Obstetrics

WASHINGTON — Balancing immunosuppression in a pregnant allograft transplant patient with the health of the woman and her fetus requires a team approach between high-risk obstetricians and transplant physicians, according to one expert speaking at a meeting sponsored by the National Kidney Foundation.

“Pregnancy in the transplant recipient, aside from the issue of renal dysfunction, poses a unique set of considerations, and that's because of immunosuppressants,” said Michelle A. Josephson, M.D., of the University of Chicago.

None of the immunosuppressants used for transplantation—cyclosporine, tacrolimus, azathioprine, steroids, rapamycin, and mycophenolate mofetil—are rated pregnancy category A, using the Food and Drug Administration classification system. In fact, most are rated category C, meaning there are no data on their use in humans during pregnancy. “All medications used to prevent rejection cross the maternal-placental interface,” she pointed out.

Despite the lack of data and potential risks, a consensus group convened in 2003 by the Women's Health Committee of the American Society of Transplantation recommended immunosuppression be maintained during pregnancy to avoid rejection.

Graft rejection can be difficult to discern during pregnancy because serum creatinine levels are low during this period, and small changes can be missed, Dr. Josephson said. In addition, abnormalities that turn up on liver function tests can have a number of etiologies. For these reasons, graft dysfunction during pregnancy warrants appropriate investigation—by biopsy if necessary.

“If rejection occurs, it can be treated with steroids,” Dr. Josephson recommended. Inadequate immunosuppression, graft instability, and rejection likely affect the graft prognosis. However, age, number of allografts, and repeat pregnancies don't seem to impact graft function and prognosis.

The consensus group also agreed that a high-risk obstetrician and a transplant physician should manage pregnant transplant patients. Obstetricians should optimize maternal health, maintain normal glycemia, ensure adequate fetal growth, and anticipate preterm birth. The transplant physician should ensure maintenance of graft function and aggressively manage hypertension and preeclampsia. Cesarean section is not indicated except for standard obstetric reasons.

During the conference, experts addressed a number of concerns for this group of patients to develop management recommendations. “We recognized that the risk of prematurity in the population was high. We realized that intrauterine growth retardation is high,” said Dr. Josephson. In addition, during pregnancy renal transplant recipients may have renal insufficiency, hypertension, and preeclampsia.

Traditionally, it was recommended to wait 2 years after transplantation to try to become pregnant. However, newer immunosuppressants have made rejection less of an issue. This opens the possibility for a more individualized approach to timing. The group agreed pregnancy could be attempted once certain criteria had been met:

▸ No graft rejection in the year after transplant.

▸ Adequate and stable graft function (creatinine level less than 1.5 mg/dL, no or minimal proteinuria).

▸ No acute infections that could impact the fetus.

▸ Maintenance of immunosuppression at stable dosing.

There are, however, special circumstances that could impact the recommendations:

▸ Rejection outcome within the first year (consider further graft assessment with biopsy and GFR).

▸ Maternal age.

▸ Comorbid factors that may impact pregnancy and graft function.

▸ The patient's history of compliance.

The timing considerations could be met at 1 year post transplant, depending on the individual.

Care Varies for Transplant Recipients

A survey of the management practices of allograft transplant recipients who are or wish to become pregnant highlights the lack of consensus on the care of these patients.

Perhaps the most important finding of the survey was that the care of these women generally has been based on experience, patient preference, or center protocol, not on any available evidence, Dr. Josephson said.

“After nearly 50 years and thousands of deliveries, we should know what we're doing, but do we?” she asked.

The Women's Health Committee of the American Society of Transplantation sent out a questionnaire to all 257 transplant centers in the United States to determine the current practices for the care of transplant recipients who wish to become or are pregnant. The response rate was 56%.

The respondents had an average of 16 years' experience in transplant medicine.

A total of 82% said they recommend that their transplant patients not try to become pregnant for some period of time after receiving the transplant. Most who recommended a waiting period said their patients should wait 1–2 years. Almost 20% recommended that their patients never become pregnant. Most respondents—about three-quarters—did not limit their patients to one pregnancy.

Regarding immunosuppressant therapy in pregnancy, most respondents felt that older drugs—cyclosporine, tacrolimus, and steroids—were probably OK to use. “What I think was really interesting was that with azathioprine—one of the safest medications and actually the one that we have, aside from steroids, the most experience with—there was a little bit of debate,” she said.

Responses varied widely concerning the safety in pregnancy of newer immunosuppressants, such as rapamycin and mycophenolate mofetil.

High-risk obstetricians most commonly managed the pregnancies of transplant recipients, making up 85% of the physicians caring for these patients. Most respondents preferred going ahead with vaginal deliveries, although one-quarter of them recommended cesarean section for these patients.

Two-thirds of respondents advised their patients not to breast-feed.

WASHINGTON — Balancing immunosuppression in a pregnant allograft transplant patient with the health of the woman and her fetus requires a team approach between high-risk obstetricians and transplant physicians, according to one expert speaking at a meeting sponsored by the National Kidney Foundation.

“Pregnancy in the transplant recipient, aside from the issue of renal dysfunction, poses a unique set of considerations, and that's because of immunosuppressants,” said Michelle A. Josephson, M.D., of the University of Chicago.

None of the immunosuppressants used for transplantation—cyclosporine, tacrolimus, azathioprine, steroids, rapamycin, and mycophenolate mofetil—are rated pregnancy category A, using the Food and Drug Administration classification system. In fact, most are rated category C, meaning there are no data on their use in humans during pregnancy. “All medications used to prevent rejection cross the maternal-placental interface,” she pointed out.

Despite the lack of data and potential risks, a consensus group convened in 2003 by the Women's Health Committee of the American Society of Transplantation recommended immunosuppression be maintained during pregnancy to avoid rejection.

Graft rejection can be difficult to discern during pregnancy because serum creatinine levels are low during this period, and small changes can be missed, Dr. Josephson said. In addition, abnormalities that turn up on liver function tests can have a number of etiologies. For these reasons, graft dysfunction during pregnancy warrants appropriate investigation—by biopsy if necessary.

“If rejection occurs, it can be treated with steroids,” Dr. Josephson recommended. Inadequate immunosuppression, graft instability, and rejection likely affect the graft prognosis. However, age, number of allografts, and repeat pregnancies don't seem to impact graft function and prognosis.

The consensus group also agreed that a high-risk obstetrician and a transplant physician should manage pregnant transplant patients. Obstetricians should optimize maternal health, maintain normal glycemia, ensure adequate fetal growth, and anticipate preterm birth. The transplant physician should ensure maintenance of graft function and aggressively manage hypertension and preeclampsia. Cesarean section is not indicated except for standard obstetric reasons.

During the conference, experts addressed a number of concerns for this group of patients to develop management recommendations. “We recognized that the risk of prematurity in the population was high. We realized that intrauterine growth retardation is high,” said Dr. Josephson. In addition, during pregnancy renal transplant recipients may have renal insufficiency, hypertension, and preeclampsia.

Traditionally, it was recommended to wait 2 years after transplantation to try to become pregnant. However, newer immunosuppressants have made rejection less of an issue. This opens the possibility for a more individualized approach to timing. The group agreed pregnancy could be attempted once certain criteria had been met:

▸ No graft rejection in the year after transplant.

▸ Adequate and stable graft function (creatinine level less than 1.5 mg/dL, no or minimal proteinuria).

▸ No acute infections that could impact the fetus.

▸ Maintenance of immunosuppression at stable dosing.

There are, however, special circumstances that could impact the recommendations:

▸ Rejection outcome within the first year (consider further graft assessment with biopsy and GFR).

▸ Maternal age.

▸ Comorbid factors that may impact pregnancy and graft function.

▸ The patient's history of compliance.

The timing considerations could be met at 1 year post transplant, depending on the individual.

Care Varies for Transplant Recipients

A survey of the management practices of allograft transplant recipients who are or wish to become pregnant highlights the lack of consensus on the care of these patients.

Perhaps the most important finding of the survey was that the care of these women generally has been based on experience, patient preference, or center protocol, not on any available evidence, Dr. Josephson said.

“After nearly 50 years and thousands of deliveries, we should know what we're doing, but do we?” she asked.

The Women's Health Committee of the American Society of Transplantation sent out a questionnaire to all 257 transplant centers in the United States to determine the current practices for the care of transplant recipients who wish to become or are pregnant. The response rate was 56%.

The respondents had an average of 16 years' experience in transplant medicine.

A total of 82% said they recommend that their transplant patients not try to become pregnant for some period of time after receiving the transplant. Most who recommended a waiting period said their patients should wait 1–2 years. Almost 20% recommended that their patients never become pregnant. Most respondents—about three-quarters—did not limit their patients to one pregnancy.

Regarding immunosuppressant therapy in pregnancy, most respondents felt that older drugs—cyclosporine, tacrolimus, and steroids—were probably OK to use. “What I think was really interesting was that with azathioprine—one of the safest medications and actually the one that we have, aside from steroids, the most experience with—there was a little bit of debate,” she said.

Responses varied widely concerning the safety in pregnancy of newer immunosuppressants, such as rapamycin and mycophenolate mofetil.

High-risk obstetricians most commonly managed the pregnancies of transplant recipients, making up 85% of the physicians caring for these patients. Most respondents preferred going ahead with vaginal deliveries, although one-quarter of them recommended cesarean section for these patients.

Two-thirds of respondents advised their patients not to breast-feed.

WASHINGTON — Balancing immunosuppression in a pregnant allograft transplant patient with the health of the woman and her fetus requires a team approach between high-risk obstetricians and transplant physicians, according to one expert speaking at a meeting sponsored by the National Kidney Foundation.

“Pregnancy in the transplant recipient, aside from the issue of renal dysfunction, poses a unique set of considerations, and that's because of immunosuppressants,” said Michelle A. Josephson, M.D., of the University of Chicago.

None of the immunosuppressants used for transplantation—cyclosporine, tacrolimus, azathioprine, steroids, rapamycin, and mycophenolate mofetil—are rated pregnancy category A, using the Food and Drug Administration classification system. In fact, most are rated category C, meaning there are no data on their use in humans during pregnancy. “All medications used to prevent rejection cross the maternal-placental interface,” she pointed out.

Despite the lack of data and potential risks, a consensus group convened in 2003 by the Women's Health Committee of the American Society of Transplantation recommended immunosuppression be maintained during pregnancy to avoid rejection.

Graft rejection can be difficult to discern during pregnancy because serum creatinine levels are low during this period, and small changes can be missed, Dr. Josephson said. In addition, abnormalities that turn up on liver function tests can have a number of etiologies. For these reasons, graft dysfunction during pregnancy warrants appropriate investigation—by biopsy if necessary.

“If rejection occurs, it can be treated with steroids,” Dr. Josephson recommended. Inadequate immunosuppression, graft instability, and rejection likely affect the graft prognosis. However, age, number of allografts, and repeat pregnancies don't seem to impact graft function and prognosis.

The consensus group also agreed that a high-risk obstetrician and a transplant physician should manage pregnant transplant patients. Obstetricians should optimize maternal health, maintain normal glycemia, ensure adequate fetal growth, and anticipate preterm birth. The transplant physician should ensure maintenance of graft function and aggressively manage hypertension and preeclampsia. Cesarean section is not indicated except for standard obstetric reasons.

During the conference, experts addressed a number of concerns for this group of patients to develop management recommendations. “We recognized that the risk of prematurity in the population was high. We realized that intrauterine growth retardation is high,” said Dr. Josephson. In addition, during pregnancy renal transplant recipients may have renal insufficiency, hypertension, and preeclampsia.

Traditionally, it was recommended to wait 2 years after transplantation to try to become pregnant. However, newer immunosuppressants have made rejection less of an issue. This opens the possibility for a more individualized approach to timing. The group agreed pregnancy could be attempted once certain criteria had been met:

▸ No graft rejection in the year after transplant.

▸ Adequate and stable graft function (creatinine level less than 1.5 mg/dL, no or minimal proteinuria).

▸ No acute infections that could impact the fetus.

▸ Maintenance of immunosuppression at stable dosing.

There are, however, special circumstances that could impact the recommendations:

▸ Rejection outcome within the first year (consider further graft assessment with biopsy and GFR).

▸ Maternal age.

▸ Comorbid factors that may impact pregnancy and graft function.

▸ The patient's history of compliance.

The timing considerations could be met at 1 year post transplant, depending on the individual.

Care Varies for Transplant Recipients

A survey of the management practices of allograft transplant recipients who are or wish to become pregnant highlights the lack of consensus on the care of these patients.

Perhaps the most important finding of the survey was that the care of these women generally has been based on experience, patient preference, or center protocol, not on any available evidence, Dr. Josephson said.

“After nearly 50 years and thousands of deliveries, we should know what we're doing, but do we?” she asked.

The Women's Health Committee of the American Society of Transplantation sent out a questionnaire to all 257 transplant centers in the United States to determine the current practices for the care of transplant recipients who wish to become or are pregnant. The response rate was 56%.

The respondents had an average of 16 years' experience in transplant medicine.

A total of 82% said they recommend that their transplant patients not try to become pregnant for some period of time after receiving the transplant. Most who recommended a waiting period said their patients should wait 1–2 years. Almost 20% recommended that their patients never become pregnant. Most respondents—about three-quarters—did not limit their patients to one pregnancy.

Regarding immunosuppressant therapy in pregnancy, most respondents felt that older drugs—cyclosporine, tacrolimus, and steroids—were probably OK to use. “What I think was really interesting was that with azathioprine—one of the safest medications and actually the one that we have, aside from steroids, the most experience with—there was a little bit of debate,” she said.

Responses varied widely concerning the safety in pregnancy of newer immunosuppressants, such as rapamycin and mycophenolate mofetil.

High-risk obstetricians most commonly managed the pregnancies of transplant recipients, making up 85% of the physicians caring for these patients. Most respondents preferred going ahead with vaginal deliveries, although one-quarter of them recommended cesarean section for these patients.

Two-thirds of respondents advised their patients not to breast-feed.

NEW ORLEANS — Neonatal and maternal mortality in California did not significantly change after the American College of Obstetricians and Gynecologists recommended vaginal births after cesarean delivery be performed only in settings with “immediately available” emergency care, according to a study.

Very low-birth-weight infants were the only group to experience significantly higher mortality associated with vaginal births after cesarean (VBACs). When the American College of Obstetricians and Gynecologists (ACOG) was contacted for comment, a representative criticized the study design and its implications.

In 1996, ACOG encouraged VBACs, John Zweifler, M.D., said at the annual conference of the Society of Teachers of Family Medicine. In 1998, the college changed its recommendations on VBACs and stated they should be attempted only where emergency care is “readily available.” The following year, ACOG further restricted the recommendations to settings where emergency care is “immediately available.” The college retained the wording of these recommendations in its latest update, Practice Bulletin No. 54 (Obstet. Gynecol. 2004;104:203–12).

“But for those of us in rural settings, this could impair our ability to do VBACs,” Dr. Zweifler said. “We were concerned that a change in ACOG guidelines would have deleterious effect on our [residency] program.”

Dr. Zweifler and research fellow Susan Hughes compared neonatal and maternal deaths from 1996 to 2002. They reviewed maternal demographics, birth data, and outcomes, noting previous C-sections and whether hospitals were in rural or urban areas. California Birth Statistical Master Files consider mortality to be associated with birth if it occurs within 72 hours of delivery, said Dr. Zweifler, director of the University of California, San Francisco's Fresno Family Medicine Residency Program.

There were more than 3.5 million single births in California in the seven years, including 2.7 million vaginal births, 456,000 primary cesarean sections, and 386,000 deliveries to women with a history of C-section. Of the women with a history of cesarean delivery, 311,000 had a repeat cesarean, and 74,000 had an attempted VBAC. There were 61,000 successful VBACs and 13,000 failed ones.

VBAC rates decreased from 1996 to 2002, reflecting national trends, Ms. Hughes said. The biggest decrease was in rural VBACs.

“There were very few maternal deaths—about 35. So statistically, there were no differences in maternal mortality between time periods or attempted VBAC, versus repeat cesareans,” Ms. Hughes said.

There was a statistically significant increase in mortality for infants weighing less than 1,500 grams. “Attempted VBACs in both time periods had higher death rates than repeat cesareans,” Ms. Hughes said.

However, there were no significant differences in mortality for infants born weighing more than 1,500 grams, including those greater than 4,000 grams.

Reliability of birth certificate data was a possible limitation of the study, Ms. Hughes said. In addition, there was no information on morbidities, such as uterine rupture or newborn encephalopathy.

“The more restrictive ACOG guidelines have not improved VBAC-related neonatal or maternal mortality,” Dr. Zweifler said.

“ACOG's recommendation is purely based on the fact there is no more catastrophic event that befalls women than uterine rupture,” said Gary Hankins, M.D., chair of the ACOG Committee on Obstetric Practice. “Studies clearly show that if you are not really available to respond to this emergency in a very quick fashion—generally less than 30 minutes—you can expect, in a significant number of cases, either the death of the baby or permanent neurologic injury of the baby from birth asphyxia.”

“That being the case, we opt to promote standards of safety, and patient safety if our first order is why these recommendations are made,” said Dr. Hankins, professor of obstetrics and gynecology at the University of Texas, Galveston.

The data used for the study—derived from Birth Statistical Master Files—are insufficient to address all the safety issues concerning VBAC deliveries, Dr. Hankins said. “I would challenge either of these people to see if they have ever stood on the front line and dealt with a woman who has had a uterine rupture.”

NEW ORLEANS — Neonatal and maternal mortality in California did not significantly change after the American College of Obstetricians and Gynecologists recommended vaginal births after cesarean delivery be performed only in settings with “immediately available” emergency care, according to a study.

Very low-birth-weight infants were the only group to experience significantly higher mortality associated with vaginal births after cesarean (VBACs). When the American College of Obstetricians and Gynecologists (ACOG) was contacted for comment, a representative criticized the study design and its implications.

In 1996, ACOG encouraged VBACs, John Zweifler, M.D., said at the annual conference of the Society of Teachers of Family Medicine. In 1998, the college changed its recommendations on VBACs and stated they should be attempted only where emergency care is “readily available.” The following year, ACOG further restricted the recommendations to settings where emergency care is “immediately available.” The college retained the wording of these recommendations in its latest update, Practice Bulletin No. 54 (Obstet. Gynecol. 2004;104:203–12).

“But for those of us in rural settings, this could impair our ability to do VBACs,” Dr. Zweifler said. “We were concerned that a change in ACOG guidelines would have deleterious effect on our [residency] program.”

Dr. Zweifler and research fellow Susan Hughes compared neonatal and maternal deaths from 1996 to 2002. They reviewed maternal demographics, birth data, and outcomes, noting previous C-sections and whether hospitals were in rural or urban areas. California Birth Statistical Master Files consider mortality to be associated with birth if it occurs within 72 hours of delivery, said Dr. Zweifler, director of the University of California, San Francisco's Fresno Family Medicine Residency Program.

There were more than 3.5 million single births in California in the seven years, including 2.7 million vaginal births, 456,000 primary cesarean sections, and 386,000 deliveries to women with a history of C-section. Of the women with a history of cesarean delivery, 311,000 had a repeat cesarean, and 74,000 had an attempted VBAC. There were 61,000 successful VBACs and 13,000 failed ones.

VBAC rates decreased from 1996 to 2002, reflecting national trends, Ms. Hughes said. The biggest decrease was in rural VBACs.

“There were very few maternal deaths—about 35. So statistically, there were no differences in maternal mortality between time periods or attempted VBAC, versus repeat cesareans,” Ms. Hughes said.

There was a statistically significant increase in mortality for infants weighing less than 1,500 grams. “Attempted VBACs in both time periods had higher death rates than repeat cesareans,” Ms. Hughes said.

However, there were no significant differences in mortality for infants born weighing more than 1,500 grams, including those greater than 4,000 grams.

Reliability of birth certificate data was a possible limitation of the study, Ms. Hughes said. In addition, there was no information on morbidities, such as uterine rupture or newborn encephalopathy.

“The more restrictive ACOG guidelines have not improved VBAC-related neonatal or maternal mortality,” Dr. Zweifler said.

“ACOG's recommendation is purely based on the fact there is no more catastrophic event that befalls women than uterine rupture,” said Gary Hankins, M.D., chair of the ACOG Committee on Obstetric Practice. “Studies clearly show that if you are not really available to respond to this emergency in a very quick fashion—generally less than 30 minutes—you can expect, in a significant number of cases, either the death of the baby or permanent neurologic injury of the baby from birth asphyxia.”

“That being the case, we opt to promote standards of safety, and patient safety if our first order is why these recommendations are made,” said Dr. Hankins, professor of obstetrics and gynecology at the University of Texas, Galveston.

The data used for the study—derived from Birth Statistical Master Files—are insufficient to address all the safety issues concerning VBAC deliveries, Dr. Hankins said. “I would challenge either of these people to see if they have ever stood on the front line and dealt with a woman who has had a uterine rupture.”

NEW ORLEANS — Neonatal and maternal mortality in California did not significantly change after the American College of Obstetricians and Gynecologists recommended vaginal births after cesarean delivery be performed only in settings with “immediately available” emergency care, according to a study.

Very low-birth-weight infants were the only group to experience significantly higher mortality associated with vaginal births after cesarean (VBACs). When the American College of Obstetricians and Gynecologists (ACOG) was contacted for comment, a representative criticized the study design and its implications.

In 1996, ACOG encouraged VBACs, John Zweifler, M.D., said at the annual conference of the Society of Teachers of Family Medicine. In 1998, the college changed its recommendations on VBACs and stated they should be attempted only where emergency care is “readily available.” The following year, ACOG further restricted the recommendations to settings where emergency care is “immediately available.” The college retained the wording of these recommendations in its latest update, Practice Bulletin No. 54 (Obstet. Gynecol. 2004;104:203–12).

“But for those of us in rural settings, this could impair our ability to do VBACs,” Dr. Zweifler said. “We were concerned that a change in ACOG guidelines would have deleterious effect on our [residency] program.”

Dr. Zweifler and research fellow Susan Hughes compared neonatal and maternal deaths from 1996 to 2002. They reviewed maternal demographics, birth data, and outcomes, noting previous C-sections and whether hospitals were in rural or urban areas. California Birth Statistical Master Files consider mortality to be associated with birth if it occurs within 72 hours of delivery, said Dr. Zweifler, director of the University of California, San Francisco's Fresno Family Medicine Residency Program.

There were more than 3.5 million single births in California in the seven years, including 2.7 million vaginal births, 456,000 primary cesarean sections, and 386,000 deliveries to women with a history of C-section. Of the women with a history of cesarean delivery, 311,000 had a repeat cesarean, and 74,000 had an attempted VBAC. There were 61,000 successful VBACs and 13,000 failed ones.

VBAC rates decreased from 1996 to 2002, reflecting national trends, Ms. Hughes said. The biggest decrease was in rural VBACs.

“There were very few maternal deaths—about 35. So statistically, there were no differences in maternal mortality between time periods or attempted VBAC, versus repeat cesareans,” Ms. Hughes said.

There was a statistically significant increase in mortality for infants weighing less than 1,500 grams. “Attempted VBACs in both time periods had higher death rates than repeat cesareans,” Ms. Hughes said.

However, there were no significant differences in mortality for infants born weighing more than 1,500 grams, including those greater than 4,000 grams.

Reliability of birth certificate data was a possible limitation of the study, Ms. Hughes said. In addition, there was no information on morbidities, such as uterine rupture or newborn encephalopathy.

“The more restrictive ACOG guidelines have not improved VBAC-related neonatal or maternal mortality,” Dr. Zweifler said.

“ACOG's recommendation is purely based on the fact there is no more catastrophic event that befalls women than uterine rupture,” said Gary Hankins, M.D., chair of the ACOG Committee on Obstetric Practice. “Studies clearly show that if you are not really available to respond to this emergency in a very quick fashion—generally less than 30 minutes—you can expect, in a significant number of cases, either the death of the baby or permanent neurologic injury of the baby from birth asphyxia.”

“That being the case, we opt to promote standards of safety, and patient safety if our first order is why these recommendations are made,” said Dr. Hankins, professor of obstetrics and gynecology at the University of Texas, Galveston.

The data used for the study—derived from Birth Statistical Master Files—are insufficient to address all the safety issues concerning VBAC deliveries, Dr. Hankins said. “I would challenge either of these people to see if they have ever stood on the front line and dealt with a woman who has had a uterine rupture.”

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800–258–4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised. “Barrier contraception should always be used in combination with other contraceptive methods.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote. Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B.Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

He did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV. If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” he said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive,” Mr. Briggs said, “but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day.”

The Food and Drug Administration's approval of a genotyping test for cystic fibrosis detection should improve screening accuracy and availability and could result in more uniform reporting of test results to physicians, experts say.

The new test—coined the “Tag-It Cystic Fibrosis Kit”—is the first multiplexed genotyping test to be cleared by the FDA as an in vitro device for diagnosing human disease.

Laboratories traditionally have purchased what are known as “analyzed specific reagents” and then have had to establish and validate assays and test kits themselves. The newly approved device, on the other hand, is a “standardized, validated testing kit. … It moves us past the 'home brews,' and makes for a more accurate test,” said Michael Watson, Ph.D., executive director of the American College of Medical Genetics.

Dr. Watson was a lead author of the clinical and laboratory guidelines for cystic fibrosis (CF) carrier screening that were published in 2001, and updated in 2004, by the ACMG and the American College of Obstetricians and Gynecologists (ACOG).

The kit is approved for use in carrier testing, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children.

It can be used to detect and identify simultaneously 39 mutations in the gene for CF—known as the cystic fibrosis transmembrane conductance regulator (CFTR) gene—as well as 4 polymorphisms.

These variations include the 23 mutations recommended in the updated ACOG-ACMG guidelines as a “core mutation panel” for carrier screening in the general population. According to the manufacturer, the kit covers additional mutations seen in the African American and Hispanic communities.

“The percent of carriers picked up in [these communities] will go up,” said Graham Henderson, marketing manager for Tm Bioscience Corp. of Toronto.

The original 2001 guidelines recommended a standard screening panel covering 25 mutations, but one mutation subsequently was found to occur less frequently than expected, and another was found not to be a true mutation.

Laboratories today typically use the recommended 23-mutation panel and then supplement this, if possible, with tests for such additional mutations when screening particular racial or ethnic groups.

According to the ACOG-ACMG guidelines, the standard “pan-ethnic” 23-mutation panel has an expected sensitivity of 80% in Caucasians of European descent, 90% in Caucasians of Northern European descent, and 97% in Ashkenazi Jews. Even when the panel is supplemented with additional mutations, there is always some “residual risk,” or “small possibility of an affected offspring,” the guidelines say.

Donna Galehouse, Ph.D., technical director of the molecular diagnostics lab at Akron (Ohio) Children's Hospital, said the new device will enable more labs to perform screening, and will enable them to accurately handle high test volumes.

If use of the device becomes a standard of care, Dr. Watson said, physicians should get more “uniform” test result reports. “Right now, residual risks vary, depending on where testing is done” for instance, he said. “Physicians have to check carefully on what exactly was done and how it translates” into clinical meaning.

According to the ACOG-ACMG guidelines, screening should be offered to couples with a family history of CF, partners of individuals with CF, and Caucasian couples of European or Ashkenazi Jewish descent that are planning a pregnancy or seeking prenatal care.

Information about CF screening should be provided to patients in other ethnic and racial groups, the guidelines say.

A survey done 2 years after the guidelines were first issued showed that the vast majority of 632 ob.gyns.—89% of the respondents—ask obstetric patients about their family history of CF and offer CF carrier screening. Nearly two-thirds offer screening to all prenatal patients.

In the gynecologic setting, practice patterns were much different. Almost one-half of physicians who responded to the survey indicated that they do not ask nonpregnant patients about their family history of CF or provide them with information about screening (Genet. Med. 2004:6;450–5). (The survey was mailed to 1,165 ACOG members—approximately half of whom participate in the College's Collaborative Ambulatory Research Network, and half of whom were randomly selected.)

Reports on CF screening, according to the guidelines, should include the reported ethnicity of the patient and the indication for testing as well as the mutations tested and the method of testing. Negative screening tests should define “as accurately as possible” the residual risk of the person tested. “This will vary by ethnic or racial group and should be so specified in the test report,” the guidelines say.

Since the CFTR gene and the most common genetic mutation causing CF were identified about 15 years ago, more than 1,300 genetic variations have been identified in the gene. Many of these, Dr. Watson said, “are rare or private to an individual or family.” The newly approved device is not indicated for use in fetal diagnostic or preimplantation testing, and it is not indicated for stand-alone diagnostic purposes, according to a statement issued by the FDA.

Physicians should “interpret test results in the context of the patient's clinical condition, ethnicity, and family history,” the statement said.

The Tag-It Cystic Fibrosis Kit is approved for use in carrier testing and can identify 39 mutations in the CF gene. Tm Bioscience Corp.

The Food and Drug Administration's approval of a genotyping test for cystic fibrosis detection should improve screening accuracy and availability and could result in more uniform reporting of test results to physicians, experts say.

The new test—coined the “Tag-It Cystic Fibrosis Kit”—is the first multiplexed genotyping test to be cleared by the FDA as an in vitro device for diagnosing human disease.

Laboratories traditionally have purchased what are known as “analyzed specific reagents” and then have had to establish and validate assays and test kits themselves. The newly approved device, on the other hand, is a “standardized, validated testing kit. … It moves us past the 'home brews,' and makes for a more accurate test,” said Michael Watson, Ph.D., executive director of the American College of Medical Genetics.

Dr. Watson was a lead author of the clinical and laboratory guidelines for cystic fibrosis (CF) carrier screening that were published in 2001, and updated in 2004, by the ACMG and the American College of Obstetricians and Gynecologists (ACOG).

The kit is approved for use in carrier testing, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children.

It can be used to detect and identify simultaneously 39 mutations in the gene for CF—known as the cystic fibrosis transmembrane conductance regulator (CFTR) gene—as well as 4 polymorphisms.

These variations include the 23 mutations recommended in the updated ACOG-ACMG guidelines as a “core mutation panel” for carrier screening in the general population. According to the manufacturer, the kit covers additional mutations seen in the African American and Hispanic communities.

“The percent of carriers picked up in [these communities] will go up,” said Graham Henderson, marketing manager for Tm Bioscience Corp. of Toronto.

The original 2001 guidelines recommended a standard screening panel covering 25 mutations, but one mutation subsequently was found to occur less frequently than expected, and another was found not to be a true mutation.

Laboratories today typically use the recommended 23-mutation panel and then supplement this, if possible, with tests for such additional mutations when screening particular racial or ethnic groups.

According to the ACOG-ACMG guidelines, the standard “pan-ethnic” 23-mutation panel has an expected sensitivity of 80% in Caucasians of European descent, 90% in Caucasians of Northern European descent, and 97% in Ashkenazi Jews. Even when the panel is supplemented with additional mutations, there is always some “residual risk,” or “small possibility of an affected offspring,” the guidelines say.

Donna Galehouse, Ph.D., technical director of the molecular diagnostics lab at Akron (Ohio) Children's Hospital, said the new device will enable more labs to perform screening, and will enable them to accurately handle high test volumes.

If use of the device becomes a standard of care, Dr. Watson said, physicians should get more “uniform” test result reports. “Right now, residual risks vary, depending on where testing is done” for instance, he said. “Physicians have to check carefully on what exactly was done and how it translates” into clinical meaning.

According to the ACOG-ACMG guidelines, screening should be offered to couples with a family history of CF, partners of individuals with CF, and Caucasian couples of European or Ashkenazi Jewish descent that are planning a pregnancy or seeking prenatal care.

Information about CF screening should be provided to patients in other ethnic and racial groups, the guidelines say.

A survey done 2 years after the guidelines were first issued showed that the vast majority of 632 ob.gyns.—89% of the respondents—ask obstetric patients about their family history of CF and offer CF carrier screening. Nearly two-thirds offer screening to all prenatal patients.

In the gynecologic setting, practice patterns were much different. Almost one-half of physicians who responded to the survey indicated that they do not ask nonpregnant patients about their family history of CF or provide them with information about screening (Genet. Med. 2004:6;450–5). (The survey was mailed to 1,165 ACOG members—approximately half of whom participate in the College's Collaborative Ambulatory Research Network, and half of whom were randomly selected.)

Reports on CF screening, according to the guidelines, should include the reported ethnicity of the patient and the indication for testing as well as the mutations tested and the method of testing. Negative screening tests should define “as accurately as possible” the residual risk of the person tested. “This will vary by ethnic or racial group and should be so specified in the test report,” the guidelines say.

Since the CFTR gene and the most common genetic mutation causing CF were identified about 15 years ago, more than 1,300 genetic variations have been identified in the gene. Many of these, Dr. Watson said, “are rare or private to an individual or family.” The newly approved device is not indicated for use in fetal diagnostic or preimplantation testing, and it is not indicated for stand-alone diagnostic purposes, according to a statement issued by the FDA.

Physicians should “interpret test results in the context of the patient's clinical condition, ethnicity, and family history,” the statement said.

The Tag-It Cystic Fibrosis Kit is approved for use in carrier testing and can identify 39 mutations in the CF gene. Tm Bioscience Corp.

The Food and Drug Administration's approval of a genotyping test for cystic fibrosis detection should improve screening accuracy and availability and could result in more uniform reporting of test results to physicians, experts say.

The new test—coined the “Tag-It Cystic Fibrosis Kit”—is the first multiplexed genotyping test to be cleared by the FDA as an in vitro device for diagnosing human disease.

Laboratories traditionally have purchased what are known as “analyzed specific reagents” and then have had to establish and validate assays and test kits themselves. The newly approved device, on the other hand, is a “standardized, validated testing kit. … It moves us past the 'home brews,' and makes for a more accurate test,” said Michael Watson, Ph.D., executive director of the American College of Medical Genetics.

Dr. Watson was a lead author of the clinical and laboratory guidelines for cystic fibrosis (CF) carrier screening that were published in 2001, and updated in 2004, by the ACMG and the American College of Obstetricians and Gynecologists (ACOG).

The kit is approved for use in carrier testing, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children.

It can be used to detect and identify simultaneously 39 mutations in the gene for CF—known as the cystic fibrosis transmembrane conductance regulator (CFTR) gene—as well as 4 polymorphisms.

These variations include the 23 mutations recommended in the updated ACOG-ACMG guidelines as a “core mutation panel” for carrier screening in the general population. According to the manufacturer, the kit covers additional mutations seen in the African American and Hispanic communities.

“The percent of carriers picked up in [these communities] will go up,” said Graham Henderson, marketing manager for Tm Bioscience Corp. of Toronto.

The original 2001 guidelines recommended a standard screening panel covering 25 mutations, but one mutation subsequently was found to occur less frequently than expected, and another was found not to be a true mutation.

Laboratories today typically use the recommended 23-mutation panel and then supplement this, if possible, with tests for such additional mutations when screening particular racial or ethnic groups.

According to the ACOG-ACMG guidelines, the standard “pan-ethnic” 23-mutation panel has an expected sensitivity of 80% in Caucasians of European descent, 90% in Caucasians of Northern European descent, and 97% in Ashkenazi Jews. Even when the panel is supplemented with additional mutations, there is always some “residual risk,” or “small possibility of an affected offspring,” the guidelines say.

Donna Galehouse, Ph.D., technical director of the molecular diagnostics lab at Akron (Ohio) Children's Hospital, said the new device will enable more labs to perform screening, and will enable them to accurately handle high test volumes.

If use of the device becomes a standard of care, Dr. Watson said, physicians should get more “uniform” test result reports. “Right now, residual risks vary, depending on where testing is done” for instance, he said. “Physicians have to check carefully on what exactly was done and how it translates” into clinical meaning.

According to the ACOG-ACMG guidelines, screening should be offered to couples with a family history of CF, partners of individuals with CF, and Caucasian couples of European or Ashkenazi Jewish descent that are planning a pregnancy or seeking prenatal care.

Information about CF screening should be provided to patients in other ethnic and racial groups, the guidelines say.

A survey done 2 years after the guidelines were first issued showed that the vast majority of 632 ob.gyns.—89% of the respondents—ask obstetric patients about their family history of CF and offer CF carrier screening. Nearly two-thirds offer screening to all prenatal patients.

In the gynecologic setting, practice patterns were much different. Almost one-half of physicians who responded to the survey indicated that they do not ask nonpregnant patients about their family history of CF or provide them with information about screening (Genet. Med. 2004:6;450–5). (The survey was mailed to 1,165 ACOG members—approximately half of whom participate in the College's Collaborative Ambulatory Research Network, and half of whom were randomly selected.)

Reports on CF screening, according to the guidelines, should include the reported ethnicity of the patient and the indication for testing as well as the mutations tested and the method of testing. Negative screening tests should define “as accurately as possible” the residual risk of the person tested. “This will vary by ethnic or racial group and should be so specified in the test report,” the guidelines say.

Since the CFTR gene and the most common genetic mutation causing CF were identified about 15 years ago, more than 1,300 genetic variations have been identified in the gene. Many of these, Dr. Watson said, “are rare or private to an individual or family.” The newly approved device is not indicated for use in fetal diagnostic or preimplantation testing, and it is not indicated for stand-alone diagnostic purposes, according to a statement issued by the FDA.

Physicians should “interpret test results in the context of the patient's clinical condition, ethnicity, and family history,” the statement said.

The Tag-It Cystic Fibrosis Kit is approved for use in carrier testing and can identify 39 mutations in the CF gene. Tm Bioscience Corp.

WASHINGTON — Despite claims to the contrary, there is still more work to do to reduce maternal morbidity and mortality in the United States, Cynthia Berg, M.D., said at a meeting sponsored by the Jacobs Institute of Women's Health.

Throughout the 20th century, maternal mortality in the United States gradually went from 900 deaths per 100,00 live births to about 10, noted Dr. Berg, who is a medical epidemiologist at the Centers for Disease Control and Prevention, Atlanta. “But in the past 20 years, there hasn't been a meaningful drop.”

As a result of this slowing in decline, “some people believe that the United States has reached an irreducible minimum,” she continued. “However, I would say there are a few pieces of evidence that would refute this claim.”

For one thing, there are large racial and ethnic disparities in the risk of pregnancy-related death. For example, “the risk for black women is four times that for non-Hispanic white women, and that is one of the largest gaps in reproductive health treatment in the United States,” Dr. Berg said. “Hispanics, Asian/Pacific Islanders, and Asian women also have a 50%–70% higher rate of pregnancy-related mortality than non-Hispanic white women.”

Disparities also appear if both race and birthplace are taken into account. Although Hispanic and Asian women born in the United States have mortality rates similar to native-born white women, Hispanic and Asian women born outside the United States have a much higher mortality risk, according to Dr. Berg.

Although maternal mortality is often the focus of research, maternal morbidity deserves more attention than it is getting, said Stacie Geller, Ph.D., director of the University of Illinois at Chicago National Center of Excellence in Women's Health. “Clearly, studying morbidity itself is important, but it also is another way to try to reduce maternal mortality.”

One study by Dr. Berg and her associates found that 43% of women experience some form of maternal morbidity, based on data from the National Hospital Discharge Survey for women giving birth between 1993 and 1997. The most common condition was obstetric trauma such as a third- or fourth-degree laceration or hematoma (10.6%), followed by infections such as amnionitis (8.4%). Rare and serious complications like hemorrhage or pulmonary and amniotic embolisms occurred in less than 0.1% of the study group.

Dr. Geller cited three factors that placed women at higher risk of adverse outcomes during their pregnancies: lack of health insurance, particular clinical diagnoses, and preventable events.

“Most [preventable events] were due to provider issues,” she said.

Dr. Geller cited a study she and her colleagues had done, which found that a woman who died from a pregnancy-related cause was two times more likely to have had a provider-related preventable event, compared with her counterpart with severe morbidity. “It's not good news, but it means we can do something about it by changing provider behavior.”

Dr. Geller recommended more use of departmental and institutional review committees to study maternal morbidity and mortality cases. She also recommended that statewide maternal death review committees expand their scope to include near-miss morbidity cases.

Some audience members disagreed with Dr. Geller's approach. “If you continue to say some of these deaths are provider related versus system related, that propagates the continuation of individualized blame for adverse outcomes in the health care system,” said Michele Curtis, M.D., of the department of obstetrics and gynecology at the University of Texas at Houston Health Science Center. “The aviation industry has demonstrated profoundly to us, as has the specialty of anesthesia, that we can, if we choose to use a system-based analysis and get away from the blame game, make much more progress on a population level.” n

WASHINGTON — Despite claims to the contrary, there is still more work to do to reduce maternal morbidity and mortality in the United States, Cynthia Berg, M.D., said at a meeting sponsored by the Jacobs Institute of Women's Health.

Throughout the 20th century, maternal mortality in the United States gradually went from 900 deaths per 100,00 live births to about 10, noted Dr. Berg, who is a medical epidemiologist at the Centers for Disease Control and Prevention, Atlanta. “But in the past 20 years, there hasn't been a meaningful drop.”

As a result of this slowing in decline, “some people believe that the United States has reached an irreducible minimum,” she continued. “However, I would say there are a few pieces of evidence that would refute this claim.”

For one thing, there are large racial and ethnic disparities in the risk of pregnancy-related death. For example, “the risk for black women is four times that for non-Hispanic white women, and that is one of the largest gaps in reproductive health treatment in the United States,” Dr. Berg said. “Hispanics, Asian/Pacific Islanders, and Asian women also have a 50%–70% higher rate of pregnancy-related mortality than non-Hispanic white women.”

Disparities also appear if both race and birthplace are taken into account. Although Hispanic and Asian women born in the United States have mortality rates similar to native-born white women, Hispanic and Asian women born outside the United States have a much higher mortality risk, according to Dr. Berg.

Although maternal mortality is often the focus of research, maternal morbidity deserves more attention than it is getting, said Stacie Geller, Ph.D., director of the University of Illinois at Chicago National Center of Excellence in Women's Health. “Clearly, studying morbidity itself is important, but it also is another way to try to reduce maternal mortality.”

One study by Dr. Berg and her associates found that 43% of women experience some form of maternal morbidity, based on data from the National Hospital Discharge Survey for women giving birth between 1993 and 1997. The most common condition was obstetric trauma such as a third- or fourth-degree laceration or hematoma (10.6%), followed by infections such as amnionitis (8.4%). Rare and serious complications like hemorrhage or pulmonary and amniotic embolisms occurred in less than 0.1% of the study group.

Dr. Geller cited three factors that placed women at higher risk of adverse outcomes during their pregnancies: lack of health insurance, particular clinical diagnoses, and preventable events.

“Most [preventable events] were due to provider issues,” she said.

Dr. Geller cited a study she and her colleagues had done, which found that a woman who died from a pregnancy-related cause was two times more likely to have had a provider-related preventable event, compared with her counterpart with severe morbidity. “It's not good news, but it means we can do something about it by changing provider behavior.”

Dr. Geller recommended more use of departmental and institutional review committees to study maternal morbidity and mortality cases. She also recommended that statewide maternal death review committees expand their scope to include near-miss morbidity cases.

Some audience members disagreed with Dr. Geller's approach. “If you continue to say some of these deaths are provider related versus system related, that propagates the continuation of individualized blame for adverse outcomes in the health care system,” said Michele Curtis, M.D., of the department of obstetrics and gynecology at the University of Texas at Houston Health Science Center. “The aviation industry has demonstrated profoundly to us, as has the specialty of anesthesia, that we can, if we choose to use a system-based analysis and get away from the blame game, make much more progress on a population level.” n

WASHINGTON — Despite claims to the contrary, there is still more work to do to reduce maternal morbidity and mortality in the United States, Cynthia Berg, M.D., said at a meeting sponsored by the Jacobs Institute of Women's Health.

Throughout the 20th century, maternal mortality in the United States gradually went from 900 deaths per 100,00 live births to about 10, noted Dr. Berg, who is a medical epidemiologist at the Centers for Disease Control and Prevention, Atlanta. “But in the past 20 years, there hasn't been a meaningful drop.”

As a result of this slowing in decline, “some people believe that the United States has reached an irreducible minimum,” she continued. “However, I would say there are a few pieces of evidence that would refute this claim.”

For one thing, there are large racial and ethnic disparities in the risk of pregnancy-related death. For example, “the risk for black women is four times that for non-Hispanic white women, and that is one of the largest gaps in reproductive health treatment in the United States,” Dr. Berg said. “Hispanics, Asian/Pacific Islanders, and Asian women also have a 50%–70% higher rate of pregnancy-related mortality than non-Hispanic white women.”

Disparities also appear if both race and birthplace are taken into account. Although Hispanic and Asian women born in the United States have mortality rates similar to native-born white women, Hispanic and Asian women born outside the United States have a much higher mortality risk, according to Dr. Berg.

Although maternal mortality is often the focus of research, maternal morbidity deserves more attention than it is getting, said Stacie Geller, Ph.D., director of the University of Illinois at Chicago National Center of Excellence in Women's Health. “Clearly, studying morbidity itself is important, but it also is another way to try to reduce maternal mortality.”

One study by Dr. Berg and her associates found that 43% of women experience some form of maternal morbidity, based on data from the National Hospital Discharge Survey for women giving birth between 1993 and 1997. The most common condition was obstetric trauma such as a third- or fourth-degree laceration or hematoma (10.6%), followed by infections such as amnionitis (8.4%). Rare and serious complications like hemorrhage or pulmonary and amniotic embolisms occurred in less than 0.1% of the study group.

Dr. Geller cited three factors that placed women at higher risk of adverse outcomes during their pregnancies: lack of health insurance, particular clinical diagnoses, and preventable events.

“Most [preventable events] were due to provider issues,” she said.

Dr. Geller cited a study she and her colleagues had done, which found that a woman who died from a pregnancy-related cause was two times more likely to have had a provider-related preventable event, compared with her counterpart with severe morbidity. “It's not good news, but it means we can do something about it by changing provider behavior.”

Dr. Geller recommended more use of departmental and institutional review committees to study maternal morbidity and mortality cases. She also recommended that statewide maternal death review committees expand their scope to include near-miss morbidity cases.

Some audience members disagreed with Dr. Geller's approach. “If you continue to say some of these deaths are provider related versus system related, that propagates the continuation of individualized blame for adverse outcomes in the health care system,” said Michele Curtis, M.D., of the department of obstetrics and gynecology at the University of Texas at Houston Health Science Center. “The aviation industry has demonstrated profoundly to us, as has the specialty of anesthesia, that we can, if we choose to use a system-based analysis and get away from the blame game, make much more progress on a population level.” n

WASHINGTON — Kidney disease can lead to complications during pregnancy—and pregnancy can worsen kidney disease, Phyllis August, M.D., said at a meeting sponsored by the National Kidney Foundation.

“Without normal renal function, pregnancy is threatened and not always successful, and pregnancy does pose a burden in women with compromised renal function,” said Dr. August, professor of medicine at the Cornell University cardiovascular center in New York.

During pregnancy, women undergo kidney and hemodynamic changes that can lead to or worsen chronic kidney disease (CKD). “The bottom line in patients with CKD or chronic renal insufficiency is that the outcome seems to be related to baseline blood pressure and the degree of renal insufficiency at the time of conception,” she said. In general, serum creatinine levels lower than 1.5 mg/dL and the absence of hypertension favor normal outcomes.

The approach to management depends on whether the patient is diagnosed with renal disease before conception or during pregnancy, or whether the disease onset occurs during pregnancy.

Encourage patients with severe CKD to wait until they have had a transplant before becoming pregnant. “Dialysis and pregnancy are not a good combination,” Dr. August said.

Pregnancy has temporary effects on renal disease. Urinary protein excretion is increased, with normal excretion ranging up to 300 mg/day during pregnancy. “Many of our patients with chronic renal disease, particularly diabetic nephropathy, can have a significant increase in urinary protein excretion,” she said. It's unknown whether this increase has any adverse effects on the underlying kidney disease.

“There is the possibility that because of all of these phenomena that pregnancy could pose a burden on the kidney in women with preexisting renal disease, leading to permanent loss of function,” Dr. August said. But there are few data on the long-term effect of pregnancy on renal function in women with CKD.

Renal disease diagnosed before conception is typically diabetic nephropathy or chronic glomerular nephritis. Previous studies suggested that earlier deliveries and smaller babies were the rule in this population. More recent data suggest that the worse the renal disease is prior to pregnancy, the worse the outcome of the pregnancy will be. Some data suggest that pregnancy does not lead to progression of diabetic nephropathy.

Management of diabetic nephropathy during pregnancy should rely on tight control of blood sugar, especially during the first trimester. There is a clear association between abnormal glucose control and fetal malformations. Also discontinue the use of ACE inhibitors and angiotensin II receptor blockers. Instead, antihypertensive therapy should be accomplished with methyldopa, labetalol, calcium antagonists, and occasional use of diuretics, Dr. August advised.

Women with a long history of type 1 diabetes should have a thorough cardiac evaluation with a stress test and an echocardiogram prior to pregnancy. Once pregnant, these patients should have a laboratory evaluation about every month, she recommended.

Many women with CKD have a risk of developing superimposed preeclampsia. The higher a woman's creatinine level is, the greater the risk. Pregnant women with preexisting CKD and preeclampsia have a higher incidence of premature delivery and restricted fetus growth than do women without CKD. “Most women with renal disease will have premature deliveries, and many will have smaller babies,” Dr. August said.

In some cases, renal disease becomes clinically apparent for the first time during pregnancy. Increased renal hemodynamics during pregnancy can unmask proteinuria. Close monitoring of blood pressure and urine during pregnancy may bring problems to light.

Renal evaluation of patients first suspected of having CKD during pregnancy is similar to that for patients who are not pregnant—serologic and function testing, and ultrasound.

A biopsy can even be performed, but it is common to avoid this measure during the third trimester of pregnancy because of anatomical and positioning issues.

Generally, only deteriorating kidney function or morbid nephritic syndrome is considered to be an indication for attempting a biopsy during pregnancy. Otherwise, it is preferred to wait until after delivery, Dr. August said.

It can be difficult to distinguish between intrinsic renal disease and preeclampsia. Renal disease can occur at any gestational age, but preeclampsia occurs after 20 weeks. Serum creatinine levels between 0.8 and 1.2 mg/dl are associated with preeclampsia, while levels of 1.5–1.8 mg/dL and higher are associated with renal disease.

“You almost never see azotemia in the setting of preeclampsia without proteinuria,” she said. In addition, intrinsic renal disease can occur with normal blood pressure, but a patient must be hypertensive to have preeclampsia.

Managing chronic renal disease during pregnancy requires a team approach that includes nephrologists. Dr. August recommends that patients be monitored frequently for preeclampsia—and for renal protection—blood pressure should be maintained within a slightly lower range than normal.

How Pregnancy Affects Kidney Function

Normal pregnancies have complex effects on the kidneys and on hemodynamics—changes that bear keeping in mind when evaluating pregnant patients with chronic kidney disease, Dr. August said.

During pregnancy, kidney size, blood flow, and glomerular filtration rate (GFR) all increase. GFR increases by as much as 50%, said Dr. August, of Cornell University in New York.

Renal vasodilation leads to increases in renin, urinary protein, aldosterone excretion, sodium and water reabsorption, glycosuria, and aminoaciduria. There are concomitant decreases in uric acid reabsorption and serum creatinine, sodium, and osmolarity. Normal serum sodium for a pregnant woman is in the 135–137 mmol/L range. Likewise, serum creatinine levels can be as low as 0.5 mg/dL and is usually 0.6 mg/dL; levels above 0.8 mg/dL indicate a decreased GFR, she said.

Uric acid levels also are lower in pregnant women—something to keep in mind when evaluating patients for possible preeclampsia, which causes serum uric acid levels to rise. In the second trimester, the normal uric acid level is usually not much higher than 3.5 mg/dL, and in the third trimester, it can go up as high as 4.5 mg/dL. “Anything higher than that is not quite normal,” Dr. August said.

Dilation of the urinary tract in pregnancy increases susceptibility to urinary tract infections. She recommends monthly screening for asymptomatic bacteriuria in pregnant women who are prone to urinary tract infections. Acute pyelonephritis can be much more serious than usual in pregnant women.

Hemodynamic changes during pregnancy include decreased blood pressure and increased cardiac output, heart rate, and respiratory rate. Some of these changes can actually be helpful for women with chronic kidney disease. Women who have been treated for hypertension and/or chronic kidney disease before pregnancy may require fewer medications during pregnancy.

WASHINGTON — Kidney disease can lead to complications during pregnancy—and pregnancy can worsen kidney disease, Phyllis August, M.D., said at a meeting sponsored by the National Kidney Foundation.

“Without normal renal function, pregnancy is threatened and not always successful, and pregnancy does pose a burden in women with compromised renal function,” said Dr. August, professor of medicine at the Cornell University cardiovascular center in New York.

During pregnancy, women undergo kidney and hemodynamic changes that can lead to or worsen chronic kidney disease (CKD). “The bottom line in patients with CKD or chronic renal insufficiency is that the outcome seems to be related to baseline blood pressure and the degree of renal insufficiency at the time of conception,” she said. In general, serum creatinine levels lower than 1.5 mg/dL and the absence of hypertension favor normal outcomes.

The approach to management depends on whether the patient is diagnosed with renal disease before conception or during pregnancy, or whether the disease onset occurs during pregnancy.

Encourage patients with severe CKD to wait until they have had a transplant before becoming pregnant. “Dialysis and pregnancy are not a good combination,” Dr. August said.

Pregnancy has temporary effects on renal disease. Urinary protein excretion is increased, with normal excretion ranging up to 300 mg/day during pregnancy. “Many of our patients with chronic renal disease, particularly diabetic nephropathy, can have a significant increase in urinary protein excretion,” she said. It's unknown whether this increase has any adverse effects on the underlying kidney disease.

“There is the possibility that because of all of these phenomena that pregnancy could pose a burden on the kidney in women with preexisting renal disease, leading to permanent loss of function,” Dr. August said. But there are few data on the long-term effect of pregnancy on renal function in women with CKD.

Renal disease diagnosed before conception is typically diabetic nephropathy or chronic glomerular nephritis. Previous studies suggested that earlier deliveries and smaller babies were the rule in this population. More recent data suggest that the worse the renal disease is prior to pregnancy, the worse the outcome of the pregnancy will be. Some data suggest that pregnancy does not lead to progression of diabetic nephropathy.

Management of diabetic nephropathy during pregnancy should rely on tight control of blood sugar, especially during the first trimester. There is a clear association between abnormal glucose control and fetal malformations. Also discontinue the use of ACE inhibitors and angiotensin II receptor blockers. Instead, antihypertensive therapy should be accomplished with methyldopa, labetalol, calcium antagonists, and occasional use of diuretics, Dr. August advised.

Women with a long history of type 1 diabetes should have a thorough cardiac evaluation with a stress test and an echocardiogram prior to pregnancy. Once pregnant, these patients should have a laboratory evaluation about every month, she recommended.

Many women with CKD have a risk of developing superimposed preeclampsia. The higher a woman's creatinine level is, the greater the risk. Pregnant women with preexisting CKD and preeclampsia have a higher incidence of premature delivery and restricted fetus growth than do women without CKD. “Most women with renal disease will have premature deliveries, and many will have smaller babies,” Dr. August said.

In some cases, renal disease becomes clinically apparent for the first time during pregnancy. Increased renal hemodynamics during pregnancy can unmask proteinuria. Close monitoring of blood pressure and urine during pregnancy may bring problems to light.

Renal evaluation of patients first suspected of having CKD during pregnancy is similar to that for patients who are not pregnant—serologic and function testing, and ultrasound.

A biopsy can even be performed, but it is common to avoid this measure during the third trimester of pregnancy because of anatomical and positioning issues.

Generally, only deteriorating kidney function or morbid nephritic syndrome is considered to be an indication for attempting a biopsy during pregnancy. Otherwise, it is preferred to wait until after delivery, Dr. August said.

It can be difficult to distinguish between intrinsic renal disease and preeclampsia. Renal disease can occur at any gestational age, but preeclampsia occurs after 20 weeks. Serum creatinine levels between 0.8 and 1.2 mg/dl are associated with preeclampsia, while levels of 1.5–1.8 mg/dL and higher are associated with renal disease.

“You almost never see azotemia in the setting of preeclampsia without proteinuria,” she said. In addition, intrinsic renal disease can occur with normal blood pressure, but a patient must be hypertensive to have preeclampsia.

Managing chronic renal disease during pregnancy requires a team approach that includes nephrologists. Dr. August recommends that patients be monitored frequently for preeclampsia—and for renal protection—blood pressure should be maintained within a slightly lower range than normal.

How Pregnancy Affects Kidney Function

Normal pregnancies have complex effects on the kidneys and on hemodynamics—changes that bear keeping in mind when evaluating pregnant patients with chronic kidney disease, Dr. August said.

During pregnancy, kidney size, blood flow, and glomerular filtration rate (GFR) all increase. GFR increases by as much as 50%, said Dr. August, of Cornell University in New York.

Renal vasodilation leads to increases in renin, urinary protein, aldosterone excretion, sodium and water reabsorption, glycosuria, and aminoaciduria. There are concomitant decreases in uric acid reabsorption and serum creatinine, sodium, and osmolarity. Normal serum sodium for a pregnant woman is in the 135–137 mmol/L range. Likewise, serum creatinine levels can be as low as 0.5 mg/dL and is usually 0.6 mg/dL; levels above 0.8 mg/dL indicate a decreased GFR, she said.

Uric acid levels also are lower in pregnant women—something to keep in mind when evaluating patients for possible preeclampsia, which causes serum uric acid levels to rise. In the second trimester, the normal uric acid level is usually not much higher than 3.5 mg/dL, and in the third trimester, it can go up as high as 4.5 mg/dL. “Anything higher than that is not quite normal,” Dr. August said.

Dilation of the urinary tract in pregnancy increases susceptibility to urinary tract infections. She recommends monthly screening for asymptomatic bacteriuria in pregnant women who are prone to urinary tract infections. Acute pyelonephritis can be much more serious than usual in pregnant women.

Hemodynamic changes during pregnancy include decreased blood pressure and increased cardiac output, heart rate, and respiratory rate. Some of these changes can actually be helpful for women with chronic kidney disease. Women who have been treated for hypertension and/or chronic kidney disease before pregnancy may require fewer medications during pregnancy.

WASHINGTON — Kidney disease can lead to complications during pregnancy—and pregnancy can worsen kidney disease, Phyllis August, M.D., said at a meeting sponsored by the National Kidney Foundation.

“Without normal renal function, pregnancy is threatened and not always successful, and pregnancy does pose a burden in women with compromised renal function,” said Dr. August, professor of medicine at the Cornell University cardiovascular center in New York.

During pregnancy, women undergo kidney and hemodynamic changes that can lead to or worsen chronic kidney disease (CKD). “The bottom line in patients with CKD or chronic renal insufficiency is that the outcome seems to be related to baseline blood pressure and the degree of renal insufficiency at the time of conception,” she said. In general, serum creatinine levels lower than 1.5 mg/dL and the absence of hypertension favor normal outcomes.

The approach to management depends on whether the patient is diagnosed with renal disease before conception or during pregnancy, or whether the disease onset occurs during pregnancy.

Encourage patients with severe CKD to wait until they have had a transplant before becoming pregnant. “Dialysis and pregnancy are not a good combination,” Dr. August said.

Pregnancy has temporary effects on renal disease. Urinary protein excretion is increased, with normal excretion ranging up to 300 mg/day during pregnancy. “Many of our patients with chronic renal disease, particularly diabetic nephropathy, can have a significant increase in urinary protein excretion,” she said. It's unknown whether this increase has any adverse effects on the underlying kidney disease.

“There is the possibility that because of all of these phenomena that pregnancy could pose a burden on the kidney in women with preexisting renal disease, leading to permanent loss of function,” Dr. August said. But there are few data on the long-term effect of pregnancy on renal function in women with CKD.

Renal disease diagnosed before conception is typically diabetic nephropathy or chronic glomerular nephritis. Previous studies suggested that earlier deliveries and smaller babies were the rule in this population. More recent data suggest that the worse the renal disease is prior to pregnancy, the worse the outcome of the pregnancy will be. Some data suggest that pregnancy does not lead to progression of diabetic nephropathy.

Management of diabetic nephropathy during pregnancy should rely on tight control of blood sugar, especially during the first trimester. There is a clear association between abnormal glucose control and fetal malformations. Also discontinue the use of ACE inhibitors and angiotensin II receptor blockers. Instead, antihypertensive therapy should be accomplished with methyldopa, labetalol, calcium antagonists, and occasional use of diuretics, Dr. August advised.

Women with a long history of type 1 diabetes should have a thorough cardiac evaluation with a stress test and an echocardiogram prior to pregnancy. Once pregnant, these patients should have a laboratory evaluation about every month, she recommended.

Many women with CKD have a risk of developing superimposed preeclampsia. The higher a woman's creatinine level is, the greater the risk. Pregnant women with preexisting CKD and preeclampsia have a higher incidence of premature delivery and restricted fetus growth than do women without CKD. “Most women with renal disease will have premature deliveries, and many will have smaller babies,” Dr. August said.

In some cases, renal disease becomes clinically apparent for the first time during pregnancy. Increased renal hemodynamics during pregnancy can unmask proteinuria. Close monitoring of blood pressure and urine during pregnancy may bring problems to light.

Renal evaluation of patients first suspected of having CKD during pregnancy is similar to that for patients who are not pregnant—serologic and function testing, and ultrasound.

A biopsy can even be performed, but it is common to avoid this measure during the third trimester of pregnancy because of anatomical and positioning issues.

Generally, only deteriorating kidney function or morbid nephritic syndrome is considered to be an indication for attempting a biopsy during pregnancy. Otherwise, it is preferred to wait until after delivery, Dr. August said.

It can be difficult to distinguish between intrinsic renal disease and preeclampsia. Renal disease can occur at any gestational age, but preeclampsia occurs after 20 weeks. Serum creatinine levels between 0.8 and 1.2 mg/dl are associated with preeclampsia, while levels of 1.5–1.8 mg/dL and higher are associated with renal disease.

“You almost never see azotemia in the setting of preeclampsia without proteinuria,” she said. In addition, intrinsic renal disease can occur with normal blood pressure, but a patient must be hypertensive to have preeclampsia.

Managing chronic renal disease during pregnancy requires a team approach that includes nephrologists. Dr. August recommends that patients be monitored frequently for preeclampsia—and for renal protection—blood pressure should be maintained within a slightly lower range than normal.

How Pregnancy Affects Kidney Function

Normal pregnancies have complex effects on the kidneys and on hemodynamics—changes that bear keeping in mind when evaluating pregnant patients with chronic kidney disease, Dr. August said.

During pregnancy, kidney size, blood flow, and glomerular filtration rate (GFR) all increase. GFR increases by as much as 50%, said Dr. August, of Cornell University in New York.

Renal vasodilation leads to increases in renin, urinary protein, aldosterone excretion, sodium and water reabsorption, glycosuria, and aminoaciduria. There are concomitant decreases in uric acid reabsorption and serum creatinine, sodium, and osmolarity. Normal serum sodium for a pregnant woman is in the 135–137 mmol/L range. Likewise, serum creatinine levels can be as low as 0.5 mg/dL and is usually 0.6 mg/dL; levels above 0.8 mg/dL indicate a decreased GFR, she said.

Uric acid levels also are lower in pregnant women—something to keep in mind when evaluating patients for possible preeclampsia, which causes serum uric acid levels to rise. In the second trimester, the normal uric acid level is usually not much higher than 3.5 mg/dL, and in the third trimester, it can go up as high as 4.5 mg/dL. “Anything higher than that is not quite normal,” Dr. August said.

Dilation of the urinary tract in pregnancy increases susceptibility to urinary tract infections. She recommends monthly screening for asymptomatic bacteriuria in pregnant women who are prone to urinary tract infections. Acute pyelonephritis can be much more serious than usual in pregnant women.

Hemodynamic changes during pregnancy include decreased blood pressure and increased cardiac output, heart rate, and respiratory rate. Some of these changes can actually be helpful for women with chronic kidney disease. Women who have been treated for hypertension and/or chronic kidney disease before pregnancy may require fewer medications during pregnancy.

WASHINGTON — Pulse wave analysis is an investigational noninvasive technique that might help doctors identify women at increased risk for preeclampsia, results of a pilot study suggest.

A distinctive peak on the augmentation index, which is a measure of aortic stiffness, distinguishes preeclampsia from other hypertensive disorders in pregnancy, according to a poster presented by Brendan J. Smyth, M.D., at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

In a normal pregnancy, the augmentation index (AIx) decreases, but in this study it stayed elevated with preeclampsia, said Dr. Smyth of Georgetown University, Washington. The AIx is the ratio of augmented systolic pressure to pulse pressure, and represents factors related to arterial function.

Dr. Smyth and his colleagues presented data on 17 preeclampsia patients from their prospective, ongoing pilot study. Pulse wave analysis was used to assess women at prepartum and postpartum sessions or within 24 hours of antihypertensive therapy. They said those with preeclampsia had a distinctive peak in the waveform.

The mean percentage for the AIx peak in preeclampsia patients was 35%, compared with 15% for an additional 16 women with chronic hypertension, 15% for 15 women with gestational diabetes, and −6% for 8 normally healthy women.

The mean percentage was 31% for five women with preeclampsia superimposed on chronic hypertension and 30% among three with preeclampsia superimposed on chronic hypertension plus diabetes mellitus.

The AIx measurement could be used to identify women at increased risk and to prevent unnecessary hospitalization.

The pilot study was supported in part by the National Center for Research Resources.

WASHINGTON — Pulse wave analysis is an investigational noninvasive technique that might help doctors identify women at increased risk for preeclampsia, results of a pilot study suggest.

A distinctive peak on the augmentation index, which is a measure of aortic stiffness, distinguishes preeclampsia from other hypertensive disorders in pregnancy, according to a poster presented by Brendan J. Smyth, M.D., at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

In a normal pregnancy, the augmentation index (AIx) decreases, but in this study it stayed elevated with preeclampsia, said Dr. Smyth of Georgetown University, Washington. The AIx is the ratio of augmented systolic pressure to pulse pressure, and represents factors related to arterial function.

Dr. Smyth and his colleagues presented data on 17 preeclampsia patients from their prospective, ongoing pilot study. Pulse wave analysis was used to assess women at prepartum and postpartum sessions or within 24 hours of antihypertensive therapy. They said those with preeclampsia had a distinctive peak in the waveform.

The mean percentage for the AIx peak in preeclampsia patients was 35%, compared with 15% for an additional 16 women with chronic hypertension, 15% for 15 women with gestational diabetes, and −6% for 8 normally healthy women.

The mean percentage was 31% for five women with preeclampsia superimposed on chronic hypertension and 30% among three with preeclampsia superimposed on chronic hypertension plus diabetes mellitus.

The AIx measurement could be used to identify women at increased risk and to prevent unnecessary hospitalization.

The pilot study was supported in part by the National Center for Research Resources.

WASHINGTON — Pulse wave analysis is an investigational noninvasive technique that might help doctors identify women at increased risk for preeclampsia, results of a pilot study suggest.

A distinctive peak on the augmentation index, which is a measure of aortic stiffness, distinguishes preeclampsia from other hypertensive disorders in pregnancy, according to a poster presented by Brendan J. Smyth, M.D., at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

In a normal pregnancy, the augmentation index (AIx) decreases, but in this study it stayed elevated with preeclampsia, said Dr. Smyth of Georgetown University, Washington. The AIx is the ratio of augmented systolic pressure to pulse pressure, and represents factors related to arterial function.

Dr. Smyth and his colleagues presented data on 17 preeclampsia patients from their prospective, ongoing pilot study. Pulse wave analysis was used to assess women at prepartum and postpartum sessions or within 24 hours of antihypertensive therapy. They said those with preeclampsia had a distinctive peak in the waveform.

The mean percentage for the AIx peak in preeclampsia patients was 35%, compared with 15% for an additional 16 women with chronic hypertension, 15% for 15 women with gestational diabetes, and −6% for 8 normally healthy women.

The mean percentage was 31% for five women with preeclampsia superimposed on chronic hypertension and 30% among three with preeclampsia superimposed on chronic hypertension plus diabetes mellitus.

The AIx measurement could be used to identify women at increased risk and to prevent unnecessary hospitalization.

The pilot study was supported in part by the National Center for Research Resources.

Meningococcal disease is almost 12 times more likely to occur in a child whose mother is pregnant, possibly due to hormonal alterations in the mucosal barriers of pregnant women that predispose them to carry the bacteria.

Elske van Gils and her colleagues at the University of Amsterdam examined family composition in 176 hospitalized children (mean age about 4 years); 88 were admitted with confirmed meningococcal disease and 88 for other reasons, mostly surgery.

Among the meningococcal cases, 17 (19%) of mothers were pregnant during the hospitalization, 6 were in their first or second trimester, and the rest were in their third trimester (Pediatrics 2005;115:590–3).

Among the controls, only 2 (2%) of mothers were pregnant. Pregnancy was associated with an increased odds ratio of 11.7, multivariate analysis showed.

Other studies have found that meningococcal infections in children are related to maternal carriage. The authors hypothesized that pregnant women may have increased or prolonged carriage rates.

Meningococcal disease is almost 12 times more likely to occur in a child whose mother is pregnant, possibly due to hormonal alterations in the mucosal barriers of pregnant women that predispose them to carry the bacteria.

Elske van Gils and her colleagues at the University of Amsterdam examined family composition in 176 hospitalized children (mean age about 4 years); 88 were admitted with confirmed meningococcal disease and 88 for other reasons, mostly surgery.

Among the meningococcal cases, 17 (19%) of mothers were pregnant during the hospitalization, 6 were in their first or second trimester, and the rest were in their third trimester (Pediatrics 2005;115:590–3).

Among the controls, only 2 (2%) of mothers were pregnant. Pregnancy was associated with an increased odds ratio of 11.7, multivariate analysis showed.

Other studies have found that meningococcal infections in children are related to maternal carriage. The authors hypothesized that pregnant women may have increased or prolonged carriage rates.

Meningococcal disease is almost 12 times more likely to occur in a child whose mother is pregnant, possibly due to hormonal alterations in the mucosal barriers of pregnant women that predispose them to carry the bacteria.

Elske van Gils and her colleagues at the University of Amsterdam examined family composition in 176 hospitalized children (mean age about 4 years); 88 were admitted with confirmed meningococcal disease and 88 for other reasons, mostly surgery.

Among the meningococcal cases, 17 (19%) of mothers were pregnant during the hospitalization, 6 were in their first or second trimester, and the rest were in their third trimester (Pediatrics 2005;115:590–3).

Among the controls, only 2 (2%) of mothers were pregnant. Pregnancy was associated with an increased odds ratio of 11.7, multivariate analysis showed.

Other studies have found that meningococcal infections in children are related to maternal carriage. The authors hypothesized that pregnant women may have increased or prolonged carriage rates.

LAS VEGAS — In multiple gestations, don't rely solely on the mother's perception of how the fetuses are positioned when monitorig fetal heart rates, Patricia M. Witcher, a registered nurse clinician, advised at a conference on fetal monitoring sponsored by Symposia Medicus.

She acknowledged that sometimes clinicians find themselves doing just that, “especially with women who have been admitted in an inpatient antepartum setting who are due to have quadruplets. She'll say, '[Baby] A is here, B is here, C is here, and D is here.' You can't rely on that.”

An ideal way to identify each fetus before heart rate monitoring would be to use ultrasound, but “that's not realistic because most people who initiate monitoring don't do ultrasound,” said Ms. Witcher, a nurse at Northside Hospital in Atlanta who specializes in labor and delivery and high-risk obstetrics.

The best way to identify each fetus is by doing simultaneous monitoring and looking for divergence of fetal heart rate tracings. “That's really the only way we have of ensuring that we have a heart rate for each fetus,” she said.

She recommends drawing a quadrant on the fetal heart rate tracing that represents the four quadrants of the mother's pelvis. Mark the fetus lowest in the pelvis as “A” and assign subsequent letters to the rest. Using a number system is another option.

“Identification of each fetus is extremely important,” she commented. “I can't tell you how many cases I see where it's not clearly labeled which fetus is which. You can figure it out if you see long-term monitoring, whether there have been interruptions in that segment. You can figure out, 'This baby was in trouble before the mother got up to go to the bathroom, so this must be baby B again,' or whichever baby is having problems.”

In a case of twins, some monitors will print the tracings of fetus A in a dark line and that of fetus B in a light line. Others use different colors of ink to help clinicians differentiate fetuses.

Ms. Witcher added that twins are synchronous in that they tend to exhibit accelerations within 15 seconds of each other in about 51% of cases.

“Synchrony is not an indicator of discordancy,” she said.

“It does not tell you whether you have discordant twins or not. If you don't have synchronous fetal heart rate patterns, it's not any indication that you have a problem with one versus the other. It's just the luck of the draw in timing if you display accelerations at the same time in those babies.”

LAS VEGAS — In multiple gestations, don't rely solely on the mother's perception of how the fetuses are positioned when monitorig fetal heart rates, Patricia M. Witcher, a registered nurse clinician, advised at a conference on fetal monitoring sponsored by Symposia Medicus.

She acknowledged that sometimes clinicians find themselves doing just that, “especially with women who have been admitted in an inpatient antepartum setting who are due to have quadruplets. She'll say, '[Baby] A is here, B is here, C is here, and D is here.' You can't rely on that.”

An ideal way to identify each fetus before heart rate monitoring would be to use ultrasound, but “that's not realistic because most people who initiate monitoring don't do ultrasound,” said Ms. Witcher, a nurse at Northside Hospital in Atlanta who specializes in labor and delivery and high-risk obstetrics.

The best way to identify each fetus is by doing simultaneous monitoring and looking for divergence of fetal heart rate tracings. “That's really the only way we have of ensuring that we have a heart rate for each fetus,” she said.

She recommends drawing a quadrant on the fetal heart rate tracing that represents the four quadrants of the mother's pelvis. Mark the fetus lowest in the pelvis as “A” and assign subsequent letters to the rest. Using a number system is another option.

“Identification of each fetus is extremely important,” she commented. “I can't tell you how many cases I see where it's not clearly labeled which fetus is which. You can figure it out if you see long-term monitoring, whether there have been interruptions in that segment. You can figure out, 'This baby was in trouble before the mother got up to go to the bathroom, so this must be baby B again,' or whichever baby is having problems.”

In a case of twins, some monitors will print the tracings of fetus A in a dark line and that of fetus B in a light line. Others use different colors of ink to help clinicians differentiate fetuses.

Ms. Witcher added that twins are synchronous in that they tend to exhibit accelerations within 15 seconds of each other in about 51% of cases.

“Synchrony is not an indicator of discordancy,” she said.

“It does not tell you whether you have discordant twins or not. If you don't have synchronous fetal heart rate patterns, it's not any indication that you have a problem with one versus the other. It's just the luck of the draw in timing if you display accelerations at the same time in those babies.”

LAS VEGAS — In multiple gestations, don't rely solely on the mother's perception of how the fetuses are positioned when monitorig fetal heart rates, Patricia M. Witcher, a registered nurse clinician, advised at a conference on fetal monitoring sponsored by Symposia Medicus.

She acknowledged that sometimes clinicians find themselves doing just that, “especially with women who have been admitted in an inpatient antepartum setting who are due to have quadruplets. She'll say, '[Baby] A is here, B is here, C is here, and D is here.' You can't rely on that.”

An ideal way to identify each fetus before heart rate monitoring would be to use ultrasound, but “that's not realistic because most people who initiate monitoring don't do ultrasound,” said Ms. Witcher, a nurse at Northside Hospital in Atlanta who specializes in labor and delivery and high-risk obstetrics.

The best way to identify each fetus is by doing simultaneous monitoring and looking for divergence of fetal heart rate tracings. “That's really the only way we have of ensuring that we have a heart rate for each fetus,” she said.

She recommends drawing a quadrant on the fetal heart rate tracing that represents the four quadrants of the mother's pelvis. Mark the fetus lowest in the pelvis as “A” and assign subsequent letters to the rest. Using a number system is another option.

“Identification of each fetus is extremely important,” she commented. “I can't tell you how many cases I see where it's not clearly labeled which fetus is which. You can figure it out if you see long-term monitoring, whether there have been interruptions in that segment. You can figure out, 'This baby was in trouble before the mother got up to go to the bathroom, so this must be baby B again,' or whichever baby is having problems.”

In a case of twins, some monitors will print the tracings of fetus A in a dark line and that of fetus B in a light line. Others use different colors of ink to help clinicians differentiate fetuses.

Ms. Witcher added that twins are synchronous in that they tend to exhibit accelerations within 15 seconds of each other in about 51% of cases.

“Synchrony is not an indicator of discordancy,” she said.

“It does not tell you whether you have discordant twins or not. If you don't have synchronous fetal heart rate patterns, it's not any indication that you have a problem with one versus the other. It's just the luck of the draw in timing if you display accelerations at the same time in those babies.”

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN