Obstetrics

SAN ANTONIO — A depression prevention course offered during pregnancy significantly reduced the incidence of major depressive episodes before delivery in a group of Hispanic women at high risk for depression, reported Huynh-Nhu Le, Ph.D., at the annual meeting of the Society for Prevention Research. She expects the intervention will ultimately result in reduced rates of postpartum depression as well.

“A lot of research is now moving away from the idea of postpartum depression to a more general idea of pregnancy-related depression. Technically, postpartum depression occurs up to 4 weeks after birth—but in some cases, it may have started before delivery. What we're trying to do is prevent these women from becoming more depressed,” she said in an interview. “To do this, we need to integrate mental health screening into primary care settings.”

Her study included 143 Hispanic women, aged 18–35 years, who were less than 24 weeks pregnant. All were considered at high risk for depression based on their history of depression or a score of 16 or higher on the Center for Epidemiologic Studies Depression Scale (CES-D). The women were randomized either to usual care or to an eight-session intervention that taught them mood regulation skills and provided information about parenting and child development.

Preliminary results from the intervention, measured 8 weeks before delivery, showed a significant decrease in the incidence of major depressive episodes in treated vs. nontreated women (1% vs. 7%), said Dr. Le of George Washington University, Washington.

SAN ANTONIO — A depression prevention course offered during pregnancy significantly reduced the incidence of major depressive episodes before delivery in a group of Hispanic women at high risk for depression, reported Huynh-Nhu Le, Ph.D., at the annual meeting of the Society for Prevention Research. She expects the intervention will ultimately result in reduced rates of postpartum depression as well.

“A lot of research is now moving away from the idea of postpartum depression to a more general idea of pregnancy-related depression. Technically, postpartum depression occurs up to 4 weeks after birth—but in some cases, it may have started before delivery. What we're trying to do is prevent these women from becoming more depressed,” she said in an interview. “To do this, we need to integrate mental health screening into primary care settings.”

Her study included 143 Hispanic women, aged 18–35 years, who were less than 24 weeks pregnant. All were considered at high risk for depression based on their history of depression or a score of 16 or higher on the Center for Epidemiologic Studies Depression Scale (CES-D). The women were randomized either to usual care or to an eight-session intervention that taught them mood regulation skills and provided information about parenting and child development.

Preliminary results from the intervention, measured 8 weeks before delivery, showed a significant decrease in the incidence of major depressive episodes in treated vs. nontreated women (1% vs. 7%), said Dr. Le of George Washington University, Washington.

SAN ANTONIO — A depression prevention course offered during pregnancy significantly reduced the incidence of major depressive episodes before delivery in a group of Hispanic women at high risk for depression, reported Huynh-Nhu Le, Ph.D., at the annual meeting of the Society for Prevention Research. She expects the intervention will ultimately result in reduced rates of postpartum depression as well.

“A lot of research is now moving away from the idea of postpartum depression to a more general idea of pregnancy-related depression. Technically, postpartum depression occurs up to 4 weeks after birth—but in some cases, it may have started before delivery. What we're trying to do is prevent these women from becoming more depressed,” she said in an interview. “To do this, we need to integrate mental health screening into primary care settings.”

Her study included 143 Hispanic women, aged 18–35 years, who were less than 24 weeks pregnant. All were considered at high risk for depression based on their history of depression or a score of 16 or higher on the Center for Epidemiologic Studies Depression Scale (CES-D). The women were randomized either to usual care or to an eight-session intervention that taught them mood regulation skills and provided information about parenting and child development.

Preliminary results from the intervention, measured 8 weeks before delivery, showed a significant decrease in the incidence of major depressive episodes in treated vs. nontreated women (1% vs. 7%), said Dr. Le of George Washington University, Washington.

TORONTO — A single-session intervention can reduce prenatal alcohol use among at-risk pregnant women, especially those with higher reported alcohol consumption at baseline, Dr. Grace Chang reported at the annual meeting of the American Psychiatric Association.

Also, partner participation significantly enhances the intervention's positive effects.

The findings suggest that “screening and assessment with a validated instrument embedded into a patient information form can provide clinicians with important information about a woman's risk status and need for some type of intervention,” said Dr. Chang of Brigham and Women's Hospital in Boston. And providing at-risk women and their partners with alcohol education and behavior management tools early in pregnancy can significantly affect subsequent risk behaviors, she said.

To assess the impact of a brief psychoeducational intervention on women identified as being at risk for alcohol consumption during pregnancy, Dr. Chang and her colleagues randomized 304 pregnant women who met predefined alcohol risk criteria and their partners to receive a diagnostic interview and the single-session intervention or the diagnostic interview alone. Potential study participants were gleaned from Boston-area obstetrical practices based on their responses to a prenatal health and habits survey, which included questions about diet, smoking, exercise, stress, and drinking.

The predefined risk criteria for study enrollment included a total score of two or more on the four-item T-ACE alcohol screening instrument and any alcohol use in the 3 months before study enrollment (while pregnant), consumption of at least one drink per day in the 6 months before study enrollment, or drinking during a previous pregnancy. The T-ACE instrument asks four questions: How many drinks does it take to make you feel high (Tolerance)? Have people ever annoyed you by criticizing your drinking (Annoyed)? Have you ever felt you ought to cut down on your drinking (Cut down)? Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener)? The need for more than two drinks as a response to the tolerance question is worth two points, while positive answers to the remaining questions are each worth one point.

All of the study participants were at less than 28 weeks' gestation at the time of the diagnostic interview and intended to carry their pregnancy to term, and all were required to select a partner to participate in the study with them. Potential participants were excluded if they were under current treatment for alcohol or drug abuse or substance abuse-related medical illness, if they had current physical dependence on alcohol requiring medically supervised detoxification, if they were unable to complete the study questionnaires, or if they intended to terminate their pregnancy before gestation.

Study participants were, on average, at 11.5 weeks' gestation at the time of the study, and nearly half expected their first child. About 79% of the subjects were white, and 80% were married. Their median age was 31.4 years, and the median education level was a 4-year college degree.

At baseline, all of the pregnant participants underwent a diagnostic interview to measure daily drinking before the study, temptation to drink in certain social situations, and awareness of prenatal health behaviors. The partners underwent a separate interview to gauge their own drinking habits, their perception of their pregnant partners' drinking, and their knowledge of prenatal health behaviors.

Those partner pairs randomized to the intervention met with one of two trained nurse-practitioners or Dr. Chang for a single 25-minute session with four components: knowledge assessment with feedback, contracting and goal setting, behavior modification, and summary. The knowledge assessment and feedback component included a discussion of both partners' thoughts and misperceptions about prenatal health behaviors relative to alcohol use.

“We did not discuss the women's actual alcohol consumption in the presence of her partner unless they disclosed it voluntarily, for reasons of privacy and safety,” Dr. Chang said. “But the knowledge assessment was the springboard for the discussion of alcohol use during pregnancy.”

In the goal-setting and contracting component, the discussion focused on prenatal drinking goals. “It was not uncommon to hear women say their goal was to have 'just one drink' per week—and the women in the study were generally older and well educated. This would lead to a discussion of the surgeon general's advisory that no amount of alcohol is safe during pregnancy,” Dr. Chang said.

In the behavior-modification segment, the pregnant subjects were encouraged to think about circumstances, such as social events, that might invite the temptation to drink during pregnancy and to develop a list of alternative behaviors, such as having something to eat or a fake drink, Dr. Chang said. “We also asked the partner to list plans for personal behavior changes that could support the pregnant woman, such as drinking less or socializing differently.” Finally, the intervention was summarized on paper and provided to the partners.

Both the intervention and control subjects had a postpartum follow-up interview to review the frequency and quantity of alcohol consumed during pregnancy as well as changes in alcohol-related health habits since enrollment. “We had a 95% follow-up rate overall, and only 3% of partners were ultimately unable to participate in one part of the study or another,” Dr. Chang noted.

The investigators used univariate and multivariate analyses to compare the intervention and control groups before and after study enrollment, and least squares regression models were used to evaluate the effect of the intervention on three dependent variables: alcohol consumption quantity, frequency, and both.

When the two groups were compared, “there were no statistically significant differences in the amount or frequency of prepregnancy alcohol consumption, and most of the women in both conditions demonstrated overall reduced alcohol consumption once enrolled,” Dr. Chang said. “Many of the women spontaneously decreased the frequency of their alcohol consumption to a mean of 5% drinking days, although fewer than 20% were abstinent.”

The results of an intention-to-treat analysis showed a significant interaction between the intervention and prenatal alcohol consumption, Dr. Chang reported. “The brief intervention was most effective in reducing the frequency of consumption among women who drank more at the time of the study enrollment,” she said. Additionally, “the intervention was more effective for heavier drinking subjects when the partner was involved.”

The analyses identified additional variables that increased the risk of prenatal alcohol consumption: prenatal alcohol use before the study, level of education, temptation to drink in social situations, and number of years of regular alcohol use.

TORONTO — A single-session intervention can reduce prenatal alcohol use among at-risk pregnant women, especially those with higher reported alcohol consumption at baseline, Dr. Grace Chang reported at the annual meeting of the American Psychiatric Association.

Also, partner participation significantly enhances the intervention's positive effects.

The findings suggest that “screening and assessment with a validated instrument embedded into a patient information form can provide clinicians with important information about a woman's risk status and need for some type of intervention,” said Dr. Chang of Brigham and Women's Hospital in Boston. And providing at-risk women and their partners with alcohol education and behavior management tools early in pregnancy can significantly affect subsequent risk behaviors, she said.

To assess the impact of a brief psychoeducational intervention on women identified as being at risk for alcohol consumption during pregnancy, Dr. Chang and her colleagues randomized 304 pregnant women who met predefined alcohol risk criteria and their partners to receive a diagnostic interview and the single-session intervention or the diagnostic interview alone. Potential study participants were gleaned from Boston-area obstetrical practices based on their responses to a prenatal health and habits survey, which included questions about diet, smoking, exercise, stress, and drinking.

The predefined risk criteria for study enrollment included a total score of two or more on the four-item T-ACE alcohol screening instrument and any alcohol use in the 3 months before study enrollment (while pregnant), consumption of at least one drink per day in the 6 months before study enrollment, or drinking during a previous pregnancy. The T-ACE instrument asks four questions: How many drinks does it take to make you feel high (Tolerance)? Have people ever annoyed you by criticizing your drinking (Annoyed)? Have you ever felt you ought to cut down on your drinking (Cut down)? Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener)? The need for more than two drinks as a response to the tolerance question is worth two points, while positive answers to the remaining questions are each worth one point.

All of the study participants were at less than 28 weeks' gestation at the time of the diagnostic interview and intended to carry their pregnancy to term, and all were required to select a partner to participate in the study with them. Potential participants were excluded if they were under current treatment for alcohol or drug abuse or substance abuse-related medical illness, if they had current physical dependence on alcohol requiring medically supervised detoxification, if they were unable to complete the study questionnaires, or if they intended to terminate their pregnancy before gestation.

Study participants were, on average, at 11.5 weeks' gestation at the time of the study, and nearly half expected their first child. About 79% of the subjects were white, and 80% were married. Their median age was 31.4 years, and the median education level was a 4-year college degree.

At baseline, all of the pregnant participants underwent a diagnostic interview to measure daily drinking before the study, temptation to drink in certain social situations, and awareness of prenatal health behaviors. The partners underwent a separate interview to gauge their own drinking habits, their perception of their pregnant partners' drinking, and their knowledge of prenatal health behaviors.

Those partner pairs randomized to the intervention met with one of two trained nurse-practitioners or Dr. Chang for a single 25-minute session with four components: knowledge assessment with feedback, contracting and goal setting, behavior modification, and summary. The knowledge assessment and feedback component included a discussion of both partners' thoughts and misperceptions about prenatal health behaviors relative to alcohol use.

“We did not discuss the women's actual alcohol consumption in the presence of her partner unless they disclosed it voluntarily, for reasons of privacy and safety,” Dr. Chang said. “But the knowledge assessment was the springboard for the discussion of alcohol use during pregnancy.”

In the goal-setting and contracting component, the discussion focused on prenatal drinking goals. “It was not uncommon to hear women say their goal was to have 'just one drink' per week—and the women in the study were generally older and well educated. This would lead to a discussion of the surgeon general's advisory that no amount of alcohol is safe during pregnancy,” Dr. Chang said.

In the behavior-modification segment, the pregnant subjects were encouraged to think about circumstances, such as social events, that might invite the temptation to drink during pregnancy and to develop a list of alternative behaviors, such as having something to eat or a fake drink, Dr. Chang said. “We also asked the partner to list plans for personal behavior changes that could support the pregnant woman, such as drinking less or socializing differently.” Finally, the intervention was summarized on paper and provided to the partners.

Both the intervention and control subjects had a postpartum follow-up interview to review the frequency and quantity of alcohol consumed during pregnancy as well as changes in alcohol-related health habits since enrollment. “We had a 95% follow-up rate overall, and only 3% of partners were ultimately unable to participate in one part of the study or another,” Dr. Chang noted.

The investigators used univariate and multivariate analyses to compare the intervention and control groups before and after study enrollment, and least squares regression models were used to evaluate the effect of the intervention on three dependent variables: alcohol consumption quantity, frequency, and both.

When the two groups were compared, “there were no statistically significant differences in the amount or frequency of prepregnancy alcohol consumption, and most of the women in both conditions demonstrated overall reduced alcohol consumption once enrolled,” Dr. Chang said. “Many of the women spontaneously decreased the frequency of their alcohol consumption to a mean of 5% drinking days, although fewer than 20% were abstinent.”

The results of an intention-to-treat analysis showed a significant interaction between the intervention and prenatal alcohol consumption, Dr. Chang reported. “The brief intervention was most effective in reducing the frequency of consumption among women who drank more at the time of the study enrollment,” she said. Additionally, “the intervention was more effective for heavier drinking subjects when the partner was involved.”

The analyses identified additional variables that increased the risk of prenatal alcohol consumption: prenatal alcohol use before the study, level of education, temptation to drink in social situations, and number of years of regular alcohol use.

TORONTO — A single-session intervention can reduce prenatal alcohol use among at-risk pregnant women, especially those with higher reported alcohol consumption at baseline, Dr. Grace Chang reported at the annual meeting of the American Psychiatric Association.

Also, partner participation significantly enhances the intervention's positive effects.

The findings suggest that “screening and assessment with a validated instrument embedded into a patient information form can provide clinicians with important information about a woman's risk status and need for some type of intervention,” said Dr. Chang of Brigham and Women's Hospital in Boston. And providing at-risk women and their partners with alcohol education and behavior management tools early in pregnancy can significantly affect subsequent risk behaviors, she said.

To assess the impact of a brief psychoeducational intervention on women identified as being at risk for alcohol consumption during pregnancy, Dr. Chang and her colleagues randomized 304 pregnant women who met predefined alcohol risk criteria and their partners to receive a diagnostic interview and the single-session intervention or the diagnostic interview alone. Potential study participants were gleaned from Boston-area obstetrical practices based on their responses to a prenatal health and habits survey, which included questions about diet, smoking, exercise, stress, and drinking.

The predefined risk criteria for study enrollment included a total score of two or more on the four-item T-ACE alcohol screening instrument and any alcohol use in the 3 months before study enrollment (while pregnant), consumption of at least one drink per day in the 6 months before study enrollment, or drinking during a previous pregnancy. The T-ACE instrument asks four questions: How many drinks does it take to make you feel high (Tolerance)? Have people ever annoyed you by criticizing your drinking (Annoyed)? Have you ever felt you ought to cut down on your drinking (Cut down)? Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener)? The need for more than two drinks as a response to the tolerance question is worth two points, while positive answers to the remaining questions are each worth one point.

All of the study participants were at less than 28 weeks' gestation at the time of the diagnostic interview and intended to carry their pregnancy to term, and all were required to select a partner to participate in the study with them. Potential participants were excluded if they were under current treatment for alcohol or drug abuse or substance abuse-related medical illness, if they had current physical dependence on alcohol requiring medically supervised detoxification, if they were unable to complete the study questionnaires, or if they intended to terminate their pregnancy before gestation.

Study participants were, on average, at 11.5 weeks' gestation at the time of the study, and nearly half expected their first child. About 79% of the subjects were white, and 80% were married. Their median age was 31.4 years, and the median education level was a 4-year college degree.

At baseline, all of the pregnant participants underwent a diagnostic interview to measure daily drinking before the study, temptation to drink in certain social situations, and awareness of prenatal health behaviors. The partners underwent a separate interview to gauge their own drinking habits, their perception of their pregnant partners' drinking, and their knowledge of prenatal health behaviors.

Those partner pairs randomized to the intervention met with one of two trained nurse-practitioners or Dr. Chang for a single 25-minute session with four components: knowledge assessment with feedback, contracting and goal setting, behavior modification, and summary. The knowledge assessment and feedback component included a discussion of both partners' thoughts and misperceptions about prenatal health behaviors relative to alcohol use.

“We did not discuss the women's actual alcohol consumption in the presence of her partner unless they disclosed it voluntarily, for reasons of privacy and safety,” Dr. Chang said. “But the knowledge assessment was the springboard for the discussion of alcohol use during pregnancy.”

In the goal-setting and contracting component, the discussion focused on prenatal drinking goals. “It was not uncommon to hear women say their goal was to have 'just one drink' per week—and the women in the study were generally older and well educated. This would lead to a discussion of the surgeon general's advisory that no amount of alcohol is safe during pregnancy,” Dr. Chang said.

In the behavior-modification segment, the pregnant subjects were encouraged to think about circumstances, such as social events, that might invite the temptation to drink during pregnancy and to develop a list of alternative behaviors, such as having something to eat or a fake drink, Dr. Chang said. “We also asked the partner to list plans for personal behavior changes that could support the pregnant woman, such as drinking less or socializing differently.” Finally, the intervention was summarized on paper and provided to the partners.

Both the intervention and control subjects had a postpartum follow-up interview to review the frequency and quantity of alcohol consumed during pregnancy as well as changes in alcohol-related health habits since enrollment. “We had a 95% follow-up rate overall, and only 3% of partners were ultimately unable to participate in one part of the study or another,” Dr. Chang noted.

The investigators used univariate and multivariate analyses to compare the intervention and control groups before and after study enrollment, and least squares regression models were used to evaluate the effect of the intervention on three dependent variables: alcohol consumption quantity, frequency, and both.

When the two groups were compared, “there were no statistically significant differences in the amount or frequency of prepregnancy alcohol consumption, and most of the women in both conditions demonstrated overall reduced alcohol consumption once enrolled,” Dr. Chang said. “Many of the women spontaneously decreased the frequency of their alcohol consumption to a mean of 5% drinking days, although fewer than 20% were abstinent.”

The results of an intention-to-treat analysis showed a significant interaction between the intervention and prenatal alcohol consumption, Dr. Chang reported. “The brief intervention was most effective in reducing the frequency of consumption among women who drank more at the time of the study enrollment,” she said. Additionally, “the intervention was more effective for heavier drinking subjects when the partner was involved.”

The analyses identified additional variables that increased the risk of prenatal alcohol consumption: prenatal alcohol use before the study, level of education, temptation to drink in social situations, and number of years of regular alcohol use.

After several years of little indication that lamotrigine was linked to specific birth defects, a major pregnancy registry has found a significant increase in the risk of oral clefts associated with first-trimester use of lamotrigine monotherapy.

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry detected “an elevated prevalence” of isolated, nonsyndromic oral clefts in infants exposed to lamotrigine monotherapy during the first trimester, when compared with a reference population, according to a “Dear Health Care Professional” letter issued by the drug's manufacturer, GlaxoSmithKline (GSK), last month.

The letter reports that there were five cases of oral clefts (three cleft palates and two cleft lips) among 564 pregnancies exposed to lamotrigine monotherapy in the first trimester, for a rate of 8.9/1,000. Based on these numbers, the prevalence of oral cleft is 24 times higher among lamotrigine-exposed neonates than the prevalence of 0.37/1,000 in the general population at the Brigham and Women's Hospital surveillance program, the letter says.

The letter notes that the prevalence of oral clefts in the Massachusetts General Hospital-run NAAED registry is also greater than the background prevalence of nonsyndromic oral clefts ranging from 0.50 to 2.16 per 1,000 reported in the literature, including studies from the United States, Australia, and Europe.

Lamotrigine, marketed as Lamictal by GSK, is approved as a treatment for seizures and for maintenance therapy in bipolar I disorder. It is classified as a pregnancy category C drug, and its label reads that while no evidence of teratogenicity has been found in animals, the drug has been found to reduce folate concentrations in rats, an effect “known to be associated with teratogenesis in animals and humans.”

Because there are no adequate and well-controlled studies in pregnant women, lamotrigine “should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus,” according to the label.

The five cases described in the GSK letter were reported by Dr. Lewis B. Holmes, chief of the genetics and teratology unit at Massachusetts General Hospital for Children, Boston, and director of the North American AED pregnancy registry, at the Teratology Society meeting in June.

“This was the first study big enough to be able to look at the frequency of specific major malformations,” Dr. Holmes said in an interview. He pointed out that earlier studies from the company registry and the United Kingdom registry with smaller sample sizes looked at all malformations and showed a modest increase in the rate of major malformations but did not have enough patients to pick up increases in specific malformations.

At the meeting, he reported that a greater risk of oral clefts was also detected in five other registries, suggesting the same association. In those registries, there were four oral clefts reported among 1,623 lamotrigine-exposed infants, for a frequency of 2.5/1,000 compared with 0.37/1,000 in the comparison group. “So this is something that women have to be told about,” Dr. Holmes said.

This information has to be put into a practical perspective, and physicians should discuss the absolute risk with patients, Dr. Holmes said. Based on the data he presented, the absolute risk of having an infant with an oral cleft is close to 1%—and is much less than 1% based on the other data—so “it's still a very small risk and it is a very treatable problem,” he pointed out.

Gerald G. Briggs, B.Pharm., a pharmacist clinical specialist at the Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., who was at the Teratology Society meeting, said that this information “is significant because this is the first report of teratogenicity in a second-generation anticonvulsant.” All of the first-generation anticonvulsants are known to have teratogenic effects.

Furthermore, none of the women whose infants had oral clefts was a smoker, which has been associated with isolated oral clefts in some studies, and all were taking folic acid supplements at conception, so folic acid did not appear to be protective, he pointed out.

GSK's letter says the company is discussing the new data with the Food and Drug Administration and regulatory officials in other countries. GSK is encouraging physicians to register pregnant women exposed to lamotrigine before the fetal outcome is known.

GSK's Lamotrigine Pregnancy Registry can be contacted for more information at 800-336-2176. Women can enroll themselves in the NAAED registry by calling 888-233-2334.

After several years of little indication that lamotrigine was linked to specific birth defects, a major pregnancy registry has found a significant increase in the risk of oral clefts associated with first-trimester use of lamotrigine monotherapy.

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry detected “an elevated prevalence” of isolated, nonsyndromic oral clefts in infants exposed to lamotrigine monotherapy during the first trimester, when compared with a reference population, according to a “Dear Health Care Professional” letter issued by the drug's manufacturer, GlaxoSmithKline (GSK), last month.

The letter reports that there were five cases of oral clefts (three cleft palates and two cleft lips) among 564 pregnancies exposed to lamotrigine monotherapy in the first trimester, for a rate of 8.9/1,000. Based on these numbers, the prevalence of oral cleft is 24 times higher among lamotrigine-exposed neonates than the prevalence of 0.37/1,000 in the general population at the Brigham and Women's Hospital surveillance program, the letter says.

The letter notes that the prevalence of oral clefts in the Massachusetts General Hospital-run NAAED registry is also greater than the background prevalence of nonsyndromic oral clefts ranging from 0.50 to 2.16 per 1,000 reported in the literature, including studies from the United States, Australia, and Europe.

Lamotrigine, marketed as Lamictal by GSK, is approved as a treatment for seizures and for maintenance therapy in bipolar I disorder. It is classified as a pregnancy category C drug, and its label reads that while no evidence of teratogenicity has been found in animals, the drug has been found to reduce folate concentrations in rats, an effect “known to be associated with teratogenesis in animals and humans.”

Because there are no adequate and well-controlled studies in pregnant women, lamotrigine “should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus,” according to the label.

The five cases described in the GSK letter were reported by Dr. Lewis B. Holmes, chief of the genetics and teratology unit at Massachusetts General Hospital for Children, Boston, and director of the North American AED pregnancy registry, at the Teratology Society meeting in June.

“This was the first study big enough to be able to look at the frequency of specific major malformations,” Dr. Holmes said in an interview. He pointed out that earlier studies from the company registry and the United Kingdom registry with smaller sample sizes looked at all malformations and showed a modest increase in the rate of major malformations but did not have enough patients to pick up increases in specific malformations.

At the meeting, he reported that a greater risk of oral clefts was also detected in five other registries, suggesting the same association. In those registries, there were four oral clefts reported among 1,623 lamotrigine-exposed infants, for a frequency of 2.5/1,000 compared with 0.37/1,000 in the comparison group. “So this is something that women have to be told about,” Dr. Holmes said.

This information has to be put into a practical perspective, and physicians should discuss the absolute risk with patients, Dr. Holmes said. Based on the data he presented, the absolute risk of having an infant with an oral cleft is close to 1%—and is much less than 1% based on the other data—so “it's still a very small risk and it is a very treatable problem,” he pointed out.

Gerald G. Briggs, B.Pharm., a pharmacist clinical specialist at the Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., who was at the Teratology Society meeting, said that this information “is significant because this is the first report of teratogenicity in a second-generation anticonvulsant.” All of the first-generation anticonvulsants are known to have teratogenic effects.

Furthermore, none of the women whose infants had oral clefts was a smoker, which has been associated with isolated oral clefts in some studies, and all were taking folic acid supplements at conception, so folic acid did not appear to be protective, he pointed out.

GSK's letter says the company is discussing the new data with the Food and Drug Administration and regulatory officials in other countries. GSK is encouraging physicians to register pregnant women exposed to lamotrigine before the fetal outcome is known.

GSK's Lamotrigine Pregnancy Registry can be contacted for more information at 800-336-2176. Women can enroll themselves in the NAAED registry by calling 888-233-2334.

After several years of little indication that lamotrigine was linked to specific birth defects, a major pregnancy registry has found a significant increase in the risk of oral clefts associated with first-trimester use of lamotrigine monotherapy.

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry detected “an elevated prevalence” of isolated, nonsyndromic oral clefts in infants exposed to lamotrigine monotherapy during the first trimester, when compared with a reference population, according to a “Dear Health Care Professional” letter issued by the drug's manufacturer, GlaxoSmithKline (GSK), last month.

The letter reports that there were five cases of oral clefts (three cleft palates and two cleft lips) among 564 pregnancies exposed to lamotrigine monotherapy in the first trimester, for a rate of 8.9/1,000. Based on these numbers, the prevalence of oral cleft is 24 times higher among lamotrigine-exposed neonates than the prevalence of 0.37/1,000 in the general population at the Brigham and Women's Hospital surveillance program, the letter says.

The letter notes that the prevalence of oral clefts in the Massachusetts General Hospital-run NAAED registry is also greater than the background prevalence of nonsyndromic oral clefts ranging from 0.50 to 2.16 per 1,000 reported in the literature, including studies from the United States, Australia, and Europe.

Lamotrigine, marketed as Lamictal by GSK, is approved as a treatment for seizures and for maintenance therapy in bipolar I disorder. It is classified as a pregnancy category C drug, and its label reads that while no evidence of teratogenicity has been found in animals, the drug has been found to reduce folate concentrations in rats, an effect “known to be associated with teratogenesis in animals and humans.”

Because there are no adequate and well-controlled studies in pregnant women, lamotrigine “should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus,” according to the label.

The five cases described in the GSK letter were reported by Dr. Lewis B. Holmes, chief of the genetics and teratology unit at Massachusetts General Hospital for Children, Boston, and director of the North American AED pregnancy registry, at the Teratology Society meeting in June.

“This was the first study big enough to be able to look at the frequency of specific major malformations,” Dr. Holmes said in an interview. He pointed out that earlier studies from the company registry and the United Kingdom registry with smaller sample sizes looked at all malformations and showed a modest increase in the rate of major malformations but did not have enough patients to pick up increases in specific malformations.

At the meeting, he reported that a greater risk of oral clefts was also detected in five other registries, suggesting the same association. In those registries, there were four oral clefts reported among 1,623 lamotrigine-exposed infants, for a frequency of 2.5/1,000 compared with 0.37/1,000 in the comparison group. “So this is something that women have to be told about,” Dr. Holmes said.

This information has to be put into a practical perspective, and physicians should discuss the absolute risk with patients, Dr. Holmes said. Based on the data he presented, the absolute risk of having an infant with an oral cleft is close to 1%—and is much less than 1% based on the other data—so “it's still a very small risk and it is a very treatable problem,” he pointed out.

Gerald G. Briggs, B.Pharm., a pharmacist clinical specialist at the Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., who was at the Teratology Society meeting, said that this information “is significant because this is the first report of teratogenicity in a second-generation anticonvulsant.” All of the first-generation anticonvulsants are known to have teratogenic effects.

Furthermore, none of the women whose infants had oral clefts was a smoker, which has been associated with isolated oral clefts in some studies, and all were taking folic acid supplements at conception, so folic acid did not appear to be protective, he pointed out.

GSK's letter says the company is discussing the new data with the Food and Drug Administration and regulatory officials in other countries. GSK is encouraging physicians to register pregnant women exposed to lamotrigine before the fetal outcome is known.

GSK's Lamotrigine Pregnancy Registry can be contacted for more information at 800-336-2176. Women can enroll themselves in the NAAED registry by calling 888-233-2334.

HOLLYWOOD, FLA. — The addition of spinal analgesia to a routine walking epidural patient-controlled analgesia regimen shortened the time to pain relief in a randomized study.

In the study of 136 patients who were randomized to receive a combined spinal-epidural (CSE) regimen or a routine epidural regimen, the CSE group achieved full analgesia satisfaction in a mean of 8 minutes, compared with 16 minutes in the epidural group.

Moreover, the addition of spinal analgesia did not affect the quality of the block, side effects, or patient satisfaction with analgesia, Dr. Shaul Cohen reported in a poster at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Patients in the CSE group received initiation by 2mg of intrathecal ropivacaine and 5 mcg sufentanil via a PENCAN 25G spinal needle followed by epidural patient-controlled analgesia (PCA). The epidural group received 20 mL of 0.04% ropivacaine plus 1 mcg/mL sufentanil plus 2 mcg/mL epinephrine epidural study solution followed by epidural PCA analgesia.

All patients received an infusion of the study solution at 4 mL/hr, and a PCA dose of 4 mL with a lockout time of 10 minutes, noted Dr. Cohen of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, N.J.

After the initial neuraxial dose administration, patients were asked to rate their pain satisfaction at each contraction. In those with a visual analog score of greater than three at 20 minutes, a 5- to 10-mL bolus of study solution was given every 10 minutes (up to 20 mL) as needed to achieve a score of three or less.

A rescue dose of 5 mL of 0.25% ropivacaine was provided every 10 minutes (up to 20 mL and until patients could no longer ambulate) to those whose score remained above three after the maximum amount of study solution had been provided; the infusion rate was increased by 2 mL/hr at each interval where an intervention was required (to a maximum of 16 mL/hr).

The CSE and epidural groups were similar with regard to weight, height, and parity. Initial pain scores were significantly higher in the CSE group (7.8 vs. 6.9), and mean PCA volume was higher in that group (22 mL vs. 13 mL), but the groups did not differ in regard to first- and second-stage duration, initial cervical dilation, total infusion time, pain scores at time of relief, intravenous Pitocin use, pruritus, sedation, nausea, vomiting, urinary retention, analgesia satisfaction overall and during the first and second stages of labor, number of patients able to ambulate, or APGAR scores, Dr. Balki noted.

HOLLYWOOD, FLA. — The addition of spinal analgesia to a routine walking epidural patient-controlled analgesia regimen shortened the time to pain relief in a randomized study.

In the study of 136 patients who were randomized to receive a combined spinal-epidural (CSE) regimen or a routine epidural regimen, the CSE group achieved full analgesia satisfaction in a mean of 8 minutes, compared with 16 minutes in the epidural group.

Moreover, the addition of spinal analgesia did not affect the quality of the block, side effects, or patient satisfaction with analgesia, Dr. Shaul Cohen reported in a poster at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Patients in the CSE group received initiation by 2mg of intrathecal ropivacaine and 5 mcg sufentanil via a PENCAN 25G spinal needle followed by epidural patient-controlled analgesia (PCA). The epidural group received 20 mL of 0.04% ropivacaine plus 1 mcg/mL sufentanil plus 2 mcg/mL epinephrine epidural study solution followed by epidural PCA analgesia.

All patients received an infusion of the study solution at 4 mL/hr, and a PCA dose of 4 mL with a lockout time of 10 minutes, noted Dr. Cohen of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, N.J.

After the initial neuraxial dose administration, patients were asked to rate their pain satisfaction at each contraction. In those with a visual analog score of greater than three at 20 minutes, a 5- to 10-mL bolus of study solution was given every 10 minutes (up to 20 mL) as needed to achieve a score of three or less.

A rescue dose of 5 mL of 0.25% ropivacaine was provided every 10 minutes (up to 20 mL and until patients could no longer ambulate) to those whose score remained above three after the maximum amount of study solution had been provided; the infusion rate was increased by 2 mL/hr at each interval where an intervention was required (to a maximum of 16 mL/hr).

The CSE and epidural groups were similar with regard to weight, height, and parity. Initial pain scores were significantly higher in the CSE group (7.8 vs. 6.9), and mean PCA volume was higher in that group (22 mL vs. 13 mL), but the groups did not differ in regard to first- and second-stage duration, initial cervical dilation, total infusion time, pain scores at time of relief, intravenous Pitocin use, pruritus, sedation, nausea, vomiting, urinary retention, analgesia satisfaction overall and during the first and second stages of labor, number of patients able to ambulate, or APGAR scores, Dr. Balki noted.

HOLLYWOOD, FLA. — The addition of spinal analgesia to a routine walking epidural patient-controlled analgesia regimen shortened the time to pain relief in a randomized study.

In the study of 136 patients who were randomized to receive a combined spinal-epidural (CSE) regimen or a routine epidural regimen, the CSE group achieved full analgesia satisfaction in a mean of 8 minutes, compared with 16 minutes in the epidural group.

Moreover, the addition of spinal analgesia did not affect the quality of the block, side effects, or patient satisfaction with analgesia, Dr. Shaul Cohen reported in a poster at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Patients in the CSE group received initiation by 2mg of intrathecal ropivacaine and 5 mcg sufentanil via a PENCAN 25G spinal needle followed by epidural patient-controlled analgesia (PCA). The epidural group received 20 mL of 0.04% ropivacaine plus 1 mcg/mL sufentanil plus 2 mcg/mL epinephrine epidural study solution followed by epidural PCA analgesia.

All patients received an infusion of the study solution at 4 mL/hr, and a PCA dose of 4 mL with a lockout time of 10 minutes, noted Dr. Cohen of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, N.J.

After the initial neuraxial dose administration, patients were asked to rate their pain satisfaction at each contraction. In those with a visual analog score of greater than three at 20 minutes, a 5- to 10-mL bolus of study solution was given every 10 minutes (up to 20 mL) as needed to achieve a score of three or less.

A rescue dose of 5 mL of 0.25% ropivacaine was provided every 10 minutes (up to 20 mL and until patients could no longer ambulate) to those whose score remained above three after the maximum amount of study solution had been provided; the infusion rate was increased by 2 mL/hr at each interval where an intervention was required (to a maximum of 16 mL/hr).

The CSE and epidural groups were similar with regard to weight, height, and parity. Initial pain scores were significantly higher in the CSE group (7.8 vs. 6.9), and mean PCA volume was higher in that group (22 mL vs. 13 mL), but the groups did not differ in regard to first- and second-stage duration, initial cervical dilation, total infusion time, pain scores at time of relief, intravenous Pitocin use, pruritus, sedation, nausea, vomiting, urinary retention, analgesia satisfaction overall and during the first and second stages of labor, number of patients able to ambulate, or APGAR scores, Dr. Balki noted.

MIAMI BEACH — Individuals born preterm have diminished short- and long-term survival, as well as diminished reproductive capacity, and women born preterm are at increased risk of giving birth to their own offspring preterm, an analysis of data from a large birth registry suggests.

Data from about 610,000 men and 578,000 women entered into the Medical Birth Registry of Norway between 1967 and 1988 were analyzed and showed an overall rate of preterm birth of 5.7%, with 5.3% among females and 6.2% among males.

Those born preterm, compared with those born between 37 and 42 weeks' gestation, had “considerably higher” perinatal and infant mortality, and the increased mortality risk persisted through adolescence, Dr. Geeta K. Swamy reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The odds ratios for early childhood death in those born extremely preterm (from 22 to 27 weeks' gestation) were 6.1 for males and 8.7 for females, and for those born very preterm (28–32 weeks' gestation), the odds ratios were 2.5 for males and 2.1 for females.

The odds ratio for late childhood death in those born extremely preterm was 6.3 for males (no females died in late childhood in this group), and for those born very preterm they were 1.9 for males, and 0.9 for females, said Dr. Swamy of Duke University, Durham, N.C.

Reproduction was significantly diminished in both men and women born extremely preterm who survived until at least age 18 years (odds ratio 0.48 for men and 0.52 for women) and in those born very preterm who survived to at least age 18 years (odds ratio 0.75 for men and 0.81 for women).

The risk for having offspring born preterm was increased only among women who were born preterm.

Approximately 17% of those born extremely preterm gave birth prematurely, compared with 7% of those born at term.

“The findings emphasize the increased need for health care and social services well beyond the neonatal and infant life periods,” Dr. Swamy said, adding that further study will analyze gender-specific causes of mortality to better determine how preterm birth affects long-term health.

A reevaluation to determine how continually improving survival rates among the extremely preterm affect overall reproduction is also warranted, Dr. Swamy concluded.

MIAMI BEACH — Individuals born preterm have diminished short- and long-term survival, as well as diminished reproductive capacity, and women born preterm are at increased risk of giving birth to their own offspring preterm, an analysis of data from a large birth registry suggests.

Data from about 610,000 men and 578,000 women entered into the Medical Birth Registry of Norway between 1967 and 1988 were analyzed and showed an overall rate of preterm birth of 5.7%, with 5.3% among females and 6.2% among males.

Those born preterm, compared with those born between 37 and 42 weeks' gestation, had “considerably higher” perinatal and infant mortality, and the increased mortality risk persisted through adolescence, Dr. Geeta K. Swamy reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The odds ratios for early childhood death in those born extremely preterm (from 22 to 27 weeks' gestation) were 6.1 for males and 8.7 for females, and for those born very preterm (28–32 weeks' gestation), the odds ratios were 2.5 for males and 2.1 for females.

The odds ratio for late childhood death in those born extremely preterm was 6.3 for males (no females died in late childhood in this group), and for those born very preterm they were 1.9 for males, and 0.9 for females, said Dr. Swamy of Duke University, Durham, N.C.

Reproduction was significantly diminished in both men and women born extremely preterm who survived until at least age 18 years (odds ratio 0.48 for men and 0.52 for women) and in those born very preterm who survived to at least age 18 years (odds ratio 0.75 for men and 0.81 for women).

The risk for having offspring born preterm was increased only among women who were born preterm.

Approximately 17% of those born extremely preterm gave birth prematurely, compared with 7% of those born at term.

“The findings emphasize the increased need for health care and social services well beyond the neonatal and infant life periods,” Dr. Swamy said, adding that further study will analyze gender-specific causes of mortality to better determine how preterm birth affects long-term health.

A reevaluation to determine how continually improving survival rates among the extremely preterm affect overall reproduction is also warranted, Dr. Swamy concluded.

MIAMI BEACH — Individuals born preterm have diminished short- and long-term survival, as well as diminished reproductive capacity, and women born preterm are at increased risk of giving birth to their own offspring preterm, an analysis of data from a large birth registry suggests.

Data from about 610,000 men and 578,000 women entered into the Medical Birth Registry of Norway between 1967 and 1988 were analyzed and showed an overall rate of preterm birth of 5.7%, with 5.3% among females and 6.2% among males.

Those born preterm, compared with those born between 37 and 42 weeks' gestation, had “considerably higher” perinatal and infant mortality, and the increased mortality risk persisted through adolescence, Dr. Geeta K. Swamy reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The odds ratios for early childhood death in those born extremely preterm (from 22 to 27 weeks' gestation) were 6.1 for males and 8.7 for females, and for those born very preterm (28–32 weeks' gestation), the odds ratios were 2.5 for males and 2.1 for females.

The odds ratio for late childhood death in those born extremely preterm was 6.3 for males (no females died in late childhood in this group), and for those born very preterm they were 1.9 for males, and 0.9 for females, said Dr. Swamy of Duke University, Durham, N.C.

Reproduction was significantly diminished in both men and women born extremely preterm who survived until at least age 18 years (odds ratio 0.48 for men and 0.52 for women) and in those born very preterm who survived to at least age 18 years (odds ratio 0.75 for men and 0.81 for women).

The risk for having offspring born preterm was increased only among women who were born preterm.

Approximately 17% of those born extremely preterm gave birth prematurely, compared with 7% of those born at term.

“The findings emphasize the increased need for health care and social services well beyond the neonatal and infant life periods,” Dr. Swamy said, adding that further study will analyze gender-specific causes of mortality to better determine how preterm birth affects long-term health.

A reevaluation to determine how continually improving survival rates among the extremely preterm affect overall reproduction is also warranted, Dr. Swamy concluded.

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

CASE How fast can your team go?

A 28-year-old G1P0 woman at 37 weeks’ gestation presents to the triage area of your labor and delivery unit with a complaint of decreased fetal movement for 24 hours. Fetal heart rate monitoring indicates a fetal heart rate of 60 bpm. The maternal heart rate is 86 bpm. By physical exam the uterus has normal tone. Cervical examination reveals that the cervix is closed and there is no umbilical cord in the vagina. Three minutes after being placed on the fetal heart rate monitor, an ultrasound exam confirms that the fetal heart rate is 60 bpm. Change in maternal position and oxygen by mask does not change the fetal heart rate. You call for a crash cesarean section. How fast can your team go?

As an obstetrical team moves to initiate a crash cesarean section, dozens of decisions need to be made in a seamless manner by a multidisciplinary operative team. Who will alert all the team members to the initiation of a crash section? Who will start the IV and place the Foley catheter? Will the consent be obtained verbally or in writing? Who will transport the patient to the operating room? Will a general anesthetic or spinal be utilized? Will a formal surgical preparation be performed or a “splash prep”? Will the obstetrician utilize a vertical or a transverse abdominal incision? What is the plan if a cesarean section is previously underway on another woman, and a crash section needs to be initiated on your patient?

Recommended intervals vary

There are no randomized clinical trials demonstrating that the faster a cesarean section is performed, the better the maternal and fetal outcome. The American College of Obstetricians and Gynecologists recommends that in an emergency, obstetrical units should be capable of initiating a cesarean section within 30 minutes of a decision to perform the procedure.¹ In Germany, the recommendation is that, in an emergency, the cesarean section should be initiated within 20 minutes.

These recommendations are based on the opinion of experts, not on prospective trials. Many authorities believe that in some clinical settings, such as with a major abruption or a cord prolapse, “decision-to-delivery” times in the 10- to 20-minute range are associated with better newborn outcomes than times in the 30- to 45-minute range.

How to improve response time?

Worldwide, many obstetrical units are unable to routinely achieve a 30-minute decision-to-incision interval.^2,3 Some studies indicate that the presence of the operative team in the hospital improves response time and newborn outcomes.⁴ Crash cesarean section simulation drills and standardization of procedures for a crash cesarean section appear to reduce the decision-to-delivery interval.⁵

Dangers and precautions

Patient safety is a primary concern in all healthcare settings. One challenge with performing a crash cesarean section is the potential that more harm than good will be done. For example:

• Women have died from anesthetic complications during attempts to perform a crash cesarean section. Anesthetic complications that have caused death include inability to maintain a patent airway, and vomiting resulting in aspiration and hypoxemia. For a patient who enters the labor and delivery unit directly from home, the risk is high that her stomach is not empty and general anesthesia is especially risky in this setting. Morbidly obese women may be at especially high risk for a major anesthetic complication.⁶
• For women with a massive placental abruption, disseminated intravascular coagulation may be present prior to initiating surgery. If a full-service blood bank is not immediately available, initiating a crash cesarean section in this setting can result in the death of the mother from surgical complications.
• Crash cesarean sections have been reported to be associated with an increased rate of obstetrical hemorrhage.⁷

It is critically important to document that the fetus has an active fetal heart rate before initiating a crash cesarean section. Sometimes, maternal vascular activity is misinterpreted as a fetal heart rate. Performing a crash cesarean section, only to discover that the fetus has been dead for many hours or days, is particularly devastating to the patient, her family, and all the care providers.

JCAHO advises simulation drills

Based on major adverse obstetrical outcomes reported by hospitals, the Joint Commission on Accreditation of Healthcare Organizations recommends that labor and delivery units regularly conduct simulated crash cesarean section procedures and debrief the entire team after the simulation.⁸ The crash cesarean section is a complex surgical procedure that requires effective communication among a multidisciplinary delivery team, including obstetricians, nurses, anesthesiologists, pediatricians, and support personnel. The Joint Commission believes that maternal and newborn outcomes will be improved by practicing crash cesarean section procedures and improving communication among members of the delivery team. Simulation training and improved communications will increase the quality of patient care throughout the labor and delivery suite.

CASE How fast can your team go?

A 28-year-old G1P0 woman at 37 weeks’ gestation presents to the triage area of your labor and delivery unit with a complaint of decreased fetal movement for 24 hours. Fetal heart rate monitoring indicates a fetal heart rate of 60 bpm. The maternal heart rate is 86 bpm. By physical exam the uterus has normal tone. Cervical examination reveals that the cervix is closed and there is no umbilical cord in the vagina. Three minutes after being placed on the fetal heart rate monitor, an ultrasound exam confirms that the fetal heart rate is 60 bpm. Change in maternal position and oxygen by mask does not change the fetal heart rate. You call for a crash cesarean section. How fast can your team go?

As an obstetrical team moves to initiate a crash cesarean section, dozens of decisions need to be made in a seamless manner by a multidisciplinary operative team. Who will alert all the team members to the initiation of a crash section? Who will start the IV and place the Foley catheter? Will the consent be obtained verbally or in writing? Who will transport the patient to the operating room? Will a general anesthetic or spinal be utilized? Will a formal surgical preparation be performed or a “splash prep”? Will the obstetrician utilize a vertical or a transverse abdominal incision? What is the plan if a cesarean section is previously underway on another woman, and a crash section needs to be initiated on your patient?

Recommended intervals vary

There are no randomized clinical trials demonstrating that the faster a cesarean section is performed, the better the maternal and fetal outcome. The American College of Obstetricians and Gynecologists recommends that in an emergency, obstetrical units should be capable of initiating a cesarean section within 30 minutes of a decision to perform the procedure.¹ In Germany, the recommendation is that, in an emergency, the cesarean section should be initiated within 20 minutes.

These recommendations are based on the opinion of experts, not on prospective trials. Many authorities believe that in some clinical settings, such as with a major abruption or a cord prolapse, “decision-to-delivery” times in the 10- to 20-minute range are associated with better newborn outcomes than times in the 30- to 45-minute range.

How to improve response time?

Worldwide, many obstetrical units are unable to routinely achieve a 30-minute decision-to-incision interval.^2,3 Some studies indicate that the presence of the operative team in the hospital improves response time and newborn outcomes.⁴ Crash cesarean section simulation drills and standardization of procedures for a crash cesarean section appear to reduce the decision-to-delivery interval.⁵

Dangers and precautions

Patient safety is a primary concern in all healthcare settings. One challenge with performing a crash cesarean section is the potential that more harm than good will be done. For example:

• Women have died from anesthetic complications during attempts to perform a crash cesarean section. Anesthetic complications that have caused death include inability to maintain a patent airway, and vomiting resulting in aspiration and hypoxemia. For a patient who enters the labor and delivery unit directly from home, the risk is high that her stomach is not empty and general anesthesia is especially risky in this setting. Morbidly obese women may be at especially high risk for a major anesthetic complication.⁶
• For women with a massive placental abruption, disseminated intravascular coagulation may be present prior to initiating surgery. If a full-service blood bank is not immediately available, initiating a crash cesarean section in this setting can result in the death of the mother from surgical complications.
• Crash cesarean sections have been reported to be associated with an increased rate of obstetrical hemorrhage.⁷

It is critically important to document that the fetus has an active fetal heart rate before initiating a crash cesarean section. Sometimes, maternal vascular activity is misinterpreted as a fetal heart rate. Performing a crash cesarean section, only to discover that the fetus has been dead for many hours or days, is particularly devastating to the patient, her family, and all the care providers.

JCAHO advises simulation drills

Based on major adverse obstetrical outcomes reported by hospitals, the Joint Commission on Accreditation of Healthcare Organizations recommends that labor and delivery units regularly conduct simulated crash cesarean section procedures and debrief the entire team after the simulation.⁸ The crash cesarean section is a complex surgical procedure that requires effective communication among a multidisciplinary delivery team, including obstetricians, nurses, anesthesiologists, pediatricians, and support personnel. The Joint Commission believes that maternal and newborn outcomes will be improved by practicing crash cesarean section procedures and improving communication among members of the delivery team. Simulation training and improved communications will increase the quality of patient care throughout the labor and delivery suite.

CASE How fast can your team go?

A 28-year-old G1P0 woman at 37 weeks’ gestation presents to the triage area of your labor and delivery unit with a complaint of decreased fetal movement for 24 hours. Fetal heart rate monitoring indicates a fetal heart rate of 60 bpm. The maternal heart rate is 86 bpm. By physical exam the uterus has normal tone. Cervical examination reveals that the cervix is closed and there is no umbilical cord in the vagina. Three minutes after being placed on the fetal heart rate monitor, an ultrasound exam confirms that the fetal heart rate is 60 bpm. Change in maternal position and oxygen by mask does not change the fetal heart rate. You call for a crash cesarean section. How fast can your team go?

As an obstetrical team moves to initiate a crash cesarean section, dozens of decisions need to be made in a seamless manner by a multidisciplinary operative team. Who will alert all the team members to the initiation of a crash section? Who will start the IV and place the Foley catheter? Will the consent be obtained verbally or in writing? Who will transport the patient to the operating room? Will a general anesthetic or spinal be utilized? Will a formal surgical preparation be performed or a “splash prep”? Will the obstetrician utilize a vertical or a transverse abdominal incision? What is the plan if a cesarean section is previously underway on another woman, and a crash section needs to be initiated on your patient?

Recommended intervals vary

There are no randomized clinical trials demonstrating that the faster a cesarean section is performed, the better the maternal and fetal outcome. The American College of Obstetricians and Gynecologists recommends that in an emergency, obstetrical units should be capable of initiating a cesarean section within 30 minutes of a decision to perform the procedure.¹ In Germany, the recommendation is that, in an emergency, the cesarean section should be initiated within 20 minutes.

These recommendations are based on the opinion of experts, not on prospective trials. Many authorities believe that in some clinical settings, such as with a major abruption or a cord prolapse, “decision-to-delivery” times in the 10- to 20-minute range are associated with better newborn outcomes than times in the 30- to 45-minute range.

How to improve response time?

Worldwide, many obstetrical units are unable to routinely achieve a 30-minute decision-to-incision interval.^2,3 Some studies indicate that the presence of the operative team in the hospital improves response time and newborn outcomes.⁴ Crash cesarean section simulation drills and standardization of procedures for a crash cesarean section appear to reduce the decision-to-delivery interval.⁵

Dangers and precautions

Patient safety is a primary concern in all healthcare settings. One challenge with performing a crash cesarean section is the potential that more harm than good will be done. For example:

• Women have died from anesthetic complications during attempts to perform a crash cesarean section. Anesthetic complications that have caused death include inability to maintain a patent airway, and vomiting resulting in aspiration and hypoxemia. For a patient who enters the labor and delivery unit directly from home, the risk is high that her stomach is not empty and general anesthesia is especially risky in this setting. Morbidly obese women may be at especially high risk for a major anesthetic complication.⁶
• For women with a massive placental abruption, disseminated intravascular coagulation may be present prior to initiating surgery. If a full-service blood bank is not immediately available, initiating a crash cesarean section in this setting can result in the death of the mother from surgical complications.
• Crash cesarean sections have been reported to be associated with an increased rate of obstetrical hemorrhage.⁷

It is critically important to document that the fetus has an active fetal heart rate before initiating a crash cesarean section. Sometimes, maternal vascular activity is misinterpreted as a fetal heart rate. Performing a crash cesarean section, only to discover that the fetus has been dead for many hours or days, is particularly devastating to the patient, her family, and all the care providers.

JCAHO advises simulation drills

Based on major adverse obstetrical outcomes reported by hospitals, the Joint Commission on Accreditation of Healthcare Organizations recommends that labor and delivery units regularly conduct simulated crash cesarean section procedures and debrief the entire team after the simulation.⁸ The crash cesarean section is a complex surgical procedure that requires effective communication among a multidisciplinary delivery team, including obstetricians, nurses, anesthesiologists, pediatricians, and support personnel. The Joint Commission believes that maternal and newborn outcomes will be improved by practicing crash cesarean section procedures and improving communication among members of the delivery team. Simulation training and improved communications will increase the quality of patient care throughout the labor and delivery suite.

TORONTO — Pregnancy could be viewed as a type of cardiovascular “stress test” that could uncover previously silent risk factors for future cardiovascular problems, according to Carl H. Hubel, Ph.D.

“Studying women during pregnancy may facilitate the identification of cardiovascular risk and offer an opportunity for early intervention to decrease their likelihood of developing problems later in life,” said Dr. Hubel of Magee Women's Research Institute in Pittsburgh.

Speaking at the annual meeting of the Society for Gynecologic Investigation, Dr. Hubel outlined his own work and that of other researchers that both show that preeclampsia and other complications relating to placental insufficiency such as low birth weight and preterm delivery are associated with an increased risk of cardiovascular events up to 30 years later.

“Metabolic factors predisposing to endothelial dysfunction such as insulin resistance, dyslipidemia, and inflammation may also predispose to preeclampsia and may later manifest as cardiovascular disease,” he said, suggesting that endothelial repair is a potential target on the horizon. “Surveillance of cardiovascular risk factors during pregnancy per se may help to identify additional subsets of women who would benefit from early and aggressive risk factor modification post partum.”

In a study of 30 women with a previous eclamptic pregnancy, Dr. Hubel and his colleagues found that 33% were taking blood pressure medications 30 years after the index pregnancy, compared with only 7% of controls (BJOG 2000;107:776–84). More recently, the same group of women also showed increased levels of C-reactive protein (CRP), an inflammatory marker of cardiovascular disease risk—and a higher prevalence of dyslipidemia, and insulin resistance compared with controls.

“We cannot rule out that preeclampsia is the cause, not the consequence, of these risk factors,” he said in an interview. “Preeclampsia has a prevalence rate of 3%–5% of pregnancies—so one would have to follow large numbers of women from preconception, through their pregnancies, and into later life just to capture enough women who develop preeclampsia to determine the answer.”

But regardless of this, he suggests women who have had preeclampsia, preterm birth, or a low-birth-weight baby should be monitored more closely for risk factors that might contribute to future cardiovascular risk.

“Perhaps this is a group of women that shouldn't wait until after age 45 to have their CRP and lipids measured,” Dr. Hubel said.

TORONTO — Pregnancy could be viewed as a type of cardiovascular “stress test” that could uncover previously silent risk factors for future cardiovascular problems, according to Carl H. Hubel, Ph.D.

“Studying women during pregnancy may facilitate the identification of cardiovascular risk and offer an opportunity for early intervention to decrease their likelihood of developing problems later in life,” said Dr. Hubel of Magee Women's Research Institute in Pittsburgh.

Speaking at the annual meeting of the Society for Gynecologic Investigation, Dr. Hubel outlined his own work and that of other researchers that both show that preeclampsia and other complications relating to placental insufficiency such as low birth weight and preterm delivery are associated with an increased risk of cardiovascular events up to 30 years later.

“Metabolic factors predisposing to endothelial dysfunction such as insulin resistance, dyslipidemia, and inflammation may also predispose to preeclampsia and may later manifest as cardiovascular disease,” he said, suggesting that endothelial repair is a potential target on the horizon. “Surveillance of cardiovascular risk factors during pregnancy per se may help to identify additional subsets of women who would benefit from early and aggressive risk factor modification post partum.”

In a study of 30 women with a previous eclamptic pregnancy, Dr. Hubel and his colleagues found that 33% were taking blood pressure medications 30 years after the index pregnancy, compared with only 7% of controls (BJOG 2000;107:776–84). More recently, the same group of women also showed increased levels of C-reactive protein (CRP), an inflammatory marker of cardiovascular disease risk—and a higher prevalence of dyslipidemia, and insulin resistance compared with controls.

“We cannot rule out that preeclampsia is the cause, not the consequence, of these risk factors,” he said in an interview. “Preeclampsia has a prevalence rate of 3%–5% of pregnancies—so one would have to follow large numbers of women from preconception, through their pregnancies, and into later life just to capture enough women who develop preeclampsia to determine the answer.”

But regardless of this, he suggests women who have had preeclampsia, preterm birth, or a low-birth-weight baby should be monitored more closely for risk factors that might contribute to future cardiovascular risk.

“Perhaps this is a group of women that shouldn't wait until after age 45 to have their CRP and lipids measured,” Dr. Hubel said.

TORONTO — Pregnancy could be viewed as a type of cardiovascular “stress test” that could uncover previously silent risk factors for future cardiovascular problems, according to Carl H. Hubel, Ph.D.

“Studying women during pregnancy may facilitate the identification of cardiovascular risk and offer an opportunity for early intervention to decrease their likelihood of developing problems later in life,” said Dr. Hubel of Magee Women's Research Institute in Pittsburgh.

Speaking at the annual meeting of the Society for Gynecologic Investigation, Dr. Hubel outlined his own work and that of other researchers that both show that preeclampsia and other complications relating to placental insufficiency such as low birth weight and preterm delivery are associated with an increased risk of cardiovascular events up to 30 years later.

“Metabolic factors predisposing to endothelial dysfunction such as insulin resistance, dyslipidemia, and inflammation may also predispose to preeclampsia and may later manifest as cardiovascular disease,” he said, suggesting that endothelial repair is a potential target on the horizon. “Surveillance of cardiovascular risk factors during pregnancy per se may help to identify additional subsets of women who would benefit from early and aggressive risk factor modification post partum.”

In a study of 30 women with a previous eclamptic pregnancy, Dr. Hubel and his colleagues found that 33% were taking blood pressure medications 30 years after the index pregnancy, compared with only 7% of controls (BJOG 2000;107:776–84). More recently, the same group of women also showed increased levels of C-reactive protein (CRP), an inflammatory marker of cardiovascular disease risk—and a higher prevalence of dyslipidemia, and insulin resistance compared with controls.

“We cannot rule out that preeclampsia is the cause, not the consequence, of these risk factors,” he said in an interview. “Preeclampsia has a prevalence rate of 3%–5% of pregnancies—so one would have to follow large numbers of women from preconception, through their pregnancies, and into later life just to capture enough women who develop preeclampsia to determine the answer.”

But regardless of this, he suggests women who have had preeclampsia, preterm birth, or a low-birth-weight baby should be monitored more closely for risk factors that might contribute to future cardiovascular risk.

“Perhaps this is a group of women that shouldn't wait until after age 45 to have their CRP and lipids measured,” Dr. Hubel said.

TORONTO — Physicians weighing the risks versus benefits of medicating nonobstetric conditions during pregnancy should consider that their dilemma is not one of fetal exposure versus nonexposure, according to Dr. Zachary N. Stowe, a psychiatrist and director of the Women's Mental Health Program at Emory University, Atlanta.

“You expose the fetus to something, be it illness or the treatment,” he said at the annual meeting of the Society for Gynecologic Investigation. And amid the growing evidence of risks associated with prenatal exposure to antidepressants is the danger of losing sight of alternative risks, he said.

“Of concern to me is that often, the treatment of mental illness is viewed as more 'optional' than, for example, [the treatment of] epilepsy, hypertension, or infection—despite the fact that there are considerably more data demonstrating that maternal depression and anxiety may have more severe sequelae, particularly with respect to child development,” Dr. Stowe said in an interview.

The impact—both short and long term—of prenatal exposure to untreated mental illness should not be underestimated, he warned. Studies show that low birth weight (LBW), small for gestational age (SGA), and preterm delivery are linked with untreated major depression and anxiety disorders. Untreated schizophrenia is also linked with LBW and SGA, as well as stillbirth and increased infant mortality.

Moreover, untreated eating disorders are associated with LBW and preterm delivery. In the long term, prenatal exposure to untreated major depression has been linked to motor delays, reactivity, attention problems, and EEG alternations in offspring. And untreated anxiety disorders are associated with conduct disorder and increased anxiety in offspring, said Dr. Stowe, who acknowledges receiving research grants and serving on the speakers' bureaus of “most pharmaceutical companies” that make antidepressants.

Even with medication, depression relapse rates are higher in pregnancy than among nonpregnant women. In a recent prospective study of 201 women with major depression, Dr. Stowe and his colleagues showed a 26% relapse rate among those who maintained their medication until delivery. Women who discontinued their medication had a relapse rate of 68% (JAMA 2006;295:499–507).

Dr. Stowe emphasized that his group's recent review of the literature shows that in almost 17,000 cases of prenatal antidepressant exposure, the highest malformation rate associated with a particular antidepressant is 3.5%. That was the rate found for paroxetine (Paxil).

He stressed that while caution is always imperative when prescribing medication during pregnancy, the Food and Drug Administration's drug categorization system is of little help to prescribers and is more useful for those seeking liability protection.

“I agree with Dr. M. Schou, who wrote in the Journal of Affective Disorders that 'when manufacturers and official agencies warn against drug treatment during pregnancy, their warnings serve to protect themselves and are of little use to clinically responsible physicians,' ” he said (J. Affect. Disord. 2001; 67:21–32).

While stressing the importance of treating mental illness in pregnancy, Dr. Stowe said it is important that physicians do not underplay fetal exposure to the medication. “The fetus doesn't get exposed to the mother's dose,” he noted. “It gets exposed to the mother's serum concentrations.” However, his extensive work documenting placental passage of antidepressants and measuring amniotic fluid concentrations of these medications shows that the fetus is exposed to “not a trivial amount. I have heard MDs tell patients that 'the baby really does not get much medication' when they are discussing other medications—which is obviously not true with antidepressants, and mostly unknown for other medications,” he said.

His recently published study measured amniotic fluid concentrations of antidepressants at approximately 10% of maternal serum concentrations (Am. J. Psychiatry 2006;163:145–7), and some of his unpublished work suggests that umbilical cord concentrations of antidepressants at delivery are typically more than 50% of maternal concentrations.

Dr. Stowe said physicians who choose to prescribe antidepressants in pregnancy should also keep the pharmacokinetics and pharmacodynamics of pregnancy in mind and be aware that maternal serum concentrations decrease over the course of pregnancy. “It is important to consider increasing the dose, if necessary, to maintain an adequate maternal response.”

In an accompanying presentation, Dr. Ruth E. Tuomala echoed Dr. Stowe's message, but in the context of a very different condition: HIV. Compared with depression, the consequences of fetal and neonatal exposure to HIV are perhaps more widely appreciated within both medical and lay circles. However, the benefits of perinatal prophylactic measures can be lost if antiretroviral therapy (ART) is inadequate, she warned.

Where physicians often try to minimize certain medication exposures during pregnancy, they should be thinking about maximizing ART in pregnant HIV-positive patients with the goal of reducing the risk of perinatal transmission, said Dr. Tuomala of Harvard Medical School, Boston.

The indications for ART in nonpregnant patients are a CD4+ count of 350 or less and a detectable viral load; however, these requirements are relaxed in pregnancy. “Thus antiretrovirals are given to many pregnant women with HIV who would not otherwise receive them [if they were not pregnant],” she said. Aggressive treatment with potent combination therapies has been shown to reduce the perinatal transmission rate to 1%, compared with a 21% transmission rate when no ART is used (J. Acquir. Immune Defic. Syndr. 2002;29:484–94), she said.

But to maximize its effectiveness, this aggressive therapy must be maintained throughout the pregnancy and the delivery. “The goal should be to minimize the maternal viral load at delivery and maximize fetal intracellular antiretroviral levels, as well as to provide postexposure prophylaxis to infants,” she said.

On the safety of ART, pregnancy outcome studies do not suggest an increase in spontaneous abortion, stillbirth, LBW, or low Apgar scores in association with these medications—and so there is no need to stop these drugs, she said. In fact, if any medication needs to be stopped because of hyperemesis, she recommends all medications be eliminated together to avoid the risk of developing resistance.

The only exception to this is efavirenz (Sustiva, Bristol-Myers Squibb), which is the only HIV medication now classified as category D because it has been linked to an increase in neural tube defects, she said. This drug should ideally be stopped before conception. “Acknowledge that HIV-infected women are choosing to get pregnant; give them preconception counseling, and get them off this drug before they conceive,” she advised. In addition, there is some suggestion of an association between nucleoside reverse transcriptase inhibitors (NRTIs) and neonatal mitochondrial toxicity syndrome.

Maternal toxicities associated with ART can include gastrointestinal problems, anemia, and/or hepatic steatosis/lactic acidosis (NRTIs); hyperglycemia (protease inhibitors); and hepatitis (nevirapine and others).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Physicians weighing the risks versus benefits of medicating nonobstetric conditions during pregnancy should consider that their dilemma is not one of fetal exposure versus nonexposure, according to Dr. Zachary N. Stowe, a psychiatrist and director of the Women's Mental Health Program at Emory University, Atlanta.

“You expose the fetus to something, be it illness or the treatment,” he said at the annual meeting of the Society for Gynecologic Investigation. And amid the growing evidence of risks associated with prenatal exposure to antidepressants is the danger of losing sight of alternative risks, he said.

“Of concern to me is that often, the treatment of mental illness is viewed as more 'optional' than, for example, [the treatment of] epilepsy, hypertension, or infection—despite the fact that there are considerably more data demonstrating that maternal depression and anxiety may have more severe sequelae, particularly with respect to child development,” Dr. Stowe said in an interview.

The impact—both short and long term—of prenatal exposure to untreated mental illness should not be underestimated, he warned. Studies show that low birth weight (LBW), small for gestational age (SGA), and preterm delivery are linked with untreated major depression and anxiety disorders. Untreated schizophrenia is also linked with LBW and SGA, as well as stillbirth and increased infant mortality.

Moreover, untreated eating disorders are associated with LBW and preterm delivery. In the long term, prenatal exposure to untreated major depression has been linked to motor delays, reactivity, attention problems, and EEG alternations in offspring. And untreated anxiety disorders are associated with conduct disorder and increased anxiety in offspring, said Dr. Stowe, who acknowledges receiving research grants and serving on the speakers' bureaus of “most pharmaceutical companies” that make antidepressants.

Even with medication, depression relapse rates are higher in pregnancy than among nonpregnant women. In a recent prospective study of 201 women with major depression, Dr. Stowe and his colleagues showed a 26% relapse rate among those who maintained their medication until delivery. Women who discontinued their medication had a relapse rate of 68% (JAMA 2006;295:499–507).

Dr. Stowe emphasized that his group's recent review of the literature shows that in almost 17,000 cases of prenatal antidepressant exposure, the highest malformation rate associated with a particular antidepressant is 3.5%. That was the rate found for paroxetine (Paxil).

He stressed that while caution is always imperative when prescribing medication during pregnancy, the Food and Drug Administration's drug categorization system is of little help to prescribers and is more useful for those seeking liability protection.

“I agree with Dr. M. Schou, who wrote in the Journal of Affective Disorders that 'when manufacturers and official agencies warn against drug treatment during pregnancy, their warnings serve to protect themselves and are of little use to clinically responsible physicians,' ” he said (J. Affect. Disord. 2001; 67:21–32).

While stressing the importance of treating mental illness in pregnancy, Dr. Stowe said it is important that physicians do not underplay fetal exposure to the medication. “The fetus doesn't get exposed to the mother's dose,” he noted. “It gets exposed to the mother's serum concentrations.” However, his extensive work documenting placental passage of antidepressants and measuring amniotic fluid concentrations of these medications shows that the fetus is exposed to “not a trivial amount. I have heard MDs tell patients that 'the baby really does not get much medication' when they are discussing other medications—which is obviously not true with antidepressants, and mostly unknown for other medications,” he said.

His recently published study measured amniotic fluid concentrations of antidepressants at approximately 10% of maternal serum concentrations (Am. J. Psychiatry 2006;163:145–7), and some of his unpublished work suggests that umbilical cord concentrations of antidepressants at delivery are typically more than 50% of maternal concentrations.

Dr. Stowe said physicians who choose to prescribe antidepressants in pregnancy should also keep the pharmacokinetics and pharmacodynamics of pregnancy in mind and be aware that maternal serum concentrations decrease over the course of pregnancy. “It is important to consider increasing the dose, if necessary, to maintain an adequate maternal response.”

In an accompanying presentation, Dr. Ruth E. Tuomala echoed Dr. Stowe's message, but in the context of a very different condition: HIV. Compared with depression, the consequences of fetal and neonatal exposure to HIV are perhaps more widely appreciated within both medical and lay circles. However, the benefits of perinatal prophylactic measures can be lost if antiretroviral therapy (ART) is inadequate, she warned.

Where physicians often try to minimize certain medication exposures during pregnancy, they should be thinking about maximizing ART in pregnant HIV-positive patients with the goal of reducing the risk of perinatal transmission, said Dr. Tuomala of Harvard Medical School, Boston.

The indications for ART in nonpregnant patients are a CD4+ count of 350 or less and a detectable viral load; however, these requirements are relaxed in pregnancy. “Thus antiretrovirals are given to many pregnant women with HIV who would not otherwise receive them [if they were not pregnant],” she said. Aggressive treatment with potent combination therapies has been shown to reduce the perinatal transmission rate to 1%, compared with a 21% transmission rate when no ART is used (J. Acquir. Immune Defic. Syndr. 2002;29:484–94), she said.

But to maximize its effectiveness, this aggressive therapy must be maintained throughout the pregnancy and the delivery. “The goal should be to minimize the maternal viral load at delivery and maximize fetal intracellular antiretroviral levels, as well as to provide postexposure prophylaxis to infants,” she said.

On the safety of ART, pregnancy outcome studies do not suggest an increase in spontaneous abortion, stillbirth, LBW, or low Apgar scores in association with these medications—and so there is no need to stop these drugs, she said. In fact, if any medication needs to be stopped because of hyperemesis, she recommends all medications be eliminated together to avoid the risk of developing resistance.

The only exception to this is efavirenz (Sustiva, Bristol-Myers Squibb), which is the only HIV medication now classified as category D because it has been linked to an increase in neural tube defects, she said. This drug should ideally be stopped before conception. “Acknowledge that HIV-infected women are choosing to get pregnant; give them preconception counseling, and get them off this drug before they conceive,” she advised. In addition, there is some suggestion of an association between nucleoside reverse transcriptase inhibitors (NRTIs) and neonatal mitochondrial toxicity syndrome.

Maternal toxicities associated with ART can include gastrointestinal problems, anemia, and/or hepatic steatosis/lactic acidosis (NRTIs); hyperglycemia (protease inhibitors); and hepatitis (nevirapine and others).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Physicians weighing the risks versus benefits of medicating nonobstetric conditions during pregnancy should consider that their dilemma is not one of fetal exposure versus nonexposure, according to Dr. Zachary N. Stowe, a psychiatrist and director of the Women's Mental Health Program at Emory University, Atlanta.

“You expose the fetus to something, be it illness or the treatment,” he said at the annual meeting of the Society for Gynecologic Investigation. And amid the growing evidence of risks associated with prenatal exposure to antidepressants is the danger of losing sight of alternative risks, he said.

“Of concern to me is that often, the treatment of mental illness is viewed as more 'optional' than, for example, [the treatment of] epilepsy, hypertension, or infection—despite the fact that there are considerably more data demonstrating that maternal depression and anxiety may have more severe sequelae, particularly with respect to child development,” Dr. Stowe said in an interview.

The impact—both short and long term—of prenatal exposure to untreated mental illness should not be underestimated, he warned. Studies show that low birth weight (LBW), small for gestational age (SGA), and preterm delivery are linked with untreated major depression and anxiety disorders. Untreated schizophrenia is also linked with LBW and SGA, as well as stillbirth and increased infant mortality.

Moreover, untreated eating disorders are associated with LBW and preterm delivery. In the long term, prenatal exposure to untreated major depression has been linked to motor delays, reactivity, attention problems, and EEG alternations in offspring. And untreated anxiety disorders are associated with conduct disorder and increased anxiety in offspring, said Dr. Stowe, who acknowledges receiving research grants and serving on the speakers' bureaus of “most pharmaceutical companies” that make antidepressants.

Even with medication, depression relapse rates are higher in pregnancy than among nonpregnant women. In a recent prospective study of 201 women with major depression, Dr. Stowe and his colleagues showed a 26% relapse rate among those who maintained their medication until delivery. Women who discontinued their medication had a relapse rate of 68% (JAMA 2006;295:499–507).

Dr. Stowe emphasized that his group's recent review of the literature shows that in almost 17,000 cases of prenatal antidepressant exposure, the highest malformation rate associated with a particular antidepressant is 3.5%. That was the rate found for paroxetine (Paxil).

He stressed that while caution is always imperative when prescribing medication during pregnancy, the Food and Drug Administration's drug categorization system is of little help to prescribers and is more useful for those seeking liability protection.

“I agree with Dr. M. Schou, who wrote in the Journal of Affective Disorders that 'when manufacturers and official agencies warn against drug treatment during pregnancy, their warnings serve to protect themselves and are of little use to clinically responsible physicians,' ” he said (J. Affect. Disord. 2001; 67:21–32).

While stressing the importance of treating mental illness in pregnancy, Dr. Stowe said it is important that physicians do not underplay fetal exposure to the medication. “The fetus doesn't get exposed to the mother's dose,” he noted. “It gets exposed to the mother's serum concentrations.” However, his extensive work documenting placental passage of antidepressants and measuring amniotic fluid concentrations of these medications shows that the fetus is exposed to “not a trivial amount. I have heard MDs tell patients that 'the baby really does not get much medication' when they are discussing other medications—which is obviously not true with antidepressants, and mostly unknown for other medications,” he said.

His recently published study measured amniotic fluid concentrations of antidepressants at approximately 10% of maternal serum concentrations (Am. J. Psychiatry 2006;163:145–7), and some of his unpublished work suggests that umbilical cord concentrations of antidepressants at delivery are typically more than 50% of maternal concentrations.

Dr. Stowe said physicians who choose to prescribe antidepressants in pregnancy should also keep the pharmacokinetics and pharmacodynamics of pregnancy in mind and be aware that maternal serum concentrations decrease over the course of pregnancy. “It is important to consider increasing the dose, if necessary, to maintain an adequate maternal response.”

In an accompanying presentation, Dr. Ruth E. Tuomala echoed Dr. Stowe's message, but in the context of a very different condition: HIV. Compared with depression, the consequences of fetal and neonatal exposure to HIV are perhaps more widely appreciated within both medical and lay circles. However, the benefits of perinatal prophylactic measures can be lost if antiretroviral therapy (ART) is inadequate, she warned.

Where physicians often try to minimize certain medication exposures during pregnancy, they should be thinking about maximizing ART in pregnant HIV-positive patients with the goal of reducing the risk of perinatal transmission, said Dr. Tuomala of Harvard Medical School, Boston.

The indications for ART in nonpregnant patients are a CD4+ count of 350 or less and a detectable viral load; however, these requirements are relaxed in pregnancy. “Thus antiretrovirals are given to many pregnant women with HIV who would not otherwise receive them [if they were not pregnant],” she said. Aggressive treatment with potent combination therapies has been shown to reduce the perinatal transmission rate to 1%, compared with a 21% transmission rate when no ART is used (J. Acquir. Immune Defic. Syndr. 2002;29:484–94), she said.

But to maximize its effectiveness, this aggressive therapy must be maintained throughout the pregnancy and the delivery. “The goal should be to minimize the maternal viral load at delivery and maximize fetal intracellular antiretroviral levels, as well as to provide postexposure prophylaxis to infants,” she said.

On the safety of ART, pregnancy outcome studies do not suggest an increase in spontaneous abortion, stillbirth, LBW, or low Apgar scores in association with these medications—and so there is no need to stop these drugs, she said. In fact, if any medication needs to be stopped because of hyperemesis, she recommends all medications be eliminated together to avoid the risk of developing resistance.

The only exception to this is efavirenz (Sustiva, Bristol-Myers Squibb), which is the only HIV medication now classified as category D because it has been linked to an increase in neural tube defects, she said. This drug should ideally be stopped before conception. “Acknowledge that HIV-infected women are choosing to get pregnant; give them preconception counseling, and get them off this drug before they conceive,” she advised. In addition, there is some suggestion of an association between nucleoside reverse transcriptase inhibitors (NRTIs) and neonatal mitochondrial toxicity syndrome.

Maternal toxicities associated with ART can include gastrointestinal problems, anemia, and/or hepatic steatosis/lactic acidosis (NRTIs); hyperglycemia (protease inhibitors); and hepatitis (nevirapine and others).

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.