Obstetrics

FAJARDO, P.R. — Surgery is the best option for treatment in children with global brachial plexus birth palsies, a study suggests.

Final shoulder function in 36 infants with such injuries who underwent surgery was fair in 22% of patients, satisfactory in 50%, good in 22%, and excellent in 6%. Final shoulder function was poor in 100% of 12 control patients who did not undergo surgery, Patricia DiTaranto, M.D., said at the annual meeting of the American Association for Hand Surgery.

Hand function in the surgery patients was fair in 19%, satisfactory in 58%, good in 17%, and excellent in 6%. Hand function in those who did not undergo surgery was poor in 25% and fair in 75%, said Dr. DiTaranto of Miami Children's Hospital.

Functional outcomes were determined using the Gilbert-Raimondi system, she noted. The children studied were born at a single institution over a 4-year period and were followed for at least 2.5 years. All had global brachial plexus injuries at birth, and the clinical findings persisted at 6-month follow-up. Those in the surgery group underwent surgical reconstruction of the brachial plexus; the surgical strategy of nerve repair and transfer focused on recovery of shoulder stability and hand function, Dr. DiTaranto noted.

FAJARDO, P.R. — Surgery is the best option for treatment in children with global brachial plexus birth palsies, a study suggests.

Final shoulder function in 36 infants with such injuries who underwent surgery was fair in 22% of patients, satisfactory in 50%, good in 22%, and excellent in 6%. Final shoulder function was poor in 100% of 12 control patients who did not undergo surgery, Patricia DiTaranto, M.D., said at the annual meeting of the American Association for Hand Surgery.

Hand function in the surgery patients was fair in 19%, satisfactory in 58%, good in 17%, and excellent in 6%. Hand function in those who did not undergo surgery was poor in 25% and fair in 75%, said Dr. DiTaranto of Miami Children's Hospital.

Functional outcomes were determined using the Gilbert-Raimondi system, she noted. The children studied were born at a single institution over a 4-year period and were followed for at least 2.5 years. All had global brachial plexus injuries at birth, and the clinical findings persisted at 6-month follow-up. Those in the surgery group underwent surgical reconstruction of the brachial plexus; the surgical strategy of nerve repair and transfer focused on recovery of shoulder stability and hand function, Dr. DiTaranto noted.

FAJARDO, P.R. — Surgery is the best option for treatment in children with global brachial plexus birth palsies, a study suggests.

Final shoulder function in 36 infants with such injuries who underwent surgery was fair in 22% of patients, satisfactory in 50%, good in 22%, and excellent in 6%. Final shoulder function was poor in 100% of 12 control patients who did not undergo surgery, Patricia DiTaranto, M.D., said at the annual meeting of the American Association for Hand Surgery.

Hand function in the surgery patients was fair in 19%, satisfactory in 58%, good in 17%, and excellent in 6%. Hand function in those who did not undergo surgery was poor in 25% and fair in 75%, said Dr. DiTaranto of Miami Children's Hospital.

Functional outcomes were determined using the Gilbert-Raimondi system, she noted. The children studied were born at a single institution over a 4-year period and were followed for at least 2.5 years. All had global brachial plexus injuries at birth, and the clinical findings persisted at 6-month follow-up. Those in the surgery group underwent surgical reconstruction of the brachial plexus; the surgical strategy of nerve repair and transfer focused on recovery of shoulder stability and hand function, Dr. DiTaranto noted.

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs

The U.S. infant mortality rate rose in 2002, the first such increase since 1958, researchers at the Centers for Disease Control and Prevention reported.

The increase, from 6.8 infant deaths/1,000 live births in 2001 to 7/1,000 live births in 2002, was primarily driven by an increase in the number of babies weighing less than 750 g at birth.

Between 2001 and 2002, the number of infants weighing less than 500 g increased by 5.1% (330 births), and the number weighing from 500 to 750 g increased by 1.9% (209 births). These changes accounted for 81% of the total increase in infant mortality between the 2 years.

Although the absolute rise in infant deaths was not very large, it is of concern, said Joyce A. Martin, one of the study's authors and a CDC epidemiologist.

“Any increase is a concern, especially when the rate had been going down steadily for 40 years,” she said in an interview.

Maternal race was not a significant factor in the increase, but age was, the researchers said. Most of the increase (82%) occurred among women aged 20–34 years, a period that is generally not considered at high risk for poor birth outcomes.

The researchers said that several factors appear to have contributed to the increase. Multiple gestations were one, but accounted for only 25% of the increase.

Maternal illness might have had an impact. In 2002, there was a slight increase in maternal anemia, diabetes, and chronic hypertension. It's difficult to assess the actual impact of these changes on the infant mortality rate. These conditions are also associated with an increased risk of medical intervention resulting in early delivery.

In 2002, 48% of very preterm births and 38% of moderate preterm births were born by cesarean—increases of more than one-third since 1990. In 2002, among birth of infants weighing 500–750 g, 65% were cesarean deliveries. The authors couldn't determine whether these increases reflected actual changes in the medical management of pregnancy, or were due to prematurity related to maternal illness.

The increased incidence of assisted reproductive technology also may have influenced the mortality rate. Although the vital records used in the study didn't contain assisted reproductive technology information, some links can be drawn from societal trends and the results of other studies, Ms. Martin said. “We know from some recent studies that even singletons conceived through ART have an increased risk of low birth weight, prematurity, and neonatal mortality,” she said. “This may have had an impact, although we can't tie the increase in mortality to ART.”

To see a copy of the report go to www.cdc.gov/nchs

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18‐fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery.

There were no significant demographic differences between the groups. The mean age of the women was 25 years.

Infant birth weight (median about 3,400 grams) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%), as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 women, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.)

Conversely, most women with third-degree tears had both sphincters intact. Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth-degree tears.

Intact external sphincters were found in a total of 67% of women who had third-degree tears and in 41% of those with fourth-degree tears. This difference, however, was not statistically significant.

There was a very strong correlation between sphincter disruption and the development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms, Dr. Nichols said at the meeting.

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) remains intact. Courtesy Dr. Catherine M. Nichols

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18‐fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery.

There were no significant demographic differences between the groups. The mean age of the women was 25 years.

Infant birth weight (median about 3,400 grams) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%), as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 women, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.)

Conversely, most women with third-degree tears had both sphincters intact. Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth-degree tears.

Intact external sphincters were found in a total of 67% of women who had third-degree tears and in 41% of those with fourth-degree tears. This difference, however, was not statistically significant.

There was a very strong correlation between sphincter disruption and the development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms, Dr. Nichols said at the meeting.

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) remains intact. Courtesy Dr. Catherine M. Nichols

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

WHITE SULPHUR SPRINGS, W.VA. — Women who experience a fourth-degree tear during delivery are significantly more likely to have persistent anal sphincter defects leading to fecal urgency or incontinence than are women with a third-degree tear, Catherine M. Nichols, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Third-degree tears are much more likely to heal without persistent sphincter defects, which are associated with up to an 18‐fold increase in the development of new postpartum bowel symptoms, said Dr. Nichols of Virginia Commonwealth University in Richmond.

Her prospective cohort study included 56 primiparous women, of whom 39 experienced a third-degree tear and 17 a fourth-degree tear at delivery.

There were no significant demographic differences between the groups. The mean age of the women was 25 years.

Infant birth weight (median about 3,400 grams) was similar in the two groups. Women who had a fourth-degree tear had a longer second stage of labor than did those with a third-degree tear (133 minutes vs. 78 minutes). Forceps deliveries occurred in 21% of the third-degree group and 47% of the fourth-degree group. Shoulder dystocia was more common in the fourth-degree group (24% vs. 13%), as was persistent occiput posterior position (24% vs. 13%) and midline episiotomy (76% vs. 49%).

After delivery, all of the women completed the Manchester Modified Bowel Function questionnaire to assess predelivery bowel function. At 6 weeks post partum, all women were examined at a dedicated perineal clinic, where they completed another questionnaire to assess new bowel symptoms and received a pelvic exam and an endoanal ultrasound exam to determine the state of both internal and external anal sphincters.

Of the 56 women, 21 (38%) reported new bowel symptoms, which were incontinency to liquid stool or gas (14 women) and fecal urgency (19 women). Among those reporting new symptoms, 59% had a fourth-degree tear and 28% had a third-degree tear.

Disruption of both sphincters was more common among fourth-degree-tear patients. (See box.)

Conversely, most women with third-degree tears had both sphincters intact. Intact internal sphincters were found in significantly more women with third-degree tears than in those with fourth-degree tears.

Intact external sphincters were found in a total of 67% of women who had third-degree tears and in 41% of those with fourth-degree tears. This difference, however, was not statistically significant.

There was a very strong correlation between sphincter disruption and the development of new symptoms. Women with an isolated defect of the external sphincter were 15.7 times more likely than those with no defects to report symptoms, and women with combined defects were 18.7 times more likely to report new symptoms, Dr. Nichols said at the meeting.

Arrows indicate an area of disruption in the external anal sphincter (circular hyperechoic region). The internal anal sphincter (adjacent circular hypoechoic region) remains intact. Courtesy Dr. Catherine M. Nichols

KEVIN FOLEY, RESEARCH/SARAH GALLANT, DESIGN

CABO SAN LUCAS, MEXICO — Higher rates of complications in babies born through assisted reproductive technology have led to malpractice lawsuits, Aubrey Milunsky, M.B., said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“There is a medicolegal industry that is evolving at breakneck speed” related to ART, said Dr. Milunsky, who chaired the conference and is professor of human genetics, pediatrics, ob.gyn., and pathology at Boston University. ART plays a role in approximately 1% of the 4 million births in the United States each year, said Dr. Milunsky, who is also director of the Center for Human Genetics, Boston.

Compared with naturally conceived pregnancies, ART pregnancies carry nearly a threefold increased risk for low birth weight and more than a fivefold increased risk for fetal or infant death. Singletons delivered after ART are 40% more likely to be small for gestational age, 54% more likely to be delivered by cesarean section, and 27% more likely to require intensive care, compared with naturally conceived singletons. Multifetal pregnancies are more common with ART.

Maternal serum screening produces more false-positive results in ART pregnancies than in naturally conceived ones.

The overall rate of birth defects is 40%‐200% higher in ART pregnancies than the background rate of 3%‐4% in the general population. Three rare “imprinting” birth defects (disorders that appear to develop more in one sex than in the other) have been reported in a handful of ART pregnancies: Beckwith-Wiedemann syndrome, Angelman's syndrome, and retinoblastoma.

When parents have gone to such great lengths to conceive a child through ART and are desperate to have a successful pregnancy, anything less than a “perfect” baby may be extra disappointing, and complications may seem extra burdensome, he added.

Sean Tipton, spokesman for the American Society for Reproductive Medicine in Washington, commented in a subsequent telephone interview, “We're not aware of any explosion in litigation in this area. It's certainly not news to anyone that children of infertility patients are not as healthy as children of healthy people.”

Complications in ART pregnancies could be attributed to the underlying cause of the infertility, the advanced age of many women who seek ART, or issues related to multiple gestations, he said.

At the meeting, Dr. Milunsky highlighted some of the key areas for potential litigation related to ART:

▸ Informed consent. It is difficult and probably rare to get truly informed consent for all stages of ART a patient may go through, such as hormonal therapy, intracytoplasmic sperm injection, manipulation of the gamete or zygote in vitro, or insertion of cells into the womb.

▸ Extreme prematurity. Birth weights under 2,500 g are 70% more common in ART singletons than in naturally conceived ones. “Even though the technology is so phenomenal in terms of saving them … the outcome is intellectually disastrous” for many of the extremely small babies, he said. As in non-ART pregnancies, damaged babies lead to lawsuits that often try to pin the blame on medical personnel.

▸ Erroneous diagnosis. Chromosomal testing of a blastomere biopsy can miss problems absent in one cell but present in others. “It's surprising, if not amazing, how often the embryo is made up of two sets of cells—normal and abnormal,” he said.

When a fertilized egg multiplies into 8‐16 cells in vitro, a gene analysis for cystic fibrosis (CF) typically involves one of those cells. But in some cases allele dropout occurs in the cell chosen for analysis, giving the false impression that the cell—and hence the blastomere—does not contain a CF mutation. At least two lawsuits resulted from missed CF diagnoses due to allele dropout.

▸ Genetic counseling. Failure to refer both parents for genetic counseling results in inadequate information gathering. “People undergoing ART rarely have a full genetic evaluation, I find,” Dr. Milunsky said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ Targeted ultrasound. Given the higher risks for complications in ART pregnancies, targeted ultrasound should be done during the second trimester in all ART pregnancies to search for detectable abnormalities.

▸ Chorionic villus sampling/amniocentesis. Don't let the parents' drive to succeed in pregnancy keep you from offering invasive testing, which can endanger the pregnancy. Your responsibility is to communicate any increased risk to the parents and give them options for management. “Let them make the choice, and you make the documentation,” he said.

CABO SAN LUCAS, MEXICO — Higher rates of complications in babies born through assisted reproductive technology have led to malpractice lawsuits, Aubrey Milunsky, M.B., said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“There is a medicolegal industry that is evolving at breakneck speed” related to ART, said Dr. Milunsky, who chaired the conference and is professor of human genetics, pediatrics, ob.gyn., and pathology at Boston University. ART plays a role in approximately 1% of the 4 million births in the United States each year, said Dr. Milunsky, who is also director of the Center for Human Genetics, Boston.

Compared with naturally conceived pregnancies, ART pregnancies carry nearly a threefold increased risk for low birth weight and more than a fivefold increased risk for fetal or infant death. Singletons delivered after ART are 40% more likely to be small for gestational age, 54% more likely to be delivered by cesarean section, and 27% more likely to require intensive care, compared with naturally conceived singletons. Multifetal pregnancies are more common with ART.

Maternal serum screening produces more false-positive results in ART pregnancies than in naturally conceived ones.

The overall rate of birth defects is 40%‐200% higher in ART pregnancies than the background rate of 3%‐4% in the general population. Three rare “imprinting” birth defects (disorders that appear to develop more in one sex than in the other) have been reported in a handful of ART pregnancies: Beckwith-Wiedemann syndrome, Angelman's syndrome, and retinoblastoma.

When parents have gone to such great lengths to conceive a child through ART and are desperate to have a successful pregnancy, anything less than a “perfect” baby may be extra disappointing, and complications may seem extra burdensome, he added.

Sean Tipton, spokesman for the American Society for Reproductive Medicine in Washington, commented in a subsequent telephone interview, “We're not aware of any explosion in litigation in this area. It's certainly not news to anyone that children of infertility patients are not as healthy as children of healthy people.”

Complications in ART pregnancies could be attributed to the underlying cause of the infertility, the advanced age of many women who seek ART, or issues related to multiple gestations, he said.

At the meeting, Dr. Milunsky highlighted some of the key areas for potential litigation related to ART:

▸ Informed consent. It is difficult and probably rare to get truly informed consent for all stages of ART a patient may go through, such as hormonal therapy, intracytoplasmic sperm injection, manipulation of the gamete or zygote in vitro, or insertion of cells into the womb.

▸ Extreme prematurity. Birth weights under 2,500 g are 70% more common in ART singletons than in naturally conceived ones. “Even though the technology is so phenomenal in terms of saving them … the outcome is intellectually disastrous” for many of the extremely small babies, he said. As in non-ART pregnancies, damaged babies lead to lawsuits that often try to pin the blame on medical personnel.

▸ Erroneous diagnosis. Chromosomal testing of a blastomere biopsy can miss problems absent in one cell but present in others. “It's surprising, if not amazing, how often the embryo is made up of two sets of cells—normal and abnormal,” he said.

When a fertilized egg multiplies into 8‐16 cells in vitro, a gene analysis for cystic fibrosis (CF) typically involves one of those cells. But in some cases allele dropout occurs in the cell chosen for analysis, giving the false impression that the cell—and hence the blastomere—does not contain a CF mutation. At least two lawsuits resulted from missed CF diagnoses due to allele dropout.

▸ Genetic counseling. Failure to refer both parents for genetic counseling results in inadequate information gathering. “People undergoing ART rarely have a full genetic evaluation, I find,” Dr. Milunsky said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ Targeted ultrasound. Given the higher risks for complications in ART pregnancies, targeted ultrasound should be done during the second trimester in all ART pregnancies to search for detectable abnormalities.

▸ Chorionic villus sampling/amniocentesis. Don't let the parents' drive to succeed in pregnancy keep you from offering invasive testing, which can endanger the pregnancy. Your responsibility is to communicate any increased risk to the parents and give them options for management. “Let them make the choice, and you make the documentation,” he said.

CABO SAN LUCAS, MEXICO — Higher rates of complications in babies born through assisted reproductive technology have led to malpractice lawsuits, Aubrey Milunsky, M.B., said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“There is a medicolegal industry that is evolving at breakneck speed” related to ART, said Dr. Milunsky, who chaired the conference and is professor of human genetics, pediatrics, ob.gyn., and pathology at Boston University. ART plays a role in approximately 1% of the 4 million births in the United States each year, said Dr. Milunsky, who is also director of the Center for Human Genetics, Boston.

Compared with naturally conceived pregnancies, ART pregnancies carry nearly a threefold increased risk for low birth weight and more than a fivefold increased risk for fetal or infant death. Singletons delivered after ART are 40% more likely to be small for gestational age, 54% more likely to be delivered by cesarean section, and 27% more likely to require intensive care, compared with naturally conceived singletons. Multifetal pregnancies are more common with ART.

Maternal serum screening produces more false-positive results in ART pregnancies than in naturally conceived ones.

The overall rate of birth defects is 40%‐200% higher in ART pregnancies than the background rate of 3%‐4% in the general population. Three rare “imprinting” birth defects (disorders that appear to develop more in one sex than in the other) have been reported in a handful of ART pregnancies: Beckwith-Wiedemann syndrome, Angelman's syndrome, and retinoblastoma.

When parents have gone to such great lengths to conceive a child through ART and are desperate to have a successful pregnancy, anything less than a “perfect” baby may be extra disappointing, and complications may seem extra burdensome, he added.

Sean Tipton, spokesman for the American Society for Reproductive Medicine in Washington, commented in a subsequent telephone interview, “We're not aware of any explosion in litigation in this area. It's certainly not news to anyone that children of infertility patients are not as healthy as children of healthy people.”

Complications in ART pregnancies could be attributed to the underlying cause of the infertility, the advanced age of many women who seek ART, or issues related to multiple gestations, he said.

At the meeting, Dr. Milunsky highlighted some of the key areas for potential litigation related to ART:

▸ Informed consent. It is difficult and probably rare to get truly informed consent for all stages of ART a patient may go through, such as hormonal therapy, intracytoplasmic sperm injection, manipulation of the gamete or zygote in vitro, or insertion of cells into the womb.

▸ Extreme prematurity. Birth weights under 2,500 g are 70% more common in ART singletons than in naturally conceived ones. “Even though the technology is so phenomenal in terms of saving them … the outcome is intellectually disastrous” for many of the extremely small babies, he said. As in non-ART pregnancies, damaged babies lead to lawsuits that often try to pin the blame on medical personnel.

▸ Erroneous diagnosis. Chromosomal testing of a blastomere biopsy can miss problems absent in one cell but present in others. “It's surprising, if not amazing, how often the embryo is made up of two sets of cells—normal and abnormal,” he said.

When a fertilized egg multiplies into 8‐16 cells in vitro, a gene analysis for cystic fibrosis (CF) typically involves one of those cells. But in some cases allele dropout occurs in the cell chosen for analysis, giving the false impression that the cell—and hence the blastomere—does not contain a CF mutation. At least two lawsuits resulted from missed CF diagnoses due to allele dropout.

▸ Genetic counseling. Failure to refer both parents for genetic counseling results in inadequate information gathering. “People undergoing ART rarely have a full genetic evaluation, I find,” Dr. Milunsky said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ Targeted ultrasound. Given the higher risks for complications in ART pregnancies, targeted ultrasound should be done during the second trimester in all ART pregnancies to search for detectable abnormalities.

▸ Chorionic villus sampling/amniocentesis. Don't let the parents' drive to succeed in pregnancy keep you from offering invasive testing, which can endanger the pregnancy. Your responsibility is to communicate any increased risk to the parents and give them options for management. “Let them make the choice, and you make the documentation,” he said.

CABO SAN LUCAS, MEXICO — Abdominal trauma during pregnancy endangers the woman and her fetus, but avoiding some common clinical errors in managing such patients can reduce these risks, according to John A. Marx, M.D.

Abdominal trauma during pregnancy is “a huge concern and underrated,” said Dr. Marx, chairman of emergency medicine at Carolinas Medical Center, Charlotte, N.C.

Abdominal trauma occurs in 1%–12% of all pregnancies and leads to hospitalization in 0.4% of such cases, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Trauma that causes a pelvic fracture leads to maternal death in 9% of cases and fetal death in 38% of cases. Placental abruption—seen in 2%–4% of women who suffer minor abdominal trauma and half of women with life-threatening abdominal trauma—results in fetal death 50%–70% of the time.

Be prepared to recognize shock early and treat it aggressively in pregnant women with abdominal trauma.

Don't rely too much on a nontender abdomen as a sign that everything is okay after abdominal trauma during pregnancy.

Dr. Marx outlined other mistakes to avoid:

▸ Failure to teach proper seat belt use. Motor vehicle accidents cause 70% of all cases of abdominal trauma in pregnancy. Compared with a belted passenger, an unbelted pregnant woman in a car crash has double the risk of vaginal bleeding and quadruple the risk of fetal death.

Advise women to place their lap belt below the uterus and across the hips and place the shoulder belt between the breasts and to the side of the abdomen. Placing the seatbelt improperly across the abdomen increases force on the uterus three- to fourfold, compared with proper seat belt use.

Air bags do protect pregnant passengers, he added. “There's a great deal of misunderstanding about this,” Dr. Marx said.

▸ Failure to order needed radiologic studies. This failure is frequently due to concern about radiating the fetus and represents “a huge error in trauma management,” he said. A dose of 5 rad or less is considered an acceptable cumulative fetal exposure. X-rays that deliver less than half a rad each include films of the anterior-posterior pelvis, lumbosacral spine, thoracic spine, and periapical or lateral views. A CT scan of the abdomen delivers 2.6 rads to the fetus, and a CT of the abdomen and pelvis delivers 3–9 rads, although helical CT decreases radiation exposure by 14%–30%. “You can still do these studies, but you can't do a bunch of them,” he said.

▸ Failure to obtain coagulation studies. The risk of disseminated intravascular coagulation increases during pregnancy.

▸ Overreliance on ultrasound to detect placental abruption. Cardiotocographic monitoring is much more sensitive, though less specific, than ultrasound in diagnosing placental abruption. All women with pregnancies of 24 weeks or greater who sustain blunt trauma to the abdomen should undergo cardiotocographic monitoring, which consists of continuous Doppler monitoring of fetal cardiac activity and electronic recording of uterine activity.

Placental abruption with a 50% tear can quadruple the risk of stillbirth, and a 75% tear increases the risk of stillbirth 39-fold.

▸ Failure to monitor the fetus for 4–24 hours. Four hours is sufficient if the trauma carries low risk, the mother is asymptomatic for placental abruption, and cardiotocographic monitoring results are normal. If the trauma affected a major bodily mechanism, the mother is symptomatic, or monitoring results are abnormal within the first 4 hours, monitor for at least 24 hours.

▸ Failure to avoid supine hypotensive syndrome. “This is another oft-missed and easy-to-treat condition,” he said. Tilting the woman's prone body up and to the left by 15–30 degrees frees the inferior vena cava from pressure from the uterus, which could otherwise cause a significant drop in systolic blood pressure.

▸ Failure to consider domestic violence. The woman's abdomen is the prime site of injury arising from domestic violence during pregnancy. If domestic violence happens once during pregnancy, there's a 60% chance it will happen again. Only 3% of pregnant women who seek care for domestic violence injuries reveal the true cause to physicians.

▸ Failure to perform a perimortem cesarean section promptly. When the woman is dead or moribund but the fetus is viable, performing a C-section within 5 minutes leads to excellent fetal outcomes. Only about 5% of fetuses survive if delivery is delayed at least 15 minutes, and most will have poor neurologic outcomes, Dr. Marx said.

CABO SAN LUCAS, MEXICO — Abdominal trauma during pregnancy endangers the woman and her fetus, but avoiding some common clinical errors in managing such patients can reduce these risks, according to John A. Marx, M.D.

Abdominal trauma during pregnancy is “a huge concern and underrated,” said Dr. Marx, chairman of emergency medicine at Carolinas Medical Center, Charlotte, N.C.

Abdominal trauma occurs in 1%–12% of all pregnancies and leads to hospitalization in 0.4% of such cases, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Trauma that causes a pelvic fracture leads to maternal death in 9% of cases and fetal death in 38% of cases. Placental abruption—seen in 2%–4% of women who suffer minor abdominal trauma and half of women with life-threatening abdominal trauma—results in fetal death 50%–70% of the time.

Be prepared to recognize shock early and treat it aggressively in pregnant women with abdominal trauma.

Don't rely too much on a nontender abdomen as a sign that everything is okay after abdominal trauma during pregnancy.

Dr. Marx outlined other mistakes to avoid:

▸ Failure to teach proper seat belt use. Motor vehicle accidents cause 70% of all cases of abdominal trauma in pregnancy. Compared with a belted passenger, an unbelted pregnant woman in a car crash has double the risk of vaginal bleeding and quadruple the risk of fetal death.

Advise women to place their lap belt below the uterus and across the hips and place the shoulder belt between the breasts and to the side of the abdomen. Placing the seatbelt improperly across the abdomen increases force on the uterus three- to fourfold, compared with proper seat belt use.

Air bags do protect pregnant passengers, he added. “There's a great deal of misunderstanding about this,” Dr. Marx said.

▸ Failure to order needed radiologic studies. This failure is frequently due to concern about radiating the fetus and represents “a huge error in trauma management,” he said. A dose of 5 rad or less is considered an acceptable cumulative fetal exposure. X-rays that deliver less than half a rad each include films of the anterior-posterior pelvis, lumbosacral spine, thoracic spine, and periapical or lateral views. A CT scan of the abdomen delivers 2.6 rads to the fetus, and a CT of the abdomen and pelvis delivers 3–9 rads, although helical CT decreases radiation exposure by 14%–30%. “You can still do these studies, but you can't do a bunch of them,” he said.

▸ Failure to obtain coagulation studies. The risk of disseminated intravascular coagulation increases during pregnancy.

▸ Overreliance on ultrasound to detect placental abruption. Cardiotocographic monitoring is much more sensitive, though less specific, than ultrasound in diagnosing placental abruption. All women with pregnancies of 24 weeks or greater who sustain blunt trauma to the abdomen should undergo cardiotocographic monitoring, which consists of continuous Doppler monitoring of fetal cardiac activity and electronic recording of uterine activity.

Placental abruption with a 50% tear can quadruple the risk of stillbirth, and a 75% tear increases the risk of stillbirth 39-fold.

▸ Failure to monitor the fetus for 4–24 hours. Four hours is sufficient if the trauma carries low risk, the mother is asymptomatic for placental abruption, and cardiotocographic monitoring results are normal. If the trauma affected a major bodily mechanism, the mother is symptomatic, or monitoring results are abnormal within the first 4 hours, monitor for at least 24 hours.

▸ Failure to avoid supine hypotensive syndrome. “This is another oft-missed and easy-to-treat condition,” he said. Tilting the woman's prone body up and to the left by 15–30 degrees frees the inferior vena cava from pressure from the uterus, which could otherwise cause a significant drop in systolic blood pressure.

▸ Failure to consider domestic violence. The woman's abdomen is the prime site of injury arising from domestic violence during pregnancy. If domestic violence happens once during pregnancy, there's a 60% chance it will happen again. Only 3% of pregnant women who seek care for domestic violence injuries reveal the true cause to physicians.

▸ Failure to perform a perimortem cesarean section promptly. When the woman is dead or moribund but the fetus is viable, performing a C-section within 5 minutes leads to excellent fetal outcomes. Only about 5% of fetuses survive if delivery is delayed at least 15 minutes, and most will have poor neurologic outcomes, Dr. Marx said.

CABO SAN LUCAS, MEXICO — Abdominal trauma during pregnancy endangers the woman and her fetus, but avoiding some common clinical errors in managing such patients can reduce these risks, according to John A. Marx, M.D.

Abdominal trauma during pregnancy is “a huge concern and underrated,” said Dr. Marx, chairman of emergency medicine at Carolinas Medical Center, Charlotte, N.C.

Abdominal trauma occurs in 1%–12% of all pregnancies and leads to hospitalization in 0.4% of such cases, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Trauma that causes a pelvic fracture leads to maternal death in 9% of cases and fetal death in 38% of cases. Placental abruption—seen in 2%–4% of women who suffer minor abdominal trauma and half of women with life-threatening abdominal trauma—results in fetal death 50%–70% of the time.

Be prepared to recognize shock early and treat it aggressively in pregnant women with abdominal trauma.

Don't rely too much on a nontender abdomen as a sign that everything is okay after abdominal trauma during pregnancy.

Dr. Marx outlined other mistakes to avoid:

▸ Failure to teach proper seat belt use. Motor vehicle accidents cause 70% of all cases of abdominal trauma in pregnancy. Compared with a belted passenger, an unbelted pregnant woman in a car crash has double the risk of vaginal bleeding and quadruple the risk of fetal death.

Advise women to place their lap belt below the uterus and across the hips and place the shoulder belt between the breasts and to the side of the abdomen. Placing the seatbelt improperly across the abdomen increases force on the uterus three- to fourfold, compared with proper seat belt use.

Air bags do protect pregnant passengers, he added. “There's a great deal of misunderstanding about this,” Dr. Marx said.

▸ Failure to order needed radiologic studies. This failure is frequently due to concern about radiating the fetus and represents “a huge error in trauma management,” he said. A dose of 5 rad or less is considered an acceptable cumulative fetal exposure. X-rays that deliver less than half a rad each include films of the anterior-posterior pelvis, lumbosacral spine, thoracic spine, and periapical or lateral views. A CT scan of the abdomen delivers 2.6 rads to the fetus, and a CT of the abdomen and pelvis delivers 3–9 rads, although helical CT decreases radiation exposure by 14%–30%. “You can still do these studies, but you can't do a bunch of them,” he said.

▸ Failure to obtain coagulation studies. The risk of disseminated intravascular coagulation increases during pregnancy.

▸ Overreliance on ultrasound to detect placental abruption. Cardiotocographic monitoring is much more sensitive, though less specific, than ultrasound in diagnosing placental abruption. All women with pregnancies of 24 weeks or greater who sustain blunt trauma to the abdomen should undergo cardiotocographic monitoring, which consists of continuous Doppler monitoring of fetal cardiac activity and electronic recording of uterine activity.

Placental abruption with a 50% tear can quadruple the risk of stillbirth, and a 75% tear increases the risk of stillbirth 39-fold.

▸ Failure to monitor the fetus for 4–24 hours. Four hours is sufficient if the trauma carries low risk, the mother is asymptomatic for placental abruption, and cardiotocographic monitoring results are normal. If the trauma affected a major bodily mechanism, the mother is symptomatic, or monitoring results are abnormal within the first 4 hours, monitor for at least 24 hours.

▸ Failure to avoid supine hypotensive syndrome. “This is another oft-missed and easy-to-treat condition,” he said. Tilting the woman's prone body up and to the left by 15–30 degrees frees the inferior vena cava from pressure from the uterus, which could otherwise cause a significant drop in systolic blood pressure.

▸ Failure to consider domestic violence. The woman's abdomen is the prime site of injury arising from domestic violence during pregnancy. If domestic violence happens once during pregnancy, there's a 60% chance it will happen again. Only 3% of pregnant women who seek care for domestic violence injuries reveal the true cause to physicians.

▸ Failure to perform a perimortem cesarean section promptly. When the woman is dead or moribund but the fetus is viable, performing a C-section within 5 minutes leads to excellent fetal outcomes. Only about 5% of fetuses survive if delivery is delayed at least 15 minutes, and most will have poor neurologic outcomes, Dr. Marx said.

CABO SAN LUCAS, MEXICO — Some obstetricians see pediatricians and neonatologists as adversaries when it comes to reducing the risk of a lawsuit after delivering a baby with low Apgar scores.

The alledged problem: Most pediatricians, neonatologists, and pediatric neurologists don't follow a 2003 monograph produced by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) that sets criteria for declaring that a newborn has hypoxic ischemic encephalopathy (HIE), which is an essential component of cerebral palsy, said O. Richard Depp, M.D., at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Until recently, pediatricians and neonatologists who saw a newborn who was not doing well and had depressed Apgar scores simply labeled the problem as HIE. “That is no longer appropriate,” said Dr. Depp, professor of ob.gyn. at Thomas Jefferson University and Drexel University, Philadelphia.

No one should presume a diagnosis of HIE until other causes have been excluded and criteria for HIE have been met, he said. (See sidebar.) Until then, the only appropriate label—and one less likely to spark litigation—is neonatal encephalopathy, which may be due to a number of causes, many of which occur before labor and delivery, according to the monograph.

“I think there is a real need for education among our colleagues in other specialties, because I don't think they've really read this,” Dr. Depp said during the conference, which was sponsored by Boston University and the Center for Human Genetics.

Not so, countered Avroy A. Fanaroff, M.B., in a commentary after Dr. Depp's talk. “Our pediatricians are trained to be very cautious about their use of terminology and to apply the ACOG criteria before they put down HIE,” he said. Dr. Fanaroff is professor and chairman of pediatrics and professor of reproductive biology at Case Western Reserve University, Cleveland.

“You practice in one of the pediatric capitals of the world,” responded Dr. Depp. He asked how many obstetricians in the audience of 150–200 people felt comfortably sure that the pediatricians in their hospitals were familiar with the monograph. Less than a handful raised their hands.

An obstetrician from Atlanta stepped up to the microphone and said, “We're fighting for our lives from the plaintiffs' attorneys, who say, 'Well, can you dispute the fact that this pediatric neurologist says this is HIE?' [The neurologist] wasn't there! He doesn't even know what he's saying!”

Dr. Depp suggested that it's time for chairs or division chiefs “to sit down and talk about how they will address this problem in a prospective manner.” At Jefferson University, he sat down with the chairpersons of pediatrics and anesthesia to negotiate an agreement on the proper use of terms such as HIE and neonatal encephalopathy.

Only recently have physicians attempted to distinguish between neonatal encephalopathy and hypoxic ischemic encephalopathy, he noted.

A 1999 international consensus statement, titled, “A template for defining a causal relation between acute intrapartum events and cerebral palsy” provided the first clear guidance and was endorsed by 16 medical organizations, including ACOG (BMJ 1999;319:1054–9).

ACOG and the AAP followed with the monograph, “Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy” (Obstet. Gynecol. 2003;102:628–36).

Dr. Fanaroff agreed that differentiating hypoxic ischemic encephalopathy from neonatal encephalopathy is a complex task. “There are a whole lot of things that need to be sorted out. There are some that are acute events, others that are chronic, others that are acute and chronic, and others that are due to genetics or infection,” Dr. Fanaroff said.

“I think we're all treading on very thin ice, and walking on eggshells” when labeling problems in a newborn's chart.

HIE Criteria Essentials

Four prerequisites must be met in proposing that hypoxic ischemic encephalopathy caused moderate to severe neonatal encephalopathy, resulting in cerebral palsy:

1. Fetal umbilical cord arterial blood obtained at delivery with evidence of metabolic acidosis (pH less than 7 and base deficit of 12 mmol/L or more).

2. Early onset of moderate or severe neonatal encephalopathy in infants born at 34 weeks' gestation or later.

3. Spastic quadriplegic or dyskinetic cerebral palsy.

4. Exclusion of other identifiable causes such as coagulation disorders, infectious conditions, trauma, or genetic disorders.

The monograph also discusses other criteria that together suggest an intrapartum insult occurred.

Source: Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy (Obstet. Gynecol. 2003;102:628–36).

CABO SAN LUCAS, MEXICO — Some obstetricians see pediatricians and neonatologists as adversaries when it comes to reducing the risk of a lawsuit after delivering a baby with low Apgar scores.

The alledged problem: Most pediatricians, neonatologists, and pediatric neurologists don't follow a 2003 monograph produced by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) that sets criteria for declaring that a newborn has hypoxic ischemic encephalopathy (HIE), which is an essential component of cerebral palsy, said O. Richard Depp, M.D., at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Until recently, pediatricians and neonatologists who saw a newborn who was not doing well and had depressed Apgar scores simply labeled the problem as HIE. “That is no longer appropriate,” said Dr. Depp, professor of ob.gyn. at Thomas Jefferson University and Drexel University, Philadelphia.

No one should presume a diagnosis of HIE until other causes have been excluded and criteria for HIE have been met, he said. (See sidebar.) Until then, the only appropriate label—and one less likely to spark litigation—is neonatal encephalopathy, which may be due to a number of causes, many of which occur before labor and delivery, according to the monograph.

“I think there is a real need for education among our colleagues in other specialties, because I don't think they've really read this,” Dr. Depp said during the conference, which was sponsored by Boston University and the Center for Human Genetics.

Not so, countered Avroy A. Fanaroff, M.B., in a commentary after Dr. Depp's talk. “Our pediatricians are trained to be very cautious about their use of terminology and to apply the ACOG criteria before they put down HIE,” he said. Dr. Fanaroff is professor and chairman of pediatrics and professor of reproductive biology at Case Western Reserve University, Cleveland.

“You practice in one of the pediatric capitals of the world,” responded Dr. Depp. He asked how many obstetricians in the audience of 150–200 people felt comfortably sure that the pediatricians in their hospitals were familiar with the monograph. Less than a handful raised their hands.

An obstetrician from Atlanta stepped up to the microphone and said, “We're fighting for our lives from the plaintiffs' attorneys, who say, 'Well, can you dispute the fact that this pediatric neurologist says this is HIE?' [The neurologist] wasn't there! He doesn't even know what he's saying!”

Dr. Depp suggested that it's time for chairs or division chiefs “to sit down and talk about how they will address this problem in a prospective manner.” At Jefferson University, he sat down with the chairpersons of pediatrics and anesthesia to negotiate an agreement on the proper use of terms such as HIE and neonatal encephalopathy.

Only recently have physicians attempted to distinguish between neonatal encephalopathy and hypoxic ischemic encephalopathy, he noted.

A 1999 international consensus statement, titled, “A template for defining a causal relation between acute intrapartum events and cerebral palsy” provided the first clear guidance and was endorsed by 16 medical organizations, including ACOG (BMJ 1999;319:1054–9).

ACOG and the AAP followed with the monograph, “Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy” (Obstet. Gynecol. 2003;102:628–36).

Dr. Fanaroff agreed that differentiating hypoxic ischemic encephalopathy from neonatal encephalopathy is a complex task. “There are a whole lot of things that need to be sorted out. There are some that are acute events, others that are chronic, others that are acute and chronic, and others that are due to genetics or infection,” Dr. Fanaroff said.

“I think we're all treading on very thin ice, and walking on eggshells” when labeling problems in a newborn's chart.

HIE Criteria Essentials

Four prerequisites must be met in proposing that hypoxic ischemic encephalopathy caused moderate to severe neonatal encephalopathy, resulting in cerebral palsy:

1. Fetal umbilical cord arterial blood obtained at delivery with evidence of metabolic acidosis (pH less than 7 and base deficit of 12 mmol/L or more).

2. Early onset of moderate or severe neonatal encephalopathy in infants born at 34 weeks' gestation or later.

3. Spastic quadriplegic or dyskinetic cerebral palsy.

4. Exclusion of other identifiable causes such as coagulation disorders, infectious conditions, trauma, or genetic disorders.

The monograph also discusses other criteria that together suggest an intrapartum insult occurred.

Source: Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy (Obstet. Gynecol. 2003;102:628–36).

CABO SAN LUCAS, MEXICO — Some obstetricians see pediatricians and neonatologists as adversaries when it comes to reducing the risk of a lawsuit after delivering a baby with low Apgar scores.

The alledged problem: Most pediatricians, neonatologists, and pediatric neurologists don't follow a 2003 monograph produced by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) that sets criteria for declaring that a newborn has hypoxic ischemic encephalopathy (HIE), which is an essential component of cerebral palsy, said O. Richard Depp, M.D., at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

Until recently, pediatricians and neonatologists who saw a newborn who was not doing well and had depressed Apgar scores simply labeled the problem as HIE. “That is no longer appropriate,” said Dr. Depp, professor of ob.gyn. at Thomas Jefferson University and Drexel University, Philadelphia.

No one should presume a diagnosis of HIE until other causes have been excluded and criteria for HIE have been met, he said. (See sidebar.) Until then, the only appropriate label—and one less likely to spark litigation—is neonatal encephalopathy, which may be due to a number of causes, many of which occur before labor and delivery, according to the monograph.

“I think there is a real need for education among our colleagues in other specialties, because I don't think they've really read this,” Dr. Depp said during the conference, which was sponsored by Boston University and the Center for Human Genetics.

Not so, countered Avroy A. Fanaroff, M.B., in a commentary after Dr. Depp's talk. “Our pediatricians are trained to be very cautious about their use of terminology and to apply the ACOG criteria before they put down HIE,” he said. Dr. Fanaroff is professor and chairman of pediatrics and professor of reproductive biology at Case Western Reserve University, Cleveland.

“You practice in one of the pediatric capitals of the world,” responded Dr. Depp. He asked how many obstetricians in the audience of 150–200 people felt comfortably sure that the pediatricians in their hospitals were familiar with the monograph. Less than a handful raised their hands.

An obstetrician from Atlanta stepped up to the microphone and said, “We're fighting for our lives from the plaintiffs' attorneys, who say, 'Well, can you dispute the fact that this pediatric neurologist says this is HIE?' [The neurologist] wasn't there! He doesn't even know what he's saying!”

Dr. Depp suggested that it's time for chairs or division chiefs “to sit down and talk about how they will address this problem in a prospective manner.” At Jefferson University, he sat down with the chairpersons of pediatrics and anesthesia to negotiate an agreement on the proper use of terms such as HIE and neonatal encephalopathy.

Only recently have physicians attempted to distinguish between neonatal encephalopathy and hypoxic ischemic encephalopathy, he noted.

A 1999 international consensus statement, titled, “A template for defining a causal relation between acute intrapartum events and cerebral palsy” provided the first clear guidance and was endorsed by 16 medical organizations, including ACOG (BMJ 1999;319:1054–9).

ACOG and the AAP followed with the monograph, “Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy” (Obstet. Gynecol. 2003;102:628–36).

Dr. Fanaroff agreed that differentiating hypoxic ischemic encephalopathy from neonatal encephalopathy is a complex task. “There are a whole lot of things that need to be sorted out. There are some that are acute events, others that are chronic, others that are acute and chronic, and others that are due to genetics or infection,” Dr. Fanaroff said.

“I think we're all treading on very thin ice, and walking on eggshells” when labeling problems in a newborn's chart.

HIE Criteria Essentials

Four prerequisites must be met in proposing that hypoxic ischemic encephalopathy caused moderate to severe neonatal encephalopathy, resulting in cerebral palsy:

1. Fetal umbilical cord arterial blood obtained at delivery with evidence of metabolic acidosis (pH less than 7 and base deficit of 12 mmol/L or more).

2. Early onset of moderate or severe neonatal encephalopathy in infants born at 34 weeks' gestation or later.

3. Spastic quadriplegic or dyskinetic cerebral palsy.

4. Exclusion of other identifiable causes such as coagulation disorders, infectious conditions, trauma, or genetic disorders.

The monograph also discusses other criteria that together suggest an intrapartum insult occurred.

Source: Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy (Obstet. Gynecol. 2003;102:628–36).

WHITE SULPHUR SPRINGS, W.VA. — A high dose of vaginal misoprostol effects more rapid termination of second-trimester pregnancy than does a low dose and is not associated with an increase in side effects or complications, Rodney K. Edwards, M.D., reported during the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Dr. Edwards presented the results of a retrospective study comparing delivery outcomes with two misoprostol induction protocols at his institution, the University of Florida.

The low-dose regimen (200 mcg every 12 hours) was in use before July 1, 2002, and the current high-dose regimen (400 mcg every 6 hours) has been in use since then.

The cohort included 147 women who sought termination of second-trimester pregnancy from 1996 to 2004. All the women were carrying a singleton fetus of 13–27 weeks' gestation (median 20 weeks).

There were 100 women in the low-dose group and 47 in the high-dose group. Their mean age was 27 years. About 36% of the women were nulliparous; 56% had a prior vaginal delivery, and 12% had a prior cesarean delivery.

The most common indication for induction was fetal anomaly. Other indications were fetal death, premature rupture of membranes, and maternal indications, such as severe preeclampsia.

The high-dose group delivered significantly quicker than the low-dose group (mean time 13.25 hours vs. 22.5 hours). In the high-dose group, 81% of patients had delivered by 24 hours, compared with 54% of the low-dose group.

More patients in the low-dose group required a second abortifacient to effect delivery (27% vs. 6%).

Four low-dose patients failed to deliver vaginally during the same hospital admission. One had a hysterotomy due to a failed induction and rupture of membranes. Three were discharged home undelivered and returned for another attempt.

One high-dose patient, who had a prior cesarean and a collagen abnormality, experienced a ruptured uterus posteriorly and underwent hysterotomy.

Side effects (nausea, vomiting, and diarrhea) were uncommon in both groups, occurring at rates of less than 5%.

Postpartum hemorrhage also occurred in fewer than 5% of patients in both groups.

Dr. Edwards reported an unexplained finding of a higher incidence of clinical chorioamnionitis in the high-dose group (17% vs. 5% in the low-dose group). Among the 100 patients for whom placental pathology was available, histologic chorioamnionitis was also more common in the high-dose group (29% vs. 11%).

“Because of this finding, we think the high-dose regimen did not cause fever and a false diagnosis of chorioamnionitis, but the group for some reason actually did have a higher incidence,” Dr. Edwards said.

He could offer no clear explanation of this finding, which he called “counterintuitive,” given that the shorter labors seen in the high-dose group might have been associated with fewer vaginal exams.

In both groups, dead fetuses were more quickly delivered than live fetuses. In the low-dose group, the median time to delivery was 23.5 hours for a live fetus and 11 hours for a dead fetus. In the high-dose group, the median time to deliver a live fetus was 15.5 hours, compared with 11 hours for a dead fetus.

When the two groups were analyzed considering only live fetuses, however, the high-dose protocol still effected earlier delivery, with a median time to delivery of 15.5 hours, compared with 23.5 hours for the low-dose group, according to Dr. Edwards.

WHITE SULPHUR SPRINGS, W.VA. — A high dose of vaginal misoprostol effects more rapid termination of second-trimester pregnancy than does a low dose and is not associated with an increase in side effects or complications, Rodney K. Edwards, M.D., reported during the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Dr. Edwards presented the results of a retrospective study comparing delivery outcomes with two misoprostol induction protocols at his institution, the University of Florida.

The low-dose regimen (200 mcg every 12 hours) was in use before July 1, 2002, and the current high-dose regimen (400 mcg every 6 hours) has been in use since then.

The cohort included 147 women who sought termination of second-trimester pregnancy from 1996 to 2004. All the women were carrying a singleton fetus of 13–27 weeks' gestation (median 20 weeks).

There were 100 women in the low-dose group and 47 in the high-dose group. Their mean age was 27 years. About 36% of the women were nulliparous; 56% had a prior vaginal delivery, and 12% had a prior cesarean delivery.

The most common indication for induction was fetal anomaly. Other indications were fetal death, premature rupture of membranes, and maternal indications, such as severe preeclampsia.

The high-dose group delivered significantly quicker than the low-dose group (mean time 13.25 hours vs. 22.5 hours). In the high-dose group, 81% of patients had delivered by 24 hours, compared with 54% of the low-dose group.

More patients in the low-dose group required a second abortifacient to effect delivery (27% vs. 6%).

Four low-dose patients failed to deliver vaginally during the same hospital admission. One had a hysterotomy due to a failed induction and rupture of membranes. Three were discharged home undelivered and returned for another attempt.

One high-dose patient, who had a prior cesarean and a collagen abnormality, experienced a ruptured uterus posteriorly and underwent hysterotomy.

Side effects (nausea, vomiting, and diarrhea) were uncommon in both groups, occurring at rates of less than 5%.

Postpartum hemorrhage also occurred in fewer than 5% of patients in both groups.

Dr. Edwards reported an unexplained finding of a higher incidence of clinical chorioamnionitis in the high-dose group (17% vs. 5% in the low-dose group). Among the 100 patients for whom placental pathology was available, histologic chorioamnionitis was also more common in the high-dose group (29% vs. 11%).

“Because of this finding, we think the high-dose regimen did not cause fever and a false diagnosis of chorioamnionitis, but the group for some reason actually did have a higher incidence,” Dr. Edwards said.

He could offer no clear explanation of this finding, which he called “counterintuitive,” given that the shorter labors seen in the high-dose group might have been associated with fewer vaginal exams.

In both groups, dead fetuses were more quickly delivered than live fetuses. In the low-dose group, the median time to delivery was 23.5 hours for a live fetus and 11 hours for a dead fetus. In the high-dose group, the median time to deliver a live fetus was 15.5 hours, compared with 11 hours for a dead fetus.

When the two groups were analyzed considering only live fetuses, however, the high-dose protocol still effected earlier delivery, with a median time to delivery of 15.5 hours, compared with 23.5 hours for the low-dose group, according to Dr. Edwards.

WHITE SULPHUR SPRINGS, W.VA. — A high dose of vaginal misoprostol effects more rapid termination of second-trimester pregnancy than does a low dose and is not associated with an increase in side effects or complications, Rodney K. Edwards, M.D., reported during the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Dr. Edwards presented the results of a retrospective study comparing delivery outcomes with two misoprostol induction protocols at his institution, the University of Florida.

The low-dose regimen (200 mcg every 12 hours) was in use before July 1, 2002, and the current high-dose regimen (400 mcg every 6 hours) has been in use since then.

The cohort included 147 women who sought termination of second-trimester pregnancy from 1996 to 2004. All the women were carrying a singleton fetus of 13–27 weeks' gestation (median 20 weeks).

There were 100 women in the low-dose group and 47 in the high-dose group. Their mean age was 27 years. About 36% of the women were nulliparous; 56% had a prior vaginal delivery, and 12% had a prior cesarean delivery.

The most common indication for induction was fetal anomaly. Other indications were fetal death, premature rupture of membranes, and maternal indications, such as severe preeclampsia.

The high-dose group delivered significantly quicker than the low-dose group (mean time 13.25 hours vs. 22.5 hours). In the high-dose group, 81% of patients had delivered by 24 hours, compared with 54% of the low-dose group.

More patients in the low-dose group required a second abortifacient to effect delivery (27% vs. 6%).

Four low-dose patients failed to deliver vaginally during the same hospital admission. One had a hysterotomy due to a failed induction and rupture of membranes. Three were discharged home undelivered and returned for another attempt.

One high-dose patient, who had a prior cesarean and a collagen abnormality, experienced a ruptured uterus posteriorly and underwent hysterotomy.

Side effects (nausea, vomiting, and diarrhea) were uncommon in both groups, occurring at rates of less than 5%.

Postpartum hemorrhage also occurred in fewer than 5% of patients in both groups.

Dr. Edwards reported an unexplained finding of a higher incidence of clinical chorioamnionitis in the high-dose group (17% vs. 5% in the low-dose group). Among the 100 patients for whom placental pathology was available, histologic chorioamnionitis was also more common in the high-dose group (29% vs. 11%).

“Because of this finding, we think the high-dose regimen did not cause fever and a false diagnosis of chorioamnionitis, but the group for some reason actually did have a higher incidence,” Dr. Edwards said.

He could offer no clear explanation of this finding, which he called “counterintuitive,” given that the shorter labors seen in the high-dose group might have been associated with fewer vaginal exams.

In both groups, dead fetuses were more quickly delivered than live fetuses. In the low-dose group, the median time to delivery was 23.5 hours for a live fetus and 11 hours for a dead fetus. In the high-dose group, the median time to deliver a live fetus was 15.5 hours, compared with 11 hours for a dead fetus.

When the two groups were analyzed considering only live fetuses, however, the high-dose protocol still effected earlier delivery, with a median time to delivery of 15.5 hours, compared with 23.5 hours for the low-dose group, according to Dr. Edwards.

WHITE SULPHUR SPRINGS, W.VA. — Occiput posterior fetal head position during a vacuum delivery incrementally increases the risk of anal sphincter injury above the risk imposed by the vacuum alone, Jennifer Wu, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

In her retrospective study, vacuum delivery from the OP position was four times more likely to result in a sphincter-injuring third- or fourth-degree tear than vacuum delivery from the occiput anterior (OA) position.

“This is an important issue to consider when weighing the risks and benefits of performing a vacuum delivery from the OP position, especially when one of the goals is to reduce the risk of maternal perineal trauma,” said Dr. Wu of the University of North Carolina, Chapel Hill.

She retrospectively analyzed a total of 393 vacuum deliveries performed at the university from 1996 to 2003. Anal sphincter injury was defined as a third‐ or fourth-degree laceration.

There were 48 deliveries from the OP position and 345 deliveries from the OA position. Women in the OP group were significantly younger than those in the OA group (24 years vs. 28 years), more likely to be nulliparous (87% vs. 74%), and more likely to have received an episiotomy (35% vs. 14%).

The infants' gestational age, head circumference, and birth weight were not significantly different between the groups.

The overall anal sphincter injury rate was 24%. Significantly more women in the OP group sustained an anal sphincter injury (42% vs. 22%).

In a multivariate analysis that took into account fetal head position, body mass index, race, nulliparity, length of second stage, episiotomy, birth weight and head circumference, the OP position was four times more likely to be associated with an anal sphincter injury than the OA position.

In a previous retrospective study of 588 forceps deliveries, Dr. Wu also found an increased anal sphincter injury rate among OP deliveries, compared with OA deliveries (51% vs. 33%).

WHITE SULPHUR SPRINGS, W.VA. — Occiput posterior fetal head position during a vacuum delivery incrementally increases the risk of anal sphincter injury above the risk imposed by the vacuum alone, Jennifer Wu, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

In her retrospective study, vacuum delivery from the OP position was four times more likely to result in a sphincter-injuring third- or fourth-degree tear than vacuum delivery from the occiput anterior (OA) position.

“This is an important issue to consider when weighing the risks and benefits of performing a vacuum delivery from the OP position, especially when one of the goals is to reduce the risk of maternal perineal trauma,” said Dr. Wu of the University of North Carolina, Chapel Hill.

She retrospectively analyzed a total of 393 vacuum deliveries performed at the university from 1996 to 2003. Anal sphincter injury was defined as a third‐ or fourth-degree laceration.

There were 48 deliveries from the OP position and 345 deliveries from the OA position. Women in the OP group were significantly younger than those in the OA group (24 years vs. 28 years), more likely to be nulliparous (87% vs. 74%), and more likely to have received an episiotomy (35% vs. 14%).

The infants' gestational age, head circumference, and birth weight were not significantly different between the groups.

The overall anal sphincter injury rate was 24%. Significantly more women in the OP group sustained an anal sphincter injury (42% vs. 22%).

In a multivariate analysis that took into account fetal head position, body mass index, race, nulliparity, length of second stage, episiotomy, birth weight and head circumference, the OP position was four times more likely to be associated with an anal sphincter injury than the OA position.

In a previous retrospective study of 588 forceps deliveries, Dr. Wu also found an increased anal sphincter injury rate among OP deliveries, compared with OA deliveries (51% vs. 33%).

WHITE SULPHUR SPRINGS, W.VA. — Occiput posterior fetal head position during a vacuum delivery incrementally increases the risk of anal sphincter injury above the risk imposed by the vacuum alone, Jennifer Wu, M.D., said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

In her retrospective study, vacuum delivery from the OP position was four times more likely to result in a sphincter-injuring third- or fourth-degree tear than vacuum delivery from the occiput anterior (OA) position.

“This is an important issue to consider when weighing the risks and benefits of performing a vacuum delivery from the OP position, especially when one of the goals is to reduce the risk of maternal perineal trauma,” said Dr. Wu of the University of North Carolina, Chapel Hill.

She retrospectively analyzed a total of 393 vacuum deliveries performed at the university from 1996 to 2003. Anal sphincter injury was defined as a third‐ or fourth-degree laceration.

There were 48 deliveries from the OP position and 345 deliveries from the OA position. Women in the OP group were significantly younger than those in the OA group (24 years vs. 28 years), more likely to be nulliparous (87% vs. 74%), and more likely to have received an episiotomy (35% vs. 14%).

The infants' gestational age, head circumference, and birth weight were not significantly different between the groups.

The overall anal sphincter injury rate was 24%. Significantly more women in the OP group sustained an anal sphincter injury (42% vs. 22%).

In a multivariate analysis that took into account fetal head position, body mass index, race, nulliparity, length of second stage, episiotomy, birth weight and head circumference, the OP position was four times more likely to be associated with an anal sphincter injury than the OA position.

In a previous retrospective study of 588 forceps deliveries, Dr. Wu also found an increased anal sphincter injury rate among OP deliveries, compared with OA deliveries (51% vs. 33%).

RANCHO MIRAGE, CALIF. — Mothers who experience high levels of stress during early pregnancy appear to convey distress signals to their fetuses, prompting them to produce high levels of hormones that speed delivery.

The phenomenon suggests the presence of a “placental clock” for parturition that may be set months before the onset of labor, said Curt A. Sandman, Ph.D., professor and vice chair of psychiatry at the University of California, Irvine.

The pattern was seen in a prospective evaluation of pregnant California women who happened to be enrolled in a comprehensive study of pregnancy outcomes when the magnitude 6.7 Northridge earthquake struck on Jan. 17, 1994, killing dozens of people and leveling thousands of homes.

Those subjects who were in their first trimester showed highly elevated levels of stress hormones, but those in their third trimester had much lower levels of stress hormones, Dr. Sandman said at a conference on sleep in infancy and childhood sponsored by the Annenberg Center for Health Sciences. Months later, women who had been exposed to the stress of the earthquake early in pregnancy were significantly more likely than other mothers to deliver early.

“An early maternal message that it's a hostile world primes the placental clock for a CRH [corticotropin-releasing hormone] response later,” he said.

Subsequent studies in 550 consecutive pregnant subjects confirmed a consistent link between high levels of maternal cortisol early in pregnancy and elevated levels of placenta-derived CRH in the third trimester. Every 1 U of cortisol (μg/dL) measured at weeks 14–16 predicted 34 U of CRH (pg/dL) at 30–32 weeks' gestation.

Elevated CRH not only seems to speed delivery, but also appears to have profound consequences on the fetal response to stimuli and, later, a child's response to stress.

The complex interaction between maternal stress, fetal CRH, pregnancy outcomes, and infant and childhood behavior has been the target of studies conducted over more than 12 years as part of the women and children's health and well-being project at UCI, Dr. Sandman explained.

More than 1,000 women and 600–700 infants have been enrolled thus far in studies that begin with extensive prenatal assessment beginning at about 10 weeks' gestation. Neuroendocrine profiles assess the maternal stress axis, while ultrasound examinations and studies of fetal behavior continue throughout pregnancy.

Infant stress examinations begin with the routine first heel-stick test received in the nursery, when researchers take advantage of a naturally occurring opportunity to evaluate salivary cortisol. Babies' responses to the stress of immunizations are also measured and temperament analyses conducted at 6–8 weeks.

The children continue to be followed. Beginning at aged 5–7 years, they are assessed with cognitive tests and structural MRI.

A number of intriguing observations have emerged from the UCI studies, including evidence that suggests stress in the womb may have far-reaching consequences on health and behavior.

The metabolic story begins early in pregnancy, with an increase in neuropeptides from the maternal hypothalamic-pituitary-adrenal stress axis. Apparently in response, the placenta produces circulating CRH, which in turn downregulates the maternal stress system, blocking communication between the hypothalamus and pituitary.

Both the quantity and the timing of stress hormone production is important.

“Women, as pregnancy advances, become immunized to the effects of stress,” explained Dr. Sandman, who said the finding explains why stress hormones were not as high in subjects who experienced the earthquake late in pregnancy.

Further research by the UCI group suggests that the fetus is very much influenced by stress signals. Fetuses exposed to high levels of stress hormones show a diminished ability to respond to new and familiar auditory stimuli. After birth, babies exposed early to high levels of stress hormones exhibit altered fear responses.

Dr. Sandman said these preliminary findings are not altogether surprising. Animal studies show that drought or famine produces smaller offspring, born early. This represents adaptation, since those animals that survive are small, requiring less food than usual in an environment of scarce resources.

Preterm birth may be an attempt to escape an inhospitable environment, identified as such by an exquisitely sensitive placenta measuring signals suggesting malnourishment or high levels of stress.

RANCHO MIRAGE, CALIF. — Mothers who experience high levels of stress during early pregnancy appear to convey distress signals to their fetuses, prompting them to produce high levels of hormones that speed delivery.

The phenomenon suggests the presence of a “placental clock” for parturition that may be set months before the onset of labor, said Curt A. Sandman, Ph.D., professor and vice chair of psychiatry at the University of California, Irvine.

The pattern was seen in a prospective evaluation of pregnant California women who happened to be enrolled in a comprehensive study of pregnancy outcomes when the magnitude 6.7 Northridge earthquake struck on Jan. 17, 1994, killing dozens of people and leveling thousands of homes.

Those subjects who were in their first trimester showed highly elevated levels of stress hormones, but those in their third trimester had much lower levels of stress hormones, Dr. Sandman said at a conference on sleep in infancy and childhood sponsored by the Annenberg Center for Health Sciences. Months later, women who had been exposed to the stress of the earthquake early in pregnancy were significantly more likely than other mothers to deliver early.

“An early maternal message that it's a hostile world primes the placental clock for a CRH [corticotropin-releasing hormone] response later,” he said.

Subsequent studies in 550 consecutive pregnant subjects confirmed a consistent link between high levels of maternal cortisol early in pregnancy and elevated levels of placenta-derived CRH in the third trimester. Every 1 U of cortisol (μg/dL) measured at weeks 14–16 predicted 34 U of CRH (pg/dL) at 30–32 weeks' gestation.

Elevated CRH not only seems to speed delivery, but also appears to have profound consequences on the fetal response to stimuli and, later, a child's response to stress.

The complex interaction between maternal stress, fetal CRH, pregnancy outcomes, and infant and childhood behavior has been the target of studies conducted over more than 12 years as part of the women and children's health and well-being project at UCI, Dr. Sandman explained.

More than 1,000 women and 600–700 infants have been enrolled thus far in studies that begin with extensive prenatal assessment beginning at about 10 weeks' gestation. Neuroendocrine profiles assess the maternal stress axis, while ultrasound examinations and studies of fetal behavior continue throughout pregnancy.

Infant stress examinations begin with the routine first heel-stick test received in the nursery, when researchers take advantage of a naturally occurring opportunity to evaluate salivary cortisol. Babies' responses to the stress of immunizations are also measured and temperament analyses conducted at 6–8 weeks.

The children continue to be followed. Beginning at aged 5–7 years, they are assessed with cognitive tests and structural MRI.

A number of intriguing observations have emerged from the UCI studies, including evidence that suggests stress in the womb may have far-reaching consequences on health and behavior.

The metabolic story begins early in pregnancy, with an increase in neuropeptides from the maternal hypothalamic-pituitary-adrenal stress axis. Apparently in response, the placenta produces circulating CRH, which in turn downregulates the maternal stress system, blocking communication between the hypothalamus and pituitary.

Both the quantity and the timing of stress hormone production is important.

“Women, as pregnancy advances, become immunized to the effects of stress,” explained Dr. Sandman, who said the finding explains why stress hormones were not as high in subjects who experienced the earthquake late in pregnancy.

Further research by the UCI group suggests that the fetus is very much influenced by stress signals. Fetuses exposed to high levels of stress hormones show a diminished ability to respond to new and familiar auditory stimuli. After birth, babies exposed early to high levels of stress hormones exhibit altered fear responses.

Dr. Sandman said these preliminary findings are not altogether surprising. Animal studies show that drought or famine produces smaller offspring, born early. This represents adaptation, since those animals that survive are small, requiring less food than usual in an environment of scarce resources.

Preterm birth may be an attempt to escape an inhospitable environment, identified as such by an exquisitely sensitive placenta measuring signals suggesting malnourishment or high levels of stress.

RANCHO MIRAGE, CALIF. — Mothers who experience high levels of stress during early pregnancy appear to convey distress signals to their fetuses, prompting them to produce high levels of hormones that speed delivery.

The phenomenon suggests the presence of a “placental clock” for parturition that may be set months before the onset of labor, said Curt A. Sandman, Ph.D., professor and vice chair of psychiatry at the University of California, Irvine.

The pattern was seen in a prospective evaluation of pregnant California women who happened to be enrolled in a comprehensive study of pregnancy outcomes when the magnitude 6.7 Northridge earthquake struck on Jan. 17, 1994, killing dozens of people and leveling thousands of homes.

Those subjects who were in their first trimester showed highly elevated levels of stress hormones, but those in their third trimester had much lower levels of stress hormones, Dr. Sandman said at a conference on sleep in infancy and childhood sponsored by the Annenberg Center for Health Sciences. Months later, women who had been exposed to the stress of the earthquake early in pregnancy were significantly more likely than other mothers to deliver early.

“An early maternal message that it's a hostile world primes the placental clock for a CRH [corticotropin-releasing hormone] response later,” he said.

Subsequent studies in 550 consecutive pregnant subjects confirmed a consistent link between high levels of maternal cortisol early in pregnancy and elevated levels of placenta-derived CRH in the third trimester. Every 1 U of cortisol (μg/dL) measured at weeks 14–16 predicted 34 U of CRH (pg/dL) at 30–32 weeks' gestation.

Elevated CRH not only seems to speed delivery, but also appears to have profound consequences on the fetal response to stimuli and, later, a child's response to stress.

The complex interaction between maternal stress, fetal CRH, pregnancy outcomes, and infant and childhood behavior has been the target of studies conducted over more than 12 years as part of the women and children's health and well-being project at UCI, Dr. Sandman explained.

More than 1,000 women and 600–700 infants have been enrolled thus far in studies that begin with extensive prenatal assessment beginning at about 10 weeks' gestation. Neuroendocrine profiles assess the maternal stress axis, while ultrasound examinations and studies of fetal behavior continue throughout pregnancy.

Infant stress examinations begin with the routine first heel-stick test received in the nursery, when researchers take advantage of a naturally occurring opportunity to evaluate salivary cortisol. Babies' responses to the stress of immunizations are also measured and temperament analyses conducted at 6–8 weeks.

The children continue to be followed. Beginning at aged 5–7 years, they are assessed with cognitive tests and structural MRI.

A number of intriguing observations have emerged from the UCI studies, including evidence that suggests stress in the womb may have far-reaching consequences on health and behavior.

The metabolic story begins early in pregnancy, with an increase in neuropeptides from the maternal hypothalamic-pituitary-adrenal stress axis. Apparently in response, the placenta produces circulating CRH, which in turn downregulates the maternal stress system, blocking communication between the hypothalamus and pituitary.

Both the quantity and the timing of stress hormone production is important.

“Women, as pregnancy advances, become immunized to the effects of stress,” explained Dr. Sandman, who said the finding explains why stress hormones were not as high in subjects who experienced the earthquake late in pregnancy.

Further research by the UCI group suggests that the fetus is very much influenced by stress signals. Fetuses exposed to high levels of stress hormones show a diminished ability to respond to new and familiar auditory stimuli. After birth, babies exposed early to high levels of stress hormones exhibit altered fear responses.

Dr. Sandman said these preliminary findings are not altogether surprising. Animal studies show that drought or famine produces smaller offspring, born early. This represents adaptation, since those animals that survive are small, requiring less food than usual in an environment of scarce resources.

Preterm birth may be an attempt to escape an inhospitable environment, identified as such by an exquisitely sensitive placenta measuring signals suggesting malnourishment or high levels of stress.

SAN DIEGO — Pregnant women who present with changing nevi should not be treated differently from other patients of similar age, Dina R. Massry, M.D., said at a melanoma update sponsored by the Scripps Clinic.

“Prompt biopsy is key,” said Dr. Massry, a dermatologist with the division of dermatology and cutaneous surgery at the Scripps Clinic-Torrey Pines, La Jolla, Calif.

While it is commonly accepted that nevi enlarge and change during pregnancy and that new nevi develop, pregnant women “may get a false sense of security and disregard something that may be potentially worrisome and not get evaluated,” she noted. Pregnant women may not be aware that they should be concerned about irregular or changing moles.

Any changing mole—especially one that has become irregular or asymmetric—could be a melanoma. Synchronous and homogeneous darkening of multiple moles “is probably normal but still should be evaluated,” she said. A delayed diagnosis of melanoma in pregnant patients illustrates that physicians should treat changing nevi exactly the same in pregnant and nonpregnant patients, and biopsy the moles promptly.

No study has identified a difference in survival rates between pregnant patients with melanoma and nonpregnant, age-matched controls, but studies consistently show an increase in median thickness among pregnant patients with melanoma, compared with nonpregnant, age-matched controls. While a delay in melanoma diagnosis is the likely cause for this difference, Dr. Massry said that there are no data to confirm or refute the possible role of growth factors that induce thicker and more rapidly growing melanomas.

In her presentation, she also addressed the following questions related to melanoma:

▸ How does one approach recurrent melanoma in pregnant patients with stage II-IV disease? CT and x-ray can be used if the benefits and risks are discussed with the patient. One study supports the use of MRI in the systemic work-up (Semin. Oncol. 2000; 27:623–32).

Another analysis (Curr. Opin. Oncol. 1999;11:129–31) reports that the manufacturers and suppliers of interferon have “sparse data” on pregnant patients that suggest babies delivered to mothers receiving interferon therapy have low birth weights, Dr. Massry said.

She added that dacarbazine is considered the best treatment for pregnant patients with advanced disease.

▸ What is the risk to the fetus in a pregnancy complicated by melanoma? Transplacental metastases occur only in patients with hematogenous dissemination of melanoma. The incidence of maternal malignancy during pregnancy is 1 per 1,000, and melanoma accounts for 8% of all cancers during pregnancy.

“About 25% of the cancer that is metastatic to the parts of conception involve the fetus,” Dr. Massry said. “Of cases with fetal involvement, 58% or so arise via melanoma.”

At birth, she advised, “you want to do a thorough evaluation of the infant, a gross microscopic examination of the placenta, and [an examination of] the cord blood buffy coat for tumor cells.”

▸ When can a woman safely become pregnant after treatment of melanoma? The commonly accepted advice is to avoid conception for 2–3 years if their lesions were 1.5 mm or smaller and 5–8 years if their lesions were greater than 1.5 mm. Part of this recommendation has to do with [when] most recurrences are likely to occur, she said. “If you're talking to a 20-year-old woman versus maybe a 40-year-old woman, the recommendations may change, depending on what their sense of urgency is” regarding childbearing.”

Some investigators support the notion of individualized recommendations depending on tumor thickness, stage of diagnosis, age of the patient, and the desire of the patient to become pregnant (Cancer 2003;9:2130–3).

▸ Is there a link between melanoma and use of oral contraceptives or hormone therapy? Older studies suggest that high-dose oral contraceptives raise the risk of melanoma, but newer studies that include epidemiologic analysis refute the earlier data. For example, a controlled study of more than 2,000 women found no relationship between the incidence of melanoma and oral contraceptive use, age at onset of use, number of years used, or proximal relationship to use (Br. J. Cancer 2002; 86:1085–92).

Dr. Massry noted that there is “a paucity of information” on hormone therapy and melanoma. Some investigators maintain that there is no reason to withhold hormone therapy from a woman if it is otherwise recommended (Climacteric 2002;5:197–200).

SAN DIEGO — Pregnant women who present with changing nevi should not be treated differently from other patients of similar age, Dina R. Massry, M.D., said at a melanoma update sponsored by the Scripps Clinic.

“Prompt biopsy is key,” said Dr. Massry, a dermatologist with the division of dermatology and cutaneous surgery at the Scripps Clinic-Torrey Pines, La Jolla, Calif.

While it is commonly accepted that nevi enlarge and change during pregnancy and that new nevi develop, pregnant women “may get a false sense of security and disregard something that may be potentially worrisome and not get evaluated,” she noted. Pregnant women may not be aware that they should be concerned about irregular or changing moles.

Any changing mole—especially one that has become irregular or asymmetric—could be a melanoma. Synchronous and homogeneous darkening of multiple moles “is probably normal but still should be evaluated,” she said. A delayed diagnosis of melanoma in pregnant patients illustrates that physicians should treat changing nevi exactly the same in pregnant and nonpregnant patients, and biopsy the moles promptly.

No study has identified a difference in survival rates between pregnant patients with melanoma and nonpregnant, age-matched controls, but studies consistently show an increase in median thickness among pregnant patients with melanoma, compared with nonpregnant, age-matched controls. While a delay in melanoma diagnosis is the likely cause for this difference, Dr. Massry said that there are no data to confirm or refute the possible role of growth factors that induce thicker and more rapidly growing melanomas.

In her presentation, she also addressed the following questions related to melanoma:

▸ How does one approach recurrent melanoma in pregnant patients with stage II-IV disease? CT and x-ray can be used if the benefits and risks are discussed with the patient. One study supports the use of MRI in the systemic work-up (Semin. Oncol. 2000; 27:623–32).

Another analysis (Curr. Opin. Oncol. 1999;11:129–31) reports that the manufacturers and suppliers of interferon have “sparse data” on pregnant patients that suggest babies delivered to mothers receiving interferon therapy have low birth weights, Dr. Massry said.

She added that dacarbazine is considered the best treatment for pregnant patients with advanced disease.

▸ What is the risk to the fetus in a pregnancy complicated by melanoma? Transplacental metastases occur only in patients with hematogenous dissemination of melanoma. The incidence of maternal malignancy during pregnancy is 1 per 1,000, and melanoma accounts for 8% of all cancers during pregnancy.

“About 25% of the cancer that is metastatic to the parts of conception involve the fetus,” Dr. Massry said. “Of cases with fetal involvement, 58% or so arise via melanoma.”

At birth, she advised, “you want to do a thorough evaluation of the infant, a gross microscopic examination of the placenta, and [an examination of] the cord blood buffy coat for tumor cells.”

▸ When can a woman safely become pregnant after treatment of melanoma? The commonly accepted advice is to avoid conception for 2–3 years if their lesions were 1.5 mm or smaller and 5–8 years if their lesions were greater than 1.5 mm. Part of this recommendation has to do with [when] most recurrences are likely to occur, she said. “If you're talking to a 20-year-old woman versus maybe a 40-year-old woman, the recommendations may change, depending on what their sense of urgency is” regarding childbearing.”

Some investigators support the notion of individualized recommendations depending on tumor thickness, stage of diagnosis, age of the patient, and the desire of the patient to become pregnant (Cancer 2003;9:2130–3).

▸ Is there a link between melanoma and use of oral contraceptives or hormone therapy? Older studies suggest that high-dose oral contraceptives raise the risk of melanoma, but newer studies that include epidemiologic analysis refute the earlier data. For example, a controlled study of more than 2,000 women found no relationship between the incidence of melanoma and oral contraceptive use, age at onset of use, number of years used, or proximal relationship to use (Br. J. Cancer 2002; 86:1085–92).

Dr. Massry noted that there is “a paucity of information” on hormone therapy and melanoma. Some investigators maintain that there is no reason to withhold hormone therapy from a woman if it is otherwise recommended (Climacteric 2002;5:197–200).

SAN DIEGO — Pregnant women who present with changing nevi should not be treated differently from other patients of similar age, Dina R. Massry, M.D., said at a melanoma update sponsored by the Scripps Clinic.

“Prompt biopsy is key,” said Dr. Massry, a dermatologist with the division of dermatology and cutaneous surgery at the Scripps Clinic-Torrey Pines, La Jolla, Calif.

While it is commonly accepted that nevi enlarge and change during pregnancy and that new nevi develop, pregnant women “may get a false sense of security and disregard something that may be potentially worrisome and not get evaluated,” she noted. Pregnant women may not be aware that they should be concerned about irregular or changing moles.

Any changing mole—especially one that has become irregular or asymmetric—could be a melanoma. Synchronous and homogeneous darkening of multiple moles “is probably normal but still should be evaluated,” she said. A delayed diagnosis of melanoma in pregnant patients illustrates that physicians should treat changing nevi exactly the same in pregnant and nonpregnant patients, and biopsy the moles promptly.

No study has identified a difference in survival rates between pregnant patients with melanoma and nonpregnant, age-matched controls, but studies consistently show an increase in median thickness among pregnant patients with melanoma, compared with nonpregnant, age-matched controls. While a delay in melanoma diagnosis is the likely cause for this difference, Dr. Massry said that there are no data to confirm or refute the possible role of growth factors that induce thicker and more rapidly growing melanomas.

In her presentation, she also addressed the following questions related to melanoma:

▸ How does one approach recurrent melanoma in pregnant patients with stage II-IV disease? CT and x-ray can be used if the benefits and risks are discussed with the patient. One study supports the use of MRI in the systemic work-up (Semin. Oncol. 2000; 27:623–32).

Another analysis (Curr. Opin. Oncol. 1999;11:129–31) reports that the manufacturers and suppliers of interferon have “sparse data” on pregnant patients that suggest babies delivered to mothers receiving interferon therapy have low birth weights, Dr. Massry said.

She added that dacarbazine is considered the best treatment for pregnant patients with advanced disease.

▸ What is the risk to the fetus in a pregnancy complicated by melanoma? Transplacental metastases occur only in patients with hematogenous dissemination of melanoma. The incidence of maternal malignancy during pregnancy is 1 per 1,000, and melanoma accounts for 8% of all cancers during pregnancy.

“About 25% of the cancer that is metastatic to the parts of conception involve the fetus,” Dr. Massry said. “Of cases with fetal involvement, 58% or so arise via melanoma.”

At birth, she advised, “you want to do a thorough evaluation of the infant, a gross microscopic examination of the placenta, and [an examination of] the cord blood buffy coat for tumor cells.”

▸ When can a woman safely become pregnant after treatment of melanoma? The commonly accepted advice is to avoid conception for 2–3 years if their lesions were 1.5 mm or smaller and 5–8 years if their lesions were greater than 1.5 mm. Part of this recommendation has to do with [when] most recurrences are likely to occur, she said. “If you're talking to a 20-year-old woman versus maybe a 40-year-old woman, the recommendations may change, depending on what their sense of urgency is” regarding childbearing.”

Some investigators support the notion of individualized recommendations depending on tumor thickness, stage of diagnosis, age of the patient, and the desire of the patient to become pregnant (Cancer 2003;9:2130–3).

▸ Is there a link between melanoma and use of oral contraceptives or hormone therapy? Older studies suggest that high-dose oral contraceptives raise the risk of melanoma, but newer studies that include epidemiologic analysis refute the earlier data. For example, a controlled study of more than 2,000 women found no relationship between the incidence of melanoma and oral contraceptive use, age at onset of use, number of years used, or proximal relationship to use (Br. J. Cancer 2002; 86:1085–92).

Dr. Massry noted that there is “a paucity of information” on hormone therapy and melanoma. Some investigators maintain that there is no reason to withhold hormone therapy from a woman if it is otherwise recommended (Climacteric 2002;5:197–200).