Obstetrics

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

BOSTON — Short-term treatment with one or more antiretroviral drugs starting in late pregnancy—in addition to or instead of single-dose nevirapine—may reduce the likelihood that HIV-infected women will transmit the virus to their newborns and that the women will develop nevirapine resistance, research has shown.

The practice of giving pregnant women with HIV a single dose of nevirapine (Viramune) during labor has significantly reduced maternal/child transmission rates in the developing world. It also has been heralded as an optimal approach for lowering the transmission rates among women in the United States who are identified as HIV positive very late in pregnancy or at the time of labor, and who also may be unlikely to follow extended treatment regimens because of lifestyle or health care inaccessibility.

There is growing evidence, however, that many women who receive this treatment develop mutated strains of the virus that resist future treatment with nevirapine and, potentially, other drugs, said James McIntyre, M.D., at a conference on retroviruses and opportunistic infections.

“While people have been lauding [single-dose nevirapine] as a stunning breakthrough, others have said it represents a less-than-optimal regimen” to which women in developing countries should not be subjected, said Dr. McIntyre of the perinatal HIV research unit at the University of Witwatersand, Johannesburg, South Africa. “In my country, this has been seen as a U.S. and pharmaceutical company conspiracy.”

The value of nevirapine monotherapy should be reassessed, Dr. McIntyre stressed, in light of new evidence suggesting that possible alternatives to the single-dose, single-drug regimen may be as effective at preventing vertical HIV transmission minus the potential for drug resistance.

In one of the studies presented at the conference, which was sponsored by the Foundation for Retrovirology and Human Health, 329 HIV-infected pregnant women in the West African nation of Cote d'Ivoire began therapy with a combination of zidovudine (AZT) and lamivudine (3TC [Epivir in the U.S.]) in their 32nd week of pregnancy through 3 days post partum, in addition to single-dose nevirapine during labor, reported lead investigator Francois Dabis, M.D., of Victor Segalen University in Bordeaux, France. The newborns in the study were treated with AZT for 1 week and a single dose of nevirapine.

The 6-week HIV type 1 (HIV-1) maternal/child transmission rate was 4.7%, representing “among the lowest transmission rates ever reported in Africa,” said Dr. Dabis. Single-dose nevirapine alone typically reduces the transmission rate from an estimated 35% to approximately 12%, he noted. (Maternal/child HIV transmission rates in the United States, where women have more access to antiretroviral therapy, are approximately 2%, according to CDC data.)

The drop in nevirapine resistance was even more dramatic, with a reported rate among the mothers of 1.1%. Although the exact mechanism for the reduced resistance rate has yet to be identified, the multidrug strategy “may impair the ability of the virus to mutate into a [nevirapine-] resistant strain,” according to Dr. Dabis.

A second study of 1,179 live births conducted in Botswana compared the effect of giving HIV-infected mothers multiweek zidovudine alone versus giving it in combination with single-dose nevirapine. Initially, each mother in the study was given zidovudine from 34 weeks' gestation and each mother/infant pair was randomized to receive blinded maternal and infant single-dose nevirapine or maternal and infant placebo. The study protocol was changed at 17 months because the infant nevirapine placebo was deemed unethical. Under the revised protocol, all infants received nevirapine as soon as possible after birth, while half of the mothers still got placebo, explained lead investigator Roger Shapiro, M.D., of Beth Israel Deaconess Medical Center in Boston.

Before the revision, the 1-month HIV transmission rates in 485 births were 5.3% in babies given nevirapine and 6.2% in babies who received placebo. In the 694 births that occurred during the revised study period, the 1-month transmission rates were 3.7% in babies born to mothers who received nevirapine and 4.3% in babies born to mothers given a placebo. The overall transmission rate for the entire study was approximately 4%, Dr. Shapiro said.

The results suggest that maternal single-dose nevirapine may not be needed to reduce mother/child transmission rates when both mother and infant are treated with zidovudine and when the infant receives nevirapine at birth—an important possibility, given that a substudy of the investigation found that 44% of the women who received the single-dose nevirapine developed resistance mutations, Dr. Shapiro noted.

Although the findings from both studies are promising, “the translation from trials to programs is incredibly challenging,” said Mary Glenn Fowler, M.D., chief of maternal-child transmission, Centers for Disease Control and Prevention, Atlanta. “It's important not to be rapidly overoptimistic. We need to see what happens when those women start therapy [after delivery].”

Advocates for AIDS research and treatment agree. A press release issued by the Elizabeth Glaser Pediatric AIDS Foundation stressed the importance of preserving single-dose nevirapine as an option: “Even simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to services and improve our ability to offer the most effective drug regimens in all instances.”

RENO, NEV. — Half of all pregnant women with hypertension have abnormal findings on echocardiography, but these abnormal findings did not predict differences in pregnancy outcomes, according to a study of 87 hypertensive patients.

Although some pregnant women with hypertension will require echocardiograms because of their clinical symptoms, the study suggests that routine echocardiograms are not indicated in otherwise asymptomatic women, investigators wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 87 pregnant women with hypertension seen over a period of more than 5 years in a single specialty clinic. The women underwent echocardiography, typically before 20 weeks of gestation, said Julie A. Gainer, D.O., of the University of Texas Southwestern Medical Center in Dallas, and associates.

Forty of the women (46%) had normal findings on echocardiography, and 47 (54%) had at least one abnormal finding. The most common abnormalities were concentric left ventricular hypertrophy, seen in 21 (24%) of the women; concentric left ventricular hypertrophy with a dilated left atrium, seen in 11 (13%) of the women; and dilated left atrium, seen in 12 (14%) of the women.

A comparison of women who had normal echocardiography results with those who had at least one abnormal finding revealed no significant differences in any measure.

The groups did not differ in any demographic variable, nor did they differ significantly in any of 10 measured pregnancy outcomes. These outcomes included the estimated gestational age at delivery, the proportion of women undergoing vaginal or cesarean delivery, the proportion with superimposed preeclampsia, and the length of their hospital stays.

RENO, NEV. — Half of all pregnant women with hypertension have abnormal findings on echocardiography, but these abnormal findings did not predict differences in pregnancy outcomes, according to a study of 87 hypertensive patients.

Although some pregnant women with hypertension will require echocardiograms because of their clinical symptoms, the study suggests that routine echocardiograms are not indicated in otherwise asymptomatic women, investigators wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 87 pregnant women with hypertension seen over a period of more than 5 years in a single specialty clinic. The women underwent echocardiography, typically before 20 weeks of gestation, said Julie A. Gainer, D.O., of the University of Texas Southwestern Medical Center in Dallas, and associates.

Forty of the women (46%) had normal findings on echocardiography, and 47 (54%) had at least one abnormal finding. The most common abnormalities were concentric left ventricular hypertrophy, seen in 21 (24%) of the women; concentric left ventricular hypertrophy with a dilated left atrium, seen in 11 (13%) of the women; and dilated left atrium, seen in 12 (14%) of the women.

A comparison of women who had normal echocardiography results with those who had at least one abnormal finding revealed no significant differences in any measure.

The groups did not differ in any demographic variable, nor did they differ significantly in any of 10 measured pregnancy outcomes. These outcomes included the estimated gestational age at delivery, the proportion of women undergoing vaginal or cesarean delivery, the proportion with superimposed preeclampsia, and the length of their hospital stays.

RENO, NEV. — Half of all pregnant women with hypertension have abnormal findings on echocardiography, but these abnormal findings did not predict differences in pregnancy outcomes, according to a study of 87 hypertensive patients.

Although some pregnant women with hypertension will require echocardiograms because of their clinical symptoms, the study suggests that routine echocardiograms are not indicated in otherwise asymptomatic women, investigators wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 87 pregnant women with hypertension seen over a period of more than 5 years in a single specialty clinic. The women underwent echocardiography, typically before 20 weeks of gestation, said Julie A. Gainer, D.O., of the University of Texas Southwestern Medical Center in Dallas, and associates.

Forty of the women (46%) had normal findings on echocardiography, and 47 (54%) had at least one abnormal finding. The most common abnormalities were concentric left ventricular hypertrophy, seen in 21 (24%) of the women; concentric left ventricular hypertrophy with a dilated left atrium, seen in 11 (13%) of the women; and dilated left atrium, seen in 12 (14%) of the women.

A comparison of women who had normal echocardiography results with those who had at least one abnormal finding revealed no significant differences in any measure.

The groups did not differ in any demographic variable, nor did they differ significantly in any of 10 measured pregnancy outcomes. These outcomes included the estimated gestational age at delivery, the proportion of women undergoing vaginal or cesarean delivery, the proportion with superimposed preeclampsia, and the length of their hospital stays.

RENO, NEV. — Sickle cell trait is associated with previously unreported signs of fetal hypoxia, placental infarcts, and possibly excess risk of fetal demise, according to a study presented in poster form at the annual meeting of the Society for Maternal-Fetal Medicine.

“In the past, we have just told these patients, 'Come in every trimester, and we will check your urine [because of increased risk for a urinary tract infection].' Maybe that's not safe,” the study's lead author, Michelle Y. Taylor, M.D., of the department of obstetrics and gynecology at the University of Mississippi Medical Center, Jackson, said in an interview.

In a case review of 131 pregnancies with confirmed sickle cell trait, in which a detailed pathological examination of the placenta was performed, the researchers found that all of the placentas had aggregates of sickled red blood cells in the intervillous space and decidual vessels.

In addition, 92% of the cases had evidence of meconium passage, suggesting hypoxia, and 50% had evidence of an ascending amniotic fluid infection.

There were frank placental infarcts in 16 cases and retroplacental hemorrhage in 11 cases.

There were 10 cases of intrauterine fetal demise (of which 4 were in the cases with infarction), and 1 neonatal death.

Intrauterine growth restriction occurred in 14 cases.

The investigation found a higher-than-expected rate of fetal loss, and no risk factors were noted other than the probability that sickling in the decidual vessels resulted in decreased placental perfusion, Dr. Taylor said in the interview.

All patients in the study were African American, and the group's average age was 24 years.

The average gestational age at delivery was 30 weeks, and all the pregnancies had to be at least 16 weeks to be in the study. A total of 123 pregnancies were singleton gestations, and 8 were twin gestations.

Hypertension was present in 16% of cases.

RENO, NEV. — Sickle cell trait is associated with previously unreported signs of fetal hypoxia, placental infarcts, and possibly excess risk of fetal demise, according to a study presented in poster form at the annual meeting of the Society for Maternal-Fetal Medicine.

“In the past, we have just told these patients, 'Come in every trimester, and we will check your urine [because of increased risk for a urinary tract infection].' Maybe that's not safe,” the study's lead author, Michelle Y. Taylor, M.D., of the department of obstetrics and gynecology at the University of Mississippi Medical Center, Jackson, said in an interview.

In a case review of 131 pregnancies with confirmed sickle cell trait, in which a detailed pathological examination of the placenta was performed, the researchers found that all of the placentas had aggregates of sickled red blood cells in the intervillous space and decidual vessels.

In addition, 92% of the cases had evidence of meconium passage, suggesting hypoxia, and 50% had evidence of an ascending amniotic fluid infection.

There were frank placental infarcts in 16 cases and retroplacental hemorrhage in 11 cases.

There were 10 cases of intrauterine fetal demise (of which 4 were in the cases with infarction), and 1 neonatal death.

Intrauterine growth restriction occurred in 14 cases.

The investigation found a higher-than-expected rate of fetal loss, and no risk factors were noted other than the probability that sickling in the decidual vessels resulted in decreased placental perfusion, Dr. Taylor said in the interview.

All patients in the study were African American, and the group's average age was 24 years.

The average gestational age at delivery was 30 weeks, and all the pregnancies had to be at least 16 weeks to be in the study. A total of 123 pregnancies were singleton gestations, and 8 were twin gestations.

Hypertension was present in 16% of cases.

RENO, NEV. — Sickle cell trait is associated with previously unreported signs of fetal hypoxia, placental infarcts, and possibly excess risk of fetal demise, according to a study presented in poster form at the annual meeting of the Society for Maternal-Fetal Medicine.

“In the past, we have just told these patients, 'Come in every trimester, and we will check your urine [because of increased risk for a urinary tract infection].' Maybe that's not safe,” the study's lead author, Michelle Y. Taylor, M.D., of the department of obstetrics and gynecology at the University of Mississippi Medical Center, Jackson, said in an interview.

In a case review of 131 pregnancies with confirmed sickle cell trait, in which a detailed pathological examination of the placenta was performed, the researchers found that all of the placentas had aggregates of sickled red blood cells in the intervillous space and decidual vessels.

In addition, 92% of the cases had evidence of meconium passage, suggesting hypoxia, and 50% had evidence of an ascending amniotic fluid infection.

There were frank placental infarcts in 16 cases and retroplacental hemorrhage in 11 cases.

There were 10 cases of intrauterine fetal demise (of which 4 were in the cases with infarction), and 1 neonatal death.

Intrauterine growth restriction occurred in 14 cases.

The investigation found a higher-than-expected rate of fetal loss, and no risk factors were noted other than the probability that sickling in the decidual vessels resulted in decreased placental perfusion, Dr. Taylor said in the interview.

All patients in the study were African American, and the group's average age was 24 years.

The average gestational age at delivery was 30 weeks, and all the pregnancies had to be at least 16 weeks to be in the study. A total of 123 pregnancies were singleton gestations, and 8 were twin gestations.

Hypertension was present in 16% of cases.

The oral pathogen Actinomyces naeslundii appears to be associated with shorter gestation resulting in preterm low birth weight, while oral Lactobacillus casei is associated with longer gestation and higher birth weight.

Increased levels of A. naeslundii could account for as much as 4%-6% of preterm low-birth-weight babies, although more research is necessary to confirm causality, said Ananda P. Dasanayake, D.D.S., of the New York University College of Dentistry, and his colleagues (J. Periodontol. 2005;76:171-7).

The epidemiologic study offers one more tantalizing glimpse at the interrelationship between oral health and systemic disease, and points up the importance of dental care during pregnancy.

“It is advisable to tell patients to seek dental care during pregnancy,” Dr. Dasanayake said in an interview. “If they have chronic periodontal disease, that can be treated—usually mechanically, by scaling and root planing, but sometimes with combination therapy that includes antibiotics.”

Dr. Dasanayake and his colleagues compared the presence of oral bacteria during the third trimester and at delivery with pregnancy outcomes in 297 primigravidas. The women's mean age was 20 years; 93% were African American. About 85% had at least a high school education. Saliva samples were obtained by expectoration after chewing on sterile paraffin wax.

Samples were tested for A. naeslundii, L. casei, Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinus, and Lactobacillus acidophilus.

Most of the women (67%) had normal vaginal deliveries. The average infant birth weight was 3,200 g and average gestational age was 39 weeks. There were 26 low-birth-weight deliveries and 28 preterm deliveries.

In a multivariate analysis, the only bacteria significantly associated with pregnancy outcomes were A. naeslundii and L. casei.

Increasing numbers of A. naeslundii were significantly associated with preterm low birth weight.

For every one-unit increase in A. naeslundii levels, there was a 60-g decrease in birth weight and a 0.17-week decrease in gestational age.

L. casei was associated with increasing gestational age.

Each unit increase in L. casei was associated with a 0.13-week increase in gestational age.

The connection between oral bacteria and preterm birth is biologically plausible, Dr. Dasanayake said.

Infections trigger inflammation and increase cytokines, which in turn can increase prostaglandins and lead to cervical dilation and uterine contraction.

Conversely, oral L. casei—which is associated with the incidence of dental caries—can have a protective effect by colonizing the vagina (migrating via elimination), where it suppresses the growth of pathogenic bacteria and inhibits bacterial vaginosis.

Because of the epidemiologic nature of the study, he said, it was not possible to separate the actual effect of either bacterial level from other contributing factors, such as drug and alcohol use or smoking.

However, two ongoing randomized controlled trials, one in South America and one in the United States, may give more specific information.

“In these studies, pregnant women are randomized into two groups—one group has their periodontal disease treated during pregnancy and one group has it treated after pregnancy,” Dr. Dasanayake said.

He added that several studies, including one of his own, have failed to find any association between oral bacteria and pregnancy outcome.

His study was performed in Sri Lanka with women who did not use tobacco, alcohol, or drugs because of cultural taboos and very low socioeconomic status. No association was seen in this group of women.

The oral pathogen Actinomyces naeslundii appears to be associated with shorter gestation resulting in preterm low birth weight, while oral Lactobacillus casei is associated with longer gestation and higher birth weight.

Increased levels of A. naeslundii could account for as much as 4%-6% of preterm low-birth-weight babies, although more research is necessary to confirm causality, said Ananda P. Dasanayake, D.D.S., of the New York University College of Dentistry, and his colleagues (J. Periodontol. 2005;76:171-7).

The epidemiologic study offers one more tantalizing glimpse at the interrelationship between oral health and systemic disease, and points up the importance of dental care during pregnancy.

“It is advisable to tell patients to seek dental care during pregnancy,” Dr. Dasanayake said in an interview. “If they have chronic periodontal disease, that can be treated—usually mechanically, by scaling and root planing, but sometimes with combination therapy that includes antibiotics.”

Dr. Dasanayake and his colleagues compared the presence of oral bacteria during the third trimester and at delivery with pregnancy outcomes in 297 primigravidas. The women's mean age was 20 years; 93% were African American. About 85% had at least a high school education. Saliva samples were obtained by expectoration after chewing on sterile paraffin wax.

Samples were tested for A. naeslundii, L. casei, Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinus, and Lactobacillus acidophilus.

Most of the women (67%) had normal vaginal deliveries. The average infant birth weight was 3,200 g and average gestational age was 39 weeks. There were 26 low-birth-weight deliveries and 28 preterm deliveries.

In a multivariate analysis, the only bacteria significantly associated with pregnancy outcomes were A. naeslundii and L. casei.

Increasing numbers of A. naeslundii were significantly associated with preterm low birth weight.

For every one-unit increase in A. naeslundii levels, there was a 60-g decrease in birth weight and a 0.17-week decrease in gestational age.

L. casei was associated with increasing gestational age.

Each unit increase in L. casei was associated with a 0.13-week increase in gestational age.

The connection between oral bacteria and preterm birth is biologically plausible, Dr. Dasanayake said.

Infections trigger inflammation and increase cytokines, which in turn can increase prostaglandins and lead to cervical dilation and uterine contraction.

Conversely, oral L. casei—which is associated with the incidence of dental caries—can have a protective effect by colonizing the vagina (migrating via elimination), where it suppresses the growth of pathogenic bacteria and inhibits bacterial vaginosis.

Because of the epidemiologic nature of the study, he said, it was not possible to separate the actual effect of either bacterial level from other contributing factors, such as drug and alcohol use or smoking.

However, two ongoing randomized controlled trials, one in South America and one in the United States, may give more specific information.

“In these studies, pregnant women are randomized into two groups—one group has their periodontal disease treated during pregnancy and one group has it treated after pregnancy,” Dr. Dasanayake said.

He added that several studies, including one of his own, have failed to find any association between oral bacteria and pregnancy outcome.

His study was performed in Sri Lanka with women who did not use tobacco, alcohol, or drugs because of cultural taboos and very low socioeconomic status. No association was seen in this group of women.

The oral pathogen Actinomyces naeslundii appears to be associated with shorter gestation resulting in preterm low birth weight, while oral Lactobacillus casei is associated with longer gestation and higher birth weight.

Increased levels of A. naeslundii could account for as much as 4%-6% of preterm low-birth-weight babies, although more research is necessary to confirm causality, said Ananda P. Dasanayake, D.D.S., of the New York University College of Dentistry, and his colleagues (J. Periodontol. 2005;76:171-7).

The epidemiologic study offers one more tantalizing glimpse at the interrelationship between oral health and systemic disease, and points up the importance of dental care during pregnancy.

“It is advisable to tell patients to seek dental care during pregnancy,” Dr. Dasanayake said in an interview. “If they have chronic periodontal disease, that can be treated—usually mechanically, by scaling and root planing, but sometimes with combination therapy that includes antibiotics.”

Dr. Dasanayake and his colleagues compared the presence of oral bacteria during the third trimester and at delivery with pregnancy outcomes in 297 primigravidas. The women's mean age was 20 years; 93% were African American. About 85% had at least a high school education. Saliva samples were obtained by expectoration after chewing on sterile paraffin wax.

Samples were tested for A. naeslundii, L. casei, Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinus, and Lactobacillus acidophilus.

Most of the women (67%) had normal vaginal deliveries. The average infant birth weight was 3,200 g and average gestational age was 39 weeks. There were 26 low-birth-weight deliveries and 28 preterm deliveries.

In a multivariate analysis, the only bacteria significantly associated with pregnancy outcomes were A. naeslundii and L. casei.

Increasing numbers of A. naeslundii were significantly associated with preterm low birth weight.

For every one-unit increase in A. naeslundii levels, there was a 60-g decrease in birth weight and a 0.17-week decrease in gestational age.

L. casei was associated with increasing gestational age.

Each unit increase in L. casei was associated with a 0.13-week increase in gestational age.

The connection between oral bacteria and preterm birth is biologically plausible, Dr. Dasanayake said.

Infections trigger inflammation and increase cytokines, which in turn can increase prostaglandins and lead to cervical dilation and uterine contraction.

Conversely, oral L. casei—which is associated with the incidence of dental caries—can have a protective effect by colonizing the vagina (migrating via elimination), where it suppresses the growth of pathogenic bacteria and inhibits bacterial vaginosis.

Because of the epidemiologic nature of the study, he said, it was not possible to separate the actual effect of either bacterial level from other contributing factors, such as drug and alcohol use or smoking.

However, two ongoing randomized controlled trials, one in South America and one in the United States, may give more specific information.

“In these studies, pregnant women are randomized into two groups—one group has their periodontal disease treated during pregnancy and one group has it treated after pregnancy,” Dr. Dasanayake said.

He added that several studies, including one of his own, have failed to find any association between oral bacteria and pregnancy outcome.

His study was performed in Sri Lanka with women who did not use tobacco, alcohol, or drugs because of cultural taboos and very low socioeconomic status. No association was seen in this group of women.

RENO, NEV. — Allowing a labor induction in a nulliparous patient to proceed for up to 18 hours is a reasonable practice that does not increase the rate of serious neonatal or maternal morbidity and results in vaginal delivery for most patients.

That finding emerged from a study presented in a poster by Charla E. Simon, M.D., and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

The investigators reported on the outcomes of 397 prospectively enrolled nulliparous patients undergoing labor induction, some of whom had a latent phase that went on for 24 hours.

During the first 18 hours, there was no great increase in the percentage of patients who went to cesarean delivery, and—although chorioamnionitis and postpartum hemorrhage became more frequent the longer an induction went on—this did not result in a greater rate of transfusion, hysterectomy, or prolonged hospitalization.

“I think the investigation shows we can be a little patient, and everything is still going to be okay,” Dr. Simon, of the department of obstetrics and gynecology at Northwestern University, Chicago, said in an interview.

After 18 hours, however, the rate of cesarean delivery increased significantly, as did the rate of infant admission to the neonatal intensive care unit.

All of the patients in Dr. Simon's investigation were at 36 weeks' gestation or later, and the outcomes were stratified by the length of the patient's latent phase of labor, which started with the initiation of oxytocin and the performance of an amniotomy and ended either with a cervical dilation of 4 cm with 80% effacement or with a 5-cm dilation with less effacement.

The cesarean rate was less than 20% for those with a latent phase of 0-6 hours. That rate increased to about 30% for those with a longer latent phase and stayed there, even for those in latent labor up to 18 hours. But after 18 hours, the rate rose to almost 70%.

The rate of postpartum hemorrhage was about 12% for those with a latent phase of 12-18 hours. It jumped to 26% for those with a latent phase longer than 18 hours.

The rate of chorioamnionitis was 10% for those with a latent phase of 6-12 hours, jumped to 28% for 12-18 hours, and fell to 16% for those latent over 18 hours.

Regarding neonatal morbidity, the percentage of infants with an Apgar score less than 7 was about 2% when the mothers had latent labor lasting 6-12 hours; it rose to 8% when mothers were latent for 12-18 hours, and to 10% when mothers were latent longer than 18 hours.

The rate of infants admitted to the neonatal intensive care unit was 6% when the mothers had a latent phase of 12-18 hours, and slightly more than 10% when latent labor was longer than 18 hours.

Overall, the study found that by 18 hours, 95% of the induced nulliparous women had entered active labor.

Source: Dr. Rochon

RENO, NEV. — Allowing a labor induction in a nulliparous patient to proceed for up to 18 hours is a reasonable practice that does not increase the rate of serious neonatal or maternal morbidity and results in vaginal delivery for most patients.

That finding emerged from a study presented in a poster by Charla E. Simon, M.D., and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

The investigators reported on the outcomes of 397 prospectively enrolled nulliparous patients undergoing labor induction, some of whom had a latent phase that went on for 24 hours.

During the first 18 hours, there was no great increase in the percentage of patients who went to cesarean delivery, and—although chorioamnionitis and postpartum hemorrhage became more frequent the longer an induction went on—this did not result in a greater rate of transfusion, hysterectomy, or prolonged hospitalization.

“I think the investigation shows we can be a little patient, and everything is still going to be okay,” Dr. Simon, of the department of obstetrics and gynecology at Northwestern University, Chicago, said in an interview.

After 18 hours, however, the rate of cesarean delivery increased significantly, as did the rate of infant admission to the neonatal intensive care unit.

All of the patients in Dr. Simon's investigation were at 36 weeks' gestation or later, and the outcomes were stratified by the length of the patient's latent phase of labor, which started with the initiation of oxytocin and the performance of an amniotomy and ended either with a cervical dilation of 4 cm with 80% effacement or with a 5-cm dilation with less effacement.

The cesarean rate was less than 20% for those with a latent phase of 0-6 hours. That rate increased to about 30% for those with a longer latent phase and stayed there, even for those in latent labor up to 18 hours. But after 18 hours, the rate rose to almost 70%.

The rate of postpartum hemorrhage was about 12% for those with a latent phase of 12-18 hours. It jumped to 26% for those with a latent phase longer than 18 hours.

The rate of chorioamnionitis was 10% for those with a latent phase of 6-12 hours, jumped to 28% for 12-18 hours, and fell to 16% for those latent over 18 hours.

Regarding neonatal morbidity, the percentage of infants with an Apgar score less than 7 was about 2% when the mothers had latent labor lasting 6-12 hours; it rose to 8% when mothers were latent for 12-18 hours, and to 10% when mothers were latent longer than 18 hours.

The rate of infants admitted to the neonatal intensive care unit was 6% when the mothers had a latent phase of 12-18 hours, and slightly more than 10% when latent labor was longer than 18 hours.

Overall, the study found that by 18 hours, 95% of the induced nulliparous women had entered active labor.

Source: Dr. Rochon

RENO, NEV. — Allowing a labor induction in a nulliparous patient to proceed for up to 18 hours is a reasonable practice that does not increase the rate of serious neonatal or maternal morbidity and results in vaginal delivery for most patients.

That finding emerged from a study presented in a poster by Charla E. Simon, M.D., and associates at the annual meeting of the Society for Maternal-Fetal Medicine.

The investigators reported on the outcomes of 397 prospectively enrolled nulliparous patients undergoing labor induction, some of whom had a latent phase that went on for 24 hours.

During the first 18 hours, there was no great increase in the percentage of patients who went to cesarean delivery, and—although chorioamnionitis and postpartum hemorrhage became more frequent the longer an induction went on—this did not result in a greater rate of transfusion, hysterectomy, or prolonged hospitalization.

“I think the investigation shows we can be a little patient, and everything is still going to be okay,” Dr. Simon, of the department of obstetrics and gynecology at Northwestern University, Chicago, said in an interview.

After 18 hours, however, the rate of cesarean delivery increased significantly, as did the rate of infant admission to the neonatal intensive care unit.

All of the patients in Dr. Simon's investigation were at 36 weeks' gestation or later, and the outcomes were stratified by the length of the patient's latent phase of labor, which started with the initiation of oxytocin and the performance of an amniotomy and ended either with a cervical dilation of 4 cm with 80% effacement or with a 5-cm dilation with less effacement.

The cesarean rate was less than 20% for those with a latent phase of 0-6 hours. That rate increased to about 30% for those with a longer latent phase and stayed there, even for those in latent labor up to 18 hours. But after 18 hours, the rate rose to almost 70%.

The rate of postpartum hemorrhage was about 12% for those with a latent phase of 12-18 hours. It jumped to 26% for those with a latent phase longer than 18 hours.

The rate of chorioamnionitis was 10% for those with a latent phase of 6-12 hours, jumped to 28% for 12-18 hours, and fell to 16% for those latent over 18 hours.

Regarding neonatal morbidity, the percentage of infants with an Apgar score less than 7 was about 2% when the mothers had latent labor lasting 6-12 hours; it rose to 8% when mothers were latent for 12-18 hours, and to 10% when mothers were latent longer than 18 hours.

The rate of infants admitted to the neonatal intensive care unit was 6% when the mothers had a latent phase of 12-18 hours, and slightly more than 10% when latent labor was longer than 18 hours.

Overall, the study found that by 18 hours, 95% of the induced nulliparous women had entered active labor.

Source: Dr. Rochon

RENO, NEV. — Digital or manual rotation of fetuses in the persistent occipitoposterior position reduces the need for instrumental deliveries and cesarean section, reported O. Reichman, M.D., and colleagues at Shaare Zedek Medical Center, Jerusalem.

In a prospective, nonrandomized study, the investigators studied 61 women with a fetus in the occipitoposterior position who had completed half of the normal second stage of labor. The first group of 30 women was allowed to continue labor without intervention. The second group of 31 women underwent digital or manual rotation, the authors wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

There were no significant differences in demographic characteristics between the two groups.

The digital maneuver entails first placing the tips of the index and middle fingers onto the edge of the part of the anterior parietal bone that overlaps the occipital bone in the area of the posterior fontanelle. Next, the clinician exerts pressure with the tips of the fingers to rotate the posterior fontanelle upward and toward the symphysis pubis.

With manual rotation, the clinician inserts the entire hand into the birth canal. He or she first positions the fingers under the lateral posterior parietal bone and the thumb on the anterior parietal bone, and then rotates the fetus's head.

Only 8 of the women in the no-rotation group (27%), compared with 24 in the rotation group (77%), experienced a spontaneous delivery, a significant difference.

A significantly greater percentage of the women in the no-rotation group underwent vacuum extraction (50% vs. 23%) and cesarean section (23% vs. 0%).

In addition, digital/manual rotation was associated with a significantly shorter second stage of labor. As a group, women who underwent digital/manual rotation had a significantly shorter mean hospital stay (3.5 days) than did women in the no-rotation group (4.4 days).

Previous epidemiologic studies have estimated the prevalence of the occipitoposterior position to be about 5%. Among such pregnancies, there is a high incidence of cesarean section, instrumental delivery, third- and fourth-degree perineal tear, postpartum hemorrhage, and puerperal infection.

Although the poster did not mention any adverse events that may have been associated with digital/manual rotation, the authors suggested that the maneuver be considered in cases of occipitoposterior malposition.

RENO, NEV. — Digital or manual rotation of fetuses in the persistent occipitoposterior position reduces the need for instrumental deliveries and cesarean section, reported O. Reichman, M.D., and colleagues at Shaare Zedek Medical Center, Jerusalem.

In a prospective, nonrandomized study, the investigators studied 61 women with a fetus in the occipitoposterior position who had completed half of the normal second stage of labor. The first group of 30 women was allowed to continue labor without intervention. The second group of 31 women underwent digital or manual rotation, the authors wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

There were no significant differences in demographic characteristics between the two groups.

The digital maneuver entails first placing the tips of the index and middle fingers onto the edge of the part of the anterior parietal bone that overlaps the occipital bone in the area of the posterior fontanelle. Next, the clinician exerts pressure with the tips of the fingers to rotate the posterior fontanelle upward and toward the symphysis pubis.

With manual rotation, the clinician inserts the entire hand into the birth canal. He or she first positions the fingers under the lateral posterior parietal bone and the thumb on the anterior parietal bone, and then rotates the fetus's head.

Only 8 of the women in the no-rotation group (27%), compared with 24 in the rotation group (77%), experienced a spontaneous delivery, a significant difference.

A significantly greater percentage of the women in the no-rotation group underwent vacuum extraction (50% vs. 23%) and cesarean section (23% vs. 0%).

In addition, digital/manual rotation was associated with a significantly shorter second stage of labor. As a group, women who underwent digital/manual rotation had a significantly shorter mean hospital stay (3.5 days) than did women in the no-rotation group (4.4 days).

Previous epidemiologic studies have estimated the prevalence of the occipitoposterior position to be about 5%. Among such pregnancies, there is a high incidence of cesarean section, instrumental delivery, third- and fourth-degree perineal tear, postpartum hemorrhage, and puerperal infection.

Although the poster did not mention any adverse events that may have been associated with digital/manual rotation, the authors suggested that the maneuver be considered in cases of occipitoposterior malposition.

RENO, NEV. — Digital or manual rotation of fetuses in the persistent occipitoposterior position reduces the need for instrumental deliveries and cesarean section, reported O. Reichman, M.D., and colleagues at Shaare Zedek Medical Center, Jerusalem.

In a prospective, nonrandomized study, the investigators studied 61 women with a fetus in the occipitoposterior position who had completed half of the normal second stage of labor. The first group of 30 women was allowed to continue labor without intervention. The second group of 31 women underwent digital or manual rotation, the authors wrote in a poster presented at the annual meeting of the Society for Maternal-Fetal Medicine.

There were no significant differences in demographic characteristics between the two groups.

The digital maneuver entails first placing the tips of the index and middle fingers onto the edge of the part of the anterior parietal bone that overlaps the occipital bone in the area of the posterior fontanelle. Next, the clinician exerts pressure with the tips of the fingers to rotate the posterior fontanelle upward and toward the symphysis pubis.

With manual rotation, the clinician inserts the entire hand into the birth canal. He or she first positions the fingers under the lateral posterior parietal bone and the thumb on the anterior parietal bone, and then rotates the fetus's head.

Only 8 of the women in the no-rotation group (27%), compared with 24 in the rotation group (77%), experienced a spontaneous delivery, a significant difference.

A significantly greater percentage of the women in the no-rotation group underwent vacuum extraction (50% vs. 23%) and cesarean section (23% vs. 0%).

In addition, digital/manual rotation was associated with a significantly shorter second stage of labor. As a group, women who underwent digital/manual rotation had a significantly shorter mean hospital stay (3.5 days) than did women in the no-rotation group (4.4 days).

Previous epidemiologic studies have estimated the prevalence of the occipitoposterior position to be about 5%. Among such pregnancies, there is a high incidence of cesarean section, instrumental delivery, third- and fourth-degree perineal tear, postpartum hemorrhage, and puerperal infection.

Although the poster did not mention any adverse events that may have been associated with digital/manual rotation, the authors suggested that the maneuver be considered in cases of occipitoposterior malposition.

RENO, NEV. — New technologies that can screen through the entire metabolite or protein compliment of a fluid will soon produce both a test that can correctly identify the patient experiencing early contractions who will deliver prematurely, and a maternal blood test perhaps 100% accurate for Down syndrome, predicted two speakers at the annual meeting of the Society for Maternal-Fetal Medicine.

These tests could be ready for the clinic in a few years, the speakers said.

In much the same way that researchers can study genomics to identify all the genes in a particular cell, and RNA transcriptomics to identify specific genes being expressed in a cell, it is now possible to study proteomics and even metabolomics, to profile all the biochemical components of a given cell, organ system, or fluid in hopes of identifying specific biomarkers for a given condition.

Using that technology, investigators have now identified a profile of amniotic fluid that predicts which patients who go into premature labor with intact membranes will deliver early and therefore warrant tocolysis, said Roberto Romero, M.D., chief of the perinatology research branch of the National Institute of Child Health and Human Development.

Dr. Romero said he and his coworkers profiled 186 metabolites from the amniotic fluid taken from 115 women who were having premature contractions, and were able to find a group of carbohydrates that correctly identified those who actually delivered preterm with 88% accuracy. The women who delivered early had low concentrations of this group of carbohydrates, while those who did not deliver had high concentrations.

The profile correctly identified 39 of 40 patients who delivered at term, 29 of 33 patients who delivered early but had no evidence of intraamniotic inflammation, and all 42 of the patients who delivered early and had evidence of inflammation.

The individual carbohydrates in the group are not unique in any way, Dr. Romero said, and he speculated that they are fetal products.

Dr. Romero declared no personal financial conflict of interest with regard to the study, but the National Institutes of Health has applied for a patent based on the team's findings.

In another presentation, Mary D'Alton, M.D., said she and her colleagues took maternal serum from 50 Down syndrome-affected pregnancies and compared it with serum from 50 unaffected pregnancies, and have been able to identify a group of six proteins that when combined as biomarkers can pick up Down syndrome with 100% accuracy.

Two of these protein biomarkers are overexpressed in Down syndrome cases and four are underexpressed, and this pattern is present in both the first and second trimesters, said Dr. D'Alton, director of the division of maternal-fetal medicine at New York-Presbyterian Hospital, New York.

Most of these proteins have not previously been known to be associated with Down syndrome, and none of them are products of the expression of genes on chromosome 21, she added.

Dr. D'Alton's study was supported by the NIH and ProteoGenix Inc. of Portland, Ore.

RENO, NEV. — New technologies that can screen through the entire metabolite or protein compliment of a fluid will soon produce both a test that can correctly identify the patient experiencing early contractions who will deliver prematurely, and a maternal blood test perhaps 100% accurate for Down syndrome, predicted two speakers at the annual meeting of the Society for Maternal-Fetal Medicine.

These tests could be ready for the clinic in a few years, the speakers said.

In much the same way that researchers can study genomics to identify all the genes in a particular cell, and RNA transcriptomics to identify specific genes being expressed in a cell, it is now possible to study proteomics and even metabolomics, to profile all the biochemical components of a given cell, organ system, or fluid in hopes of identifying specific biomarkers for a given condition.

Using that technology, investigators have now identified a profile of amniotic fluid that predicts which patients who go into premature labor with intact membranes will deliver early and therefore warrant tocolysis, said Roberto Romero, M.D., chief of the perinatology research branch of the National Institute of Child Health and Human Development.

Dr. Romero said he and his coworkers profiled 186 metabolites from the amniotic fluid taken from 115 women who were having premature contractions, and were able to find a group of carbohydrates that correctly identified those who actually delivered preterm with 88% accuracy. The women who delivered early had low concentrations of this group of carbohydrates, while those who did not deliver had high concentrations.

The profile correctly identified 39 of 40 patients who delivered at term, 29 of 33 patients who delivered early but had no evidence of intraamniotic inflammation, and all 42 of the patients who delivered early and had evidence of inflammation.

The individual carbohydrates in the group are not unique in any way, Dr. Romero said, and he speculated that they are fetal products.

Dr. Romero declared no personal financial conflict of interest with regard to the study, but the National Institutes of Health has applied for a patent based on the team's findings.

In another presentation, Mary D'Alton, M.D., said she and her colleagues took maternal serum from 50 Down syndrome-affected pregnancies and compared it with serum from 50 unaffected pregnancies, and have been able to identify a group of six proteins that when combined as biomarkers can pick up Down syndrome with 100% accuracy.

Two of these protein biomarkers are overexpressed in Down syndrome cases and four are underexpressed, and this pattern is present in both the first and second trimesters, said Dr. D'Alton, director of the division of maternal-fetal medicine at New York-Presbyterian Hospital, New York.

Most of these proteins have not previously been known to be associated with Down syndrome, and none of them are products of the expression of genes on chromosome 21, she added.

Dr. D'Alton's study was supported by the NIH and ProteoGenix Inc. of Portland, Ore.

RENO, NEV. — New technologies that can screen through the entire metabolite or protein compliment of a fluid will soon produce both a test that can correctly identify the patient experiencing early contractions who will deliver prematurely, and a maternal blood test perhaps 100% accurate for Down syndrome, predicted two speakers at the annual meeting of the Society for Maternal-Fetal Medicine.

These tests could be ready for the clinic in a few years, the speakers said.

In much the same way that researchers can study genomics to identify all the genes in a particular cell, and RNA transcriptomics to identify specific genes being expressed in a cell, it is now possible to study proteomics and even metabolomics, to profile all the biochemical components of a given cell, organ system, or fluid in hopes of identifying specific biomarkers for a given condition.

Using that technology, investigators have now identified a profile of amniotic fluid that predicts which patients who go into premature labor with intact membranes will deliver early and therefore warrant tocolysis, said Roberto Romero, M.D., chief of the perinatology research branch of the National Institute of Child Health and Human Development.

Dr. Romero said he and his coworkers profiled 186 metabolites from the amniotic fluid taken from 115 women who were having premature contractions, and were able to find a group of carbohydrates that correctly identified those who actually delivered preterm with 88% accuracy. The women who delivered early had low concentrations of this group of carbohydrates, while those who did not deliver had high concentrations.

The profile correctly identified 39 of 40 patients who delivered at term, 29 of 33 patients who delivered early but had no evidence of intraamniotic inflammation, and all 42 of the patients who delivered early and had evidence of inflammation.

The individual carbohydrates in the group are not unique in any way, Dr. Romero said, and he speculated that they are fetal products.

Dr. Romero declared no personal financial conflict of interest with regard to the study, but the National Institutes of Health has applied for a patent based on the team's findings.

In another presentation, Mary D'Alton, M.D., said she and her colleagues took maternal serum from 50 Down syndrome-affected pregnancies and compared it with serum from 50 unaffected pregnancies, and have been able to identify a group of six proteins that when combined as biomarkers can pick up Down syndrome with 100% accuracy.

Two of these protein biomarkers are overexpressed in Down syndrome cases and four are underexpressed, and this pattern is present in both the first and second trimesters, said Dr. D'Alton, director of the division of maternal-fetal medicine at New York-Presbyterian Hospital, New York.

Most of these proteins have not previously been known to be associated with Down syndrome, and none of them are products of the expression of genes on chromosome 21, she added.

Dr. D'Alton's study was supported by the NIH and ProteoGenix Inc. of Portland, Ore.

RENO, NEV. — While many physicians commonly use oral tocolysis maintenance after intravenous tocolysis in patients with preterm labor because they have a clinical impression of its effectiveness, solid evidence for this practice has been lacking until recently, according to Perkin Stang, M.D., of Wayne State University, Detroit, and colleagues.

Their population-based historical cohort study suggests that pregnant patients who are not maintained on oral tocolysis are more than twice as likely to deliver prematurely as are those who do receive oral maintenance, the investigators reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 170,258 patients from a perinatal database in the state of Schleswig-Holstein, Germany.

Of those patients, 9,542 with preterm labor who received intravenous tocolysis were included in the study. Women with premature rupture of membranes and medically indicated inductions before 37 weeks of gestation were excluded from the analysis.

Investigators compared 4,936 women who received oral maintenance tocolysis with a β-sympathomimetic agent to 4,536 women who did not receive oral tocolysis. (Data were unavailable for the remaining 70 patients.)

In the oral tocolysis group, 366 patients (7%) delivered prematurely versus 1,094 patients (24%) in the control group.

After adjusting the results for possible confounding variables such as prior preterm delivery, cerclage, incompetent cervix, duration of intravenous tocolysis, and obesity, investigators calculated an odds ratio of 2.4 for preterm delivery in patients who were not maintained on oral tocolysis.

RENO, NEV. — While many physicians commonly use oral tocolysis maintenance after intravenous tocolysis in patients with preterm labor because they have a clinical impression of its effectiveness, solid evidence for this practice has been lacking until recently, according to Perkin Stang, M.D., of Wayne State University, Detroit, and colleagues.

Their population-based historical cohort study suggests that pregnant patients who are not maintained on oral tocolysis are more than twice as likely to deliver prematurely as are those who do receive oral maintenance, the investigators reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 170,258 patients from a perinatal database in the state of Schleswig-Holstein, Germany.

Of those patients, 9,542 with preterm labor who received intravenous tocolysis were included in the study. Women with premature rupture of membranes and medically indicated inductions before 37 weeks of gestation were excluded from the analysis.

Investigators compared 4,936 women who received oral maintenance tocolysis with a β-sympathomimetic agent to 4,536 women who did not receive oral tocolysis. (Data were unavailable for the remaining 70 patients.)

In the oral tocolysis group, 366 patients (7%) delivered prematurely versus 1,094 patients (24%) in the control group.

After adjusting the results for possible confounding variables such as prior preterm delivery, cerclage, incompetent cervix, duration of intravenous tocolysis, and obesity, investigators calculated an odds ratio of 2.4 for preterm delivery in patients who were not maintained on oral tocolysis.

RENO, NEV. — While many physicians commonly use oral tocolysis maintenance after intravenous tocolysis in patients with preterm labor because they have a clinical impression of its effectiveness, solid evidence for this practice has been lacking until recently, according to Perkin Stang, M.D., of Wayne State University, Detroit, and colleagues.

Their population-based historical cohort study suggests that pregnant patients who are not maintained on oral tocolysis are more than twice as likely to deliver prematurely as are those who do receive oral maintenance, the investigators reported in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

The study involved 170,258 patients from a perinatal database in the state of Schleswig-Holstein, Germany.

Of those patients, 9,542 with preterm labor who received intravenous tocolysis were included in the study. Women with premature rupture of membranes and medically indicated inductions before 37 weeks of gestation were excluded from the analysis.

Investigators compared 4,936 women who received oral maintenance tocolysis with a β-sympathomimetic agent to 4,536 women who did not receive oral tocolysis. (Data were unavailable for the remaining 70 patients.)

In the oral tocolysis group, 366 patients (7%) delivered prematurely versus 1,094 patients (24%) in the control group.

After adjusting the results for possible confounding variables such as prior preterm delivery, cerclage, incompetent cervix, duration of intravenous tocolysis, and obesity, investigators calculated an odds ratio of 2.4 for preterm delivery in patients who were not maintained on oral tocolysis.

RENO, NEV. — First-trimester aneuploidy screening is practical not just in the context of clinical trials but also in the everyday world of the clinic, according to a poster presented by Sriram C. Perni, M.D., and colleagues at the annual meeting of the Society for Maternal-Fetal Medicine.

Among 2,515 women evaluated at a single institution, trisomy 21 was detected in 91% of 22 pregnancies when the false-positive rate was set to 5% and in 77% of 22 pregnancies when the false-positive rate was set to 1%.

In that same group, trisomy 18 was detected in all eight affected pregnancies, whether the false-positive rate was set to 5% or 1%.

Aneuploidy screening in the first trimester relies on an algorithm incorporating four pieces of data: maternal age, blood levels of pregnancy-associated plasma protein A (PAPP-A), blood levels of free β-human chorionic gonadotrophin (free β-hCG), and ultrasound measurements of fetal nuchal translucency, Dr. Perni said.

A large, multicenter, clinical trial involving 8,514 patients found this algorithm to have a good sensitivity and an acceptable false-positive rate (N. Engl. J. Med. 2003;349:1405-13).

But it remained unclear whether the algorithm would perform as well in the real-world setting of a single institution, reported Dr. Perni and his colleagues at Weill Medical College of Cornell University, New York.

At their clinic, 4,883 pregnant women, who together had 5,167 fetuses, were offered first-trimester aneuploidy screening, and 2,515 women agreed.

Of those pregnancies, there were a total of 37 aneuploid fetuses—1 with trisomy 13, 8 with trisomy 18, 22 with trisomy 21, 4 with 45X, 1 with 47XXY, and 1 with triploidy.

Of the 22 cases of trisomy 21, 3 resulted in a live birth, and 19 were electively terminated. All eight fetuses with trisomy 18 were electively terminated.

Asked in an interview whether first-trimester aneuploidy screening remained controversial, Dr. Perni replied, “I don't think it's controversial, but right now it's not the standard of care. There needs to be more evidence that it's reproducible at a single institution like this.

“This is a very, very good test,” continued Dr. Perni, who disclaimed any financial interest in the test.

“It can be done very early and has a very good detection rate for fixed false-positive rates,” he said.

He said that many insurance carriers in New York City do cover the screening test. And while the test has become “almost the standard of care” in certain parts of the United States, “it just hasn't become vogue over the whole country.”

He added, “I think the most exciting thing about this is that we can get information for couples and women specifically very early on to help them determine what they want to do.”

RENO, NEV. — First-trimester aneuploidy screening is practical not just in the context of clinical trials but also in the everyday world of the clinic, according to a poster presented by Sriram C. Perni, M.D., and colleagues at the annual meeting of the Society for Maternal-Fetal Medicine.

Among 2,515 women evaluated at a single institution, trisomy 21 was detected in 91% of 22 pregnancies when the false-positive rate was set to 5% and in 77% of 22 pregnancies when the false-positive rate was set to 1%.

In that same group, trisomy 18 was detected in all eight affected pregnancies, whether the false-positive rate was set to 5% or 1%.

Aneuploidy screening in the first trimester relies on an algorithm incorporating four pieces of data: maternal age, blood levels of pregnancy-associated plasma protein A (PAPP-A), blood levels of free β-human chorionic gonadotrophin (free β-hCG), and ultrasound measurements of fetal nuchal translucency, Dr. Perni said.

A large, multicenter, clinical trial involving 8,514 patients found this algorithm to have a good sensitivity and an acceptable false-positive rate (N. Engl. J. Med. 2003;349:1405-13).

But it remained unclear whether the algorithm would perform as well in the real-world setting of a single institution, reported Dr. Perni and his colleagues at Weill Medical College of Cornell University, New York.

At their clinic, 4,883 pregnant women, who together had 5,167 fetuses, were offered first-trimester aneuploidy screening, and 2,515 women agreed.

Of those pregnancies, there were a total of 37 aneuploid fetuses—1 with trisomy 13, 8 with trisomy 18, 22 with trisomy 21, 4 with 45X, 1 with 47XXY, and 1 with triploidy.

Of the 22 cases of trisomy 21, 3 resulted in a live birth, and 19 were electively terminated. All eight fetuses with trisomy 18 were electively terminated.

Asked in an interview whether first-trimester aneuploidy screening remained controversial, Dr. Perni replied, “I don't think it's controversial, but right now it's not the standard of care. There needs to be more evidence that it's reproducible at a single institution like this.

“This is a very, very good test,” continued Dr. Perni, who disclaimed any financial interest in the test.

“It can be done very early and has a very good detection rate for fixed false-positive rates,” he said.

He said that many insurance carriers in New York City do cover the screening test. And while the test has become “almost the standard of care” in certain parts of the United States, “it just hasn't become vogue over the whole country.”

He added, “I think the most exciting thing about this is that we can get information for couples and women specifically very early on to help them determine what they want to do.”

RENO, NEV. — First-trimester aneuploidy screening is practical not just in the context of clinical trials but also in the everyday world of the clinic, according to a poster presented by Sriram C. Perni, M.D., and colleagues at the annual meeting of the Society for Maternal-Fetal Medicine.

Among 2,515 women evaluated at a single institution, trisomy 21 was detected in 91% of 22 pregnancies when the false-positive rate was set to 5% and in 77% of 22 pregnancies when the false-positive rate was set to 1%.

In that same group, trisomy 18 was detected in all eight affected pregnancies, whether the false-positive rate was set to 5% or 1%.

Aneuploidy screening in the first trimester relies on an algorithm incorporating four pieces of data: maternal age, blood levels of pregnancy-associated plasma protein A (PAPP-A), blood levels of free β-human chorionic gonadotrophin (free β-hCG), and ultrasound measurements of fetal nuchal translucency, Dr. Perni said.

A large, multicenter, clinical trial involving 8,514 patients found this algorithm to have a good sensitivity and an acceptable false-positive rate (N. Engl. J. Med. 2003;349:1405-13).

But it remained unclear whether the algorithm would perform as well in the real-world setting of a single institution, reported Dr. Perni and his colleagues at Weill Medical College of Cornell University, New York.

At their clinic, 4,883 pregnant women, who together had 5,167 fetuses, were offered first-trimester aneuploidy screening, and 2,515 women agreed.

Of those pregnancies, there were a total of 37 aneuploid fetuses—1 with trisomy 13, 8 with trisomy 18, 22 with trisomy 21, 4 with 45X, 1 with 47XXY, and 1 with triploidy.

Of the 22 cases of trisomy 21, 3 resulted in a live birth, and 19 were electively terminated. All eight fetuses with trisomy 18 were electively terminated.

Asked in an interview whether first-trimester aneuploidy screening remained controversial, Dr. Perni replied, “I don't think it's controversial, but right now it's not the standard of care. There needs to be more evidence that it's reproducible at a single institution like this.

“This is a very, very good test,” continued Dr. Perni, who disclaimed any financial interest in the test.

“It can be done very early and has a very good detection rate for fixed false-positive rates,” he said.

He said that many insurance carriers in New York City do cover the screening test. And while the test has become “almost the standard of care” in certain parts of the United States, “it just hasn't become vogue over the whole country.”

He added, “I think the most exciting thing about this is that we can get information for couples and women specifically very early on to help them determine what they want to do.”

RENO, NEV. — Newer, less invasive techniques have decreased morbidity associated with fetal surgery, but morbidity is still a concern in these surgeries, Robert H. Bell, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

The morbidity data come from a retrospective study of all fetal surgeries at the University of California, San Francisco, between July 1985 and May 2003, said Dr. Bell of the university.

During the early days of fetal surgery, most of the procedures involved open hysterotomy. Then fetal endoscopy (FETENDO) became popular, and now ultrasound-guided radiofrequency ablation (RFA) is the dominant procedure.

In all, 187 women with a mean maternal age of 29 (range 19-43) were treated during this period. Nine cases were marked by procedure-related fetal demise. Of the remaining 178 procedures, 79 involved a laparotomy and hysterotomy, 68 involved FETENDO, and 31 involved RFA.

Indications for the procedures included congenital diaphragmatic hernia in 38% of cases, monochorionic twin complications in 31%, hydrops in 11.8%, meningomyelocele in 8.6%, teratomas in 6.4%, and urinary obstruction in 2.1%.

The average gestational age for both hysterotomy and FETENDO was about 25 weeks, but RFA was done significantly earlier, at an average gestational age of about 21 weeks.

There were no significant differences in gestational age at delivery, with hysterotomy patients delivering at an average of 30.1 weeks, FETENDO patients delivering at 30.4 weeks, and RFA patients delivering at 32.7 weeks.

“Premature delivery, sadly, at this point is [a matter of] 'when' and not 'if,'” Dr. Bell said, although he pointed out that the data, averaged over a number of years of surgical experience, do not reflect recent improvements in lengthening pregnancies.

Premature rupture of membranes (PROM) is the primary cause of preterm delivery in these cases, and the rates of PROM are 52% in hysterotomy patients, 44% in FETENDO patients, and a significantly lower 13% in RFA patients.

About a quarter of the hysterotomy and FETENDO patients suffered pulmonary edema, a complication Dr. Bell attributed to deep inhalational anesthesia in the hysterotomy patients and the use of tocolytics in both hysterotomy and FETENDO patients.

None of the RFA patients suffered pulmonary edema (a statistically significant difference), reflecting recent changes in the treatment algorithm for preterm labor.

Another impressive improvement occurred in the average length of the patient's hospital stay. Although Dr. Bell said that clinicians at his institution are very cautious in managing patients in terms of surveillance and limitations of movement, the average length of stay has declined significantly from 11.9 days in the hysterotomy patients, to 7.9 days in the FETENDO patients, to 2.5 days in the RFA patients. And this understates the degree of improvement, since many RFA patients can now go home within 24 hours.

RENO, NEV. — Newer, less invasive techniques have decreased morbidity associated with fetal surgery, but morbidity is still a concern in these surgeries, Robert H. Bell, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

The morbidity data come from a retrospective study of all fetal surgeries at the University of California, San Francisco, between July 1985 and May 2003, said Dr. Bell of the university.

During the early days of fetal surgery, most of the procedures involved open hysterotomy. Then fetal endoscopy (FETENDO) became popular, and now ultrasound-guided radiofrequency ablation (RFA) is the dominant procedure.

In all, 187 women with a mean maternal age of 29 (range 19-43) were treated during this period. Nine cases were marked by procedure-related fetal demise. Of the remaining 178 procedures, 79 involved a laparotomy and hysterotomy, 68 involved FETENDO, and 31 involved RFA.

Indications for the procedures included congenital diaphragmatic hernia in 38% of cases, monochorionic twin complications in 31%, hydrops in 11.8%, meningomyelocele in 8.6%, teratomas in 6.4%, and urinary obstruction in 2.1%.

The average gestational age for both hysterotomy and FETENDO was about 25 weeks, but RFA was done significantly earlier, at an average gestational age of about 21 weeks.

There were no significant differences in gestational age at delivery, with hysterotomy patients delivering at an average of 30.1 weeks, FETENDO patients delivering at 30.4 weeks, and RFA patients delivering at 32.7 weeks.

“Premature delivery, sadly, at this point is [a matter of] 'when' and not 'if,'” Dr. Bell said, although he pointed out that the data, averaged over a number of years of surgical experience, do not reflect recent improvements in lengthening pregnancies.

Premature rupture of membranes (PROM) is the primary cause of preterm delivery in these cases, and the rates of PROM are 52% in hysterotomy patients, 44% in FETENDO patients, and a significantly lower 13% in RFA patients.

About a quarter of the hysterotomy and FETENDO patients suffered pulmonary edema, a complication Dr. Bell attributed to deep inhalational anesthesia in the hysterotomy patients and the use of tocolytics in both hysterotomy and FETENDO patients.

None of the RFA patients suffered pulmonary edema (a statistically significant difference), reflecting recent changes in the treatment algorithm for preterm labor.

Another impressive improvement occurred in the average length of the patient's hospital stay. Although Dr. Bell said that clinicians at his institution are very cautious in managing patients in terms of surveillance and limitations of movement, the average length of stay has declined significantly from 11.9 days in the hysterotomy patients, to 7.9 days in the FETENDO patients, to 2.5 days in the RFA patients. And this understates the degree of improvement, since many RFA patients can now go home within 24 hours.

RENO, NEV. — Newer, less invasive techniques have decreased morbidity associated with fetal surgery, but morbidity is still a concern in these surgeries, Robert H. Bell, M.D., said at the annual meeting of the Society for Maternal-Fetal Medicine.

The morbidity data come from a retrospective study of all fetal surgeries at the University of California, San Francisco, between July 1985 and May 2003, said Dr. Bell of the university.

During the early days of fetal surgery, most of the procedures involved open hysterotomy. Then fetal endoscopy (FETENDO) became popular, and now ultrasound-guided radiofrequency ablation (RFA) is the dominant procedure.

In all, 187 women with a mean maternal age of 29 (range 19-43) were treated during this period. Nine cases were marked by procedure-related fetal demise. Of the remaining 178 procedures, 79 involved a laparotomy and hysterotomy, 68 involved FETENDO, and 31 involved RFA.

Indications for the procedures included congenital diaphragmatic hernia in 38% of cases, monochorionic twin complications in 31%, hydrops in 11.8%, meningomyelocele in 8.6%, teratomas in 6.4%, and urinary obstruction in 2.1%.

The average gestational age for both hysterotomy and FETENDO was about 25 weeks, but RFA was done significantly earlier, at an average gestational age of about 21 weeks.

There were no significant differences in gestational age at delivery, with hysterotomy patients delivering at an average of 30.1 weeks, FETENDO patients delivering at 30.4 weeks, and RFA patients delivering at 32.7 weeks.

“Premature delivery, sadly, at this point is [a matter of] 'when' and not 'if,'” Dr. Bell said, although he pointed out that the data, averaged over a number of years of surgical experience, do not reflect recent improvements in lengthening pregnancies.

Premature rupture of membranes (PROM) is the primary cause of preterm delivery in these cases, and the rates of PROM are 52% in hysterotomy patients, 44% in FETENDO patients, and a significantly lower 13% in RFA patients.

About a quarter of the hysterotomy and FETENDO patients suffered pulmonary edema, a complication Dr. Bell attributed to deep inhalational anesthesia in the hysterotomy patients and the use of tocolytics in both hysterotomy and FETENDO patients.

None of the RFA patients suffered pulmonary edema (a statistically significant difference), reflecting recent changes in the treatment algorithm for preterm labor.

Another impressive improvement occurred in the average length of the patient's hospital stay. Although Dr. Bell said that clinicians at his institution are very cautious in managing patients in terms of surveillance and limitations of movement, the average length of stay has declined significantly from 11.9 days in the hysterotomy patients, to 7.9 days in the FETENDO patients, to 2.5 days in the RFA patients. And this understates the degree of improvement, since many RFA patients can now go home within 24 hours.