Obstetrics

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Women who have had preeclampsia are at increased risk of cardiovascular disease later in life, suggesting that they should be targeted for primary prevention, according to a British review published online in the British Medical Journal.

Meanwhile, an accompanying population-based prospective study in Norway suggests that cardiovascular risk factors are associated with a higher risk of preeclampsia.

“The underlying link between preeclampsia and cardiovascular disease is unclear. Although preeclampsia may initiate endothelial damage, it is thought to be more likely that preeclampsia and cardiovascular disease have a common pathogenesis rooted in shared risk markers,” wrote Dr. Laura Magee and Dr. Peter von Dadelszen of the University of British Columbia, Vancouver, in a commentary accompanying the two studies (BMJ 2007 Nov. 2 [Epub doi.10.113/bmj.39337.427500.80]).

In the first study–a review of cohort studies in all languages between 1960 and 2006 covering more than 3 million women–British researchers found an increased risk for vascular disease among women who'd had preeclampsia, compared with those who never had the disorder. The relative risks for women with a history of preeclampsia were 3.7 for hypertension after a mean weighted follow-up of 14 years, 2.2 for ischemic heart disease after 12 years, 1.8 for stroke after 10 years, 1.8 for venous thromboembolism after almost 5 years.

No increase in the risk of any cancer was found, including breast cancer, after 17 years, wrote Leanne Bellamy, a medical student at Imperial College School of Medicine, London, and her associates (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39335.385301.BE]).

The overall risk of mortality was elevated following preeclampsia, with a relative risk of 1.49 after 14.5 years.

“We must recognise that these women are still young, their absolute risk of cardiovascular disease is low over the short term, and their risk will evolve over subsequent decades,” wrote Dr. Magee and Dr. von Dadelszen in their commentary. “As such, we have an opportunity for primary prevention, especially as cardiovascular disease is largely preventable.”

They added, however, that the findings so far do not help physicians guide their primary prevention strategy. No evidence supports how to screen younger women for risk factors, and while recommending lifestyle change is good for all patients, such a recommendation “is not enough to change their behavior,” the authors wrote. “However, women might be more receptive if they have had a complicated pregnancy. Perhaps we could tailor the advice to women with newborns and young children,” they wrote.

The Norwegian study tracked 3,494 women who gave birth after participating in the Nord-Trøndelag health study to link cardiovascular risk factors and preeclampsia risk. The women were linked to diagnoses for preeclampsia through the Norway birth registry (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39366.416817.BE]).

After adjustment, the odds ratio for preeclampsia in women with a baseline systolic blood pressure greater than 130 mm Hg (highest fifth) was 7.3, compared with those with a systolic blood pressure less than 111 mm Hg (lowest fifth). Similarly, the odds ratio for women with a diastolic blood pressure greater than 78 mm Hg was 6.3, compared with those whose diastolic pressure was less than 64 mm Hg.

Women who were overweight or obese had a higher risk of preeclampsia than did women of normal weight, and the risk for preeclampsia rose with increasing waist circumference.

In addition, there was a weak association between pregnancy lipid levels in the clinically normal range and preeclampsia, and a stronger association with lipid levels above the normal range.

“We found that cardiovascular risk factors that were present years before pregnancy are associated with a risk of preeclampsia,” wrote Elisabeth Balstad Magnussen, a research fellow at the Norwegian University of Science and Technology, Trondheim, and associates. “This finding suggests that unfavourable cardiovascular and metabolic profiles may represent primary causes of preeclampsia and that these factors predispose both to preeclampsia and to subsequent cardiovascular disease. This does not, however, rule out the possibility that the pre-eclamptic process in itself may also contribute to cardiovascular risk.

Women who have had preeclampsia are at increased risk of cardiovascular disease later in life, suggesting that they should be targeted for primary prevention, according to a British review published online in the British Medical Journal.

Meanwhile, an accompanying population-based prospective study in Norway suggests that cardiovascular risk factors are associated with a higher risk of preeclampsia.

“The underlying link between preeclampsia and cardiovascular disease is unclear. Although preeclampsia may initiate endothelial damage, it is thought to be more likely that preeclampsia and cardiovascular disease have a common pathogenesis rooted in shared risk markers,” wrote Dr. Laura Magee and Dr. Peter von Dadelszen of the University of British Columbia, Vancouver, in a commentary accompanying the two studies (BMJ 2007 Nov. 2 [Epub doi.10.113/bmj.39337.427500.80]).

In the first study–a review of cohort studies in all languages between 1960 and 2006 covering more than 3 million women–British researchers found an increased risk for vascular disease among women who'd had preeclampsia, compared with those who never had the disorder. The relative risks for women with a history of preeclampsia were 3.7 for hypertension after a mean weighted follow-up of 14 years, 2.2 for ischemic heart disease after 12 years, 1.8 for stroke after 10 years, 1.8 for venous thromboembolism after almost 5 years.

No increase in the risk of any cancer was found, including breast cancer, after 17 years, wrote Leanne Bellamy, a medical student at Imperial College School of Medicine, London, and her associates (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39335.385301.BE]).

The overall risk of mortality was elevated following preeclampsia, with a relative risk of 1.49 after 14.5 years.

“We must recognise that these women are still young, their absolute risk of cardiovascular disease is low over the short term, and their risk will evolve over subsequent decades,” wrote Dr. Magee and Dr. von Dadelszen in their commentary. “As such, we have an opportunity for primary prevention, especially as cardiovascular disease is largely preventable.”

They added, however, that the findings so far do not help physicians guide their primary prevention strategy. No evidence supports how to screen younger women for risk factors, and while recommending lifestyle change is good for all patients, such a recommendation “is not enough to change their behavior,” the authors wrote. “However, women might be more receptive if they have had a complicated pregnancy. Perhaps we could tailor the advice to women with newborns and young children,” they wrote.

The Norwegian study tracked 3,494 women who gave birth after participating in the Nord-Trøndelag health study to link cardiovascular risk factors and preeclampsia risk. The women were linked to diagnoses for preeclampsia through the Norway birth registry (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39366.416817.BE]).

After adjustment, the odds ratio for preeclampsia in women with a baseline systolic blood pressure greater than 130 mm Hg (highest fifth) was 7.3, compared with those with a systolic blood pressure less than 111 mm Hg (lowest fifth). Similarly, the odds ratio for women with a diastolic blood pressure greater than 78 mm Hg was 6.3, compared with those whose diastolic pressure was less than 64 mm Hg.

Women who were overweight or obese had a higher risk of preeclampsia than did women of normal weight, and the risk for preeclampsia rose with increasing waist circumference.

In addition, there was a weak association between pregnancy lipid levels in the clinically normal range and preeclampsia, and a stronger association with lipid levels above the normal range.

“We found that cardiovascular risk factors that were present years before pregnancy are associated with a risk of preeclampsia,” wrote Elisabeth Balstad Magnussen, a research fellow at the Norwegian University of Science and Technology, Trondheim, and associates. “This finding suggests that unfavourable cardiovascular and metabolic profiles may represent primary causes of preeclampsia and that these factors predispose both to preeclampsia and to subsequent cardiovascular disease. This does not, however, rule out the possibility that the pre-eclamptic process in itself may also contribute to cardiovascular risk.

Women who have had preeclampsia are at increased risk of cardiovascular disease later in life, suggesting that they should be targeted for primary prevention, according to a British review published online in the British Medical Journal.

Meanwhile, an accompanying population-based prospective study in Norway suggests that cardiovascular risk factors are associated with a higher risk of preeclampsia.

“The underlying link between preeclampsia and cardiovascular disease is unclear. Although preeclampsia may initiate endothelial damage, it is thought to be more likely that preeclampsia and cardiovascular disease have a common pathogenesis rooted in shared risk markers,” wrote Dr. Laura Magee and Dr. Peter von Dadelszen of the University of British Columbia, Vancouver, in a commentary accompanying the two studies (BMJ 2007 Nov. 2 [Epub doi.10.113/bmj.39337.427500.80]).

In the first study–a review of cohort studies in all languages between 1960 and 2006 covering more than 3 million women–British researchers found an increased risk for vascular disease among women who'd had preeclampsia, compared with those who never had the disorder. The relative risks for women with a history of preeclampsia were 3.7 for hypertension after a mean weighted follow-up of 14 years, 2.2 for ischemic heart disease after 12 years, 1.8 for stroke after 10 years, 1.8 for venous thromboembolism after almost 5 years.

No increase in the risk of any cancer was found, including breast cancer, after 17 years, wrote Leanne Bellamy, a medical student at Imperial College School of Medicine, London, and her associates (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39335.385301.BE]).

The overall risk of mortality was elevated following preeclampsia, with a relative risk of 1.49 after 14.5 years.

“We must recognise that these women are still young, their absolute risk of cardiovascular disease is low over the short term, and their risk will evolve over subsequent decades,” wrote Dr. Magee and Dr. von Dadelszen in their commentary. “As such, we have an opportunity for primary prevention, especially as cardiovascular disease is largely preventable.”

They added, however, that the findings so far do not help physicians guide their primary prevention strategy. No evidence supports how to screen younger women for risk factors, and while recommending lifestyle change is good for all patients, such a recommendation “is not enough to change their behavior,” the authors wrote. “However, women might be more receptive if they have had a complicated pregnancy. Perhaps we could tailor the advice to women with newborns and young children,” they wrote.

The Norwegian study tracked 3,494 women who gave birth after participating in the Nord-Trøndelag health study to link cardiovascular risk factors and preeclampsia risk. The women were linked to diagnoses for preeclampsia through the Norway birth registry (BMJ 2007 Nov. 2 [Epub doi:10.1136/bmj.39366.416817.BE]).

After adjustment, the odds ratio for preeclampsia in women with a baseline systolic blood pressure greater than 130 mm Hg (highest fifth) was 7.3, compared with those with a systolic blood pressure less than 111 mm Hg (lowest fifth). Similarly, the odds ratio for women with a diastolic blood pressure greater than 78 mm Hg was 6.3, compared with those whose diastolic pressure was less than 64 mm Hg.

Women who were overweight or obese had a higher risk of preeclampsia than did women of normal weight, and the risk for preeclampsia rose with increasing waist circumference.

In addition, there was a weak association between pregnancy lipid levels in the clinically normal range and preeclampsia, and a stronger association with lipid levels above the normal range.

“We found that cardiovascular risk factors that were present years before pregnancy are associated with a risk of preeclampsia,” wrote Elisabeth Balstad Magnussen, a research fellow at the Norwegian University of Science and Technology, Trondheim, and associates. “This finding suggests that unfavourable cardiovascular and metabolic profiles may represent primary causes of preeclampsia and that these factors predispose both to preeclampsia and to subsequent cardiovascular disease. This does not, however, rule out the possibility that the pre-eclamptic process in itself may also contribute to cardiovascular risk.

AMSTERDAM — Seeing and presumptively treating all women with previous gestational diabetes mellitus early in their subsequent pregnancies—without rescreening them—is likely to improve maternal and fetal outcomes, Dr. Christina S. Cotzias said at the annual meeting of the European Association for the Study of Diabetes.

Recurrence rates of GDM in subsequent pregnancies among women who had the condition in a previous pregnancy range from about 30% to 70%, depending on the population studied. In general, the heavier and less Caucasian the population, the greater the GDM recurrence rate. And among women who do have GDM recurrence, some studies have suggested that glucose intolerance may occur earlier in subsequent pregnancies than in the initial one, said Dr. Cotzias of the obstetrics/gynecology department at West Middlesex University Hospital, Isleworth, England.

“In a heavy, multiethnic, insulin-resistant population, seeing all women with a history of GDM early in their next pregnancy to start treatment for GDM seems to optimize fetomaternal outcomes. To leave this population until screening is performed could be detrimental for both mother and baby,” she said.

Middlesex hospital's obstetric unit serves a multiethnic community with a high Asian prevalence. More than 70% of the center's GDM population is non-Caucasian. All pregnant women are asked if they had GDM in a prior pregnancy, and if so, they are immediately referred to a combined obstetric/endocrine clinic, where they receive education and counseling about GDM and its implications, diet and exercise, and self blood glucose monitoring.

Primigravidas and women who do not report having had GDM in a previous pregnancy are selectively screened for GDM based on a long list of risk factors, including family history of diabetes, maternal obesity (body mass index greater than 30 kg/m

Women identified with risk factors are screened at 28 weeks with a 50-g oral glucose challenge, and if the result is 7.8 mmol/L (140 mg/dL) or greater, a formal 75-g oral glucose tolerance test is done. If the fasting glucose at the time of the test is above 6 mmol/L (108 mg/dL) or if the 2-hour value is greater than 9 mmol/L (162 mg/dL), the patient then receives the GDM education and counseling. Insulin therapy is initiated if the patient's glucose values exceed 6 mmol/L (108 mg/dL) fasting and 8 mmol/L (144 mg/dL) at 2 hours postprandial with lifestyle modification alone. Women who receive insulin therapy are delivered between 38–40 weeks' gestation, Dr. Cotzias noted.

A retrospective case note analysis was performed for 419 women who were treated for GDM at Middlesex Hospital during 2000–2005, of whom 123 (29%) had GDM in a prior pregnancy and 296 (71%) did not. Those with previous GDM were significantly older (median age 34 vs. 32 years), and heavier (BMI 29 vs. 27), but there were no differences in ethnicity between the groups, both of which were approximately one-half Asian, one-quarter white, and about one-fifth black; the remainder were other ethnicities.

Hemoglobin A_1c levels were significantly higher among the women with previous GDM: 27% were at or above 7%, compared with just 15% among those newly diagnosed with GDM. The women with previous GDM were seen in the obstetric/endocrine clinic sooner in their pregnancies than were those without the history (median 16 vs. 32 weeks). They were much more likely to require insulin therapy (67% vs. 47%), and to be started on insulin sooner (25 vs. 34 weeks' gestation).

Importantly, of the 82 women in the previous GDM group who required insulin, nearly two-thirds (48, or 59%) needed it prior to 28 weeks' gestation, the time of routine GDM screening. “If we waited to screen those women, we would miss nearly 60% of those who need insulin before 28 weeks,” Dr. Cotzias noted.

Exactly half of each group had spontaneous vaginal delivery; cesarean section rates also did not differ significantly in the two groups (44% of those with previous GDM and 40% of those without). There were no significant differences between the two groups in any neonatal outcome. Of the women who came back for follow-up after delivery, 23% of 66 with previous GDM and 22% of the 188 without—an insignificant difference—had abnormal glucose tolerance test results. “I extrapolate the findings to suggest that if I left these women until 28 weeks' gestation and then started [treatment], I would have missed the boat and had worse outcomes. I can't prove it, but that's what the data suggest,” Dr. Cotzias said.

To leave this population until screening is done may be detrimental for both mother and baby. DR. COTZIAS

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — Seeing and presumptively treating all women with previous gestational diabetes mellitus early in their subsequent pregnancies—without rescreening them—is likely to improve maternal and fetal outcomes, Dr. Christina S. Cotzias said at the annual meeting of the European Association for the Study of Diabetes.

Recurrence rates of GDM in subsequent pregnancies among women who had the condition in a previous pregnancy range from about 30% to 70%, depending on the population studied. In general, the heavier and less Caucasian the population, the greater the GDM recurrence rate. And among women who do have GDM recurrence, some studies have suggested that glucose intolerance may occur earlier in subsequent pregnancies than in the initial one, said Dr. Cotzias of the obstetrics/gynecology department at West Middlesex University Hospital, Isleworth, England.

“In a heavy, multiethnic, insulin-resistant population, seeing all women with a history of GDM early in their next pregnancy to start treatment for GDM seems to optimize fetomaternal outcomes. To leave this population until screening is performed could be detrimental for both mother and baby,” she said.

Middlesex hospital's obstetric unit serves a multiethnic community with a high Asian prevalence. More than 70% of the center's GDM population is non-Caucasian. All pregnant women are asked if they had GDM in a prior pregnancy, and if so, they are immediately referred to a combined obstetric/endocrine clinic, where they receive education and counseling about GDM and its implications, diet and exercise, and self blood glucose monitoring.

Primigravidas and women who do not report having had GDM in a previous pregnancy are selectively screened for GDM based on a long list of risk factors, including family history of diabetes, maternal obesity (body mass index greater than 30 kg/m

Women identified with risk factors are screened at 28 weeks with a 50-g oral glucose challenge, and if the result is 7.8 mmol/L (140 mg/dL) or greater, a formal 75-g oral glucose tolerance test is done. If the fasting glucose at the time of the test is above 6 mmol/L (108 mg/dL) or if the 2-hour value is greater than 9 mmol/L (162 mg/dL), the patient then receives the GDM education and counseling. Insulin therapy is initiated if the patient's glucose values exceed 6 mmol/L (108 mg/dL) fasting and 8 mmol/L (144 mg/dL) at 2 hours postprandial with lifestyle modification alone. Women who receive insulin therapy are delivered between 38–40 weeks' gestation, Dr. Cotzias noted.

A retrospective case note analysis was performed for 419 women who were treated for GDM at Middlesex Hospital during 2000–2005, of whom 123 (29%) had GDM in a prior pregnancy and 296 (71%) did not. Those with previous GDM were significantly older (median age 34 vs. 32 years), and heavier (BMI 29 vs. 27), but there were no differences in ethnicity between the groups, both of which were approximately one-half Asian, one-quarter white, and about one-fifth black; the remainder were other ethnicities.

Hemoglobin A_1c levels were significantly higher among the women with previous GDM: 27% were at or above 7%, compared with just 15% among those newly diagnosed with GDM. The women with previous GDM were seen in the obstetric/endocrine clinic sooner in their pregnancies than were those without the history (median 16 vs. 32 weeks). They were much more likely to require insulin therapy (67% vs. 47%), and to be started on insulin sooner (25 vs. 34 weeks' gestation).

Importantly, of the 82 women in the previous GDM group who required insulin, nearly two-thirds (48, or 59%) needed it prior to 28 weeks' gestation, the time of routine GDM screening. “If we waited to screen those women, we would miss nearly 60% of those who need insulin before 28 weeks,” Dr. Cotzias noted.

Exactly half of each group had spontaneous vaginal delivery; cesarean section rates also did not differ significantly in the two groups (44% of those with previous GDM and 40% of those without). There were no significant differences between the two groups in any neonatal outcome. Of the women who came back for follow-up after delivery, 23% of 66 with previous GDM and 22% of the 188 without—an insignificant difference—had abnormal glucose tolerance test results. “I extrapolate the findings to suggest that if I left these women until 28 weeks' gestation and then started [treatment], I would have missed the boat and had worse outcomes. I can't prove it, but that's what the data suggest,” Dr. Cotzias said.

To leave this population until screening is done may be detrimental for both mother and baby. DR. COTZIAS

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — Seeing and presumptively treating all women with previous gestational diabetes mellitus early in their subsequent pregnancies—without rescreening them—is likely to improve maternal and fetal outcomes, Dr. Christina S. Cotzias said at the annual meeting of the European Association for the Study of Diabetes.

Recurrence rates of GDM in subsequent pregnancies among women who had the condition in a previous pregnancy range from about 30% to 70%, depending on the population studied. In general, the heavier and less Caucasian the population, the greater the GDM recurrence rate. And among women who do have GDM recurrence, some studies have suggested that glucose intolerance may occur earlier in subsequent pregnancies than in the initial one, said Dr. Cotzias of the obstetrics/gynecology department at West Middlesex University Hospital, Isleworth, England.

“In a heavy, multiethnic, insulin-resistant population, seeing all women with a history of GDM early in their next pregnancy to start treatment for GDM seems to optimize fetomaternal outcomes. To leave this population until screening is performed could be detrimental for both mother and baby,” she said.

Middlesex hospital's obstetric unit serves a multiethnic community with a high Asian prevalence. More than 70% of the center's GDM population is non-Caucasian. All pregnant women are asked if they had GDM in a prior pregnancy, and if so, they are immediately referred to a combined obstetric/endocrine clinic, where they receive education and counseling about GDM and its implications, diet and exercise, and self blood glucose monitoring.

Primigravidas and women who do not report having had GDM in a previous pregnancy are selectively screened for GDM based on a long list of risk factors, including family history of diabetes, maternal obesity (body mass index greater than 30 kg/m

Women identified with risk factors are screened at 28 weeks with a 50-g oral glucose challenge, and if the result is 7.8 mmol/L (140 mg/dL) or greater, a formal 75-g oral glucose tolerance test is done. If the fasting glucose at the time of the test is above 6 mmol/L (108 mg/dL) or if the 2-hour value is greater than 9 mmol/L (162 mg/dL), the patient then receives the GDM education and counseling. Insulin therapy is initiated if the patient's glucose values exceed 6 mmol/L (108 mg/dL) fasting and 8 mmol/L (144 mg/dL) at 2 hours postprandial with lifestyle modification alone. Women who receive insulin therapy are delivered between 38–40 weeks' gestation, Dr. Cotzias noted.

A retrospective case note analysis was performed for 419 women who were treated for GDM at Middlesex Hospital during 2000–2005, of whom 123 (29%) had GDM in a prior pregnancy and 296 (71%) did not. Those with previous GDM were significantly older (median age 34 vs. 32 years), and heavier (BMI 29 vs. 27), but there were no differences in ethnicity between the groups, both of which were approximately one-half Asian, one-quarter white, and about one-fifth black; the remainder were other ethnicities.

Hemoglobin A_1c levels were significantly higher among the women with previous GDM: 27% were at or above 7%, compared with just 15% among those newly diagnosed with GDM. The women with previous GDM were seen in the obstetric/endocrine clinic sooner in their pregnancies than were those without the history (median 16 vs. 32 weeks). They were much more likely to require insulin therapy (67% vs. 47%), and to be started on insulin sooner (25 vs. 34 weeks' gestation).

Importantly, of the 82 women in the previous GDM group who required insulin, nearly two-thirds (48, or 59%) needed it prior to 28 weeks' gestation, the time of routine GDM screening. “If we waited to screen those women, we would miss nearly 60% of those who need insulin before 28 weeks,” Dr. Cotzias noted.

Exactly half of each group had spontaneous vaginal delivery; cesarean section rates also did not differ significantly in the two groups (44% of those with previous GDM and 40% of those without). There were no significant differences between the two groups in any neonatal outcome. Of the women who came back for follow-up after delivery, 23% of 66 with previous GDM and 22% of the 188 without—an insignificant difference—had abnormal glucose tolerance test results. “I extrapolate the findings to suggest that if I left these women until 28 weeks' gestation and then started [treatment], I would have missed the boat and had worse outcomes. I can't prove it, but that's what the data suggest,” Dr. Cotzias said.

To leave this population until screening is done may be detrimental for both mother and baby. DR. COTZIAS

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — In pregnancy, maternal hepatitis C virus infection may have a negative impact on both maternal and neonatal health, results from a population-based study in Washington State demonstrated.

“Further prospective studies are needed, but I think this brings up the question of whether screening needs to be reevaluated in pregnant women,” Dr. Steven Pergam said at the annual meeting of the Infectious Diseases Society of America.

“Current recommendations by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have recommended screening high-risk patients. This is based mainly on the risk of perinatal transmission. Universal screening has been modeled in a number of studies and it has not been felt to be cost effective,” Dr. Pergam added.

He and his colleagues used Washington State singleton birth records and Comprehensive Hospital Abstract Reporting System data from 2003–2005 to identify hepatitis C virus (HCV) infection in mothers. “HCV information was added to the Washington State birth database in 2003, providing us a great opportunity to look at some of these outcomes,” said Dr. Pergam, a fellow in infectious diseases at the University of Washington, Seattle.

The researchers matched HCV-positive mothers in a ratio of 1:4 with HCV-negative mothers who were randomly selected from the same data set and evaluated maternal and neonatal outcomes associated with HCV.

Of the 240,131 singleton births studied, 506 were born to HCV-positive mothers with a mean age of 30 years and were matched with 2,022 born to HCV-negative mothers with a mean age of 28 years.

HCV-positive mothers who had excess weight gain during pregnancy, according to Institute of Medicine Guidelines, were 2.5 times more likely than their HCV-negative counterparts to develop gestational diabetes.

Compared with infants born to HCV-negative mothers, infants born to HCV-positive mothers were 2.2 times more likely to have low birth weight, 1.5 times more likely to be small for gestational age, 2.8 times more likely to require neonatal intensive care unit admission, and 2.4 times more likely to require assisted ventilation.

A subanalysis of infants born to 124 drug-using HCV-positive mothers revealed that the adverse outcomes of low birth weight, and being small for gestational age fall out as associated adverse outcomes. “It's not surprising that drug use would be a driving factor in these issues,” he said.

'I think this brings up the question of whether screening needs to be reevaluated in pregnant women.' DR. PERGAM

SAN DIEGO — In pregnancy, maternal hepatitis C virus infection may have a negative impact on both maternal and neonatal health, results from a population-based study in Washington State demonstrated.

“Further prospective studies are needed, but I think this brings up the question of whether screening needs to be reevaluated in pregnant women,” Dr. Steven Pergam said at the annual meeting of the Infectious Diseases Society of America.

“Current recommendations by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have recommended screening high-risk patients. This is based mainly on the risk of perinatal transmission. Universal screening has been modeled in a number of studies and it has not been felt to be cost effective,” Dr. Pergam added.

He and his colleagues used Washington State singleton birth records and Comprehensive Hospital Abstract Reporting System data from 2003–2005 to identify hepatitis C virus (HCV) infection in mothers. “HCV information was added to the Washington State birth database in 2003, providing us a great opportunity to look at some of these outcomes,” said Dr. Pergam, a fellow in infectious diseases at the University of Washington, Seattle.

The researchers matched HCV-positive mothers in a ratio of 1:4 with HCV-negative mothers who were randomly selected from the same data set and evaluated maternal and neonatal outcomes associated with HCV.

Of the 240,131 singleton births studied, 506 were born to HCV-positive mothers with a mean age of 30 years and were matched with 2,022 born to HCV-negative mothers with a mean age of 28 years.

HCV-positive mothers who had excess weight gain during pregnancy, according to Institute of Medicine Guidelines, were 2.5 times more likely than their HCV-negative counterparts to develop gestational diabetes.

Compared with infants born to HCV-negative mothers, infants born to HCV-positive mothers were 2.2 times more likely to have low birth weight, 1.5 times more likely to be small for gestational age, 2.8 times more likely to require neonatal intensive care unit admission, and 2.4 times more likely to require assisted ventilation.

A subanalysis of infants born to 124 drug-using HCV-positive mothers revealed that the adverse outcomes of low birth weight, and being small for gestational age fall out as associated adverse outcomes. “It's not surprising that drug use would be a driving factor in these issues,” he said.

'I think this brings up the question of whether screening needs to be reevaluated in pregnant women.' DR. PERGAM

SAN DIEGO — In pregnancy, maternal hepatitis C virus infection may have a negative impact on both maternal and neonatal health, results from a population-based study in Washington State demonstrated.

“Further prospective studies are needed, but I think this brings up the question of whether screening needs to be reevaluated in pregnant women,” Dr. Steven Pergam said at the annual meeting of the Infectious Diseases Society of America.

“Current recommendations by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have recommended screening high-risk patients. This is based mainly on the risk of perinatal transmission. Universal screening has been modeled in a number of studies and it has not been felt to be cost effective,” Dr. Pergam added.

He and his colleagues used Washington State singleton birth records and Comprehensive Hospital Abstract Reporting System data from 2003–2005 to identify hepatitis C virus (HCV) infection in mothers. “HCV information was added to the Washington State birth database in 2003, providing us a great opportunity to look at some of these outcomes,” said Dr. Pergam, a fellow in infectious diseases at the University of Washington, Seattle.

The researchers matched HCV-positive mothers in a ratio of 1:4 with HCV-negative mothers who were randomly selected from the same data set and evaluated maternal and neonatal outcomes associated with HCV.

Of the 240,131 singleton births studied, 506 were born to HCV-positive mothers with a mean age of 30 years and were matched with 2,022 born to HCV-negative mothers with a mean age of 28 years.

HCV-positive mothers who had excess weight gain during pregnancy, according to Institute of Medicine Guidelines, were 2.5 times more likely than their HCV-negative counterparts to develop gestational diabetes.

Compared with infants born to HCV-negative mothers, infants born to HCV-positive mothers were 2.2 times more likely to have low birth weight, 1.5 times more likely to be small for gestational age, 2.8 times more likely to require neonatal intensive care unit admission, and 2.4 times more likely to require assisted ventilation.

A subanalysis of infants born to 124 drug-using HCV-positive mothers revealed that the adverse outcomes of low birth weight, and being small for gestational age fall out as associated adverse outcomes. “It's not surprising that drug use would be a driving factor in these issues,” he said.

'I think this brings up the question of whether screening needs to be reevaluated in pregnant women.' DR. PERGAM

In humans, the highly pathogenic H5N1 avian influenza virus can spread beyond the lungs and also can cross the placenta to the fetus, according to research published in the Lancet.

Chinese researchers examined the postmortem tissues of two adults, a 35-year-old man from Jiangxi province and a 24-year-old woman from Anhui province who was 4 months pregnant. Both individuals were confirmed as infected with H5N1 by the Chinese Centre for Disease Control and Prevention (Lancet 2007;370:1137–45).

Examination of tissues from the respiratory, digestive, and central nervous systems, and from other organs found viral genetic material and antigens to the virus.

In the respiratory system, the researchers found signs that H5N1 had affected, among other tissues, the alveoli, in contrast to human influenza, which mainly targets the upper respiratory tract.

In the pregnant woman, the researchers found infected cells in the placenta and, in the fetus, they found viral sequences in the lungs, circulating mononuclear cells, and the liver.

The woman had been admitted after 6 days of fever, cough, and shortness of breath. She had handled ill birds 2 weeks before admission and died 2.5 days after, despite treatment with antibiotics and corticosteroids. No antivirals were given, the investigators noted. The man died 27 days after developing fever and productive cough. Admitted to hospital with a 6-day history of symptoms, he was first administered corticosteroids, followed by an antiviral, and then antifungal treatments.

The researchers said their findings help shed light on how H5N1 infections progress, which will be important for public health officials to watch because that strain of virus is feared as the most likely to result in a pandemic.

“Little is known about the specific effects in organs and cells targeted by the virus,” wrote the researchers, led by Dr. Jiang Gu of Peking University in Beijing. “The infection initially seemed to be restricted to the lungs, but later reports have suggested that influenza A H5N1 could disseminate beyond the lungs. … These newly obtained data are important in the clinical, pathological, and epidemiological investigation of human H5N1 infection and have implications for public-health and health care providers.”

In all, the researchers found viral genetic material and antigens in epithelial cells of the lungs and trachea, T cells of the lymph nodes, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. They found viral genomic sequences but no antigens in the intestinal mucosa.

The route of infection for the central nervous system could be through the blood-brain barrier or through respiratory system nerves after replicating in tissues there, the researchers write. For the intestines, the virus could be bloodborne but could occur through the ingestion of respiratory secretions, they added.

How the vertical infection of the fetus would affect the fetus is unclear. Human influenza strains infecting a pregnant female have not been shown to affect the fetus, but since H5N1 also has effects on humans not seen from human strains, such as viremia, “the likelihood of virus reaching the uterus and placenta is probably higher in avian influenza than in human influenza,” they wrote.

In an accompanying commentary, Dr. Wai Fu Ng of Princess Margaret Hospital in Hong Kong and Prof. Ka Fai To of Chinese University of Hong Kong raise questions about the effects of the vertical infection route.

“The absence of pathological changes in the immunologically incompetent fetus is taken as evidence that viral replication itself is not pathogenic,” they wrote. “Speculation about the fate of the fetus if the mother survived the infection is interesting. With the development of antibodies in the mother and their transplacental crossing into the fetus, pathological lesions in the fetus may result.”

In humans, the highly pathogenic H5N1 avian influenza virus can spread beyond the lungs and also can cross the placenta to the fetus, according to research published in the Lancet.

Chinese researchers examined the postmortem tissues of two adults, a 35-year-old man from Jiangxi province and a 24-year-old woman from Anhui province who was 4 months pregnant. Both individuals were confirmed as infected with H5N1 by the Chinese Centre for Disease Control and Prevention (Lancet 2007;370:1137–45).

Examination of tissues from the respiratory, digestive, and central nervous systems, and from other organs found viral genetic material and antigens to the virus.

In the respiratory system, the researchers found signs that H5N1 had affected, among other tissues, the alveoli, in contrast to human influenza, which mainly targets the upper respiratory tract.

In the pregnant woman, the researchers found infected cells in the placenta and, in the fetus, they found viral sequences in the lungs, circulating mononuclear cells, and the liver.

The woman had been admitted after 6 days of fever, cough, and shortness of breath. She had handled ill birds 2 weeks before admission and died 2.5 days after, despite treatment with antibiotics and corticosteroids. No antivirals were given, the investigators noted. The man died 27 days after developing fever and productive cough. Admitted to hospital with a 6-day history of symptoms, he was first administered corticosteroids, followed by an antiviral, and then antifungal treatments.

The researchers said their findings help shed light on how H5N1 infections progress, which will be important for public health officials to watch because that strain of virus is feared as the most likely to result in a pandemic.

“Little is known about the specific effects in organs and cells targeted by the virus,” wrote the researchers, led by Dr. Jiang Gu of Peking University in Beijing. “The infection initially seemed to be restricted to the lungs, but later reports have suggested that influenza A H5N1 could disseminate beyond the lungs. … These newly obtained data are important in the clinical, pathological, and epidemiological investigation of human H5N1 infection and have implications for public-health and health care providers.”

In all, the researchers found viral genetic material and antigens in epithelial cells of the lungs and trachea, T cells of the lymph nodes, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. They found viral genomic sequences but no antigens in the intestinal mucosa.

The route of infection for the central nervous system could be through the blood-brain barrier or through respiratory system nerves after replicating in tissues there, the researchers write. For the intestines, the virus could be bloodborne but could occur through the ingestion of respiratory secretions, they added.

How the vertical infection of the fetus would affect the fetus is unclear. Human influenza strains infecting a pregnant female have not been shown to affect the fetus, but since H5N1 also has effects on humans not seen from human strains, such as viremia, “the likelihood of virus reaching the uterus and placenta is probably higher in avian influenza than in human influenza,” they wrote.

In an accompanying commentary, Dr. Wai Fu Ng of Princess Margaret Hospital in Hong Kong and Prof. Ka Fai To of Chinese University of Hong Kong raise questions about the effects of the vertical infection route.

“The absence of pathological changes in the immunologically incompetent fetus is taken as evidence that viral replication itself is not pathogenic,” they wrote. “Speculation about the fate of the fetus if the mother survived the infection is interesting. With the development of antibodies in the mother and their transplacental crossing into the fetus, pathological lesions in the fetus may result.”

In humans, the highly pathogenic H5N1 avian influenza virus can spread beyond the lungs and also can cross the placenta to the fetus, according to research published in the Lancet.

Chinese researchers examined the postmortem tissues of two adults, a 35-year-old man from Jiangxi province and a 24-year-old woman from Anhui province who was 4 months pregnant. Both individuals were confirmed as infected with H5N1 by the Chinese Centre for Disease Control and Prevention (Lancet 2007;370:1137–45).

Examination of tissues from the respiratory, digestive, and central nervous systems, and from other organs found viral genetic material and antigens to the virus.

In the respiratory system, the researchers found signs that H5N1 had affected, among other tissues, the alveoli, in contrast to human influenza, which mainly targets the upper respiratory tract.

In the pregnant woman, the researchers found infected cells in the placenta and, in the fetus, they found viral sequences in the lungs, circulating mononuclear cells, and the liver.

The woman had been admitted after 6 days of fever, cough, and shortness of breath. She had handled ill birds 2 weeks before admission and died 2.5 days after, despite treatment with antibiotics and corticosteroids. No antivirals were given, the investigators noted. The man died 27 days after developing fever and productive cough. Admitted to hospital with a 6-day history of symptoms, he was first administered corticosteroids, followed by an antiviral, and then antifungal treatments.

The researchers said their findings help shed light on how H5N1 infections progress, which will be important for public health officials to watch because that strain of virus is feared as the most likely to result in a pandemic.

“Little is known about the specific effects in organs and cells targeted by the virus,” wrote the researchers, led by Dr. Jiang Gu of Peking University in Beijing. “The infection initially seemed to be restricted to the lungs, but later reports have suggested that influenza A H5N1 could disseminate beyond the lungs. … These newly obtained data are important in the clinical, pathological, and epidemiological investigation of human H5N1 infection and have implications for public-health and health care providers.”

In all, the researchers found viral genetic material and antigens in epithelial cells of the lungs and trachea, T cells of the lymph nodes, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. They found viral genomic sequences but no antigens in the intestinal mucosa.

The route of infection for the central nervous system could be through the blood-brain barrier or through respiratory system nerves after replicating in tissues there, the researchers write. For the intestines, the virus could be bloodborne but could occur through the ingestion of respiratory secretions, they added.

How the vertical infection of the fetus would affect the fetus is unclear. Human influenza strains infecting a pregnant female have not been shown to affect the fetus, but since H5N1 also has effects on humans not seen from human strains, such as viremia, “the likelihood of virus reaching the uterus and placenta is probably higher in avian influenza than in human influenza,” they wrote.

In an accompanying commentary, Dr. Wai Fu Ng of Princess Margaret Hospital in Hong Kong and Prof. Ka Fai To of Chinese University of Hong Kong raise questions about the effects of the vertical infection route.

“The absence of pathological changes in the immunologically incompetent fetus is taken as evidence that viral replication itself is not pathogenic,” they wrote. “Speculation about the fate of the fetus if the mother survived the infection is interesting. With the development of antibodies in the mother and their transplacental crossing into the fetus, pathological lesions in the fetus may result.”

SAN FRANCISCO — Several studies have shown that women who develop urinary incontinence during pregnancy are more likely to have postpartum and long-term incontinence. A separate randomized, controlled study suggests that cesarean delivery may protect against development of postpartum urinary incontinence.

Does that mean that women with incontinence during pregnancy should be delivered by C-section to keep the incontinence from getting worse?

No, said Dr. Sharon K. Knight at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco. In general, 3 months after delivery the prevalence of postpartum incontinence is 9%–31%, and the incidence is 7%–15%, data suggest.

Studies show that about half of women develop transient urinary incontinence during pregnancy, which increases the risk for postpartum incontinence. The same studies report that the mode of delivery did not affect the risk of incontinence, said Dr. Knight of the university.

The one randomized study that suggested cesarean delivery might decrease the risk of postpartum incontinence had methodological problems and found a short-term benefit only in women who had no previous incontinence, she added.

That study randomized women to a trial of labor or cesarean delivery for breech babies, and the incontinence rate was a secondary outcome measure. Three months after delivery, the vaginal delivery group had nearly twice the rate of incontinence as the C-section group, but that difference had disappeared by the 2-year follow-up (Am. J. Obstet. Gynecol. 2004;191:917–27). Many of these women went on to have more babies after the study, which complicates the 2-year results because it's unknown whether they were delivered vaginally or by cesarean section, Dr. Knight noted.

Retrospective studies of women who delivered exclusively by one mode or the other have produced conflicting results on incontinence rates, but the largest population-based studies found no difference based on mode of delivery, she said.

Epidemiologic studies report that primiparous women have twice the rate of stress incontinence as nulliparous women.

By ages 50–65 years, “just being a woman puts you at high risk of having urinary incontinence,” Dr. Knight said.

SAN FRANCISCO — Several studies have shown that women who develop urinary incontinence during pregnancy are more likely to have postpartum and long-term incontinence. A separate randomized, controlled study suggests that cesarean delivery may protect against development of postpartum urinary incontinence.

Does that mean that women with incontinence during pregnancy should be delivered by C-section to keep the incontinence from getting worse?

No, said Dr. Sharon K. Knight at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco. In general, 3 months after delivery the prevalence of postpartum incontinence is 9%–31%, and the incidence is 7%–15%, data suggest.

Studies show that about half of women develop transient urinary incontinence during pregnancy, which increases the risk for postpartum incontinence. The same studies report that the mode of delivery did not affect the risk of incontinence, said Dr. Knight of the university.

The one randomized study that suggested cesarean delivery might decrease the risk of postpartum incontinence had methodological problems and found a short-term benefit only in women who had no previous incontinence, she added.

That study randomized women to a trial of labor or cesarean delivery for breech babies, and the incontinence rate was a secondary outcome measure. Three months after delivery, the vaginal delivery group had nearly twice the rate of incontinence as the C-section group, but that difference had disappeared by the 2-year follow-up (Am. J. Obstet. Gynecol. 2004;191:917–27). Many of these women went on to have more babies after the study, which complicates the 2-year results because it's unknown whether they were delivered vaginally or by cesarean section, Dr. Knight noted.

Retrospective studies of women who delivered exclusively by one mode or the other have produced conflicting results on incontinence rates, but the largest population-based studies found no difference based on mode of delivery, she said.

Epidemiologic studies report that primiparous women have twice the rate of stress incontinence as nulliparous women.

By ages 50–65 years, “just being a woman puts you at high risk of having urinary incontinence,” Dr. Knight said.

SAN FRANCISCO — Several studies have shown that women who develop urinary incontinence during pregnancy are more likely to have postpartum and long-term incontinence. A separate randomized, controlled study suggests that cesarean delivery may protect against development of postpartum urinary incontinence.

Does that mean that women with incontinence during pregnancy should be delivered by C-section to keep the incontinence from getting worse?

No, said Dr. Sharon K. Knight at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco. In general, 3 months after delivery the prevalence of postpartum incontinence is 9%–31%, and the incidence is 7%–15%, data suggest.

Studies show that about half of women develop transient urinary incontinence during pregnancy, which increases the risk for postpartum incontinence. The same studies report that the mode of delivery did not affect the risk of incontinence, said Dr. Knight of the university.

The one randomized study that suggested cesarean delivery might decrease the risk of postpartum incontinence had methodological problems and found a short-term benefit only in women who had no previous incontinence, she added.

That study randomized women to a trial of labor or cesarean delivery for breech babies, and the incontinence rate was a secondary outcome measure. Three months after delivery, the vaginal delivery group had nearly twice the rate of incontinence as the C-section group, but that difference had disappeared by the 2-year follow-up (Am. J. Obstet. Gynecol. 2004;191:917–27). Many of these women went on to have more babies after the study, which complicates the 2-year results because it's unknown whether they were delivered vaginally or by cesarean section, Dr. Knight noted.

Retrospective studies of women who delivered exclusively by one mode or the other have produced conflicting results on incontinence rates, but the largest population-based studies found no difference based on mode of delivery, she said.

Epidemiologic studies report that primiparous women have twice the rate of stress incontinence as nulliparous women.

By ages 50–65 years, “just being a woman puts you at high risk of having urinary incontinence,” Dr. Knight said.

BOSTON — The administration of supplemental perioperative oxygen did not decrease the risk of endometritis or wound infection associated with cesarean delivery in a randomized, double-blind study, Dr. Carolyn Gardella reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Based on colorectal surgery literature indicating that the administration of perioperative oxygen significantly decreases surgical infection rates, Dr. Gardella and colleagues at the University of Washington, Seattle, hypothesized that the same strategy might similarly decrease the incidence of surgical infections in women undergoing cesarean delivery.

To test the hypothesis, the investigators randomly assigned 143 women who were undergoing cesarean delivery under regional anesthesia after the onset of labor or rupture of membranes to receive 30% or 80% inspired oxygen via nonrebreather masks during surgery and for 2 hours after surgery between October 2002 and April 2007.

The 74 women assigned to the 30% oxygen group and 69 assigned to the 80% oxygen group represented approximately one-quarter of the planned data accrual, said Dr. Gardella.

“Our institutional postpartum endometritis rate was 15%. Assuming this as a baseline, and with an 80% study power, we determined we would need 225 women per study arm to detect a 50% decrease in the infection rate, and we planned to do an interim analysis at 25%,” she said.

The study population excluded women who were undergoing elective cesarean section prior to onset of labor or rupture of membranes “because the risk of infection in this population is so low,” Dr. Gardella noted.

“We also excluded women with truly emergent cesarean sections because we couldn't implement [the oxygen protocol] during an emergency, and [we excluded] those with clinical chorioamnionitis because it was too difficult for us to tell whether or not their infection was true postpartum wound infection or just a continuation of the chorioamnionitis.” Although women undergoing planned general endotracheal anesthesia were also excluded, those who were converted from regional to general were not, she said.

Blinded oxygen delivery during the study was a challenge, Dr. Gardella said. “In the colorectal surgery data, patients were under general anesthesia, so it was easy to dial up their oxygen. We were dealing with women undergoing regional anesthesia, so we developed a system where we could maintain blinding by giving all of the women 15 liters flow, but then used an oxygen blender under cover to blend 100% oxygen with air in order to establish two separate groups,” she said, noting that only the anesthesiologists were aware of patients' study assignments during and following the operation.

Dorsum venous oxygen was used as a proxy for arterial oxygen. In pretrial testing on volunteers, “we were able to achieve different oxygen levels using this method,” she said.

Postoperative infection was defined clinically as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery. Secondary outcomes were length of hospital stay, whether the wound separated, and whether there was readmission for infection.

Antepartum and intrapartum characteristics were similar in both study groups. “We had a variable increase in the number of women with complications such as hypertension or preeclampsia assigned to the 30% [versus] the 80% group, and diabetes was slightly more likely in the 80% group, though the increases were not statistically significant,” said Dr. Gardella. Gestational age at delivery was approximately 38 weeks in both groups. The duration of labor was slightly longer in the 30% group, and those women were also slightly more likely to have intact membranes, she said.

The incidence of group B streptococcus was approximately 25% in the study population, “which is consistent with the prevalence in our labor and delivery population as a whole,” said Dr. Gardella. “The use of antibiotics in labor, primarily for group B strep prophylaxis, was between 34% and 40%.”

Deviations in study protocol were observed in eight patients from each group, Dr. Gardella reported. “In the 30% group, two patients were converted to endotracheal anesthesia, three patients required an increase in inspired oxygen because of neonatal distress observed in the operating room, and three patients had intermittent mask use either during the surgical procedure because of vomiting, nausea, or claustrophobia, or after surgery because they wanted to feel closer to their baby without the mask,” she said. In the 80% group, three were converted to general endotracheal anesthesia and five had intermittent mask use.

An analysis of patient outcomes showed that 25% of the women receiving 80% oxygen, compared with 14% of those receiving 30% oxygen, developed postpartum cellulitis or endometritis, or received intravenous antibiotics for either of those conditions, Dr. Gardella reported.

“Hospital readmission and wound separation were also more common in the 80% group,” she said. “None of the numbers reached statistical significance because the study was not powered for that, but the data [were trending] in the wrong direction.” Because the P value exceeded the P value for futility, suggesting the observed differences were unlikely to reach statistical significance with continued recruitment, the trial was stopped.

The study was limited by a number of considerations. The median duration of oxygen therapy was less than planned, there was significant overlap in the median level of venous oxygen in the 80% group and the 30% group, and it's possible a therapeutic level was not achieved, and the dorsum of the foot was used as a proxy measure of oxygen delivery. Finally, the outcome may have been 'muddled by antibiotic overuse in the study population, Dr. Gardella said.

BOSTON — The administration of supplemental perioperative oxygen did not decrease the risk of endometritis or wound infection associated with cesarean delivery in a randomized, double-blind study, Dr. Carolyn Gardella reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Based on colorectal surgery literature indicating that the administration of perioperative oxygen significantly decreases surgical infection rates, Dr. Gardella and colleagues at the University of Washington, Seattle, hypothesized that the same strategy might similarly decrease the incidence of surgical infections in women undergoing cesarean delivery.

To test the hypothesis, the investigators randomly assigned 143 women who were undergoing cesarean delivery under regional anesthesia after the onset of labor or rupture of membranes to receive 30% or 80% inspired oxygen via nonrebreather masks during surgery and for 2 hours after surgery between October 2002 and April 2007.

The 74 women assigned to the 30% oxygen group and 69 assigned to the 80% oxygen group represented approximately one-quarter of the planned data accrual, said Dr. Gardella.

“Our institutional postpartum endometritis rate was 15%. Assuming this as a baseline, and with an 80% study power, we determined we would need 225 women per study arm to detect a 50% decrease in the infection rate, and we planned to do an interim analysis at 25%,” she said.

The study population excluded women who were undergoing elective cesarean section prior to onset of labor or rupture of membranes “because the risk of infection in this population is so low,” Dr. Gardella noted.

“We also excluded women with truly emergent cesarean sections because we couldn't implement [the oxygen protocol] during an emergency, and [we excluded] those with clinical chorioamnionitis because it was too difficult for us to tell whether or not their infection was true postpartum wound infection or just a continuation of the chorioamnionitis.” Although women undergoing planned general endotracheal anesthesia were also excluded, those who were converted from regional to general were not, she said.

Blinded oxygen delivery during the study was a challenge, Dr. Gardella said. “In the colorectal surgery data, patients were under general anesthesia, so it was easy to dial up their oxygen. We were dealing with women undergoing regional anesthesia, so we developed a system where we could maintain blinding by giving all of the women 15 liters flow, but then used an oxygen blender under cover to blend 100% oxygen with air in order to establish two separate groups,” she said, noting that only the anesthesiologists were aware of patients' study assignments during and following the operation.

Dorsum venous oxygen was used as a proxy for arterial oxygen. In pretrial testing on volunteers, “we were able to achieve different oxygen levels using this method,” she said.

Postoperative infection was defined clinically as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery. Secondary outcomes were length of hospital stay, whether the wound separated, and whether there was readmission for infection.

Antepartum and intrapartum characteristics were similar in both study groups. “We had a variable increase in the number of women with complications such as hypertension or preeclampsia assigned to the 30% [versus] the 80% group, and diabetes was slightly more likely in the 80% group, though the increases were not statistically significant,” said Dr. Gardella. Gestational age at delivery was approximately 38 weeks in both groups. The duration of labor was slightly longer in the 30% group, and those women were also slightly more likely to have intact membranes, she said.

The incidence of group B streptococcus was approximately 25% in the study population, “which is consistent with the prevalence in our labor and delivery population as a whole,” said Dr. Gardella. “The use of antibiotics in labor, primarily for group B strep prophylaxis, was between 34% and 40%.”

Deviations in study protocol were observed in eight patients from each group, Dr. Gardella reported. “In the 30% group, two patients were converted to endotracheal anesthesia, three patients required an increase in inspired oxygen because of neonatal distress observed in the operating room, and three patients had intermittent mask use either during the surgical procedure because of vomiting, nausea, or claustrophobia, or after surgery because they wanted to feel closer to their baby without the mask,” she said. In the 80% group, three were converted to general endotracheal anesthesia and five had intermittent mask use.

An analysis of patient outcomes showed that 25% of the women receiving 80% oxygen, compared with 14% of those receiving 30% oxygen, developed postpartum cellulitis or endometritis, or received intravenous antibiotics for either of those conditions, Dr. Gardella reported.

“Hospital readmission and wound separation were also more common in the 80% group,” she said. “None of the numbers reached statistical significance because the study was not powered for that, but the data [were trending] in the wrong direction.” Because the P value exceeded the P value for futility, suggesting the observed differences were unlikely to reach statistical significance with continued recruitment, the trial was stopped.

The study was limited by a number of considerations. The median duration of oxygen therapy was less than planned, there was significant overlap in the median level of venous oxygen in the 80% group and the 30% group, and it's possible a therapeutic level was not achieved, and the dorsum of the foot was used as a proxy measure of oxygen delivery. Finally, the outcome may have been 'muddled by antibiotic overuse in the study population, Dr. Gardella said.

BOSTON — The administration of supplemental perioperative oxygen did not decrease the risk of endometritis or wound infection associated with cesarean delivery in a randomized, double-blind study, Dr. Carolyn Gardella reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Based on colorectal surgery literature indicating that the administration of perioperative oxygen significantly decreases surgical infection rates, Dr. Gardella and colleagues at the University of Washington, Seattle, hypothesized that the same strategy might similarly decrease the incidence of surgical infections in women undergoing cesarean delivery.

To test the hypothesis, the investigators randomly assigned 143 women who were undergoing cesarean delivery under regional anesthesia after the onset of labor or rupture of membranes to receive 30% or 80% inspired oxygen via nonrebreather masks during surgery and for 2 hours after surgery between October 2002 and April 2007.

The 74 women assigned to the 30% oxygen group and 69 assigned to the 80% oxygen group represented approximately one-quarter of the planned data accrual, said Dr. Gardella.

“Our institutional postpartum endometritis rate was 15%. Assuming this as a baseline, and with an 80% study power, we determined we would need 225 women per study arm to detect a 50% decrease in the infection rate, and we planned to do an interim analysis at 25%,” she said.

The study population excluded women who were undergoing elective cesarean section prior to onset of labor or rupture of membranes “because the risk of infection in this population is so low,” Dr. Gardella noted.

“We also excluded women with truly emergent cesarean sections because we couldn't implement [the oxygen protocol] during an emergency, and [we excluded] those with clinical chorioamnionitis because it was too difficult for us to tell whether or not their infection was true postpartum wound infection or just a continuation of the chorioamnionitis.” Although women undergoing planned general endotracheal anesthesia were also excluded, those who were converted from regional to general were not, she said.

Blinded oxygen delivery during the study was a challenge, Dr. Gardella said. “In the colorectal surgery data, patients were under general anesthesia, so it was easy to dial up their oxygen. We were dealing with women undergoing regional anesthesia, so we developed a system where we could maintain blinding by giving all of the women 15 liters flow, but then used an oxygen blender under cover to blend 100% oxygen with air in order to establish two separate groups,” she said, noting that only the anesthesiologists were aware of patients' study assignments during and following the operation.

Dorsum venous oxygen was used as a proxy for arterial oxygen. In pretrial testing on volunteers, “we were able to achieve different oxygen levels using this method,” she said.

Postoperative infection was defined clinically as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery. Secondary outcomes were length of hospital stay, whether the wound separated, and whether there was readmission for infection.

Antepartum and intrapartum characteristics were similar in both study groups. “We had a variable increase in the number of women with complications such as hypertension or preeclampsia assigned to the 30% [versus] the 80% group, and diabetes was slightly more likely in the 80% group, though the increases were not statistically significant,” said Dr. Gardella. Gestational age at delivery was approximately 38 weeks in both groups. The duration of labor was slightly longer in the 30% group, and those women were also slightly more likely to have intact membranes, she said.

The incidence of group B streptococcus was approximately 25% in the study population, “which is consistent with the prevalence in our labor and delivery population as a whole,” said Dr. Gardella. “The use of antibiotics in labor, primarily for group B strep prophylaxis, was between 34% and 40%.”

Deviations in study protocol were observed in eight patients from each group, Dr. Gardella reported. “In the 30% group, two patients were converted to endotracheal anesthesia, three patients required an increase in inspired oxygen because of neonatal distress observed in the operating room, and three patients had intermittent mask use either during the surgical procedure because of vomiting, nausea, or claustrophobia, or after surgery because they wanted to feel closer to their baby without the mask,” she said. In the 80% group, three were converted to general endotracheal anesthesia and five had intermittent mask use.

An analysis of patient outcomes showed that 25% of the women receiving 80% oxygen, compared with 14% of those receiving 30% oxygen, developed postpartum cellulitis or endometritis, or received intravenous antibiotics for either of those conditions, Dr. Gardella reported.

“Hospital readmission and wound separation were also more common in the 80% group,” she said. “None of the numbers reached statistical significance because the study was not powered for that, but the data [were trending] in the wrong direction.” Because the P value exceeded the P value for futility, suggesting the observed differences were unlikely to reach statistical significance with continued recruitment, the trial was stopped.

The study was limited by a number of considerations. The median duration of oxygen therapy was less than planned, there was significant overlap in the median level of venous oxygen in the 80% group and the 30% group, and it's possible a therapeutic level was not achieved, and the dorsum of the foot was used as a proxy measure of oxygen delivery. Finally, the outcome may have been 'muddled by antibiotic overuse in the study population, Dr. Gardella said.

SAN FRANCISCO — Experts have clashed in the past few years over whether to treat mild preeclampsia, but the data support treatment, Dr. William M. Gilbert said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

There's widespread agreement that giving magnesium sulfate to pregnant women with severe preeclampsia is beneficial. Until recently, however, studies grouped together patients with any severity of disease or focused exclusively on severe preeclampsia.

One medical journal took the unusual step in 2003 of publishing a randomized, controlled trial of magnesium sulfate for mild preeclampsia despite the study being underpowered to show statistical significance. The 220-patient study found no difference in outcomes (Obstet. Gynecol. 2003;101:217–20). The editors emphasized that a large, randomized, controlled trial should be undertaken to see if treatment would benefit patients with mild preeclampsia, “which is most of the disease we see,” said Dr. Gilbert, professor of obstetrics and gynecology at the University of California, Davis.

That led to a 2004 editorial in another journal saying that previous studies that had addressed either only severe preeclampsia or all levels of preeclampsia combined did not show a decrease in the risk of maternal or neonatal morbidity after magnesium sulfate treatment.

“I would disagree with that statement entirely,” commented Dr. Gilbert. The editorial argued that because the significance of the 2003 study on mild preeclampsia was not clear, magnesium sulfate should not be given routinely to patients with mild preeclampsia (Am. J. Obstet. Gynecol. 2004;190:1520–6).

That editorial put clinicians in a tight spot—damned if they treated mild preeclampsia, damned if they didn't treat it and patients had strokes, seizures, or other adverse outcomes, Dr. Gilbert said.

To the rescue came a 2006 study from a hospital that gave magnesium sulfate to all preeclamptic patients for a 5-year period and then treated only severe disease in the following 4.5 years. The incidence of eclampsia more than doubled and the risk of maternal or neonatal morbidity secondary to seizures increased when patients with mild preeclampsia went untreated, compared with treating all preeclampsia (Obstet. Gynecol. 2006;108:826–32).

Among the 6,431 women with preeclampsia in the second half of the study, 1 of every 358 women treated for severe preeclampsia developed seizures, compared with 1 of every 92 women with untreated mild preeclampsia. The study found no serious toxicity from magnesium sulfate treatment.

“Women with mild disease who did not get magnesium sulfate had a much higher risk than women with severe disease who got magnesium,” Dr. Gilbert noted.

Before treating, be sure you've got a diagnosis of preeclampsia, which requires a consistently elevated blood pressure and ruling out other causes of high blood pressure, he added. Some clinicians treat prematurely based on one reading that shows mildly elevated blood pressure, when taking a second reading between contractions or giving an epidural dose will lower the blood pressure reading to normal ranges.

On the other hand, “If I have a woman who comes in with a blood pressure of 220/120 mm Hg, I'm not going to wait 6 hours to get a second reading,” but will go ahead and start magnesium sulfate, he said.

Magnesium sulfate treatment traditionally has been continued for 24 hours after delivery because about a third of women with preeclampsia will seize post partum, usually within the first 24 hours. A randomized study of 200 patients found, however, that 12 hours of postpartum treatment was as good as 24 hours in patients with mild disease—those with relatively lower blood pressures and no gestational diabetes (Obstet. Gynecol. 2006;108:833–8).

SAN FRANCISCO — Experts have clashed in the past few years over whether to treat mild preeclampsia, but the data support treatment, Dr. William M. Gilbert said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

There's widespread agreement that giving magnesium sulfate to pregnant women with severe preeclampsia is beneficial. Until recently, however, studies grouped together patients with any severity of disease or focused exclusively on severe preeclampsia.

One medical journal took the unusual step in 2003 of publishing a randomized, controlled trial of magnesium sulfate for mild preeclampsia despite the study being underpowered to show statistical significance. The 220-patient study found no difference in outcomes (Obstet. Gynecol. 2003;101:217–20). The editors emphasized that a large, randomized, controlled trial should be undertaken to see if treatment would benefit patients with mild preeclampsia, “which is most of the disease we see,” said Dr. Gilbert, professor of obstetrics and gynecology at the University of California, Davis.

That led to a 2004 editorial in another journal saying that previous studies that had addressed either only severe preeclampsia or all levels of preeclampsia combined did not show a decrease in the risk of maternal or neonatal morbidity after magnesium sulfate treatment.

“I would disagree with that statement entirely,” commented Dr. Gilbert. The editorial argued that because the significance of the 2003 study on mild preeclampsia was not clear, magnesium sulfate should not be given routinely to patients with mild preeclampsia (Am. J. Obstet. Gynecol. 2004;190:1520–6).

That editorial put clinicians in a tight spot—damned if they treated mild preeclampsia, damned if they didn't treat it and patients had strokes, seizures, or other adverse outcomes, Dr. Gilbert said.

To the rescue came a 2006 study from a hospital that gave magnesium sulfate to all preeclamptic patients for a 5-year period and then treated only severe disease in the following 4.5 years. The incidence of eclampsia more than doubled and the risk of maternal or neonatal morbidity secondary to seizures increased when patients with mild preeclampsia went untreated, compared with treating all preeclampsia (Obstet. Gynecol. 2006;108:826–32).

Among the 6,431 women with preeclampsia in the second half of the study, 1 of every 358 women treated for severe preeclampsia developed seizures, compared with 1 of every 92 women with untreated mild preeclampsia. The study found no serious toxicity from magnesium sulfate treatment.

“Women with mild disease who did not get magnesium sulfate had a much higher risk than women with severe disease who got magnesium,” Dr. Gilbert noted.

Before treating, be sure you've got a diagnosis of preeclampsia, which requires a consistently elevated blood pressure and ruling out other causes of high blood pressure, he added. Some clinicians treat prematurely based on one reading that shows mildly elevated blood pressure, when taking a second reading between contractions or giving an epidural dose will lower the blood pressure reading to normal ranges.

On the other hand, “If I have a woman who comes in with a blood pressure of 220/120 mm Hg, I'm not going to wait 6 hours to get a second reading,” but will go ahead and start magnesium sulfate, he said.

Magnesium sulfate treatment traditionally has been continued for 24 hours after delivery because about a third of women with preeclampsia will seize post partum, usually within the first 24 hours. A randomized study of 200 patients found, however, that 12 hours of postpartum treatment was as good as 24 hours in patients with mild disease—those with relatively lower blood pressures and no gestational diabetes (Obstet. Gynecol. 2006;108:833–8).

SAN FRANCISCO — Experts have clashed in the past few years over whether to treat mild preeclampsia, but the data support treatment, Dr. William M. Gilbert said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

There's widespread agreement that giving magnesium sulfate to pregnant women with severe preeclampsia is beneficial. Until recently, however, studies grouped together patients with any severity of disease or focused exclusively on severe preeclampsia.

One medical journal took the unusual step in 2003 of publishing a randomized, controlled trial of magnesium sulfate for mild preeclampsia despite the study being underpowered to show statistical significance. The 220-patient study found no difference in outcomes (Obstet. Gynecol. 2003;101:217–20). The editors emphasized that a large, randomized, controlled trial should be undertaken to see if treatment would benefit patients with mild preeclampsia, “which is most of the disease we see,” said Dr. Gilbert, professor of obstetrics and gynecology at the University of California, Davis.

That led to a 2004 editorial in another journal saying that previous studies that had addressed either only severe preeclampsia or all levels of preeclampsia combined did not show a decrease in the risk of maternal or neonatal morbidity after magnesium sulfate treatment.

“I would disagree with that statement entirely,” commented Dr. Gilbert. The editorial argued that because the significance of the 2003 study on mild preeclampsia was not clear, magnesium sulfate should not be given routinely to patients with mild preeclampsia (Am. J. Obstet. Gynecol. 2004;190:1520–6).

That editorial put clinicians in a tight spot—damned if they treated mild preeclampsia, damned if they didn't treat it and patients had strokes, seizures, or other adverse outcomes, Dr. Gilbert said.

To the rescue came a 2006 study from a hospital that gave magnesium sulfate to all preeclamptic patients for a 5-year period and then treated only severe disease in the following 4.5 years. The incidence of eclampsia more than doubled and the risk of maternal or neonatal morbidity secondary to seizures increased when patients with mild preeclampsia went untreated, compared with treating all preeclampsia (Obstet. Gynecol. 2006;108:826–32).

Among the 6,431 women with preeclampsia in the second half of the study, 1 of every 358 women treated for severe preeclampsia developed seizures, compared with 1 of every 92 women with untreated mild preeclampsia. The study found no serious toxicity from magnesium sulfate treatment.

“Women with mild disease who did not get magnesium sulfate had a much higher risk than women with severe disease who got magnesium,” Dr. Gilbert noted.

Before treating, be sure you've got a diagnosis of preeclampsia, which requires a consistently elevated blood pressure and ruling out other causes of high blood pressure, he added. Some clinicians treat prematurely based on one reading that shows mildly elevated blood pressure, when taking a second reading between contractions or giving an epidural dose will lower the blood pressure reading to normal ranges.

On the other hand, “If I have a woman who comes in with a blood pressure of 220/120 mm Hg, I'm not going to wait 6 hours to get a second reading,” but will go ahead and start magnesium sulfate, he said.

Magnesium sulfate treatment traditionally has been continued for 24 hours after delivery because about a third of women with preeclampsia will seize post partum, usually within the first 24 hours. A randomized study of 200 patients found, however, that 12 hours of postpartum treatment was as good as 24 hours in patients with mild disease—those with relatively lower blood pressures and no gestational diabetes (Obstet. Gynecol. 2006;108:833–8).

SAN FRANCISCO — Selectively screening patients for substance abuse in pregnancy is ineffective, Dr. Allison S. Bryant said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

“Everyone should be screened. If you don't want to be screening everybody, then you probably should be screening no one,” said Dr. Bryant, a perinatologist who is also an assistant adjunct professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences.

Universal screening doesn't take much time—perhaps 30 seconds for a woman who is not using alcohol or drugs during pregnancy or 5–10 minutes for patients who are actively using substances, she said.

The first step in screening is to ask every patient about substance use. “It provides an opportunity for a conversation with every patient,” Dr. Bryant said.

Think of potential substance abuse when you see a medical history of frequent hospitalizations, unusual trauma or infections, frequent falls or bruises, chronic mental illness, or diabetes, cirrhosis, hepatitis, or pancreatitis, Dr. Bryant advised.

“I can't tell you how many times during my fellowship I did consults on patients admitted with raging pancreatitis in pregnancy, and they'd had million-dollar work-ups, and nowhere in the medical charts was there documentation about whether they reported using alcohol during pregnancy,” she added.

Some patient behaviors may flag the need for more aggressive screening—behaviors like slurred speech and/or unsteady gait, agitation, disorientation, an appearance of euphoria, or prescription drug-seeking.

Physical clues that should trigger more aggressive screening include tremors, multiple needle marks, inflamed or eroded nasal mucosa, alterations in vital signs, and the dilated or constricted pupils typical of heroin or amphetamine use.

More aggressive screening usually means administering a urine toxicology test, best used after a positive interview screen.

Under most state laws, physicians must obtain consent for a maternal toxicology screen, whereas toxicology screening of infants can be performed without maternal consent.

“Sometimes I see patients who had screening due to acute labor or partial premature rupture of membranes. In our particular setting, I don't think that's warranted,” she said.

“Patients who present with an abruption, on the other hand, probably all should be consented for a tox screen for cocaine use.”

Among pregnant women, approximately 15% abuse alcohol, 20% smoke cigarettes, 2% abuse marijuana, 0.3% abuse cocaine, and 0.7% use other illicit drugs, according to a national survey from 1996 to 1998.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases, Dr. Bryant said.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases. DR. BRYANT

SAN FRANCISCO — Selectively screening patients for substance abuse in pregnancy is ineffective, Dr. Allison S. Bryant said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

“Everyone should be screened. If you don't want to be screening everybody, then you probably should be screening no one,” said Dr. Bryant, a perinatologist who is also an assistant adjunct professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences.

Universal screening doesn't take much time—perhaps 30 seconds for a woman who is not using alcohol or drugs during pregnancy or 5–10 minutes for patients who are actively using substances, she said.

The first step in screening is to ask every patient about substance use. “It provides an opportunity for a conversation with every patient,” Dr. Bryant said.

Think of potential substance abuse when you see a medical history of frequent hospitalizations, unusual trauma or infections, frequent falls or bruises, chronic mental illness, or diabetes, cirrhosis, hepatitis, or pancreatitis, Dr. Bryant advised.

“I can't tell you how many times during my fellowship I did consults on patients admitted with raging pancreatitis in pregnancy, and they'd had million-dollar work-ups, and nowhere in the medical charts was there documentation about whether they reported using alcohol during pregnancy,” she added.

Some patient behaviors may flag the need for more aggressive screening—behaviors like slurred speech and/or unsteady gait, agitation, disorientation, an appearance of euphoria, or prescription drug-seeking.

Physical clues that should trigger more aggressive screening include tremors, multiple needle marks, inflamed or eroded nasal mucosa, alterations in vital signs, and the dilated or constricted pupils typical of heroin or amphetamine use.

More aggressive screening usually means administering a urine toxicology test, best used after a positive interview screen.

Under most state laws, physicians must obtain consent for a maternal toxicology screen, whereas toxicology screening of infants can be performed without maternal consent.

“Sometimes I see patients who had screening due to acute labor or partial premature rupture of membranes. In our particular setting, I don't think that's warranted,” she said.

“Patients who present with an abruption, on the other hand, probably all should be consented for a tox screen for cocaine use.”

Among pregnant women, approximately 15% abuse alcohol, 20% smoke cigarettes, 2% abuse marijuana, 0.3% abuse cocaine, and 0.7% use other illicit drugs, according to a national survey from 1996 to 1998.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases, Dr. Bryant said.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases. DR. BRYANT

SAN FRANCISCO — Selectively screening patients for substance abuse in pregnancy is ineffective, Dr. Allison S. Bryant said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

“Everyone should be screened. If you don't want to be screening everybody, then you probably should be screening no one,” said Dr. Bryant, a perinatologist who is also an assistant adjunct professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences.

Universal screening doesn't take much time—perhaps 30 seconds for a woman who is not using alcohol or drugs during pregnancy or 5–10 minutes for patients who are actively using substances, she said.

The first step in screening is to ask every patient about substance use. “It provides an opportunity for a conversation with every patient,” Dr. Bryant said.

Think of potential substance abuse when you see a medical history of frequent hospitalizations, unusual trauma or infections, frequent falls or bruises, chronic mental illness, or diabetes, cirrhosis, hepatitis, or pancreatitis, Dr. Bryant advised.

“I can't tell you how many times during my fellowship I did consults on patients admitted with raging pancreatitis in pregnancy, and they'd had million-dollar work-ups, and nowhere in the medical charts was there documentation about whether they reported using alcohol during pregnancy,” she added.

Some patient behaviors may flag the need for more aggressive screening—behaviors like slurred speech and/or unsteady gait, agitation, disorientation, an appearance of euphoria, or prescription drug-seeking.

Physical clues that should trigger more aggressive screening include tremors, multiple needle marks, inflamed or eroded nasal mucosa, alterations in vital signs, and the dilated or constricted pupils typical of heroin or amphetamine use.

More aggressive screening usually means administering a urine toxicology test, best used after a positive interview screen.

Under most state laws, physicians must obtain consent for a maternal toxicology screen, whereas toxicology screening of infants can be performed without maternal consent.

“Sometimes I see patients who had screening due to acute labor or partial premature rupture of membranes. In our particular setting, I don't think that's warranted,” she said.

“Patients who present with an abruption, on the other hand, probably all should be consented for a tox screen for cocaine use.”

Among pregnant women, approximately 15% abuse alcohol, 20% smoke cigarettes, 2% abuse marijuana, 0.3% abuse cocaine, and 0.7% use other illicit drugs, according to a national survey from 1996 to 1998.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases, Dr. Bryant said.

Studies suggest that treatment of substance abuse is as effective as treating other chronic diseases. DR. BRYANT

SAN FRANCISCO — When it comes to relieving labor pain, there's nothing like an epidural.

Beyond that, however, some nonpharmacologic strategies compete well with opioids, the next most common pharmacologic option for treating labor pain, Judith T. Bishop said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

Nonpharmacologic techniques should be considered for women who arrive at the labor-and-delivery room too late to get an epidural, women who want to try an unmedicated birth, or women who want to incorporate nonpharmacologic options as stepping-stones to possible use of pain-relieving medications later in labor, she said.

Epidurals or spinal analgesia were received by 76% of 1,573 women who were delivering singletons in U.S. hospitals and who were surveyed for the 2006 Listening to Mothers II Survey Report.

Among those who received epidurals or spinal analgesia, 81% said that they were very helpful, according to the report compiled for the nonprofit organization Childbirth Connection by Eugene R. Declerq, Ph.D., professor of maternal and child health at Boston University, and associates.

Besides epidurals, “the interesting thing is that immersion in a tub or hands-on techniques came up a little bit above the effectiveness of narcotics” for relieving labor pain, although they were less often used than narcotics, said Ms. Bishop, a certified nurse-midwife and professor of ob.gyn. and reproductive sciences at the University of California.

“Many of the other nonpharmacologic techniques are not far behind” in effectiveness, she added. (See box.)

Overall, 69% of women used one or more nonpharmacologic techniques to relieve discomfort in labor.

Ms. Bishop reviewed the evidence for some nonpharmacologic strategies that had been identified as effective by one or more of three published reviews of the literature.

▸ Continuous labor support. This category is a catchall of steps taken usually by a doula, midwife, or nurse.

Continuous labor support typically includes touch, massage, application of cold or heat, and other strategies for physical comfort plus emotional support, a steady flow of information to the mother, and facilitation of communication between the mother and the health care providers.

A 2003 Cochrane meta-analysis of 15 randomized, controlled studies with 12,791 women found significant decreases in use of regional analgesia, forceps, or cesarean births and increased likelihood of vaginal birth with continuous labor support.

Women reported 33% less dissatisfaction with labor regardless of pain, compared with unsupported control groups.

A separate 2003 review of studies found less striking results, but concluded that all women should have support during labor and that starting support earlier in labor rather than later maximizes the benefits.

▸ Water immersion. Putting a laboring woman in a warm bath was associated with decreased pain (particularly during the first 30 minutes) and decreased use of epidurals, according to a 2004 Cochrane meta-analysis of eight randomized, controlled trials with 2,939 women.

Two studies found that tub immersion during early labor (before 5-cm dilation) may prolong labor. Individual studies found fewer fetal malpositions in tub-immersed women and no increased rate of infection in those who rupture membranes while in the tub.

“There should be no barriers to women getting into a tub due to misconceptions regarding infection” risk, Ms. Bishop said.

▸ Hypnosis. A very old strategy recently repackaged under the term “hypnobirthing,” hypnotic pain relief techniques carry the disadvantages of time and costs needed for training, and the lengthy time needed to implement this into practice, she said.

A 2006 Cochrane review of five trials with 749 women found suggestions of effectiveness in decreasing the need for pharmacologic pain relief and increasing vaginal deliveries and patient satisfaction with pain relief. No adverse outcomes were seen, but hypnosis generally is contraindicated in women with a history of psychosis, she added.

▸ Intradermal water injections. Four randomized, controlled studies found significant reductions in severe back pain for 45–90 minutes but no decrease in requests for medication for abdominal pain using this strategy.

Intradermal water injections involve injecting 0.05–0.1 mL of sterile water into four locations on the lower back—two over each posterior superior iliac spine, and two located 3 cm below and 1 cm medial to the posterior superior iliac spine.

Injections seem to be more effective earlier rather than later in labor. The injections are painful for 20–30 seconds, and the counterirritation of the injection pain may be a mechanism of action for relieving the back pain, she speculated.

▸ Acupuncture. Although the overall evidence that acupuncture can reduce labor pain is encouraging, “it's really difficult to find an acupuncturist willing to be on call to come into labor” rooms, Ms. Bishop said. Midwives in some European countries can take a course to provide acupuncture to patients, something that should be tried in the United States, she added.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — When it comes to relieving labor pain, there's nothing like an epidural.

Beyond that, however, some nonpharmacologic strategies compete well with opioids, the next most common pharmacologic option for treating labor pain, Judith T. Bishop said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

Nonpharmacologic techniques should be considered for women who arrive at the labor-and-delivery room too late to get an epidural, women who want to try an unmedicated birth, or women who want to incorporate nonpharmacologic options as stepping-stones to possible use of pain-relieving medications later in labor, she said.

Epidurals or spinal analgesia were received by 76% of 1,573 women who were delivering singletons in U.S. hospitals and who were surveyed for the 2006 Listening to Mothers II Survey Report.

Among those who received epidurals or spinal analgesia, 81% said that they were very helpful, according to the report compiled for the nonprofit organization Childbirth Connection by Eugene R. Declerq, Ph.D., professor of maternal and child health at Boston University, and associates.

Besides epidurals, “the interesting thing is that immersion in a tub or hands-on techniques came up a little bit above the effectiveness of narcotics” for relieving labor pain, although they were less often used than narcotics, said Ms. Bishop, a certified nurse-midwife and professor of ob.gyn. and reproductive sciences at the University of California.

“Many of the other nonpharmacologic techniques are not far behind” in effectiveness, she added. (See box.)

Overall, 69% of women used one or more nonpharmacologic techniques to relieve discomfort in labor.

Ms. Bishop reviewed the evidence for some nonpharmacologic strategies that had been identified as effective by one or more of three published reviews of the literature.

▸ Continuous labor support. This category is a catchall of steps taken usually by a doula, midwife, or nurse.

Continuous labor support typically includes touch, massage, application of cold or heat, and other strategies for physical comfort plus emotional support, a steady flow of information to the mother, and facilitation of communication between the mother and the health care providers.

A 2003 Cochrane meta-analysis of 15 randomized, controlled studies with 12,791 women found significant decreases in use of regional analgesia, forceps, or cesarean births and increased likelihood of vaginal birth with continuous labor support.

Women reported 33% less dissatisfaction with labor regardless of pain, compared with unsupported control groups.

A separate 2003 review of studies found less striking results, but concluded that all women should have support during labor and that starting support earlier in labor rather than later maximizes the benefits.

▸ Water immersion. Putting a laboring woman in a warm bath was associated with decreased pain (particularly during the first 30 minutes) and decreased use of epidurals, according to a 2004 Cochrane meta-analysis of eight randomized, controlled trials with 2,939 women.

Two studies found that tub immersion during early labor (before 5-cm dilation) may prolong labor. Individual studies found fewer fetal malpositions in tub-immersed women and no increased rate of infection in those who rupture membranes while in the tub.

“There should be no barriers to women getting into a tub due to misconceptions regarding infection” risk, Ms. Bishop said.

▸ Hypnosis. A very old strategy recently repackaged under the term “hypnobirthing,” hypnotic pain relief techniques carry the disadvantages of time and costs needed for training, and the lengthy time needed to implement this into practice, she said.

A 2006 Cochrane review of five trials with 749 women found suggestions of effectiveness in decreasing the need for pharmacologic pain relief and increasing vaginal deliveries and patient satisfaction with pain relief. No adverse outcomes were seen, but hypnosis generally is contraindicated in women with a history of psychosis, she added.

▸ Intradermal water injections. Four randomized, controlled studies found significant reductions in severe back pain for 45–90 minutes but no decrease in requests for medication for abdominal pain using this strategy.

Intradermal water injections involve injecting 0.05–0.1 mL of sterile water into four locations on the lower back—two over each posterior superior iliac spine, and two located 3 cm below and 1 cm medial to the posterior superior iliac spine.

Injections seem to be more effective earlier rather than later in labor. The injections are painful for 20–30 seconds, and the counterirritation of the injection pain may be a mechanism of action for relieving the back pain, she speculated.

▸ Acupuncture. Although the overall evidence that acupuncture can reduce labor pain is encouraging, “it's really difficult to find an acupuncturist willing to be on call to come into labor” rooms, Ms. Bishop said. Midwives in some European countries can take a course to provide acupuncture to patients, something that should be tried in the United States, she added.

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SAN FRANCISCO — When it comes to relieving labor pain, there's nothing like an epidural.

Beyond that, however, some nonpharmacologic strategies compete well with opioids, the next most common pharmacologic option for treating labor pain, Judith T. Bishop said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

Nonpharmacologic techniques should be considered for women who arrive at the labor-and-delivery room too late to get an epidural, women who want to try an unmedicated birth, or women who want to incorporate nonpharmacologic options as stepping-stones to possible use of pain-relieving medications later in labor, she said.

Epidurals or spinal analgesia were received by 76% of 1,573 women who were delivering singletons in U.S. hospitals and who were surveyed for the 2006 Listening to Mothers II Survey Report.

Among those who received epidurals or spinal analgesia, 81% said that they were very helpful, according to the report compiled for the nonprofit organization Childbirth Connection by Eugene R. Declerq, Ph.D., professor of maternal and child health at Boston University, and associates.

Besides epidurals, “the interesting thing is that immersion in a tub or hands-on techniques came up a little bit above the effectiveness of narcotics” for relieving labor pain, although they were less often used than narcotics, said Ms. Bishop, a certified nurse-midwife and professor of ob.gyn. and reproductive sciences at the University of California.

“Many of the other nonpharmacologic techniques are not far behind” in effectiveness, she added. (See box.)

Overall, 69% of women used one or more nonpharmacologic techniques to relieve discomfort in labor.

Ms. Bishop reviewed the evidence for some nonpharmacologic strategies that had been identified as effective by one or more of three published reviews of the literature.

▸ Continuous labor support. This category is a catchall of steps taken usually by a doula, midwife, or nurse.

Continuous labor support typically includes touch, massage, application of cold or heat, and other strategies for physical comfort plus emotional support, a steady flow of information to the mother, and facilitation of communication between the mother and the health care providers.

A 2003 Cochrane meta-analysis of 15 randomized, controlled studies with 12,791 women found significant decreases in use of regional analgesia, forceps, or cesarean births and increased likelihood of vaginal birth with continuous labor support.

Women reported 33% less dissatisfaction with labor regardless of pain, compared with unsupported control groups.

A separate 2003 review of studies found less striking results, but concluded that all women should have support during labor and that starting support earlier in labor rather than later maximizes the benefits.

▸ Water immersion. Putting a laboring woman in a warm bath was associated with decreased pain (particularly during the first 30 minutes) and decreased use of epidurals, according to a 2004 Cochrane meta-analysis of eight randomized, controlled trials with 2,939 women.

Two studies found that tub immersion during early labor (before 5-cm dilation) may prolong labor. Individual studies found fewer fetal malpositions in tub-immersed women and no increased rate of infection in those who rupture membranes while in the tub.

“There should be no barriers to women getting into a tub due to misconceptions regarding infection” risk, Ms. Bishop said.

▸ Hypnosis. A very old strategy recently repackaged under the term “hypnobirthing,” hypnotic pain relief techniques carry the disadvantages of time and costs needed for training, and the lengthy time needed to implement this into practice, she said.

A 2006 Cochrane review of five trials with 749 women found suggestions of effectiveness in decreasing the need for pharmacologic pain relief and increasing vaginal deliveries and patient satisfaction with pain relief. No adverse outcomes were seen, but hypnosis generally is contraindicated in women with a history of psychosis, she added.

▸ Intradermal water injections. Four randomized, controlled studies found significant reductions in severe back pain for 45–90 minutes but no decrease in requests for medication for abdominal pain using this strategy.

Intradermal water injections involve injecting 0.05–0.1 mL of sterile water into four locations on the lower back—two over each posterior superior iliac spine, and two located 3 cm below and 1 cm medial to the posterior superior iliac spine.

Injections seem to be more effective earlier rather than later in labor. The injections are painful for 20–30 seconds, and the counterirritation of the injection pain may be a mechanism of action for relieving the back pain, she speculated.

▸ Acupuncture. Although the overall evidence that acupuncture can reduce labor pain is encouraging, “it's really difficult to find an acupuncturist willing to be on call to come into labor” rooms, Ms. Bishop said. Midwives in some European countries can take a course to provide acupuncture to patients, something that should be tried in the United States, she added.

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