the VIP trial; the primary outcomes were also similar. To focus on low-risk women, the study enrolled only nulliparous women with singleton pregnancies who were normotensive; the study also had other exclusion criteria. The average BMI of women in the study was 24.

The rate of preeclampsia was 6% in the supplement group and 5% in the control group, a difference that was not statistically significant (N. Engl. J. Med. 2006;354:1796–806).

Although results from both studies put to rest the idea of high-dosage prenatal vitamin C and E supplements, many pregnant women are currently taking these vitamins at high dosages, said Dr. Shennan, a professor of obstetrics at King's College London and the second principal investigator for the VIP trial. That fact is especially worrying given the suggestion of harm from these dosages in a metaanalysis that included the VIP and ACTS trials as well as two small, earlier studies. All four studies used the same supplement dosages, and they together involved more than 4,500 pregnant women.

Overall, women in the vitamin group had a roughly 50% higher rate of gestational hypertension, and a nearly twofold higher rate of both treatment with an antihypertensive agent and treatment with magnesium sulfate for preeclampsia, Dr. Shennan reported.

The rate of stillbirths was also twice as high in women who received vitamin supplements compared with those in the control group. All of the differences were statistically significant.

The VIP trial's high dosages contrasted with typical prenatal dosages, such as 120 mg of vitamin C or 30 IU of vitamin E. James E. Reinaker/Elsevier Global Medical News

LISBON — A metaanalysis of results from two major trials of prenatal supplementation with high dosages of vitamins C and E has raised concern about possible adverse effects, such as an increased risk of stillbirths and of gestational hypertension.

More stillbirths are “a worry, but it is an exploratory analysis. We'll need to look at the results from other studies” that are still in progress, Dr. Andrew H. Shennan said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Although results from the two recent trials—which together involved more than 4,000 women—showed that high dosages of vitamin C and E supplements had no benefit for preventing preeclampsia and may have caused harm, experts continued to endorse the underlying hypothesis that treatment with one or more antioxidant agents might prevent preeclampsia.

“There is a sound academic basis to think that oxidative stress plays a role in preeclampsia,” said Dr. Lucilla Poston, a professor in the maternal and fetal research unit at King's College London, and co-principle investigator for one of the trials.

“We don't want people to go away thinking that this is the end of oxidative stress in preeclampsia. Preeclampsia is a very rapid situation, with accelerated oxidative stress. We need to think about [intervening at] the etiology of oxidative stress and the enzymes that produce superoxides,” Dr. Poston said.

The Vitamins in Preeclampsia (VIP) trial enrolled about 2,400 pregnant women at week 14–21 gestational age who were at high risk for preeclampsia at 26 centers, 25 of them in the United Kingdom. The women were randomized to placebo or daily supplementation with 1 g vitamin C and 400 IU vitamin E daily through delivery. The high dosages of the two vitamins contrast with the content of a typical prenatal vitamin, which often contains 120 mg of vitamin C and 30 IU of vitamin E.

The primary end point was preeclampsia incidence. To qualify as high risk, women had to have at least one condition from a prespecified list that included a history of preeclampsia before 37 weeks in the preceding pregnancy, gestational hypertension, preconception diabetes, body mass index (kg/m

Preeclampsia occurred in 15% of women on the vitamin supplement and in 16% of those on placebo, a nonsignificant difference (Lancet 2006;367:1145–54).

The second trial reported in April was the Australian Collaborative Trial of Supplements (ACTS), which enrolled 1,877 pregnant women at 14–22 weeks gestational age who were at low risk for preeclampsia, at nine centers in Australia. The vitamin supplement dosages were the same as the dosages in the VIP trial; the primary outcomes were also similar. To focus on low-risk women, the study enrolled only nulliparous women with singleton pregnancies who were normotensive; the study also had other exclusion criteria. The average BMI of women in the study was 24.

The rate of preeclampsia was 6% in the supplement group and 5% in the control group, a difference that was not statistically significant (N. Engl. J. Med. 2006;354:1796–806).

Although results from both studies put to rest the idea of high-dosage prenatal vitamin C and E supplements, many pregnant women are currently taking these vitamins at high dosages, said Dr. Shennan, a professor of obstetrics at King's College London and the second principal investigator for the VIP trial. That fact is especially worrying given the suggestion of harm from these dosages in a metaanalysis that included the VIP and ACTS trials as well as two small, earlier studies. All four studies used the same supplement dosages, and they together involved more than 4,500 pregnant women.

Overall, women in the vitamin group had a roughly 50% higher rate of gestational hypertension, and a nearly twofold higher rate of both treatment with an antihypertensive agent and treatment with magnesium sulfate for preeclampsia, Dr. Shennan reported.

The rate of stillbirths was also twice as high in women who received vitamin supplements compared with those in the control group. All of the differences were statistically significant.

The VIP trial's high dosages contrasted with typical prenatal dosages, such as 120 mg of vitamin C or 30 IU of vitamin E. James E. Reinaker/Elsevier Global Medical News

LISBON — A metaanalysis of results from two major trials of prenatal supplementation with high dosages of vitamins C and E has raised concern about possible adverse effects, such as an increased risk of stillbirths and of gestational hypertension.

More stillbirths are “a worry, but it is an exploratory analysis. We'll need to look at the results from other studies” that are still in progress, Dr. Andrew H. Shennan said at the 15th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Although results from the two recent trials—which together involved more than 4,000 women—showed that high dosages of vitamin C and E supplements had no benefit for preventing preeclampsia and may have caused harm, experts continued to endorse the underlying hypothesis that treatment with one or more antioxidant agents might prevent preeclampsia.

“There is a sound academic basis to think that oxidative stress plays a role in preeclampsia,” said Dr. Lucilla Poston, a professor in the maternal and fetal research unit at King's College London, and co-principle investigator for one of the trials.

“We don't want people to go away thinking that this is the end of oxidative stress in preeclampsia. Preeclampsia is a very rapid situation, with accelerated oxidative stress. We need to think about [intervening at] the etiology of oxidative stress and the enzymes that produce superoxides,” Dr. Poston said.

The Vitamins in Preeclampsia (VIP) trial enrolled about 2,400 pregnant women at week 14–21 gestational age who were at high risk for preeclampsia at 26 centers, 25 of them in the United Kingdom. The women were randomized to placebo or daily supplementation with 1 g vitamin C and 400 IU vitamin E daily through delivery. The high dosages of the two vitamins contrast with the content of a typical prenatal vitamin, which often contains 120 mg of vitamin C and 30 IU of vitamin E.

The primary end point was preeclampsia incidence. To qualify as high risk, women had to have at least one condition from a prespecified list that included a history of preeclampsia before 37 weeks in the preceding pregnancy, gestational hypertension, preconception diabetes, body mass index (kg/m

Preeclampsia occurred in 15% of women on the vitamin supplement and in 16% of those on placebo, a nonsignificant difference (Lancet 2006;367:1145–54).

The second trial reported in April was the Australian Collaborative Trial of Supplements (ACTS), which enrolled 1,877 pregnant women at 14–22 weeks gestational age who were at low risk for preeclampsia, at nine centers in Australia. The vitamin supplement dosages were the same as the dosages in the VIP trial; the primary outcomes were also similar. To focus on low-risk women, the study enrolled only nulliparous women with singleton pregnancies who were normotensive; the study also had other exclusion criteria. The average BMI of women in the study was 24.

The rate of preeclampsia was 6% in the supplement group and 5% in the control group, a difference that was not statistically significant (N. Engl. J. Med. 2006;354:1796–806).

Although results from both studies put to rest the idea of high-dosage prenatal vitamin C and E supplements, many pregnant women are currently taking these vitamins at high dosages, said Dr. Shennan, a professor of obstetrics at King's College London and the second principal investigator for the VIP trial. That fact is especially worrying given the suggestion of harm from these dosages in a metaanalysis that included the VIP and ACTS trials as well as two small, earlier studies. All four studies used the same supplement dosages, and they together involved more than 4,500 pregnant women.

Overall, women in the vitamin group had a roughly 50% higher rate of gestational hypertension, and a nearly twofold higher rate of both treatment with an antihypertensive agent and treatment with magnesium sulfate for preeclampsia, Dr. Shennan reported.

The rate of stillbirths was also twice as high in women who received vitamin supplements compared with those in the control group. All of the differences were statistically significant.

The VIP trial's high dosages contrasted with typical prenatal dosages, such as 120 mg of vitamin C or 30 IU of vitamin E. James E. Reinaker/Elsevier Global Medical News

CHICAGO — Tight blood pressure control is crucial in caring for pregnant women with diabetic nephropathy, but medication management must factor in potential fetal risks, Dr. Phyllis August said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

In reviewing the management strategies for pregnant women with pre-existing diabetic nephropathy and lupus nephropathy, she noted that the most effective management begins even before conception. Yet even though preconception counseling can improve outcomes, physicians typically care for gravid women who already have significant disease.

“Overall, the outcome in pregnancy is related to the baseline blood pressure and level of renal function at the beginning of pregnancy,” said Dr. August, professor of medicine at the Weil Medical College of Cornell University, New York.

ACE inhibitors and angiotensin-receptor blockers (ARBs) are vital in the treatment of diabetic nephropathy in women who are trying to conceive, but these agents are potentially quite harmful to the developing fetus, she noted.

To derive the maximal benefit from these medications, Dr. August suggested switching to a safer agent (such as methyldopa or labetalol) as soon as a patient misses her menstrual period. “The overwhelming evidence for the adverse effects of ACE inhibitors and ARBs relates to second and third trimester exposure,” she said.

Dr. August also recommended performing a cardiac evaluation before conception in women with long-standing type 1 diabetes.

“Significant renal disease is associated with preeclampsia and renal complications,” she noted. Chronic kidney disease also increases the risk of intrauterine growth retardation and pre-term birth.

In the past, women with diabetic nephropathy tended to have a high rate of maternal complications, including overt nephropathy, hypertension, and death due to unrecognized coronary artery disease.

However, the outcomes for pregnant women with diabetic nephropathy have improved. A recent study detected no difference in the rate of decline in renal function between a group of women with diabetic nephropathy who became pregnant and another group that did not.

Lupus nephropathy can be quite challenging for both patients and physicians, Dr. August noted. “There is a poor outcome when the disease is active at conception,” she said. A high percentage of patients—as many as 50%–80%—will experience a disease flare during pregnancy if they have active disease at conception. On the other hand, only 10%–40% of women who are in remission at conception will have a flare.

Physicians may safely use azathioprine to treat pregnant women with lupus nephritis. Dr. August also advocated delivery during the third trimester in gravid women whose lupus nephritis is deteriorating quickly. The mother's condition often improves quickly after delivery.

Women with lupus and antiphospholipid antibody syndrome are also at higher risk of fetal loss, arterial and venous thrombosis, renal vasculitis, and preeclampsia. Women with this syndrome may benefit from taking low-molecular-weight heparin, with or without aspirin.

Although the outlook has improved for women with certain types of chronic kidney disease who wish to bear children, the chance of a good pregnancy outcome in women with end-stage renal disease on dialysis remains poor.

Women on dialysis who do get pregnant have a high incidence of adverse outcomes such as second trimester pregnancy loss, prematurity, and congenital abnormalities. For these women, attempting pregnancy “should never be encouraged,” Dr. August said.

CHICAGO — Tight blood pressure control is crucial in caring for pregnant women with diabetic nephropathy, but medication management must factor in potential fetal risks, Dr. Phyllis August said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

In reviewing the management strategies for pregnant women with pre-existing diabetic nephropathy and lupus nephropathy, she noted that the most effective management begins even before conception. Yet even though preconception counseling can improve outcomes, physicians typically care for gravid women who already have significant disease.

“Overall, the outcome in pregnancy is related to the baseline blood pressure and level of renal function at the beginning of pregnancy,” said Dr. August, professor of medicine at the Weil Medical College of Cornell University, New York.

ACE inhibitors and angiotensin-receptor blockers (ARBs) are vital in the treatment of diabetic nephropathy in women who are trying to conceive, but these agents are potentially quite harmful to the developing fetus, she noted.

To derive the maximal benefit from these medications, Dr. August suggested switching to a safer agent (such as methyldopa or labetalol) as soon as a patient misses her menstrual period. “The overwhelming evidence for the adverse effects of ACE inhibitors and ARBs relates to second and third trimester exposure,” she said.

Dr. August also recommended performing a cardiac evaluation before conception in women with long-standing type 1 diabetes.

“Significant renal disease is associated with preeclampsia and renal complications,” she noted. Chronic kidney disease also increases the risk of intrauterine growth retardation and pre-term birth.

In the past, women with diabetic nephropathy tended to have a high rate of maternal complications, including overt nephropathy, hypertension, and death due to unrecognized coronary artery disease.

However, the outcomes for pregnant women with diabetic nephropathy have improved. A recent study detected no difference in the rate of decline in renal function between a group of women with diabetic nephropathy who became pregnant and another group that did not.

Lupus nephropathy can be quite challenging for both patients and physicians, Dr. August noted. “There is a poor outcome when the disease is active at conception,” she said. A high percentage of patients—as many as 50%–80%—will experience a disease flare during pregnancy if they have active disease at conception. On the other hand, only 10%–40% of women who are in remission at conception will have a flare.

Physicians may safely use azathioprine to treat pregnant women with lupus nephritis. Dr. August also advocated delivery during the third trimester in gravid women whose lupus nephritis is deteriorating quickly. The mother's condition often improves quickly after delivery.

Women with lupus and antiphospholipid antibody syndrome are also at higher risk of fetal loss, arterial and venous thrombosis, renal vasculitis, and preeclampsia. Women with this syndrome may benefit from taking low-molecular-weight heparin, with or without aspirin.

Although the outlook has improved for women with certain types of chronic kidney disease who wish to bear children, the chance of a good pregnancy outcome in women with end-stage renal disease on dialysis remains poor.

Women on dialysis who do get pregnant have a high incidence of adverse outcomes such as second trimester pregnancy loss, prematurity, and congenital abnormalities. For these women, attempting pregnancy “should never be encouraged,” Dr. August said.

CHICAGO — Tight blood pressure control is crucial in caring for pregnant women with diabetic nephropathy, but medication management must factor in potential fetal risks, Dr. Phyllis August said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

In reviewing the management strategies for pregnant women with pre-existing diabetic nephropathy and lupus nephropathy, she noted that the most effective management begins even before conception. Yet even though preconception counseling can improve outcomes, physicians typically care for gravid women who already have significant disease.

“Overall, the outcome in pregnancy is related to the baseline blood pressure and level of renal function at the beginning of pregnancy,” said Dr. August, professor of medicine at the Weil Medical College of Cornell University, New York.

ACE inhibitors and angiotensin-receptor blockers (ARBs) are vital in the treatment of diabetic nephropathy in women who are trying to conceive, but these agents are potentially quite harmful to the developing fetus, she noted.

To derive the maximal benefit from these medications, Dr. August suggested switching to a safer agent (such as methyldopa or labetalol) as soon as a patient misses her menstrual period. “The overwhelming evidence for the adverse effects of ACE inhibitors and ARBs relates to second and third trimester exposure,” she said.

Dr. August also recommended performing a cardiac evaluation before conception in women with long-standing type 1 diabetes.

“Significant renal disease is associated with preeclampsia and renal complications,” she noted. Chronic kidney disease also increases the risk of intrauterine growth retardation and pre-term birth.

In the past, women with diabetic nephropathy tended to have a high rate of maternal complications, including overt nephropathy, hypertension, and death due to unrecognized coronary artery disease.

However, the outcomes for pregnant women with diabetic nephropathy have improved. A recent study detected no difference in the rate of decline in renal function between a group of women with diabetic nephropathy who became pregnant and another group that did not.

Lupus nephropathy can be quite challenging for both patients and physicians, Dr. August noted. “There is a poor outcome when the disease is active at conception,” she said. A high percentage of patients—as many as 50%–80%—will experience a disease flare during pregnancy if they have active disease at conception. On the other hand, only 10%–40% of women who are in remission at conception will have a flare.

Physicians may safely use azathioprine to treat pregnant women with lupus nephritis. Dr. August also advocated delivery during the third trimester in gravid women whose lupus nephritis is deteriorating quickly. The mother's condition often improves quickly after delivery.

Women with lupus and antiphospholipid antibody syndrome are also at higher risk of fetal loss, arterial and venous thrombosis, renal vasculitis, and preeclampsia. Women with this syndrome may benefit from taking low-molecular-weight heparin, with or without aspirin.

Although the outlook has improved for women with certain types of chronic kidney disease who wish to bear children, the chance of a good pregnancy outcome in women with end-stage renal disease on dialysis remains poor.

Women on dialysis who do get pregnant have a high incidence of adverse outcomes such as second trimester pregnancy loss, prematurity, and congenital abnormalities. For these women, attempting pregnancy “should never be encouraged,” Dr. August said.