Kate Johnson

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, Dr. Pal said in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” Dr. Pal said.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, Dr. Pal said in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” Dr. Pal said.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, Dr. Pal said in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” Dr. Pal said.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — High-dose antioxidant supplementation may be harmful in pregnant women at risk for preeclampsia, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

The study, comparing placebo with high daily doses of vitamins C (1,000 mg) and E (400 IU) in high-risk women, suggested that high doses of these vitamins conveyed no protective effect against preeclampsia. In fact, these large doses of the two antioxidants were associated with a greater risk of low birth weight, gestational hypertension, and an arterial cord pH less than 7, reported Lucilla Poston, Ph.D., lead author and professor of fetal health at Guy's, King's, and St. Thomas's School of Medicine in London.

The study, fast-tracked to the Lancet, (published online March 30, 2006, doi:10.1016/S0140–6736(06)68433-X) should not be misinterpreted as evidence against regular prenatal vitamins, which include much lower doses of antioxidants, Dr. Poston said in an interview. “There's no suggestion that women taking pregnancy vitamins had any adverse effects,” she said.

This is the first study to suggest a risk of high-dose antioxidants in pregnancy, and contrasts with previous work by the same group of investigators that suggested a protective effect of supplementation (Lancet 1999;354:810–6).

“It's quite possible that our previous findings were an error as a result of our small numbers,” Dr. Poston said, explaining that the previous study included only 160 women, with an 8% rate of preeclampsia.

She said although it has long been accepted that preeclampsia is associated with oxidative stress, her results suggest that rather than being the cause, oxidative stress may simply be a consequence of the condition. “I'm afraid to say that oxidative stress is probably an innocent bystander in preeclampsia as a result of the disease process,” she noted.

The study analyzed 2,395 pregnant women who were at risk for preeclampsia and randomized them at 14–22 weeks' gestation to either high-dose antioxidant therapy or placebo. Subjects who were already taking prenatal vitamins at randomization were allowed to continue taking them.

High-dose antioxidant therapy failed to protect against preeclampsia, which occurred in 15% of the high-dose antioxidant group and 16% of the placebo group.

There also was an association between high-dose antioxidant therapy and low birth weight, defined as less than 2.5 kg. Low-birth-weight babies comprised 28% of the babies in the high-dose antioxidant group, compared with 24% of the placebo group (risk ratio 1.15).

Regarding secondary outcomes, high-dose antioxidant therapy again compared unfavorably with placebo, resulting in higher risks of arterial cord pH less than 7 (RR 2.2), intravenous antihypertensive therapy (RR 1.9), magnesium sulfate therapy for preeclampsia (RR 1.8), gestational hypertension (RR 1.5), and antenatal steroid use (RR 1.4).

An additional exploratory analysis of the data revealed that high-dose antioxidants were associated with a greater risk of stillbirth (RR 2.7), but a lower risk of death due to immaturity (RR 0.2), although these results could be due to chance, since they were generated from a posthoc analysis, she said.

The harmful potential of large doses of antioxidants is troubling, but consistent with some controversial evidence that high-dose vitamin E has an adverse effect on mortality and morbidity in people with cardiovascular disease, Dr. Poston noted.

“Oxidative stress is involved in a lot of biological processes and it could be there is some fundamental biological process that depends on a little bit of oxidative stress,” she said.

The study raises ethical concerns about ongoing antioxidant research in populations that are at risk for preeclampsia, said Dr. Poston. However, she said she has contacted investigators on similar U.S. (National Institutes of Health) and Canadian (Medical Research Council) studies who have decided, after performing interim analyses, to continue their studies.

Another smaller study presented in poster form at the meeting also found no protective effect of high-dose antioxidant therapy against preeclampsia. The study was conducted in a normal, nulliparous population, however, rather than a high-risk group. In fact, there was a trend toward higher preeclampsia rates among women taking high doses of antioxidants (16.7%) compared with those taking placebo (9.7%), said Dr. Heather Mertz, an ob.gyn. at Wake Forest University, Winston-Salem, N.C.

The study of 177 women did show a significant benefit of high-dose antioxidant therapy on neonatal outcome, Dr. Mertz said in an interview. But overall, Dr. Mertz said, her study did not provide enough evidence to counsel patients either for or against high-dose antioxidant therapy during pregnancy.

'It's quite possible that our previous findings were an error as a result of our small numbers.' DR. POSTON

TORONTO — High-dose antioxidant supplementation may be harmful in pregnant women at risk for preeclampsia, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

The study, comparing placebo with high daily doses of vitamins C (1,000 mg) and E (400 IU) in high-risk women, suggested that high doses of these vitamins conveyed no protective effect against preeclampsia. In fact, these large doses of the two antioxidants were associated with a greater risk of low birth weight, gestational hypertension, and an arterial cord pH less than 7, reported Lucilla Poston, Ph.D., lead author and professor of fetal health at Guy's, King's, and St. Thomas's School of Medicine in London.

The study, fast-tracked to the Lancet, (published online March 30, 2006, doi:10.1016/S0140–6736(06)68433-X) should not be misinterpreted as evidence against regular prenatal vitamins, which include much lower doses of antioxidants, Dr. Poston said in an interview. “There's no suggestion that women taking pregnancy vitamins had any adverse effects,” she said.

This is the first study to suggest a risk of high-dose antioxidants in pregnancy, and contrasts with previous work by the same group of investigators that suggested a protective effect of supplementation (Lancet 1999;354:810–6).

“It's quite possible that our previous findings were an error as a result of our small numbers,” Dr. Poston said, explaining that the previous study included only 160 women, with an 8% rate of preeclampsia.

She said although it has long been accepted that preeclampsia is associated with oxidative stress, her results suggest that rather than being the cause, oxidative stress may simply be a consequence of the condition. “I'm afraid to say that oxidative stress is probably an innocent bystander in preeclampsia as a result of the disease process,” she noted.

The study analyzed 2,395 pregnant women who were at risk for preeclampsia and randomized them at 14–22 weeks' gestation to either high-dose antioxidant therapy or placebo. Subjects who were already taking prenatal vitamins at randomization were allowed to continue taking them.

High-dose antioxidant therapy failed to protect against preeclampsia, which occurred in 15% of the high-dose antioxidant group and 16% of the placebo group.

There also was an association between high-dose antioxidant therapy and low birth weight, defined as less than 2.5 kg. Low-birth-weight babies comprised 28% of the babies in the high-dose antioxidant group, compared with 24% of the placebo group (risk ratio 1.15).

Regarding secondary outcomes, high-dose antioxidant therapy again compared unfavorably with placebo, resulting in higher risks of arterial cord pH less than 7 (RR 2.2), intravenous antihypertensive therapy (RR 1.9), magnesium sulfate therapy for preeclampsia (RR 1.8), gestational hypertension (RR 1.5), and antenatal steroid use (RR 1.4).

An additional exploratory analysis of the data revealed that high-dose antioxidants were associated with a greater risk of stillbirth (RR 2.7), but a lower risk of death due to immaturity (RR 0.2), although these results could be due to chance, since they were generated from a posthoc analysis, she said.

The harmful potential of large doses of antioxidants is troubling, but consistent with some controversial evidence that high-dose vitamin E has an adverse effect on mortality and morbidity in people with cardiovascular disease, Dr. Poston noted.

“Oxidative stress is involved in a lot of biological processes and it could be there is some fundamental biological process that depends on a little bit of oxidative stress,” she said.

The study raises ethical concerns about ongoing antioxidant research in populations that are at risk for preeclampsia, said Dr. Poston. However, she said she has contacted investigators on similar U.S. (National Institutes of Health) and Canadian (Medical Research Council) studies who have decided, after performing interim analyses, to continue their studies.

Another smaller study presented in poster form at the meeting also found no protective effect of high-dose antioxidant therapy against preeclampsia. The study was conducted in a normal, nulliparous population, however, rather than a high-risk group. In fact, there was a trend toward higher preeclampsia rates among women taking high doses of antioxidants (16.7%) compared with those taking placebo (9.7%), said Dr. Heather Mertz, an ob.gyn. at Wake Forest University, Winston-Salem, N.C.

The study of 177 women did show a significant benefit of high-dose antioxidant therapy on neonatal outcome, Dr. Mertz said in an interview. But overall, Dr. Mertz said, her study did not provide enough evidence to counsel patients either for or against high-dose antioxidant therapy during pregnancy.

'It's quite possible that our previous findings were an error as a result of our small numbers.' DR. POSTON

TORONTO — High-dose antioxidant supplementation may be harmful in pregnant women at risk for preeclampsia, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

The study, comparing placebo with high daily doses of vitamins C (1,000 mg) and E (400 IU) in high-risk women, suggested that high doses of these vitamins conveyed no protective effect against preeclampsia. In fact, these large doses of the two antioxidants were associated with a greater risk of low birth weight, gestational hypertension, and an arterial cord pH less than 7, reported Lucilla Poston, Ph.D., lead author and professor of fetal health at Guy's, King's, and St. Thomas's School of Medicine in London.

The study, fast-tracked to the Lancet, (published online March 30, 2006, doi:10.1016/S0140–6736(06)68433-X) should not be misinterpreted as evidence against regular prenatal vitamins, which include much lower doses of antioxidants, Dr. Poston said in an interview. “There's no suggestion that women taking pregnancy vitamins had any adverse effects,” she said.

This is the first study to suggest a risk of high-dose antioxidants in pregnancy, and contrasts with previous work by the same group of investigators that suggested a protective effect of supplementation (Lancet 1999;354:810–6).

“It's quite possible that our previous findings were an error as a result of our small numbers,” Dr. Poston said, explaining that the previous study included only 160 women, with an 8% rate of preeclampsia.

She said although it has long been accepted that preeclampsia is associated with oxidative stress, her results suggest that rather than being the cause, oxidative stress may simply be a consequence of the condition. “I'm afraid to say that oxidative stress is probably an innocent bystander in preeclampsia as a result of the disease process,” she noted.

The study analyzed 2,395 pregnant women who were at risk for preeclampsia and randomized them at 14–22 weeks' gestation to either high-dose antioxidant therapy or placebo. Subjects who were already taking prenatal vitamins at randomization were allowed to continue taking them.

High-dose antioxidant therapy failed to protect against preeclampsia, which occurred in 15% of the high-dose antioxidant group and 16% of the placebo group.

There also was an association between high-dose antioxidant therapy and low birth weight, defined as less than 2.5 kg. Low-birth-weight babies comprised 28% of the babies in the high-dose antioxidant group, compared with 24% of the placebo group (risk ratio 1.15).

Regarding secondary outcomes, high-dose antioxidant therapy again compared unfavorably with placebo, resulting in higher risks of arterial cord pH less than 7 (RR 2.2), intravenous antihypertensive therapy (RR 1.9), magnesium sulfate therapy for preeclampsia (RR 1.8), gestational hypertension (RR 1.5), and antenatal steroid use (RR 1.4).

An additional exploratory analysis of the data revealed that high-dose antioxidants were associated with a greater risk of stillbirth (RR 2.7), but a lower risk of death due to immaturity (RR 0.2), although these results could be due to chance, since they were generated from a posthoc analysis, she said.

The harmful potential of large doses of antioxidants is troubling, but consistent with some controversial evidence that high-dose vitamin E has an adverse effect on mortality and morbidity in people with cardiovascular disease, Dr. Poston noted.

“Oxidative stress is involved in a lot of biological processes and it could be there is some fundamental biological process that depends on a little bit of oxidative stress,” she said.

The study raises ethical concerns about ongoing antioxidant research in populations that are at risk for preeclampsia, said Dr. Poston. However, she said she has contacted investigators on similar U.S. (National Institutes of Health) and Canadian (Medical Research Council) studies who have decided, after performing interim analyses, to continue their studies.

Another smaller study presented in poster form at the meeting also found no protective effect of high-dose antioxidant therapy against preeclampsia. The study was conducted in a normal, nulliparous population, however, rather than a high-risk group. In fact, there was a trend toward higher preeclampsia rates among women taking high doses of antioxidants (16.7%) compared with those taking placebo (9.7%), said Dr. Heather Mertz, an ob.gyn. at Wake Forest University, Winston-Salem, N.C.

The study of 177 women did show a significant benefit of high-dose antioxidant therapy on neonatal outcome, Dr. Mertz said in an interview. But overall, Dr. Mertz said, her study did not provide enough evidence to counsel patients either for or against high-dose antioxidant therapy during pregnancy.

'It's quite possible that our previous findings were an error as a result of our small numbers.' DR. POSTON

TORONTO — Transdermal nitroglycerin improved neonatal outcome but did not significantly delay delivery according to the results of the Canadian Preterm Labour Nitroglycerin Trial.

“Given that there is no standard of care [for the management of preterm labor] and that no tocolytic has been shown to improve outcome, this is potentially very exciting,” said principal investigator Dr. Graeme N. Smith of Queen's University in Kingston, Ontario. His center and several others have already adopted this approach as standard, he said in an interview.

The study, which he presented at the annual meeting of the Society for Gynecologic Investigation, randomized 158 women between 24 and 32 weeks' gestation and in preterm labor either to placebo (81 patients) or a transdermal nitroglycerin, or glyceryl trinitrate (GTN), patch (77).

The primary outcome measured was a neonatal morbidity composite which included one or more of the following: chronic lung disease, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and perinatal mortality. The secondary outcome was the time to delivery.

Upon entry into the study and before randomization, all women received a 500-mL saline bolus (0.9%) to offset the potentially dehydrating effects of GTN. The GTN patch delivered a dose of 0.4 mg/hr and was replaced once after 24 hours.

In the 153 women left in the final analysis, neonatal outcome was significantly improved in those receiving the GTN patch, with a composite score of 3, compared with a score of 11 in the placebo group, for a relative risk of 0.29. This effect was limited to those who were at 28 weeks' gestation or less. There was one case of chronic lung disease in the GTN group, compared with seven in placebo; two cases of IVH in the GTN group, compared with one in placebo; and no cases of NEC, PVL, or perinatal mortality in the GTN group, compared with two, two, and three cases, respectively, in the placebo group.

Although there was no significant effect of GTN on time to delivery, the medication resulted in a nonsignificant 7-day prolongation of pregnancy, said Dr. Smith, suggesting that the effect might have reached significance with higher numbers.

GTN is a smooth muscle relaxant and thus might relax the smooth muscle of the uterus, he said. This effect was not observed, so he suggested the improvement in neonatal outcome might result from improved blood flow to the placenta or uterus. Side effects were seen more in the GTN group, with a relative risk of 1.41, headache being the most common.

TORONTO — Transdermal nitroglycerin improved neonatal outcome but did not significantly delay delivery according to the results of the Canadian Preterm Labour Nitroglycerin Trial.

“Given that there is no standard of care [for the management of preterm labor] and that no tocolytic has been shown to improve outcome, this is potentially very exciting,” said principal investigator Dr. Graeme N. Smith of Queen's University in Kingston, Ontario. His center and several others have already adopted this approach as standard, he said in an interview.

The study, which he presented at the annual meeting of the Society for Gynecologic Investigation, randomized 158 women between 24 and 32 weeks' gestation and in preterm labor either to placebo (81 patients) or a transdermal nitroglycerin, or glyceryl trinitrate (GTN), patch (77).

The primary outcome measured was a neonatal morbidity composite which included one or more of the following: chronic lung disease, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and perinatal mortality. The secondary outcome was the time to delivery.

Upon entry into the study and before randomization, all women received a 500-mL saline bolus (0.9%) to offset the potentially dehydrating effects of GTN. The GTN patch delivered a dose of 0.4 mg/hr and was replaced once after 24 hours.

In the 153 women left in the final analysis, neonatal outcome was significantly improved in those receiving the GTN patch, with a composite score of 3, compared with a score of 11 in the placebo group, for a relative risk of 0.29. This effect was limited to those who were at 28 weeks' gestation or less. There was one case of chronic lung disease in the GTN group, compared with seven in placebo; two cases of IVH in the GTN group, compared with one in placebo; and no cases of NEC, PVL, or perinatal mortality in the GTN group, compared with two, two, and three cases, respectively, in the placebo group.

Although there was no significant effect of GTN on time to delivery, the medication resulted in a nonsignificant 7-day prolongation of pregnancy, said Dr. Smith, suggesting that the effect might have reached significance with higher numbers.

GTN is a smooth muscle relaxant and thus might relax the smooth muscle of the uterus, he said. This effect was not observed, so he suggested the improvement in neonatal outcome might result from improved blood flow to the placenta or uterus. Side effects were seen more in the GTN group, with a relative risk of 1.41, headache being the most common.

TORONTO — Transdermal nitroglycerin improved neonatal outcome but did not significantly delay delivery according to the results of the Canadian Preterm Labour Nitroglycerin Trial.

“Given that there is no standard of care [for the management of preterm labor] and that no tocolytic has been shown to improve outcome, this is potentially very exciting,” said principal investigator Dr. Graeme N. Smith of Queen's University in Kingston, Ontario. His center and several others have already adopted this approach as standard, he said in an interview.

The study, which he presented at the annual meeting of the Society for Gynecologic Investigation, randomized 158 women between 24 and 32 weeks' gestation and in preterm labor either to placebo (81 patients) or a transdermal nitroglycerin, or glyceryl trinitrate (GTN), patch (77).

The primary outcome measured was a neonatal morbidity composite which included one or more of the following: chronic lung disease, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and perinatal mortality. The secondary outcome was the time to delivery.

Upon entry into the study and before randomization, all women received a 500-mL saline bolus (0.9%) to offset the potentially dehydrating effects of GTN. The GTN patch delivered a dose of 0.4 mg/hr and was replaced once after 24 hours.

In the 153 women left in the final analysis, neonatal outcome was significantly improved in those receiving the GTN patch, with a composite score of 3, compared with a score of 11 in the placebo group, for a relative risk of 0.29. This effect was limited to those who were at 28 weeks' gestation or less. There was one case of chronic lung disease in the GTN group, compared with seven in placebo; two cases of IVH in the GTN group, compared with one in placebo; and no cases of NEC, PVL, or perinatal mortality in the GTN group, compared with two, two, and three cases, respectively, in the placebo group.

Although there was no significant effect of GTN on time to delivery, the medication resulted in a nonsignificant 7-day prolongation of pregnancy, said Dr. Smith, suggesting that the effect might have reached significance with higher numbers.

GTN is a smooth muscle relaxant and thus might relax the smooth muscle of the uterus, he said. This effect was not observed, so he suggested the improvement in neonatal outcome might result from improved blood flow to the placenta or uterus. Side effects were seen more in the GTN group, with a relative risk of 1.41, headache being the most common.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which Mr. Johnstone presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women who were aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23% had indicated before conception that they were dieting to lose weight.

However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%).

This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11b hydroxysteroid dehydrogenase type 2 (11b HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

“These findings suggest that influences associated with dieting behavior can alter the timing of parturition,” concluded Mr. Johnstone.

In addition to animal data that support the link between preconception undernutrition and preterm birth, Mr. Johnstone said that human data show a significant increase in the incidence of preterm delivery related to the 1944–1945 famine in the Netherlands.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which Mr. Johnstone presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women who were aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23% had indicated before conception that they were dieting to lose weight.

However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%).

This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11b hydroxysteroid dehydrogenase type 2 (11b HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

“These findings suggest that influences associated with dieting behavior can alter the timing of parturition,” concluded Mr. Johnstone.

In addition to animal data that support the link between preconception undernutrition and preterm birth, Mr. Johnstone said that human data show a significant increase in the incidence of preterm delivery related to the 1944–1945 famine in the Netherlands.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which Mr. Johnstone presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women who were aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23% had indicated before conception that they were dieting to lose weight.

However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%).

This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11b hydroxysteroid dehydrogenase type 2 (11b HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

“These findings suggest that influences associated with dieting behavior can alter the timing of parturition,” concluded Mr. Johnstone.

In addition to animal data that support the link between preconception undernutrition and preterm birth, Mr. Johnstone said that human data show a significant increase in the incidence of preterm delivery related to the 1944–1945 famine in the Netherlands.

Community health centers are clinically understaffed and probably will face increasing shortages that may limit their expansion, according to a study by the rural health research centers of both the University of Washington, Seattle, and the University of South Carolina, Columbia, and by the National Association of Community Health Centers (JAMA 2006;295:1042–9).

“Workforce shortages may impede the expansion of the U.S. [community health center] safety net, particularly in rural areas,” reported Dr. Roger A. Rosenblatt from the University of Washington, Seattle, and his colleagues.

The study surveyed 846 federally funded community health centers (CHCs) within the 50 states and the District of Columbia. Mailed questionnaires and telephone surveys asked CHC chief executive officers about staffing and recruiting patterns, use of federal and state recruitment programs, and perceived barriers to recruitment.

Responses were obtained from 79% of the population and revealed that funded clinical staff vacancies are common. The average CHC has 13% of its family physician full-time equivalent positions unfilled. Rural CHCs reported a significantly higher proportion of these vacancies, as well as recruiting difficulties, compared with their urban counterparts, with more than one-third of rural CHCs reporting that they had been trying to recruit a family physician for more than 7 months. “It would require more than 400 FTE family physicians to fill all the vacancies for this discipline,” noted the authors.

Some of the greatest recruitment difficulties were reported for obstetrician/gynecologists and psychiatrists; rural locations reported more than 20% of funded positions vacant, and they had more recruitment difficulties, compared with urban CHCs. Dentists' vacancies also were indicated, with more than half of rural CHCs reporting a vacant position for 7 months or longer. Less difficulty was reported in recruiting nurse-practitioners and physician assistants, with no significant rural-urban differences.

When asked to indicate perceived barriers to recruitment and retention of both rural and urban CHC physicians and nurses, respondents consistently noted the inability to offer competitive compensation packages.

“The lack of spousal employment opportunities, lack of cultural activities and opportunities, lack of adequate housing, and poor-quality schools were perceived as disproportionately greater barriers for rural centers,” noted the authors. Survey respondents suggested three potential interventions to address these perceived barriers: better capacity to provide annual salary increases, more National Health Service Corps loan repayment incentives, and greater visibility of CHCs as desirable practice opportunities during training.

“The clinical role of CHCs is dependent on primary care clinicians, both physicians and nonphysician clinicians,” the authors wrote, noting that the declining production of family physicians from residency programs “may lead to serious workforce shortages, particularly in rural CHCs.”

Roughly 66% of the responding CHCs indicated their plans to expand as part of a federal 5-year initiative to increase spending on CHCs by at least $2.2 billion through fiscal year 2006. However, the decline in “physicians choosing generalist careers may be the rate-limiting step in the nation's ability to staff CHCs and may lead to renewed shortages of safety-net and rural physicians generally,” they wrote.

The authors made several suggestions, including the following, for federal and state governments, as well as for CHCs:

▸ Bolstering elements of the Health Professions Educational Assistance Act of 1976, the only federal program aimed at encouraging primary care clinicians who are likely to practice in underserved areas.

▸ Increasing the use of nurse-practitioners and physician assistants.

▸ Creating new alliances between CHCs and primary care training programs.

▸ Expanding the National Health Service Corps and related programs that provide financial incentives to attract health care clinicians to underserved areas.

▸ Developing new approaches to loan repayment plans.

▸ Creating additional incentives for rural areas.

Community health centers are clinically understaffed and probably will face increasing shortages that may limit their expansion, according to a study by the rural health research centers of both the University of Washington, Seattle, and the University of South Carolina, Columbia, and by the National Association of Community Health Centers (JAMA 2006;295:1042–9).

“Workforce shortages may impede the expansion of the U.S. [community health center] safety net, particularly in rural areas,” reported Dr. Roger A. Rosenblatt from the University of Washington, Seattle, and his colleagues.

The study surveyed 846 federally funded community health centers (CHCs) within the 50 states and the District of Columbia. Mailed questionnaires and telephone surveys asked CHC chief executive officers about staffing and recruiting patterns, use of federal and state recruitment programs, and perceived barriers to recruitment.

Responses were obtained from 79% of the population and revealed that funded clinical staff vacancies are common. The average CHC has 13% of its family physician full-time equivalent positions unfilled. Rural CHCs reported a significantly higher proportion of these vacancies, as well as recruiting difficulties, compared with their urban counterparts, with more than one-third of rural CHCs reporting that they had been trying to recruit a family physician for more than 7 months. “It would require more than 400 FTE family physicians to fill all the vacancies for this discipline,” noted the authors.

Some of the greatest recruitment difficulties were reported for obstetrician/gynecologists and psychiatrists; rural locations reported more than 20% of funded positions vacant, and they had more recruitment difficulties, compared with urban CHCs. Dentists' vacancies also were indicated, with more than half of rural CHCs reporting a vacant position for 7 months or longer. Less difficulty was reported in recruiting nurse-practitioners and physician assistants, with no significant rural-urban differences.

When asked to indicate perceived barriers to recruitment and retention of both rural and urban CHC physicians and nurses, respondents consistently noted the inability to offer competitive compensation packages.

“The lack of spousal employment opportunities, lack of cultural activities and opportunities, lack of adequate housing, and poor-quality schools were perceived as disproportionately greater barriers for rural centers,” noted the authors. Survey respondents suggested three potential interventions to address these perceived barriers: better capacity to provide annual salary increases, more National Health Service Corps loan repayment incentives, and greater visibility of CHCs as desirable practice opportunities during training.

“The clinical role of CHCs is dependent on primary care clinicians, both physicians and nonphysician clinicians,” the authors wrote, noting that the declining production of family physicians from residency programs “may lead to serious workforce shortages, particularly in rural CHCs.”

Roughly 66% of the responding CHCs indicated their plans to expand as part of a federal 5-year initiative to increase spending on CHCs by at least $2.2 billion through fiscal year 2006. However, the decline in “physicians choosing generalist careers may be the rate-limiting step in the nation's ability to staff CHCs and may lead to renewed shortages of safety-net and rural physicians generally,” they wrote.

The authors made several suggestions, including the following, for federal and state governments, as well as for CHCs:

▸ Bolstering elements of the Health Professions Educational Assistance Act of 1976, the only federal program aimed at encouraging primary care clinicians who are likely to practice in underserved areas.

▸ Increasing the use of nurse-practitioners and physician assistants.

▸ Creating new alliances between CHCs and primary care training programs.

▸ Expanding the National Health Service Corps and related programs that provide financial incentives to attract health care clinicians to underserved areas.

▸ Developing new approaches to loan repayment plans.

▸ Creating additional incentives for rural areas.

Community health centers are clinically understaffed and probably will face increasing shortages that may limit their expansion, according to a study by the rural health research centers of both the University of Washington, Seattle, and the University of South Carolina, Columbia, and by the National Association of Community Health Centers (JAMA 2006;295:1042–9).

“Workforce shortages may impede the expansion of the U.S. [community health center] safety net, particularly in rural areas,” reported Dr. Roger A. Rosenblatt from the University of Washington, Seattle, and his colleagues.

The study surveyed 846 federally funded community health centers (CHCs) within the 50 states and the District of Columbia. Mailed questionnaires and telephone surveys asked CHC chief executive officers about staffing and recruiting patterns, use of federal and state recruitment programs, and perceived barriers to recruitment.

Responses were obtained from 79% of the population and revealed that funded clinical staff vacancies are common. The average CHC has 13% of its family physician full-time equivalent positions unfilled. Rural CHCs reported a significantly higher proportion of these vacancies, as well as recruiting difficulties, compared with their urban counterparts, with more than one-third of rural CHCs reporting that they had been trying to recruit a family physician for more than 7 months. “It would require more than 400 FTE family physicians to fill all the vacancies for this discipline,” noted the authors.

Some of the greatest recruitment difficulties were reported for obstetrician/gynecologists and psychiatrists; rural locations reported more than 20% of funded positions vacant, and they had more recruitment difficulties, compared with urban CHCs. Dentists' vacancies also were indicated, with more than half of rural CHCs reporting a vacant position for 7 months or longer. Less difficulty was reported in recruiting nurse-practitioners and physician assistants, with no significant rural-urban differences.

When asked to indicate perceived barriers to recruitment and retention of both rural and urban CHC physicians and nurses, respondents consistently noted the inability to offer competitive compensation packages.

“The lack of spousal employment opportunities, lack of cultural activities and opportunities, lack of adequate housing, and poor-quality schools were perceived as disproportionately greater barriers for rural centers,” noted the authors. Survey respondents suggested three potential interventions to address these perceived barriers: better capacity to provide annual salary increases, more National Health Service Corps loan repayment incentives, and greater visibility of CHCs as desirable practice opportunities during training.

“The clinical role of CHCs is dependent on primary care clinicians, both physicians and nonphysician clinicians,” the authors wrote, noting that the declining production of family physicians from residency programs “may lead to serious workforce shortages, particularly in rural CHCs.”

Roughly 66% of the responding CHCs indicated their plans to expand as part of a federal 5-year initiative to increase spending on CHCs by at least $2.2 billion through fiscal year 2006. However, the decline in “physicians choosing generalist careers may be the rate-limiting step in the nation's ability to staff CHCs and may lead to renewed shortages of safety-net and rural physicians generally,” they wrote.

The authors made several suggestions, including the following, for federal and state governments, as well as for CHCs:

▸ Bolstering elements of the Health Professions Educational Assistance Act of 1976, the only federal program aimed at encouraging primary care clinicians who are likely to practice in underserved areas.

▸ Increasing the use of nurse-practitioners and physician assistants.

▸ Creating new alliances between CHCs and primary care training programs.

▸ Expanding the National Health Service Corps and related programs that provide financial incentives to attract health care clinicians to underserved areas.

▸ Developing new approaches to loan repayment plans.

▸ Creating additional incentives for rural areas.

TORONTO — Women with pelvic organ prolapse may be at more risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%. After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — Women with pelvic organ prolapse may be at more risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%. After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — Women with pelvic organ prolapse may be at more risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal in an interview.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or more who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%. After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal.

“We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake,” she suggested.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which he presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23.3% had indicated before conception that they were dieting to lose weight. However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight-loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%). This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11β hydroxysteroid dehydrogenase type 2 (11β HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which he presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23.3% had indicated before conception that they were dieting to lose weight. However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight-loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%). This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11β hydroxysteroid dehydrogenase type 2 (11β HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

TORONTO — Women who diet to lose weight before getting pregnant could be at increased risk of giving birth prematurely, according to Jim Johnstone of the department of physiology at the University of Toronto.

The findings, which he presented at the annual meeting of the Society for Gynecologic Investigation, come from a subset of the Southampton Women's Survey, in which 12,500 women aged 24–34 years were interviewed before they became pregnant, and then 3,000 were followed through their subsequent pregnancies.

In Mr. Johnstone's sample of 605 of these pregnant women, 23.3% had indicated before conception that they were dieting to lose weight. However, the time interval between the survey interview and their subsequent pregnancy was not recorded.

The analysis revealed that women who became pregnant after a weight-loss diet were significantly more likely to give birth prematurely, compared with women who did not diet (11% vs. 5%). This finding was independent of maternal body mass index, smoking status, exercise, socioeconomic status, ethnicity, and infant gender.

In addition, a total of 50 placental samples selected randomly from the group at term showed that—compared with nondieters—dieters had decreased levels of the enzyme 11β hydroxysteroid dehydrogenase type 2 (11β HSD2), indicating increased fetal exposure to cortisol, as well as increased levels of cyclooxygenase-2 (COX-2), indicating an increased placental capacity to produce prostaglandins.

TORONTO — Recurrent pregnancy loss was not associated with inherited maternal thrombophilias in a prospective study, adding weight to the evidence against screening for such disorders in patients presenting with a history of first-trimester miscarriage.

“It's probably more important to rule out other possible etiological factors,” said lead investigator Dr. Sony Sierra in an interview.

The study, which she presented at the annual meeting of the Society for Gynecologic Investigation, genotyped 915 Hutterite women for inherited thrombophilia polymorphisms including Factor V Leiden (FVL) Arg506Gln, the MTHFR Ala222Val, and the prothrombin G20210A variants. A total of 141 women were identified with inherited thrombophilias and were prospectively followed through 342 pregnancies.

The rate of fetal loss, defined as loss at or before 20 weeks of gestation, was 16% in the cohort, which is comparable to the rate found in the general population, reported Dr. Sierra, of the department of obstetrics and gynecology at the University of British Columbia in Vancouver.

“We also found that the majority of miscarriages occurred at less than 12 weeks—and since there has been evidence to suggest that thrombophilias could be associated with later fetal loss beyond 20 weeks, our findings just lend further support to the data that for early miscarriage there is no significant association,” she said.

Genotype analysis was performed on a subset of 72 live offspring and compared with maternal and paternal genotyping. The analysis revealed an expected transmission rate of the MTHFR Val allele to offspring; however, there were significantly fewer children born with the FVL allele (28) than expected (37). (There were no parental carriers of the prothrombin 20210A allele.)

“The significant deficit of children who inherit the FVL Gln allele from either heterozygous parent suggests that there may be preferential early loss of fetuses with this polymorphism,” said Dr. Sierra. “This unexpected result suggests selection against inherited thrombophilic variants during embryogenesis.”

TORONTO — Recurrent pregnancy loss was not associated with inherited maternal thrombophilias in a prospective study, adding weight to the evidence against screening for such disorders in patients presenting with a history of first-trimester miscarriage.

“It's probably more important to rule out other possible etiological factors,” said lead investigator Dr. Sony Sierra in an interview.

The study, which she presented at the annual meeting of the Society for Gynecologic Investigation, genotyped 915 Hutterite women for inherited thrombophilia polymorphisms including Factor V Leiden (FVL) Arg506Gln, the MTHFR Ala222Val, and the prothrombin G20210A variants. A total of 141 women were identified with inherited thrombophilias and were prospectively followed through 342 pregnancies.

The rate of fetal loss, defined as loss at or before 20 weeks of gestation, was 16% in the cohort, which is comparable to the rate found in the general population, reported Dr. Sierra, of the department of obstetrics and gynecology at the University of British Columbia in Vancouver.

“We also found that the majority of miscarriages occurred at less than 12 weeks—and since there has been evidence to suggest that thrombophilias could be associated with later fetal loss beyond 20 weeks, our findings just lend further support to the data that for early miscarriage there is no significant association,” she said.

Genotype analysis was performed on a subset of 72 live offspring and compared with maternal and paternal genotyping. The analysis revealed an expected transmission rate of the MTHFR Val allele to offspring; however, there were significantly fewer children born with the FVL allele (28) than expected (37). (There were no parental carriers of the prothrombin 20210A allele.)

“The significant deficit of children who inherit the FVL Gln allele from either heterozygous parent suggests that there may be preferential early loss of fetuses with this polymorphism,” said Dr. Sierra. “This unexpected result suggests selection against inherited thrombophilic variants during embryogenesis.”

TORONTO — Recurrent pregnancy loss was not associated with inherited maternal thrombophilias in a prospective study, adding weight to the evidence against screening for such disorders in patients presenting with a history of first-trimester miscarriage.

“It's probably more important to rule out other possible etiological factors,” said lead investigator Dr. Sony Sierra in an interview.

The study, which she presented at the annual meeting of the Society for Gynecologic Investigation, genotyped 915 Hutterite women for inherited thrombophilia polymorphisms including Factor V Leiden (FVL) Arg506Gln, the MTHFR Ala222Val, and the prothrombin G20210A variants. A total of 141 women were identified with inherited thrombophilias and were prospectively followed through 342 pregnancies.

The rate of fetal loss, defined as loss at or before 20 weeks of gestation, was 16% in the cohort, which is comparable to the rate found in the general population, reported Dr. Sierra, of the department of obstetrics and gynecology at the University of British Columbia in Vancouver.

“We also found that the majority of miscarriages occurred at less than 12 weeks—and since there has been evidence to suggest that thrombophilias could be associated with later fetal loss beyond 20 weeks, our findings just lend further support to the data that for early miscarriage there is no significant association,” she said.

Genotype analysis was performed on a subset of 72 live offspring and compared with maternal and paternal genotyping. The analysis revealed an expected transmission rate of the MTHFR Val allele to offspring; however, there were significantly fewer children born with the FVL allele (28) than expected (37). (There were no parental carriers of the prothrombin 20210A allele.)

“The significant deficit of children who inherit the FVL Gln allele from either heterozygous parent suggests that there may be preferential early loss of fetuses with this polymorphism,” said Dr. Sierra. “This unexpected result suggests selection against inherited thrombophilic variants during embryogenesis.”

TORONTO — Women whose first babies are delivered by cesarean section face an elevated risk of placenta previa and placental abruption in their second pregnancies. And with two previous cesarean deliveries the risk of placenta previa is increased further in the third pregnancy, according to a study by Dr. Darios Getahun of the Robert Wood Johnson Medical School in New Brunswick, N.J., and his colleagues.

The study, which was recently published (Obstet. Gynecol. 2006;107:771–8), was presented as a poster at the annual meeting of the Society for Gynecologic Investigation.

“Although cesarean section has previously been reported as a risk factor for placenta previa, it has not been previously associated with abruption,” Dr. Getahun said in an interview at the meeting. “Cesarean section causes scarring of the uterine wall, with the result that placentation may not be optimal. That's why it may be leading to abruption,” he explained.

The study included a cohort of women from the Missouri longitudinally linked live birth and fetal death data files. Singleton births were analyzed for 156,475 women whose first two consecutive births occurred in the 1989–1997 study period, and 31,102 women whose first three consecutive births occurred within that period.

Among 40,472 women whose first delivery was by cesarean section, the relative risk of placenta previa was 1.5, and that of placental abruption was 1.3 in the second pregnancy, compared with women whose first delivery was vaginal.

There was a dose response noted for the risk of placenta previa, but not for placental abruption risk. Therefore, when both the first and second deliveries were by cesarean section, the risk of placenta previa doubled in the third pregnancy, but the risk of placental abruption did not increase further, compared with women whose first two deliveries were vaginal.

The interval between pregnancies also was analyzed, and the study found that for cesarean deliveries, but not vaginal ones, an interval of less than 1 year was associated with a relative risk of 1.7 for placenta previa and 1.5 for placental abruption.

TORONTO — Women whose first babies are delivered by cesarean section face an elevated risk of placenta previa and placental abruption in their second pregnancies. And with two previous cesarean deliveries the risk of placenta previa is increased further in the third pregnancy, according to a study by Dr. Darios Getahun of the Robert Wood Johnson Medical School in New Brunswick, N.J., and his colleagues.

The study, which was recently published (Obstet. Gynecol. 2006;107:771–8), was presented as a poster at the annual meeting of the Society for Gynecologic Investigation.

“Although cesarean section has previously been reported as a risk factor for placenta previa, it has not been previously associated with abruption,” Dr. Getahun said in an interview at the meeting. “Cesarean section causes scarring of the uterine wall, with the result that placentation may not be optimal. That's why it may be leading to abruption,” he explained.

The study included a cohort of women from the Missouri longitudinally linked live birth and fetal death data files. Singleton births were analyzed for 156,475 women whose first two consecutive births occurred in the 1989–1997 study period, and 31,102 women whose first three consecutive births occurred within that period.

Among 40,472 women whose first delivery was by cesarean section, the relative risk of placenta previa was 1.5, and that of placental abruption was 1.3 in the second pregnancy, compared with women whose first delivery was vaginal.

There was a dose response noted for the risk of placenta previa, but not for placental abruption risk. Therefore, when both the first and second deliveries were by cesarean section, the risk of placenta previa doubled in the third pregnancy, but the risk of placental abruption did not increase further, compared with women whose first two deliveries were vaginal.

The interval between pregnancies also was analyzed, and the study found that for cesarean deliveries, but not vaginal ones, an interval of less than 1 year was associated with a relative risk of 1.7 for placenta previa and 1.5 for placental abruption.

TORONTO — Women whose first babies are delivered by cesarean section face an elevated risk of placenta previa and placental abruption in their second pregnancies. And with two previous cesarean deliveries the risk of placenta previa is increased further in the third pregnancy, according to a study by Dr. Darios Getahun of the Robert Wood Johnson Medical School in New Brunswick, N.J., and his colleagues.

The study, which was recently published (Obstet. Gynecol. 2006;107:771–8), was presented as a poster at the annual meeting of the Society for Gynecologic Investigation.

“Although cesarean section has previously been reported as a risk factor for placenta previa, it has not been previously associated with abruption,” Dr. Getahun said in an interview at the meeting. “Cesarean section causes scarring of the uterine wall, with the result that placentation may not be optimal. That's why it may be leading to abruption,” he explained.

The study included a cohort of women from the Missouri longitudinally linked live birth and fetal death data files. Singleton births were analyzed for 156,475 women whose first two consecutive births occurred in the 1989–1997 study period, and 31,102 women whose first three consecutive births occurred within that period.

Among 40,472 women whose first delivery was by cesarean section, the relative risk of placenta previa was 1.5, and that of placental abruption was 1.3 in the second pregnancy, compared with women whose first delivery was vaginal.

There was a dose response noted for the risk of placenta previa, but not for placental abruption risk. Therefore, when both the first and second deliveries were by cesarean section, the risk of placenta previa doubled in the third pregnancy, but the risk of placental abruption did not increase further, compared with women whose first two deliveries were vaginal.

The interval between pregnancies also was analyzed, and the study found that for cesarean deliveries, but not vaginal ones, an interval of less than 1 year was associated with a relative risk of 1.7 for placenta previa and 1.5 for placental abruption.

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”