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Early Epidurals Don't Impact Operative Delivery
HOLLYWOOD, FLA. — Epidural analgesia given in early labor has been shown to have no significant effect on the risk of operative delivery in patients with spontaneous labor, and the same appears to hold true for patients with induced labor, according to data presented at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.
In a series of 796 consecutive women with induced labor who requested early pain relief, the operative delivery rates were similar in those who did and did not receive early labor epidural analgesia (28% and 27%), Dr. Philip E. Hess reported.
Because labor induction is known to be associated with higher operative delivery rates, there was concern that the effects of epidural analgesia in induced labor might be different from its effects in spontaneous labor, Dr. Hess wrote in a poster.
The findings will hopefully put to rest the debate over whether there is a benefit with regard to operative delivery rates with delayed epidurals, Dr. Cynthia A. Wong said during a poster review session that she moderated. Dr. Wong of Northwestern University, Chicago, was lead author on a major study showing no benefit of delaying epidural analgesia in women with spontaneous labor (N. Engl. J. Med. 2005;352:655–65).
In the current study, patients undergoing labor induction who requested early pain relief (prior to 4-cm dilation) received parenteral opioid or labor epidural analgesia according to their obstetrician's protocol, reported Dr. Hess of Beth Israel Deaconess Medical Center in Boston.
A total of 350 women received epidural analgesia, and 446 received parenteral opioid. The groups were demographically similar, except the average body mass index was higher in the group that did not receive early epidural analgesia. The groups were also similar to a comparison group of 503 women with spontaneous labor who had a 21% operative delivery rate, significantly lower than the rates in the induced labor groups, he noted.
HOLLYWOOD, FLA. — Epidural analgesia given in early labor has been shown to have no significant effect on the risk of operative delivery in patients with spontaneous labor, and the same appears to hold true for patients with induced labor, according to data presented at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.
In a series of 796 consecutive women with induced labor who requested early pain relief, the operative delivery rates were similar in those who did and did not receive early labor epidural analgesia (28% and 27%), Dr. Philip E. Hess reported.
Because labor induction is known to be associated with higher operative delivery rates, there was concern that the effects of epidural analgesia in induced labor might be different from its effects in spontaneous labor, Dr. Hess wrote in a poster.
The findings will hopefully put to rest the debate over whether there is a benefit with regard to operative delivery rates with delayed epidurals, Dr. Cynthia A. Wong said during a poster review session that she moderated. Dr. Wong of Northwestern University, Chicago, was lead author on a major study showing no benefit of delaying epidural analgesia in women with spontaneous labor (N. Engl. J. Med. 2005;352:655–65).
In the current study, patients undergoing labor induction who requested early pain relief (prior to 4-cm dilation) received parenteral opioid or labor epidural analgesia according to their obstetrician's protocol, reported Dr. Hess of Beth Israel Deaconess Medical Center in Boston.
A total of 350 women received epidural analgesia, and 446 received parenteral opioid. The groups were demographically similar, except the average body mass index was higher in the group that did not receive early epidural analgesia. The groups were also similar to a comparison group of 503 women with spontaneous labor who had a 21% operative delivery rate, significantly lower than the rates in the induced labor groups, he noted.
HOLLYWOOD, FLA. — Epidural analgesia given in early labor has been shown to have no significant effect on the risk of operative delivery in patients with spontaneous labor, and the same appears to hold true for patients with induced labor, according to data presented at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.
In a series of 796 consecutive women with induced labor who requested early pain relief, the operative delivery rates were similar in those who did and did not receive early labor epidural analgesia (28% and 27%), Dr. Philip E. Hess reported.
Because labor induction is known to be associated with higher operative delivery rates, there was concern that the effects of epidural analgesia in induced labor might be different from its effects in spontaneous labor, Dr. Hess wrote in a poster.
The findings will hopefully put to rest the debate over whether there is a benefit with regard to operative delivery rates with delayed epidurals, Dr. Cynthia A. Wong said during a poster review session that she moderated. Dr. Wong of Northwestern University, Chicago, was lead author on a major study showing no benefit of delaying epidural analgesia in women with spontaneous labor (N. Engl. J. Med. 2005;352:655–65).
In the current study, patients undergoing labor induction who requested early pain relief (prior to 4-cm dilation) received parenteral opioid or labor epidural analgesia according to their obstetrician's protocol, reported Dr. Hess of Beth Israel Deaconess Medical Center in Boston.
A total of 350 women received epidural analgesia, and 446 received parenteral opioid. The groups were demographically similar, except the average body mass index was higher in the group that did not receive early epidural analgesia. The groups were also similar to a comparison group of 503 women with spontaneous labor who had a 21% operative delivery rate, significantly lower than the rates in the induced labor groups, he noted.
High Folate Hikes Odds of Twinning After IVF
A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.
“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).
“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.
High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.
Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.
Younger maternal age also was associated with an increased rate of twinning.
Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.
This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.
In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.
It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).
Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.
A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.
“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).
“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.
High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.
Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.
Younger maternal age also was associated with an increased rate of twinning.
Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.
This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.
In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.
It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).
Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.
A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.
“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).
“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.
High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.
Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.
Younger maternal age also was associated with an increased rate of twinning.
Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.
This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.
In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.
It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).
Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.
Cesarean May Not Avert Levator Ani Injury
TUCSON, ARIZ. — One woman in four suffers neuropathic injury to the levator ani with her first delivery, according to a novel study that used pre- and postpartum concentric needle electromyographic examinations to study muscle function.
Cesarean sections performed during labor were not protective in the study conducted by Dr. Alison C. Weidner and her associates at Duke University Medical Center and presented at the annual meeting of the Society of Gynecologic Surgeons.
Initial EMG studies were performed on 58 primiparous women in the early third trimester, providing baseline data on muscle function at four separate sites of the levator ani. A quantitative amplitude analysis provided data on muscle function at rest and during moderate and maximum voluntary contractions.
Information was collected on the subjects' labor and delivery patterns, and follow-up examinations were performed 6 weeks and 6 months post partum.
The mean age of the subjects was 29 years, and their mean body mass index was 25 kg/m
Evidence of neuropathic injury was seen in 14 (24%) of 58 subjects at the 6-week examination and 17 (29%) of 58 at the 6-month examination, said Dr. Weidner, chief of the division of urogynecology at the Durham, N.C., institution.
Some women who demonstrated neuropathic injury at 6 weeks were normal by 6 months, while a few who seemed normal at 6 weeks showed evidence of injury at 6 months.
Dr. Weidner said patterns of muscle recruitment in women who exhibited injury only at 6 months suggest that muscle atrophy takes time, and that the full extent of damage was not clear at the 6-week visit.
“My point is that all of the patients who had this pattern were actually suffering levator injury at the time of delivery,” although it could not be measured initially, she explained.
A close look at obstetric variables revealed findings that Dr. Weidner called “striking.”
For example, the 11 women who underwent a C-section during labor suffered injury rates equivalent to those seen in the 36 women who had spontaneous vaginal deliveries and nearly as high as the 8 who had operative vaginal deliveries.
Only the three women who had elective C-sections seemed to be spared significant levels of injury, with just one woman showing injury at one of the four levator ani sites measured at 6 months post partum.
That C-section was not protective in the context of labor surprised Dr. Weidner, since only 2 of those 11 patients progressed far enough in labor to push.
Another interesting finding was the role of a prolonged second stage of labor in women who received epidural anesthesia, which has historically been assumed to lead to greater injury to the pelvic floor. In fact, a shorter duration of epidural analgesia during labor and operative vaginal delivery were independently associated with a higher rate of injury in a logistic regression analysis.
A formal discussant of Dr. Weidner's paper, Dr. Michael Aronson of the University of Massachusetts, Worcester, said the study constituted “a very important contribution to the literature” that may shed light on potentially modifiable mechanisms of injury during labor and delivery.
TUCSON, ARIZ. — One woman in four suffers neuropathic injury to the levator ani with her first delivery, according to a novel study that used pre- and postpartum concentric needle electromyographic examinations to study muscle function.
Cesarean sections performed during labor were not protective in the study conducted by Dr. Alison C. Weidner and her associates at Duke University Medical Center and presented at the annual meeting of the Society of Gynecologic Surgeons.
Initial EMG studies were performed on 58 primiparous women in the early third trimester, providing baseline data on muscle function at four separate sites of the levator ani. A quantitative amplitude analysis provided data on muscle function at rest and during moderate and maximum voluntary contractions.
Information was collected on the subjects' labor and delivery patterns, and follow-up examinations were performed 6 weeks and 6 months post partum.
The mean age of the subjects was 29 years, and their mean body mass index was 25 kg/m
Evidence of neuropathic injury was seen in 14 (24%) of 58 subjects at the 6-week examination and 17 (29%) of 58 at the 6-month examination, said Dr. Weidner, chief of the division of urogynecology at the Durham, N.C., institution.
Some women who demonstrated neuropathic injury at 6 weeks were normal by 6 months, while a few who seemed normal at 6 weeks showed evidence of injury at 6 months.
Dr. Weidner said patterns of muscle recruitment in women who exhibited injury only at 6 months suggest that muscle atrophy takes time, and that the full extent of damage was not clear at the 6-week visit.
“My point is that all of the patients who had this pattern were actually suffering levator injury at the time of delivery,” although it could not be measured initially, she explained.
A close look at obstetric variables revealed findings that Dr. Weidner called “striking.”
For example, the 11 women who underwent a C-section during labor suffered injury rates equivalent to those seen in the 36 women who had spontaneous vaginal deliveries and nearly as high as the 8 who had operative vaginal deliveries.
Only the three women who had elective C-sections seemed to be spared significant levels of injury, with just one woman showing injury at one of the four levator ani sites measured at 6 months post partum.
That C-section was not protective in the context of labor surprised Dr. Weidner, since only 2 of those 11 patients progressed far enough in labor to push.
Another interesting finding was the role of a prolonged second stage of labor in women who received epidural anesthesia, which has historically been assumed to lead to greater injury to the pelvic floor. In fact, a shorter duration of epidural analgesia during labor and operative vaginal delivery were independently associated with a higher rate of injury in a logistic regression analysis.
A formal discussant of Dr. Weidner's paper, Dr. Michael Aronson of the University of Massachusetts, Worcester, said the study constituted “a very important contribution to the literature” that may shed light on potentially modifiable mechanisms of injury during labor and delivery.
TUCSON, ARIZ. — One woman in four suffers neuropathic injury to the levator ani with her first delivery, according to a novel study that used pre- and postpartum concentric needle electromyographic examinations to study muscle function.
Cesarean sections performed during labor were not protective in the study conducted by Dr. Alison C. Weidner and her associates at Duke University Medical Center and presented at the annual meeting of the Society of Gynecologic Surgeons.
Initial EMG studies were performed on 58 primiparous women in the early third trimester, providing baseline data on muscle function at four separate sites of the levator ani. A quantitative amplitude analysis provided data on muscle function at rest and during moderate and maximum voluntary contractions.
Information was collected on the subjects' labor and delivery patterns, and follow-up examinations were performed 6 weeks and 6 months post partum.
The mean age of the subjects was 29 years, and their mean body mass index was 25 kg/m
Evidence of neuropathic injury was seen in 14 (24%) of 58 subjects at the 6-week examination and 17 (29%) of 58 at the 6-month examination, said Dr. Weidner, chief of the division of urogynecology at the Durham, N.C., institution.
Some women who demonstrated neuropathic injury at 6 weeks were normal by 6 months, while a few who seemed normal at 6 weeks showed evidence of injury at 6 months.
Dr. Weidner said patterns of muscle recruitment in women who exhibited injury only at 6 months suggest that muscle atrophy takes time, and that the full extent of damage was not clear at the 6-week visit.
“My point is that all of the patients who had this pattern were actually suffering levator injury at the time of delivery,” although it could not be measured initially, she explained.
A close look at obstetric variables revealed findings that Dr. Weidner called “striking.”
For example, the 11 women who underwent a C-section during labor suffered injury rates equivalent to those seen in the 36 women who had spontaneous vaginal deliveries and nearly as high as the 8 who had operative vaginal deliveries.
Only the three women who had elective C-sections seemed to be spared significant levels of injury, with just one woman showing injury at one of the four levator ani sites measured at 6 months post partum.
That C-section was not protective in the context of labor surprised Dr. Weidner, since only 2 of those 11 patients progressed far enough in labor to push.
Another interesting finding was the role of a prolonged second stage of labor in women who received epidural anesthesia, which has historically been assumed to lead to greater injury to the pelvic floor. In fact, a shorter duration of epidural analgesia during labor and operative vaginal delivery were independently associated with a higher rate of injury in a logistic regression analysis.
A formal discussant of Dr. Weidner's paper, Dr. Michael Aronson of the University of Massachusetts, Worcester, said the study constituted “a very important contribution to the literature” that may shed light on potentially modifiable mechanisms of injury during labor and delivery.
Sphincter Tear Rate Falling in Vaginal Births
TUCSON, ARIZ. — The rate of anal sphincter laceration during vaginal delivery has declined sharply in recent years, paralleling modifications in obstetric practice, a University of Southern California study revealed.
Anal sphincter laceration occurred in 11.2% of vaginal deliveries at the colossal Los Angeles County/USC Medical Center in 1996, compared with 7.9% in 2004, with about a 6% reduction in risk every year after 1996, reported Dr. Steven Minaglia at the annual meeting of the Society of Gynecologic Surgeons.
“Changes in obstetric practice, such as the increase in cesarean section and the decrease in operative delivery and episiotomy, may have contributed to the dramatic reduction in sphincter laceration,” Dr. Minaglia said.
During the time period studied, episiotomies declined from 9% to 8% of vaginal deliveries, vacuum deliveries from 5.1% to 2.9%, and forceps deliveries from 1.7% to 0%. “Of note, the C-section rate went from 18.2% to 32.3%,” he said.
The retrospective study assessed characteristics in 1,703 patients who had an anal sphincter laceration and 14,964 who did not have such an injury, for a total of 16,667 singleton vaginal deliveries at greater than 20 weeks of gestation. Younger age, lower parity, and higher birth weight all were associated with a higher likelihood of an anal sphincter laceration.
Other important risk factors independently associated with a laceration included vacuum delivery (odds ratio 3.19), forceps delivery (OR 2.79), episiotomy (OR 1.36), shoulder dystocia (OR 2.03), and gestational age (OR 1.03, about a 4% increased risk for each week of gestation).
Dr. Minaglia, of the division of female pelvic medicine and reconstructive surgery, encouraged a further minimization of modifiable risk factors such as episiotomy and operative delivery to minimize long-term harm associated with sphincter laceration.
A second study presented at the meeting found similar risk factors at the University of New Mexico Hospital in Albuquerque, where episiotomy and operative vaginal delivery rates are 5%–25% lower than national rates.
The case-control study matched 350 women who sustained a third- or fourth-degree anal sphincter laceration to 716 women matched by gestational age and chronologic time of delivery who did not have a laceration.
The risk of an anal sphincter laceration increased with vacuum extraction (OR 5.96), forceps extraction (OR 11.05), and episiotomy (OR 2.34,); as well as maternal age (OR 1.09 per year); and infant weight (OR 1.09 per 100 g).
As in the USC study, multiparity was protective, reported Dr. Alana Williams and associates in a poster presentation.
TUCSON, ARIZ. — The rate of anal sphincter laceration during vaginal delivery has declined sharply in recent years, paralleling modifications in obstetric practice, a University of Southern California study revealed.
Anal sphincter laceration occurred in 11.2% of vaginal deliveries at the colossal Los Angeles County/USC Medical Center in 1996, compared with 7.9% in 2004, with about a 6% reduction in risk every year after 1996, reported Dr. Steven Minaglia at the annual meeting of the Society of Gynecologic Surgeons.
“Changes in obstetric practice, such as the increase in cesarean section and the decrease in operative delivery and episiotomy, may have contributed to the dramatic reduction in sphincter laceration,” Dr. Minaglia said.
During the time period studied, episiotomies declined from 9% to 8% of vaginal deliveries, vacuum deliveries from 5.1% to 2.9%, and forceps deliveries from 1.7% to 0%. “Of note, the C-section rate went from 18.2% to 32.3%,” he said.
The retrospective study assessed characteristics in 1,703 patients who had an anal sphincter laceration and 14,964 who did not have such an injury, for a total of 16,667 singleton vaginal deliveries at greater than 20 weeks of gestation. Younger age, lower parity, and higher birth weight all were associated with a higher likelihood of an anal sphincter laceration.
Other important risk factors independently associated with a laceration included vacuum delivery (odds ratio 3.19), forceps delivery (OR 2.79), episiotomy (OR 1.36), shoulder dystocia (OR 2.03), and gestational age (OR 1.03, about a 4% increased risk for each week of gestation).
Dr. Minaglia, of the division of female pelvic medicine and reconstructive surgery, encouraged a further minimization of modifiable risk factors such as episiotomy and operative delivery to minimize long-term harm associated with sphincter laceration.
A second study presented at the meeting found similar risk factors at the University of New Mexico Hospital in Albuquerque, where episiotomy and operative vaginal delivery rates are 5%–25% lower than national rates.
The case-control study matched 350 women who sustained a third- or fourth-degree anal sphincter laceration to 716 women matched by gestational age and chronologic time of delivery who did not have a laceration.
The risk of an anal sphincter laceration increased with vacuum extraction (OR 5.96), forceps extraction (OR 11.05), and episiotomy (OR 2.34,); as well as maternal age (OR 1.09 per year); and infant weight (OR 1.09 per 100 g).
As in the USC study, multiparity was protective, reported Dr. Alana Williams and associates in a poster presentation.
TUCSON, ARIZ. — The rate of anal sphincter laceration during vaginal delivery has declined sharply in recent years, paralleling modifications in obstetric practice, a University of Southern California study revealed.
Anal sphincter laceration occurred in 11.2% of vaginal deliveries at the colossal Los Angeles County/USC Medical Center in 1996, compared with 7.9% in 2004, with about a 6% reduction in risk every year after 1996, reported Dr. Steven Minaglia at the annual meeting of the Society of Gynecologic Surgeons.
“Changes in obstetric practice, such as the increase in cesarean section and the decrease in operative delivery and episiotomy, may have contributed to the dramatic reduction in sphincter laceration,” Dr. Minaglia said.
During the time period studied, episiotomies declined from 9% to 8% of vaginal deliveries, vacuum deliveries from 5.1% to 2.9%, and forceps deliveries from 1.7% to 0%. “Of note, the C-section rate went from 18.2% to 32.3%,” he said.
The retrospective study assessed characteristics in 1,703 patients who had an anal sphincter laceration and 14,964 who did not have such an injury, for a total of 16,667 singleton vaginal deliveries at greater than 20 weeks of gestation. Younger age, lower parity, and higher birth weight all were associated with a higher likelihood of an anal sphincter laceration.
Other important risk factors independently associated with a laceration included vacuum delivery (odds ratio 3.19), forceps delivery (OR 2.79), episiotomy (OR 1.36), shoulder dystocia (OR 2.03), and gestational age (OR 1.03, about a 4% increased risk for each week of gestation).
Dr. Minaglia, of the division of female pelvic medicine and reconstructive surgery, encouraged a further minimization of modifiable risk factors such as episiotomy and operative delivery to minimize long-term harm associated with sphincter laceration.
A second study presented at the meeting found similar risk factors at the University of New Mexico Hospital in Albuquerque, where episiotomy and operative vaginal delivery rates are 5%–25% lower than national rates.
The case-control study matched 350 women who sustained a third- or fourth-degree anal sphincter laceration to 716 women matched by gestational age and chronologic time of delivery who did not have a laceration.
The risk of an anal sphincter laceration increased with vacuum extraction (OR 5.96), forceps extraction (OR 11.05), and episiotomy (OR 2.34,); as well as maternal age (OR 1.09 per year); and infant weight (OR 1.09 per 100 g).
As in the USC study, multiparity was protective, reported Dr. Alana Williams and associates in a poster presentation.
With Help, Diabetic Mothers Can Breast-Feed
Offering women with type 1 diabetes support to breast-feed their newborns led to similar rates of breast-feeding among diabetic and nondiabetic women at 4 months after delivery despite high rates of morbidity in infants born to diabetic mothers, a Danish study found.
Exclusive breast-feeding is recommended for the first 4–6 months of life for all infants. Some previous reports have suggested that diabetic women may resort to early weaning because of fluctuating maternal blood glucose values and frequent episodes of symptomatic hypoglycemia.
In the current study, 86% of 102 diabetic mothers were breast-feeding 5 days after delivery, despite anticipated difficulties in initiating breast-feeding because of infant morbidities, reported Edna Stage, R.N., and her associates.
It is the largest prospective study of nursing mothers with type 1 diabetes.
Four months after delivery, 54% of the diabetic mothers were exclusively breast-feeding, compared with 50% of 9,654 randomly selected Danish women interviewed in a separate study on lactation. Among the diabetic mothers, 14% were partly breast-feeding 4 months after delivery and 32% were not breast-feeding, compared with 26% and 24%, respectively, of the control group of mothers. Neonatal morbidity occurred in 25 (45%) of 55 infants who were still exclusively breast-feeding at 4 months and in 30 (73%) of 47 infants who were not exclusively breast-feeding by 4 months, said Ms. Stage of Copenhagen University Hospital and her associates (Diabetes Care 2006;29:771–4).
Neonatal morbidity was defined as a need for continuous positive airway pressure for more than 1 hour, antibiotic treatment, IV glucose, or phototherapy.
Previous experience breast-feeding increased sixfold the likelihood of long-term exclusive breast-feeding among the diabetic mothers, and higher educational levels (more than 10 years of school) increased the likelihood sevenfold, the investigators said.
Trends toward less success in long-term breast-feeding among diabetic mothers who smoked, or who had a nonvaginal delivery, did not hold up as independent predictors after multiple logistic regression analysis. The small number of smokers in the study may have reduced the odds of finding an association between smoking and lactation, an association identified in previous studies.
The investigators studied all women with type 1 diabetes delivering consecutively at the hospital from May 2001 to February 2003. The results did not include two women who did not want to participate, two who were not invited to participate because of an investigator's vacation, and one woman who could not be identified 4 months after delivery.
During pregnancy, the diabetic women were offered prenatal classes with information on breast-feeding and a visit to the neonatal intensive care unit. In addition, a diabetes nurse specialist offered individual counseling on the benefits of breast feeding and described the possibility of using a breast pump if the infant's ability to suck was impaired.
Neonates stayed with their mothers for the first 2 hours of life, and 47% first nursed during this time. They then were admitted to the neonatal intensive care unit for 24 hours, where they received artificial feedings of mother's milk or low-immunogen formula milk, mainly by nasogastric tube, every 3 hours to prevent hypoglycemia. During that time, they also averaged two breast-feedings. Severe hypoglycemia in 30% of infants was treated with IV glucose.
The rate of breast-feeding during this early period might have been improved if the mothers had been allowed to sleep near the infants in the neonatal ICU, the investigators suggested.
“We believe that the [prenatal] classes and individual counseling about benefits and difficulties in initiating breast-feeding offered to the women were valuable,” Ms. Stage and her associates wrote.
Offering women with type 1 diabetes support to breast-feed their newborns led to similar rates of breast-feeding among diabetic and nondiabetic women at 4 months after delivery despite high rates of morbidity in infants born to diabetic mothers, a Danish study found.
Exclusive breast-feeding is recommended for the first 4–6 months of life for all infants. Some previous reports have suggested that diabetic women may resort to early weaning because of fluctuating maternal blood glucose values and frequent episodes of symptomatic hypoglycemia.
In the current study, 86% of 102 diabetic mothers were breast-feeding 5 days after delivery, despite anticipated difficulties in initiating breast-feeding because of infant morbidities, reported Edna Stage, R.N., and her associates.
It is the largest prospective study of nursing mothers with type 1 diabetes.
Four months after delivery, 54% of the diabetic mothers were exclusively breast-feeding, compared with 50% of 9,654 randomly selected Danish women interviewed in a separate study on lactation. Among the diabetic mothers, 14% were partly breast-feeding 4 months after delivery and 32% were not breast-feeding, compared with 26% and 24%, respectively, of the control group of mothers. Neonatal morbidity occurred in 25 (45%) of 55 infants who were still exclusively breast-feeding at 4 months and in 30 (73%) of 47 infants who were not exclusively breast-feeding by 4 months, said Ms. Stage of Copenhagen University Hospital and her associates (Diabetes Care 2006;29:771–4).
Neonatal morbidity was defined as a need for continuous positive airway pressure for more than 1 hour, antibiotic treatment, IV glucose, or phototherapy.
Previous experience breast-feeding increased sixfold the likelihood of long-term exclusive breast-feeding among the diabetic mothers, and higher educational levels (more than 10 years of school) increased the likelihood sevenfold, the investigators said.
Trends toward less success in long-term breast-feeding among diabetic mothers who smoked, or who had a nonvaginal delivery, did not hold up as independent predictors after multiple logistic regression analysis. The small number of smokers in the study may have reduced the odds of finding an association between smoking and lactation, an association identified in previous studies.
The investigators studied all women with type 1 diabetes delivering consecutively at the hospital from May 2001 to February 2003. The results did not include two women who did not want to participate, two who were not invited to participate because of an investigator's vacation, and one woman who could not be identified 4 months after delivery.
During pregnancy, the diabetic women were offered prenatal classes with information on breast-feeding and a visit to the neonatal intensive care unit. In addition, a diabetes nurse specialist offered individual counseling on the benefits of breast feeding and described the possibility of using a breast pump if the infant's ability to suck was impaired.
Neonates stayed with their mothers for the first 2 hours of life, and 47% first nursed during this time. They then were admitted to the neonatal intensive care unit for 24 hours, where they received artificial feedings of mother's milk or low-immunogen formula milk, mainly by nasogastric tube, every 3 hours to prevent hypoglycemia. During that time, they also averaged two breast-feedings. Severe hypoglycemia in 30% of infants was treated with IV glucose.
The rate of breast-feeding during this early period might have been improved if the mothers had been allowed to sleep near the infants in the neonatal ICU, the investigators suggested.
“We believe that the [prenatal] classes and individual counseling about benefits and difficulties in initiating breast-feeding offered to the women were valuable,” Ms. Stage and her associates wrote.
Offering women with type 1 diabetes support to breast-feed their newborns led to similar rates of breast-feeding among diabetic and nondiabetic women at 4 months after delivery despite high rates of morbidity in infants born to diabetic mothers, a Danish study found.
Exclusive breast-feeding is recommended for the first 4–6 months of life for all infants. Some previous reports have suggested that diabetic women may resort to early weaning because of fluctuating maternal blood glucose values and frequent episodes of symptomatic hypoglycemia.
In the current study, 86% of 102 diabetic mothers were breast-feeding 5 days after delivery, despite anticipated difficulties in initiating breast-feeding because of infant morbidities, reported Edna Stage, R.N., and her associates.
It is the largest prospective study of nursing mothers with type 1 diabetes.
Four months after delivery, 54% of the diabetic mothers were exclusively breast-feeding, compared with 50% of 9,654 randomly selected Danish women interviewed in a separate study on lactation. Among the diabetic mothers, 14% were partly breast-feeding 4 months after delivery and 32% were not breast-feeding, compared with 26% and 24%, respectively, of the control group of mothers. Neonatal morbidity occurred in 25 (45%) of 55 infants who were still exclusively breast-feeding at 4 months and in 30 (73%) of 47 infants who were not exclusively breast-feeding by 4 months, said Ms. Stage of Copenhagen University Hospital and her associates (Diabetes Care 2006;29:771–4).
Neonatal morbidity was defined as a need for continuous positive airway pressure for more than 1 hour, antibiotic treatment, IV glucose, or phototherapy.
Previous experience breast-feeding increased sixfold the likelihood of long-term exclusive breast-feeding among the diabetic mothers, and higher educational levels (more than 10 years of school) increased the likelihood sevenfold, the investigators said.
Trends toward less success in long-term breast-feeding among diabetic mothers who smoked, or who had a nonvaginal delivery, did not hold up as independent predictors after multiple logistic regression analysis. The small number of smokers in the study may have reduced the odds of finding an association between smoking and lactation, an association identified in previous studies.
The investigators studied all women with type 1 diabetes delivering consecutively at the hospital from May 2001 to February 2003. The results did not include two women who did not want to participate, two who were not invited to participate because of an investigator's vacation, and one woman who could not be identified 4 months after delivery.
During pregnancy, the diabetic women were offered prenatal classes with information on breast-feeding and a visit to the neonatal intensive care unit. In addition, a diabetes nurse specialist offered individual counseling on the benefits of breast feeding and described the possibility of using a breast pump if the infant's ability to suck was impaired.
Neonates stayed with their mothers for the first 2 hours of life, and 47% first nursed during this time. They then were admitted to the neonatal intensive care unit for 24 hours, where they received artificial feedings of mother's milk or low-immunogen formula milk, mainly by nasogastric tube, every 3 hours to prevent hypoglycemia. During that time, they also averaged two breast-feedings. Severe hypoglycemia in 30% of infants was treated with IV glucose.
The rate of breast-feeding during this early period might have been improved if the mothers had been allowed to sleep near the infants in the neonatal ICU, the investigators suggested.
“We believe that the [prenatal] classes and individual counseling about benefits and difficulties in initiating breast-feeding offered to the women were valuable,” Ms. Stage and her associates wrote.
Periodontitis + High CRP Raise Preeclampsia Risk : The presence of both factors in pregnant women more than doubled the risk of either factor by itself.
TORONTO — A combination of maternal periodontal disease and high levels of maternal C-reactive protein is associated with a significantly increased risk of preeclampsia, compared with either risk factor alone, according to a new analysis of the Oral Conditions and Pregnancy Study.
“There seems to be some type of synergy when both are combined,” said Dr. Michael S. Ruma, who presented the findings at the annual meeting of the Society for Gynecologic Investigation.
A secondary analysis of 775 healthy pregnant women who had oral examinations and C-reactive protein (CRP) levels measured at enrollment (less than 26 weeks' gestation) found that preeclampsia was more common in those with high CRP levels alone (OR 2.6), and those with moderate to severe periodontal disease (PD) alone (OR 2.0)—but a combination of high CRP levels and moderate to severe PD increased the odds ratio to 7.0.
A total of 31 women (4%) developed preeclampsia in the cohort. The rate of preeclampsia was greater among women with a high CRP level (above the 75th percentile) than for women with a low CRP level (at or below the 75th percentile): 7% and 3%, respectively. The addition of mild PD to the elevated CRP level significantly increased the risk of preeclampsia from an odds ratio of 2.6 to 6.0 and moderate to severe PD increased it further (OR 7.0).
“Maternal systemic inflammation may be in the causal pathway between periodontal disease and the development of preeclampsia,” said Dr. Ruma of the University of North Carolina at Chapel Hill. However, he said, future research is required to further understand this phenomenon. “Both periodontitis and preeclampsia are multifactorial, but the implication is that inflammation in the mother is leading to systemic disease,” he said in an interview.
A separate study presented at the meeting suggests that such maternal inflammation may also be transferred to the fetus—particularly in the setting of maternal smoking. In a study of 277 women, Dr. John P. Newnham of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, Western Australia, and his colleagues found that 12% of women with PD had babies who were small for gestational age (SGA), compared with 2% of women who had healthy gums (“Gum Disease Again Tied to Pregnancy Outcomes,” OB.GYN. NEWS, June 1, 2005, p. 28). Further analysis of this study, which was presented at the meeting, found this effect is significantly increased (25%) in women who smoke. Additionally, the researchers found that in smokers, both with and without PD, inflammatory markers (CRP and tumor necrosis factor-β) were significantly elevated in umbilical cord blood, indicating an inflammatory response in the fetus.
“The thing I found absolutely fascinating was this marked inflammation in the fetus at birth as a result of the woman smoking in pregnancy—and PD added further to it,” Dr. Newnham said in an interview. “Smoking not only increases the risk of PD, which everyone has known for a long time, but smoking increased the inflammatory markers in the cord blood and PD added to this.”
Although the absence of PD is associated with better obstetric outcomes, it is not known whether treating PD during pregnancy is beneficial or harmful, said Dr. Newnham. “We are in equipoise. We know inflamed periodontal tissue can release cytokines and prostaglandins,” he said, leading some to hypothesize that the treatment of PD could temporarily increase maternal systemic inflammation.
TORONTO — A combination of maternal periodontal disease and high levels of maternal C-reactive protein is associated with a significantly increased risk of preeclampsia, compared with either risk factor alone, according to a new analysis of the Oral Conditions and Pregnancy Study.
“There seems to be some type of synergy when both are combined,” said Dr. Michael S. Ruma, who presented the findings at the annual meeting of the Society for Gynecologic Investigation.
A secondary analysis of 775 healthy pregnant women who had oral examinations and C-reactive protein (CRP) levels measured at enrollment (less than 26 weeks' gestation) found that preeclampsia was more common in those with high CRP levels alone (OR 2.6), and those with moderate to severe periodontal disease (PD) alone (OR 2.0)—but a combination of high CRP levels and moderate to severe PD increased the odds ratio to 7.0.
A total of 31 women (4%) developed preeclampsia in the cohort. The rate of preeclampsia was greater among women with a high CRP level (above the 75th percentile) than for women with a low CRP level (at or below the 75th percentile): 7% and 3%, respectively. The addition of mild PD to the elevated CRP level significantly increased the risk of preeclampsia from an odds ratio of 2.6 to 6.0 and moderate to severe PD increased it further (OR 7.0).
“Maternal systemic inflammation may be in the causal pathway between periodontal disease and the development of preeclampsia,” said Dr. Ruma of the University of North Carolina at Chapel Hill. However, he said, future research is required to further understand this phenomenon. “Both periodontitis and preeclampsia are multifactorial, but the implication is that inflammation in the mother is leading to systemic disease,” he said in an interview.
A separate study presented at the meeting suggests that such maternal inflammation may also be transferred to the fetus—particularly in the setting of maternal smoking. In a study of 277 women, Dr. John P. Newnham of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, Western Australia, and his colleagues found that 12% of women with PD had babies who were small for gestational age (SGA), compared with 2% of women who had healthy gums (“Gum Disease Again Tied to Pregnancy Outcomes,” OB.GYN. NEWS, June 1, 2005, p. 28). Further analysis of this study, which was presented at the meeting, found this effect is significantly increased (25%) in women who smoke. Additionally, the researchers found that in smokers, both with and without PD, inflammatory markers (CRP and tumor necrosis factor-β) were significantly elevated in umbilical cord blood, indicating an inflammatory response in the fetus.
“The thing I found absolutely fascinating was this marked inflammation in the fetus at birth as a result of the woman smoking in pregnancy—and PD added further to it,” Dr. Newnham said in an interview. “Smoking not only increases the risk of PD, which everyone has known for a long time, but smoking increased the inflammatory markers in the cord blood and PD added to this.”
Although the absence of PD is associated with better obstetric outcomes, it is not known whether treating PD during pregnancy is beneficial or harmful, said Dr. Newnham. “We are in equipoise. We know inflamed periodontal tissue can release cytokines and prostaglandins,” he said, leading some to hypothesize that the treatment of PD could temporarily increase maternal systemic inflammation.
TORONTO — A combination of maternal periodontal disease and high levels of maternal C-reactive protein is associated with a significantly increased risk of preeclampsia, compared with either risk factor alone, according to a new analysis of the Oral Conditions and Pregnancy Study.
“There seems to be some type of synergy when both are combined,” said Dr. Michael S. Ruma, who presented the findings at the annual meeting of the Society for Gynecologic Investigation.
A secondary analysis of 775 healthy pregnant women who had oral examinations and C-reactive protein (CRP) levels measured at enrollment (less than 26 weeks' gestation) found that preeclampsia was more common in those with high CRP levels alone (OR 2.6), and those with moderate to severe periodontal disease (PD) alone (OR 2.0)—but a combination of high CRP levels and moderate to severe PD increased the odds ratio to 7.0.
A total of 31 women (4%) developed preeclampsia in the cohort. The rate of preeclampsia was greater among women with a high CRP level (above the 75th percentile) than for women with a low CRP level (at or below the 75th percentile): 7% and 3%, respectively. The addition of mild PD to the elevated CRP level significantly increased the risk of preeclampsia from an odds ratio of 2.6 to 6.0 and moderate to severe PD increased it further (OR 7.0).
“Maternal systemic inflammation may be in the causal pathway between periodontal disease and the development of preeclampsia,” said Dr. Ruma of the University of North Carolina at Chapel Hill. However, he said, future research is required to further understand this phenomenon. “Both periodontitis and preeclampsia are multifactorial, but the implication is that inflammation in the mother is leading to systemic disease,” he said in an interview.
A separate study presented at the meeting suggests that such maternal inflammation may also be transferred to the fetus—particularly in the setting of maternal smoking. In a study of 277 women, Dr. John P. Newnham of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, Western Australia, and his colleagues found that 12% of women with PD had babies who were small for gestational age (SGA), compared with 2% of women who had healthy gums (“Gum Disease Again Tied to Pregnancy Outcomes,” OB.GYN. NEWS, June 1, 2005, p. 28). Further analysis of this study, which was presented at the meeting, found this effect is significantly increased (25%) in women who smoke. Additionally, the researchers found that in smokers, both with and without PD, inflammatory markers (CRP and tumor necrosis factor-β) were significantly elevated in umbilical cord blood, indicating an inflammatory response in the fetus.
“The thing I found absolutely fascinating was this marked inflammation in the fetus at birth as a result of the woman smoking in pregnancy—and PD added further to it,” Dr. Newnham said in an interview. “Smoking not only increases the risk of PD, which everyone has known for a long time, but smoking increased the inflammatory markers in the cord blood and PD added to this.”
Although the absence of PD is associated with better obstetric outcomes, it is not known whether treating PD during pregnancy is beneficial or harmful, said Dr. Newnham. “We are in equipoise. We know inflamed periodontal tissue can release cytokines and prostaglandins,” he said, leading some to hypothesize that the treatment of PD could temporarily increase maternal systemic inflammation.
Management of lupus flare
Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.1
If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.
90% of lupus cases are in reproductive-age women
SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).
Counsel the patient, gauge the risks
The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).2
As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study3 proposed the acronym PATH to help identify high-risk patients:
Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension
TABLE 1
Factors that increase the likelihood of a good outcome
|
Disease quiescence is not an infallible sign
One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.
Renal disease and hypertension
Nephritis
Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.4 Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.
Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.
Hypertension
When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.
Diagnosis of antiphospholipid syndrome
Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.
Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.
Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.
Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.
Does pregnancy bring on lupus flare?
Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.5 Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.
Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.6 This variability is due in part to differences in disease activity of the patients when they entered the studies.
One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.
The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs
Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years
Potential adverse outcomes
Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.
Diagnosis and initial management
Preventive treatments
Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.
Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.
The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.
The differential diagnosis
It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.
TABLE 2
Clinical features of preeclampsia vs lupus flare*
| FEATURE | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| Hypertension | Present | Present |
| Proteinuria | Present | Present |
| Edema | Present | Present |
| Malar rash | Absent | Present |
| Arthritis | Absent | Present |
| Photophobia | Absent | Present |
| Oral ulcers | Absent | Present |
| Serositis | Absent | Present |
| Seizures | Present | Present |
| *Denoting presence or absence does not suggest absolute presence or absence, but rather, the likely compatibility with the diagnosis. | ||
Is it lupus flare or preeclampsia?
The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.
A few easy tests can help (TABLE 3), but the most important are:
- positive ANA screen,
- active urinary sediment,
- hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
- high titers of anti-ds-DNA.
TABLE 3
Tests that help tell lupus flare from preeclampsia
| TEST | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| PTT | Usually normal | May be abnormal |
| Platelet count | Normal or reduced | Normal or reduced |
| Urinalysis | Normal sediment | Active sediment |
| ANA | Usually negative | Usually positive |
| Anti-ds-DNA | Usually negative | Usually positive |
| AST | May be abnormal | May be abnormal |
| ALT | May be abnormal | May be abnormal |
| Lupus anticoagulant | Negative | May be positive |
| Hemolysis | May be present | Usually absent |
| Complement levels | Usually normal | Usually reduced |
| WBC | Increased | Decreased |
| SFlt-1* | Increased | Normal |
| *Investigational and not widely available for clinical use. | ||
Aggressive drug therapy is imperative
Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.
The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.
Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.
The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.
Even a healthy lupus patient who fulfills all the accepted criteria for a safe pregnancy can take a disastrous turn
A 28-year-old G0 with SLE since age 11 presented for preconception consultation. She was on no medications, with normal blood pressure and no evidence of disease activity for more than 2 years. Physical examination and laboratory findings were normal, including serum creatinine 0.7 mg/dL; less than 30 mg protein in a 24-hour urine collection; creatinine clearance 110 mL/min; and lupus anticoagulant, anti-cardiolipin antibodies, anti-Ro, and anti-La were negative.
Green light
One year later, she returned for follow-up and to inform her obstetrician that she was getting married and wished to conceive. She had no SLE activity since her last visit. Repeat laboratory studies were unchanged. She was given medical clearance to attempt conception, and told that she met all the criteria that would make her a suitable candidate for pregnancy.
7 weeks All findings normal
Three months later, a single intrauterine gestation of approximately 7 weeks was confirmed. Laboratory studies and physical examination were normal, and she reported no SLE-related symptoms.
11 weeks Lupus flare
Four weeks later, at her next prenatal visit, a 3+ proteinuria and blood pressure of 140/90 mm Hg were noted. Her rheumatologist made a diagnosis of lupus flare with probable nephritis. Oral prednisone was begun, with rapid taper. Clinical response was good. She remained on prednisone, 10 mg/day.
14 weeks Recurrence
A recurrence of lupus flare with probable nephritis was diagnosed and her oral prednisone dose was increased. One week later the patient seemed to worsen. She was admitted for steroid pulse therapy. Initially, she improved, but then continued to worsen.
16 weeks Cyclophosphamide therapy
After counseling, she was begun on cyclophosphamide, but her condition continued to deteriorate. Renal function worsened and the patient, now with nephrotic proteinuria, was profoundly edematous and hypoalbuminemic with a rising serum creatinine.
18 weeks Dilatation and evacuation
Ultrasound evaluation of the fetus revealed evidence of early growth restriction. After much discussion, the patient underwent dilatation and evacuation.
Cerebral infarct and anticoagulation
Her lupus flare did not abate. More aggressive medical therapy ensued. Transfer to the intensive care unit with intubation was necessary. She subsequently had an ischemic cerebral infarct requiring anticoagulation.
The next 7 weeks Lupus remission
Over the next several weeks, the patient improved. She had some residual sequelae from the cerebral infarct, but was doing well, with her lupus flare in remission. She was responding well to rehabilitation therapy.
Fatal cerebrovascular accident
One day before anticipated discharge to home, she had a massive cerebrovascular accident and died.
A vivid reminder
This case vividly illustrates the difficulties we must be prepared to manage in lupus pregnancies.
The foremost concern is that even the best candidates for pregnancy can have unfavorable outcomes when this highly unpredictable disease flares.
These women can become severely ill. Ideally, their care should be provided at a facility where expertise in maternal-fetal medicine, anesthesiology, rheumatology, neonatology, and critical care medicine can be readily mobilized to deal with the occasionally catastrophic complications. Even with all of this expertise available, maternal and fetal mortality will not be preventable in all cases.
Pregnancy termination does not necessarily result in amelioration of the lupus flare or its sequelae.
Patients with SLE must be informed of the unpredictability of this disease during pregnancy. The entire family, where appropriate and desired, should be included in the information-sharing process.
A team approach, both pre- and postconception, will help to maximize (but not guarantee) the likelihood of a successful outcome for mother and child.
Refractory flares: Focus on damage control
In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.
Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.
The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.8
Early delivery: When and how
In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.
Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.
Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.
Cesarean section may be reserved for accepted obstetric indications.
Cytotoxic therapy
Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.
Cyclophosphamide
This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.9 Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.
Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.
Azathioprine
An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.
The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.
Methotrexate
Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.
Thrombosis requires swift anticoagulation
In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.10)
1. Repke JT. Hypertensive disorders of pregnancy: differentiating preeclampsia from active systemic lupus erythematosus. J Reprod Med. 1998;43:350-354.
2. Petri M. Hopkins Lupus Pregnancy Center: 1987–1996. Rheum Dis Clin North Am. 1997;23:1-13.
3. Clowse MEB, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol. 2006;107:293-299.
4. Moroni G, Quaglini S, Banfi G, et al. Pregnancy in lupus nephritis. Am J Kid Dis. 2002;40:713-720.
5. Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy: the Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 1991;34:1538-1545.
6. Khamashta MA, Ruiz-Irastorza G, Hughes GRV. Systemic lupus erythematosus flares during pregnancy. Rheum Dis Clin North Am. 1997;23:15-30.
7. Mascola MA, Repke JT. Obstetric management of the high risk lupus pregnancy. Rheum Dis Clin North Am. 1997;23:119-132.
8. Williams WW, Ecker JL, Thadhani RI, Rahemtullah A. Case 38-2005: a 29-year-old pregnant woman with the nephritic syndrome and hypertension. N Engl J Med. 2005;353:2590-2600.
9. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121-2131.
10. Hahn BH. Systemic lupus erythematosus. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:1960-1967.
The author reports no financial relationships relevant to this article.
Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.1
If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.
90% of lupus cases are in reproductive-age women
SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).
Counsel the patient, gauge the risks
The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).2
As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study3 proposed the acronym PATH to help identify high-risk patients:
Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension
TABLE 1
Factors that increase the likelihood of a good outcome
|
Disease quiescence is not an infallible sign
One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.
Renal disease and hypertension
Nephritis
Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.4 Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.
Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.
Hypertension
When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.
Diagnosis of antiphospholipid syndrome
Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.
Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.
Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.
Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.
Does pregnancy bring on lupus flare?
Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.5 Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.
Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.6 This variability is due in part to differences in disease activity of the patients when they entered the studies.
One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.
The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs
Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years
Potential adverse outcomes
Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.
Diagnosis and initial management
Preventive treatments
Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.
Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.
The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.
The differential diagnosis
It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.
TABLE 2
Clinical features of preeclampsia vs lupus flare*
| FEATURE | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| Hypertension | Present | Present |
| Proteinuria | Present | Present |
| Edema | Present | Present |
| Malar rash | Absent | Present |
| Arthritis | Absent | Present |
| Photophobia | Absent | Present |
| Oral ulcers | Absent | Present |
| Serositis | Absent | Present |
| Seizures | Present | Present |
| *Denoting presence or absence does not suggest absolute presence or absence, but rather, the likely compatibility with the diagnosis. | ||
Is it lupus flare or preeclampsia?
The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.
A few easy tests can help (TABLE 3), but the most important are:
- positive ANA screen,
- active urinary sediment,
- hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
- high titers of anti-ds-DNA.
TABLE 3
Tests that help tell lupus flare from preeclampsia
| TEST | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| PTT | Usually normal | May be abnormal |
| Platelet count | Normal or reduced | Normal or reduced |
| Urinalysis | Normal sediment | Active sediment |
| ANA | Usually negative | Usually positive |
| Anti-ds-DNA | Usually negative | Usually positive |
| AST | May be abnormal | May be abnormal |
| ALT | May be abnormal | May be abnormal |
| Lupus anticoagulant | Negative | May be positive |
| Hemolysis | May be present | Usually absent |
| Complement levels | Usually normal | Usually reduced |
| WBC | Increased | Decreased |
| SFlt-1* | Increased | Normal |
| *Investigational and not widely available for clinical use. | ||
Aggressive drug therapy is imperative
Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.
The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.
Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.
The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.
Even a healthy lupus patient who fulfills all the accepted criteria for a safe pregnancy can take a disastrous turn
A 28-year-old G0 with SLE since age 11 presented for preconception consultation. She was on no medications, with normal blood pressure and no evidence of disease activity for more than 2 years. Physical examination and laboratory findings were normal, including serum creatinine 0.7 mg/dL; less than 30 mg protein in a 24-hour urine collection; creatinine clearance 110 mL/min; and lupus anticoagulant, anti-cardiolipin antibodies, anti-Ro, and anti-La were negative.
Green light
One year later, she returned for follow-up and to inform her obstetrician that she was getting married and wished to conceive. She had no SLE activity since her last visit. Repeat laboratory studies were unchanged. She was given medical clearance to attempt conception, and told that she met all the criteria that would make her a suitable candidate for pregnancy.
7 weeks All findings normal
Three months later, a single intrauterine gestation of approximately 7 weeks was confirmed. Laboratory studies and physical examination were normal, and she reported no SLE-related symptoms.
11 weeks Lupus flare
Four weeks later, at her next prenatal visit, a 3+ proteinuria and blood pressure of 140/90 mm Hg were noted. Her rheumatologist made a diagnosis of lupus flare with probable nephritis. Oral prednisone was begun, with rapid taper. Clinical response was good. She remained on prednisone, 10 mg/day.
14 weeks Recurrence
A recurrence of lupus flare with probable nephritis was diagnosed and her oral prednisone dose was increased. One week later the patient seemed to worsen. She was admitted for steroid pulse therapy. Initially, she improved, but then continued to worsen.
16 weeks Cyclophosphamide therapy
After counseling, she was begun on cyclophosphamide, but her condition continued to deteriorate. Renal function worsened and the patient, now with nephrotic proteinuria, was profoundly edematous and hypoalbuminemic with a rising serum creatinine.
18 weeks Dilatation and evacuation
Ultrasound evaluation of the fetus revealed evidence of early growth restriction. After much discussion, the patient underwent dilatation and evacuation.
Cerebral infarct and anticoagulation
Her lupus flare did not abate. More aggressive medical therapy ensued. Transfer to the intensive care unit with intubation was necessary. She subsequently had an ischemic cerebral infarct requiring anticoagulation.
The next 7 weeks Lupus remission
Over the next several weeks, the patient improved. She had some residual sequelae from the cerebral infarct, but was doing well, with her lupus flare in remission. She was responding well to rehabilitation therapy.
Fatal cerebrovascular accident
One day before anticipated discharge to home, she had a massive cerebrovascular accident and died.
A vivid reminder
This case vividly illustrates the difficulties we must be prepared to manage in lupus pregnancies.
The foremost concern is that even the best candidates for pregnancy can have unfavorable outcomes when this highly unpredictable disease flares.
These women can become severely ill. Ideally, their care should be provided at a facility where expertise in maternal-fetal medicine, anesthesiology, rheumatology, neonatology, and critical care medicine can be readily mobilized to deal with the occasionally catastrophic complications. Even with all of this expertise available, maternal and fetal mortality will not be preventable in all cases.
Pregnancy termination does not necessarily result in amelioration of the lupus flare or its sequelae.
Patients with SLE must be informed of the unpredictability of this disease during pregnancy. The entire family, where appropriate and desired, should be included in the information-sharing process.
A team approach, both pre- and postconception, will help to maximize (but not guarantee) the likelihood of a successful outcome for mother and child.
Refractory flares: Focus on damage control
In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.
Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.
The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.8
Early delivery: When and how
In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.
Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.
Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.
Cesarean section may be reserved for accepted obstetric indications.
Cytotoxic therapy
Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.
Cyclophosphamide
This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.9 Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.
Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.
Azathioprine
An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.
The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.
Methotrexate
Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.
Thrombosis requires swift anticoagulation
In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.10)
Still, lupus flare during pregnancy is a medical and obstetric emergency, and a persistent obstetric dilemma. The most difficult dilemma is how to differentiate a lupus flare from preeclampsia, as both may present with worsening blood pressure, proteinuria and deteriorating renal function, and edema.1
If anticipated and handled quickly, most outcomes will be good for mother and fetus, but occasional severe consequences of lupus flare resulting in loss of mother, fetus, or both, are not always avoidable.
90% of lupus cases are in reproductive-age women
SLE is an autoimmune disease that affects virtually all organ systems. Specific clinical and laboratory criteria must be met to establish the diagnosis. About 90% of all cases are in women in the reproductive age range, with an overrepresentation of African Americans. The overall prevalence of lupus is approximately 15 to 50 per 100,000 population (both sexes, all ages).
Counsel the patient, gauge the risks
The most important first step is the preconception visit. While early prenatal care is better than late presentation, the best option is a preconception visit so that the relative risks of pregnancy may be assessed and discussed, and alterations to medication regimens can be made prior to establishment of a pregnancy (TABLE 1).2
As lupus patients are at increased risk for early pregnancy loss, the preconception visit may also allow for identification of risk factors and risk assessment. A recent study3 proposed the acronym PATH to help identify high-risk patients:
Proteinuria
Antiphospholipid syndrome
Thrombocytopenia
Hypertension
TABLE 1
Factors that increase the likelihood of a good outcome
|
Disease quiescence is not an infallible sign
One of the better indicators of a favorable prognosis for pregnancy is disease quiescence for at least 6 months, and preferably more than 12 months, prior to conception. A number of factors go into the definition of “disease quiescence” including blood pressure control, need for immunosuppressive medication, renal function, and overall physician global assessment, to name but a few, and these factors will be briefly reviewed.
Renal disease and hypertension
Nephritis
Patients with SLE not infrequently have hypertension secondary to renal involvement, specifically lupus nephritis. Nephritis is generally the most serious of lupus manifestations, and if not aggressively treated can lead to nephrotic syndrome, edema and end-stage renal disease in more than 50% of patients within 2 to 3 years.4 Patients with this complication, especially in the setting of proliferative glomerulonephritis, have a poorer prognosis for pregnancy.
Accelerated atherosclerotic vascular disease may also affect these patients—in addition to nephritis—and may herald poor placental function and fetal growth.
Hypertension
When there is coexisting hypertension, antihypertensive agents that are safe for use in pregnancy are preferred, such as beta-blockers, calcium channel blockers, and alpha methyldopa. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided during the second and third trimester due to adverse effects on fetal renal function.
Diagnosis of antiphospholipid syndrome
Patients with SLE may have associated antiphospholipid antibodies. Screening tests such as antinuclear antibodies (ANA) and activated partial thromboplastin times (aPTT) are not very reliable and have relatively poor positive predictive value, although in the case of ANA, when the diagnosis of lupus is suspected, repetitive negative ANA titers make SLE unlikely. Anti-double stranded DNA is quite specific to SLE, and elevations in the Anti-ds-DNA titers correlate well with SLE disease activity, and can be helpful in making the diagnosis of a lupus flare.
Other antibodies such as Anti-Ro (SS-A) and Anti-La (SS-B) may be useful for predicting and managing for neonatal lupus syndromes, but are not very useful in maternal management.
Additional tests for anticardiolipin, lupus anticoagulant (Russell viper venom test), and beta-2-glycoprotein are also of use.
Diagnosis of APLS requires positive serologies (at least twice, separated by a minimum of 2 weeks), thrombosis, and/or recurrent early pregnancy loss.
Does pregnancy bring on lupus flare?
Whether or not pregnancy increases the incidence of lupus flare is a continuing controversy, stemming from variable definitions of “flare.” Universally accepted criteria have been lacking in published studies.5 Consensus indicates, however, that lupus flares are more common in pregnancy than in nonpregnant controls.
Some studies suggest that SLE flares are more common in the second and third trimesters, but the data are not clear on this point.6 This variability is due in part to differences in disease activity of the patients when they entered the studies.
One may conclude that for any given patient it is impossible to accurately predict whether she will experience a lupus flare, and if she does, when it will occur, and to what level of severity it will rise.
The mainstay of management: is to aggressively treat the lupus flare before irreparable maternal harm occurs
Nephritis is the most serious of lupus manifestations, and if not aggressively treated, can lead to nephrotic syndrome, edema, and end-stage renal disease in more than 50% of patients within 2 to 3 years
Potential adverse outcomes
Predicting who will have a lupus flare and its degree of severity may be difficult if not impossible, but there is little doubt that a significant percentage of women with SLE will experience a flare of some degree. How a lupus flare will affect the pregnancy is uncertain, as well. SLE activity in pregnancy has been linked to adverse outcomes ranging from increased risk of miscarriage to preterm delivery.
Diagnosis and initial management
Preventive treatments
Steroids. SLE flares being somewhat more common in pregnancy than in the nonpregnant patient has led to the belief in some centers that prophylactic administration of steroids to prevent flares would have beneficial pregnancy effects. To date, however, no conclusive evidence supports this approach. In fact, steroid use in particular has been associated in some series with higher rates of premature rupture of membranes (both term and preterm), preeclampsia, and gestational diabetes.
Hydroxychloroquine. It has been suggested that SLE patients whose disease has been controlled with hydroxychloroquine need not discontinue this therapy due to the pregnancy.
The risks of this agent in pregnancy—which are not thought to be significant—are far outweighed by the potential maternal and fetal benefits of averting a lupus flare.
The differential diagnosis
It is imperative, before starting a management strategy, to determine if in fact a lupus flare is the correct diagnosis. Many features of a lupus flare can be confused with features of normal pregnancy, or pregnancy associated complications such as preeclampsia (TABLE 2). The differential diagnosis includes most commonly preeclampsia, but diagnoses such as immune thrombocytopenia, poststreptococcal glomerulonephritis, and hemolyticuremic syndrome must also be considered.
TABLE 2
Clinical features of preeclampsia vs lupus flare*
| FEATURE | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| Hypertension | Present | Present |
| Proteinuria | Present | Present |
| Edema | Present | Present |
| Malar rash | Absent | Present |
| Arthritis | Absent | Present |
| Photophobia | Absent | Present |
| Oral ulcers | Absent | Present |
| Serositis | Absent | Present |
| Seizures | Present | Present |
| *Denoting presence or absence does not suggest absolute presence or absence, but rather, the likely compatibility with the diagnosis. | ||
Is it lupus flare or preeclampsia?
The most frequent cause for uncertainty is whether the diagnosis is lupus flare or preeclampsia. It is important to find their distinguishing features, because therapy for these 2 conditions is radically different.
A few easy tests can help (TABLE 3), but the most important are:
- positive ANA screen,
- active urinary sediment,
- hypocomplementemia (C3, C4, or CH 50—the latter is an assay of total serum hemolytic complement), and
- high titers of anti-ds-DNA.
TABLE 3
Tests that help tell lupus flare from preeclampsia
| TEST | PREECLAMPSIA | LUPUS FLARE |
|---|---|---|
| PTT | Usually normal | May be abnormal |
| Platelet count | Normal or reduced | Normal or reduced |
| Urinalysis | Normal sediment | Active sediment |
| ANA | Usually negative | Usually positive |
| Anti-ds-DNA | Usually negative | Usually positive |
| AST | May be abnormal | May be abnormal |
| ALT | May be abnormal | May be abnormal |
| Lupus anticoagulant | Negative | May be positive |
| Hemolysis | May be present | Usually absent |
| Complement levels | Usually normal | Usually reduced |
| WBC | Increased | Decreased |
| SFlt-1* | Increased | Normal |
| *Investigational and not widely available for clinical use. | ||
Aggressive drug therapy is imperative
Management of lupus flare depends on aggressive drug therapy. The choice of therapy is determined by whether the patient is currently on an immunosuppressive regimen, and if so, the types and doses of medications, and whether this is her first flare during the pregnancy.
The usual initial therapy is glucocorticoids, or the so-called steroid “pulses,” typically consisting of very high doses of steroids administered either orally or intravenously over a 3-day period. This strategy has had some success in ameliorating lupus flares, particularly lupus nephritis.
Dosage. Methylprednisolone, 1,000 mg/day intravenously, for 3 days followed by oral prednisone, 0.5 to 1.0 mg/kg per day, provides better survival than lower steroid doses in patients with diffuse proliferative glomerulonephritis.
The intravenous route is preferred because of its rapid response, though long-term outcome is probably not altered.
Even a healthy lupus patient who fulfills all the accepted criteria for a safe pregnancy can take a disastrous turn
A 28-year-old G0 with SLE since age 11 presented for preconception consultation. She was on no medications, with normal blood pressure and no evidence of disease activity for more than 2 years. Physical examination and laboratory findings were normal, including serum creatinine 0.7 mg/dL; less than 30 mg protein in a 24-hour urine collection; creatinine clearance 110 mL/min; and lupus anticoagulant, anti-cardiolipin antibodies, anti-Ro, and anti-La were negative.
Green light
One year later, she returned for follow-up and to inform her obstetrician that she was getting married and wished to conceive. She had no SLE activity since her last visit. Repeat laboratory studies were unchanged. She was given medical clearance to attempt conception, and told that she met all the criteria that would make her a suitable candidate for pregnancy.
7 weeks All findings normal
Three months later, a single intrauterine gestation of approximately 7 weeks was confirmed. Laboratory studies and physical examination were normal, and she reported no SLE-related symptoms.
11 weeks Lupus flare
Four weeks later, at her next prenatal visit, a 3+ proteinuria and blood pressure of 140/90 mm Hg were noted. Her rheumatologist made a diagnosis of lupus flare with probable nephritis. Oral prednisone was begun, with rapid taper. Clinical response was good. She remained on prednisone, 10 mg/day.
14 weeks Recurrence
A recurrence of lupus flare with probable nephritis was diagnosed and her oral prednisone dose was increased. One week later the patient seemed to worsen. She was admitted for steroid pulse therapy. Initially, she improved, but then continued to worsen.
16 weeks Cyclophosphamide therapy
After counseling, she was begun on cyclophosphamide, but her condition continued to deteriorate. Renal function worsened and the patient, now with nephrotic proteinuria, was profoundly edematous and hypoalbuminemic with a rising serum creatinine.
18 weeks Dilatation and evacuation
Ultrasound evaluation of the fetus revealed evidence of early growth restriction. After much discussion, the patient underwent dilatation and evacuation.
Cerebral infarct and anticoagulation
Her lupus flare did not abate. More aggressive medical therapy ensued. Transfer to the intensive care unit with intubation was necessary. She subsequently had an ischemic cerebral infarct requiring anticoagulation.
The next 7 weeks Lupus remission
Over the next several weeks, the patient improved. She had some residual sequelae from the cerebral infarct, but was doing well, with her lupus flare in remission. She was responding well to rehabilitation therapy.
Fatal cerebrovascular accident
One day before anticipated discharge to home, she had a massive cerebrovascular accident and died.
A vivid reminder
This case vividly illustrates the difficulties we must be prepared to manage in lupus pregnancies.
The foremost concern is that even the best candidates for pregnancy can have unfavorable outcomes when this highly unpredictable disease flares.
These women can become severely ill. Ideally, their care should be provided at a facility where expertise in maternal-fetal medicine, anesthesiology, rheumatology, neonatology, and critical care medicine can be readily mobilized to deal with the occasionally catastrophic complications. Even with all of this expertise available, maternal and fetal mortality will not be preventable in all cases.
Pregnancy termination does not necessarily result in amelioration of the lupus flare or its sequelae.
Patients with SLE must be informed of the unpredictability of this disease during pregnancy. The entire family, where appropriate and desired, should be included in the information-sharing process.
A team approach, both pre- and postconception, will help to maximize (but not guarantee) the likelihood of a successful outcome for mother and child.
Refractory flares: Focus on damage control
In pregnancy, most lupus flares involve nephritis and the systemic effects of nephritis, such as hypertension, proteinuria, and renal failure. In some cases, however, steroid pulse therapy fails to suppress these sequelae, or recurrent flares seem to become refractory to steroid pulse therapy.
Any evidence for pregnancy termination? In such cases it is essential that appropriate medical decisions be made on behalf of the mother. No conclusive data suggest that pregnancy termination ameliorates a lupus flare, although some anecdotes suggest this possibility.
The mainstay of management is to aggressively treat the lupus flare before irreparable maternal harm occurs.8
Early delivery: When and how
In advanced pregnancies it may be worthwhile considering early delivery so that the fetus may be spared any adverse consequences of maternal cytotoxic therapy, which would be the next step in management.
Amniocentesis for gestations earlier than 34 weeks may assist in guiding the decision for betamethasone administration for the purpose of accelerating maturation of fetal lungs.
Tertiary care facilities are needed. Generally, if aggressive cytotoxic therapy is indicated, delivery of the fetus is indicated after 32 weeks. Such deliveries should occur at tertiary or quaternary care facilities where both adult and neonatal intensivists are available.
Cesarean section may be reserved for accepted obstetric indications.
Cytotoxic therapy
Remote from term, it may be necessary to commence cytotoxic therapy while allowing gestation to progress.
Cyclophosphamide
This is the preferred agent with respect to efficacy, especially for management of glomerulonephritis.9 Unlike steroid therapy, which may show effects within 24 hours, cyclophosphamide therapy may take from 2 to 3 weeks to several months to achieve a satisfactory clinical response.
Warn of potential ovarian failure. It is important that the patient be informed that prolonged therapy with cyclophosphamide might lead to premature ovarian failure and subsequent infertility.
Azathioprine
An alternative, less toxic immunosuppressive agent that can be used is azathioprine. However, it is also less efficacious in treating severe nephritis. In pregnancy, the preferred role for azathioprine may be in the management of an initial, mild flare. Like cyclophosphamide, azathioprine may take several weeks to be effective.
The combination of glucocorticoids and azathioprine may be more effective than glucocorticoids alone in preventing recurrence of lupus flares, data indicate.
Methotrexate
Although this agent has also been used to manage lupus flares, it is generally effective in treating symptoms of arthritis and dermatitis, with little or no efficacy for life-threatening forms of SLE flares.
Thrombosis requires swift anticoagulation
In patients with SLE and antiphospholipid antibodies, the risk of thrombosis is increased. The ideal management during pregnancy is debatable, if the patient has no history of thrombosis. But in the setting of a lupus flare with either arterial or venous thrombosis, there is no debate. These patients require swift anticoagulation with either unfractionated or low molecular weight heparin. (Long-term therapy with a combination of heparin and glucocorticoids increases the risk of maternal osteoporosis.10)
1. Repke JT. Hypertensive disorders of pregnancy: differentiating preeclampsia from active systemic lupus erythematosus. J Reprod Med. 1998;43:350-354.
2. Petri M. Hopkins Lupus Pregnancy Center: 1987–1996. Rheum Dis Clin North Am. 1997;23:1-13.
3. Clowse MEB, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol. 2006;107:293-299.
4. Moroni G, Quaglini S, Banfi G, et al. Pregnancy in lupus nephritis. Am J Kid Dis. 2002;40:713-720.
5. Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy: the Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 1991;34:1538-1545.
6. Khamashta MA, Ruiz-Irastorza G, Hughes GRV. Systemic lupus erythematosus flares during pregnancy. Rheum Dis Clin North Am. 1997;23:15-30.
7. Mascola MA, Repke JT. Obstetric management of the high risk lupus pregnancy. Rheum Dis Clin North Am. 1997;23:119-132.
8. Williams WW, Ecker JL, Thadhani RI, Rahemtullah A. Case 38-2005: a 29-year-old pregnant woman with the nephritic syndrome and hypertension. N Engl J Med. 2005;353:2590-2600.
9. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121-2131.
10. Hahn BH. Systemic lupus erythematosus. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:1960-1967.
The author reports no financial relationships relevant to this article.
1. Repke JT. Hypertensive disorders of pregnancy: differentiating preeclampsia from active systemic lupus erythematosus. J Reprod Med. 1998;43:350-354.
2. Petri M. Hopkins Lupus Pregnancy Center: 1987–1996. Rheum Dis Clin North Am. 1997;23:1-13.
3. Clowse MEB, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol. 2006;107:293-299.
4. Moroni G, Quaglini S, Banfi G, et al. Pregnancy in lupus nephritis. Am J Kid Dis. 2002;40:713-720.
5. Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy: the Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 1991;34:1538-1545.
6. Khamashta MA, Ruiz-Irastorza G, Hughes GRV. Systemic lupus erythematosus flares during pregnancy. Rheum Dis Clin North Am. 1997;23:15-30.
7. Mascola MA, Repke JT. Obstetric management of the high risk lupus pregnancy. Rheum Dis Clin North Am. 1997;23:119-132.
8. Williams WW, Ecker JL, Thadhani RI, Rahemtullah A. Case 38-2005: a 29-year-old pregnant woman with the nephritic syndrome and hypertension. N Engl J Med. 2005;353:2590-2600.
9. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121-2131.
10. Hahn BH. Systemic lupus erythematosus. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:1960-1967.
The author reports no financial relationships relevant to this article.
Preconception Dieting Raises Preterm Risk
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.
Success Rates Similar for Preterm, Term VBAC
MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.
“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.
One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).
Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.
VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.
Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.
MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.
“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.
One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).
Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.
VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.
Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.
MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.
“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.
One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).
Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.
VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.
Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.
Lupus Treatment Advised Despite Pregnancy Concern
SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.
Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.
The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.
Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.
Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.
Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.
There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.
SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.
Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.
The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.
Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.
Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.
Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.
There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.
SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.
Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.
The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.
Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.
Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.
Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.
There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.