Obstetrics

When women receive an influenza vaccine during pregnancy, their babies benefit, according to a series of studies presented at the annual meeting of the Infectious Diseases Society of America in Philadelphia.

Three separate studies highlighted during a press conference all reached the same conclusion: that maternal vaccination enhances the well-being of newborns and infants when pregnancies coincide with influenza season.

The “Mother's Gift Study,” led by Dr. Mark C. Steinhoff of Cincinnati Children's Hospital Medical Center, tracked birth weights of infants born to 340 Bangladeshi mothers who were randomized to receive inactivated trivalent influenza (study group) or pneumococcal 23v vaccine (control) during the third trimester of pregnancy. The efficacy of vaccination was determined by comparing flulike respiratory illnesses with fever in the two groups over time, as the spread of the influenza virus waxed and waned.

During late 2004 and early 2005, little difference was seen in flulike illnesses between the two groups. But during a peak period of flu infection—February 2005 to November 2005—there was a 49% reduction in such illnesses among vaccinated women. Infants born to mothers immunized during flu season were significantly larger than those born to mothers who received the control vaccine during the same period—a mean of 3,186 g, compared with a mean of 2,972 g for infants born to nonimmunized mothers.

The striking difference in birth weights suggests that, in addition to those who were overtly ill, many unvaccinated mothers were exposed to mild cases of influenza that may have had an effect on the nutrition delivered to the placenta, said Dr. Steinhoff.

The theory makes sense because many other mild infections, including urinary tract infections, have been known to have a similarly detrimental effect on the developing fetus.

Evidence of healthier birth weights from a randomized controlled trial provide “very strong evidence that receiving the vaccination makes a difference,” said Dr. Steinhoff.

Further support for maternal seasonal influenza vaccination came from Saad B. Omer, Ph.D., of Emory University's Rollins School of Public Health in Atlanta.

He presented results of a retrospective study of health records from the Georgia Pregnancy Risk Assessment Monitoring System (PRAMS) designed to calculate the impact of maternal influenza immunization on prematurity and birth weight in a U.S. population.

A total of 6,410 births occurred between June 2004 and September 2006, with just 15% of infants born to mothers who were immunized for influenza during their pregnancies.

Immunized mothers were 70% less likely to give birth prematurely during widespread influenza activity periods, with an odds ratio of 0.3 (0.1-0.7), he said.

When potential confounders were controlled for, the likelihood of delivering a baby small for gestational age (SGA) was reduced by 70% as well, Dr. Omer reported at the press conference. The study results remained significant even after maternal age, race, insurance status, and prepregnancy maternal weight were controlled for.

In a third study, Yale University researchers investigated the impact of maternal immunization during pregnancy on the health of their infants from birth to 1 year of life.

Preliminary results of a matched case-control study (157 cases, 195 matched controls) found a 79% reduction in hospitalization among the infants aged 0-12 months when their mothers were vaccinated during pregnancy, reported Dr. Mariette Vázquez, a pediatrician at Yale, New Haven, Conn.

Protection appeared greatest (an 85% reduction in hospitalizations) among the most vulnerable infants, those 6 months or younger. Influenza vaccine is not recommended for children younger than age 6 months. When unvaccinated mothers were asked why they did not receive the flu shot during pregnancy, as recommended by the American College of Obstetricians and Gynecologists, most said they were never offered the vaccine, Dr. Vázquez said.

Findings from previous studies suggest that a “cultural change” may be necessary for obstetricians to become more involved in influenza vaccination campaigns, said Dr. William Schaffner, moderator of the press conference and a preventive medicine specialist from Vanderbilt University Medical Center in Nashville, Tenn.

While pediatricians consider vaccination a key part of their practices, obstetricians' offices aren't set up to order, store, and deliver vaccines, he said. However, evidence presented at the meeting of a “powerfully protective” effect on infants when their mothers are vaccinated during pregnancy may help to spur obstetricians to take a more active role in influenza prevention efforts, Dr. Schaffner predicted.

Dr. Steinhoff reported that he has received research grants from vaccine manufacturers Wyeth and Sarnoff-Aventis.

When women receive an influenza vaccine during pregnancy, their babies benefit, according to a series of studies presented at the annual meeting of the Infectious Diseases Society of America in Philadelphia.

Three separate studies highlighted during a press conference all reached the same conclusion: that maternal vaccination enhances the well-being of newborns and infants when pregnancies coincide with influenza season.

The “Mother's Gift Study,” led by Dr. Mark C. Steinhoff of Cincinnati Children's Hospital Medical Center, tracked birth weights of infants born to 340 Bangladeshi mothers who were randomized to receive inactivated trivalent influenza (study group) or pneumococcal 23v vaccine (control) during the third trimester of pregnancy. The efficacy of vaccination was determined by comparing flulike respiratory illnesses with fever in the two groups over time, as the spread of the influenza virus waxed and waned.

During late 2004 and early 2005, little difference was seen in flulike illnesses between the two groups. But during a peak period of flu infection—February 2005 to November 2005—there was a 49% reduction in such illnesses among vaccinated women. Infants born to mothers immunized during flu season were significantly larger than those born to mothers who received the control vaccine during the same period—a mean of 3,186 g, compared with a mean of 2,972 g for infants born to nonimmunized mothers.

The striking difference in birth weights suggests that, in addition to those who were overtly ill, many unvaccinated mothers were exposed to mild cases of influenza that may have had an effect on the nutrition delivered to the placenta, said Dr. Steinhoff.

The theory makes sense because many other mild infections, including urinary tract infections, have been known to have a similarly detrimental effect on the developing fetus.

Evidence of healthier birth weights from a randomized controlled trial provide “very strong evidence that receiving the vaccination makes a difference,” said Dr. Steinhoff.

Further support for maternal seasonal influenza vaccination came from Saad B. Omer, Ph.D., of Emory University's Rollins School of Public Health in Atlanta.

He presented results of a retrospective study of health records from the Georgia Pregnancy Risk Assessment Monitoring System (PRAMS) designed to calculate the impact of maternal influenza immunization on prematurity and birth weight in a U.S. population.

A total of 6,410 births occurred between June 2004 and September 2006, with just 15% of infants born to mothers who were immunized for influenza during their pregnancies.

Immunized mothers were 70% less likely to give birth prematurely during widespread influenza activity periods, with an odds ratio of 0.3 (0.1-0.7), he said.

When potential confounders were controlled for, the likelihood of delivering a baby small for gestational age (SGA) was reduced by 70% as well, Dr. Omer reported at the press conference. The study results remained significant even after maternal age, race, insurance status, and prepregnancy maternal weight were controlled for.

In a third study, Yale University researchers investigated the impact of maternal immunization during pregnancy on the health of their infants from birth to 1 year of life.

Preliminary results of a matched case-control study (157 cases, 195 matched controls) found a 79% reduction in hospitalization among the infants aged 0-12 months when their mothers were vaccinated during pregnancy, reported Dr. Mariette Vázquez, a pediatrician at Yale, New Haven, Conn.

Protection appeared greatest (an 85% reduction in hospitalizations) among the most vulnerable infants, those 6 months or younger. Influenza vaccine is not recommended for children younger than age 6 months. When unvaccinated mothers were asked why they did not receive the flu shot during pregnancy, as recommended by the American College of Obstetricians and Gynecologists, most said they were never offered the vaccine, Dr. Vázquez said.

Findings from previous studies suggest that a “cultural change” may be necessary for obstetricians to become more involved in influenza vaccination campaigns, said Dr. William Schaffner, moderator of the press conference and a preventive medicine specialist from Vanderbilt University Medical Center in Nashville, Tenn.

While pediatricians consider vaccination a key part of their practices, obstetricians' offices aren't set up to order, store, and deliver vaccines, he said. However, evidence presented at the meeting of a “powerfully protective” effect on infants when their mothers are vaccinated during pregnancy may help to spur obstetricians to take a more active role in influenza prevention efforts, Dr. Schaffner predicted.

Dr. Steinhoff reported that he has received research grants from vaccine manufacturers Wyeth and Sarnoff-Aventis.

When women receive an influenza vaccine during pregnancy, their babies benefit, according to a series of studies presented at the annual meeting of the Infectious Diseases Society of America in Philadelphia.

Three separate studies highlighted during a press conference all reached the same conclusion: that maternal vaccination enhances the well-being of newborns and infants when pregnancies coincide with influenza season.

The “Mother's Gift Study,” led by Dr. Mark C. Steinhoff of Cincinnati Children's Hospital Medical Center, tracked birth weights of infants born to 340 Bangladeshi mothers who were randomized to receive inactivated trivalent influenza (study group) or pneumococcal 23v vaccine (control) during the third trimester of pregnancy. The efficacy of vaccination was determined by comparing flulike respiratory illnesses with fever in the two groups over time, as the spread of the influenza virus waxed and waned.

During late 2004 and early 2005, little difference was seen in flulike illnesses between the two groups. But during a peak period of flu infection—February 2005 to November 2005—there was a 49% reduction in such illnesses among vaccinated women. Infants born to mothers immunized during flu season were significantly larger than those born to mothers who received the control vaccine during the same period—a mean of 3,186 g, compared with a mean of 2,972 g for infants born to nonimmunized mothers.

The striking difference in birth weights suggests that, in addition to those who were overtly ill, many unvaccinated mothers were exposed to mild cases of influenza that may have had an effect on the nutrition delivered to the placenta, said Dr. Steinhoff.

The theory makes sense because many other mild infections, including urinary tract infections, have been known to have a similarly detrimental effect on the developing fetus.

Evidence of healthier birth weights from a randomized controlled trial provide “very strong evidence that receiving the vaccination makes a difference,” said Dr. Steinhoff.

Further support for maternal seasonal influenza vaccination came from Saad B. Omer, Ph.D., of Emory University's Rollins School of Public Health in Atlanta.

He presented results of a retrospective study of health records from the Georgia Pregnancy Risk Assessment Monitoring System (PRAMS) designed to calculate the impact of maternal influenza immunization on prematurity and birth weight in a U.S. population.

A total of 6,410 births occurred between June 2004 and September 2006, with just 15% of infants born to mothers who were immunized for influenza during their pregnancies.

Immunized mothers were 70% less likely to give birth prematurely during widespread influenza activity periods, with an odds ratio of 0.3 (0.1-0.7), he said.

When potential confounders were controlled for, the likelihood of delivering a baby small for gestational age (SGA) was reduced by 70% as well, Dr. Omer reported at the press conference. The study results remained significant even after maternal age, race, insurance status, and prepregnancy maternal weight were controlled for.

In a third study, Yale University researchers investigated the impact of maternal immunization during pregnancy on the health of their infants from birth to 1 year of life.

Preliminary results of a matched case-control study (157 cases, 195 matched controls) found a 79% reduction in hospitalization among the infants aged 0-12 months when their mothers were vaccinated during pregnancy, reported Dr. Mariette Vázquez, a pediatrician at Yale, New Haven, Conn.

Protection appeared greatest (an 85% reduction in hospitalizations) among the most vulnerable infants, those 6 months or younger. Influenza vaccine is not recommended for children younger than age 6 months. When unvaccinated mothers were asked why they did not receive the flu shot during pregnancy, as recommended by the American College of Obstetricians and Gynecologists, most said they were never offered the vaccine, Dr. Vázquez said.

Findings from previous studies suggest that a “cultural change” may be necessary for obstetricians to become more involved in influenza vaccination campaigns, said Dr. William Schaffner, moderator of the press conference and a preventive medicine specialist from Vanderbilt University Medical Center in Nashville, Tenn.

While pediatricians consider vaccination a key part of their practices, obstetricians' offices aren't set up to order, store, and deliver vaccines, he said. However, evidence presented at the meeting of a “powerfully protective” effect on infants when their mothers are vaccinated during pregnancy may help to spur obstetricians to take a more active role in influenza prevention efforts, Dr. Schaffner predicted.

Dr. Steinhoff reported that he has received research grants from vaccine manufacturers Wyeth and Sarnoff-Aventis.

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until a woman has acquired the majority of her bone mass appears to have a protective effect on bones, astudy of more than 600 women found.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis. Most prior adolescent pregnancy studies, for instance, are limited to the immediate postpartum period,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, residency program director in the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women over 49 years old who presented for bone density scanning at one of four radiology groups in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. They defined osteoporosis as a T score of −2.5 or lower at the lumbar spine, the femoral neck, or the total femur.

The mean age of the study participants was 62 years, and 50% were either current or past smokers. Slightly more than one-quarter (27%) were using or had used a bisphosphonate, 64% were using or had used hormonal therapy, and 5% had used steroids.

Women with any breastfeeding had a significantly lower prevalence of osteoporosis (8%) than women who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Within the group of women who breastfed, those who were younger than age 27 years at their first pregnancy had a significantly higher prevalence of osteoporosis, compared with those who were 27 years of age and older at their first pregnancy (11% vs. 5%), he reported.

Of the women who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy when they were younger than age 27 and who had no history of breastfeeding (5% vs. 16%).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Based on the current evidence, along with these results, women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

Dr. Schnatz acknowledged certain limitations of the study, including its retrospective design.

The study was supported by an unrestricted grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

Women with any breastfeeding had a lower prevalence of osteoporosis than women who did not breastfeed.

Source DR. SCHNATZ

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until a woman has acquired the majority of her bone mass appears to have a protective effect on bones, astudy of more than 600 women found.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis. Most prior adolescent pregnancy studies, for instance, are limited to the immediate postpartum period,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, residency program director in the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women over 49 years old who presented for bone density scanning at one of four radiology groups in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. They defined osteoporosis as a T score of −2.5 or lower at the lumbar spine, the femoral neck, or the total femur.

The mean age of the study participants was 62 years, and 50% were either current or past smokers. Slightly more than one-quarter (27%) were using or had used a bisphosphonate, 64% were using or had used hormonal therapy, and 5% had used steroids.

Women with any breastfeeding had a significantly lower prevalence of osteoporosis (8%) than women who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Within the group of women who breastfed, those who were younger than age 27 years at their first pregnancy had a significantly higher prevalence of osteoporosis, compared with those who were 27 years of age and older at their first pregnancy (11% vs. 5%), he reported.

Of the women who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy when they were younger than age 27 and who had no history of breastfeeding (5% vs. 16%).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Based on the current evidence, along with these results, women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

Dr. Schnatz acknowledged certain limitations of the study, including its retrospective design.

The study was supported by an unrestricted grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

Women with any breastfeeding had a lower prevalence of osteoporosis than women who did not breastfeed.

Source DR. SCHNATZ

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until a woman has acquired the majority of her bone mass appears to have a protective effect on bones, astudy of more than 600 women found.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis. Most prior adolescent pregnancy studies, for instance, are limited to the immediate postpartum period,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, residency program director in the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women over 49 years old who presented for bone density scanning at one of four radiology groups in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. They defined osteoporosis as a T score of −2.5 or lower at the lumbar spine, the femoral neck, or the total femur.

The mean age of the study participants was 62 years, and 50% were either current or past smokers. Slightly more than one-quarter (27%) were using or had used a bisphosphonate, 64% were using or had used hormonal therapy, and 5% had used steroids.

Women with any breastfeeding had a significantly lower prevalence of osteoporosis (8%) than women who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Within the group of women who breastfed, those who were younger than age 27 years at their first pregnancy had a significantly higher prevalence of osteoporosis, compared with those who were 27 years of age and older at their first pregnancy (11% vs. 5%), he reported.

Of the women who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy when they were younger than age 27 and who had no history of breastfeeding (5% vs. 16%).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Based on the current evidence, along with these results, women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

Dr. Schnatz acknowledged certain limitations of the study, including its retrospective design.

The study was supported by an unrestricted grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

Women with any breastfeeding had a lower prevalence of osteoporosis than women who did not breastfeed.

Source DR. SCHNATZ

Reprinted with permission from Medical Malpractice Verdicts, Settlements and Experts, Lewis Laska, Editor, (800) 298-6288.

Did Patient Require Clearance for Surgery?
A 36-year-old man was admitted to the defendant hospital with congestive heart failure and shortness of breath. CT angiography revealed cardiomegaly and several enlarged mediastinal lymph nodes. His medical history included cigarette smoking and ongoing treatment for tuberculosis and diabetes.

Echocardiography performed soon after the man's admission revealed diffuse hypokinesis consistent with cardiomyopathy and an ejection fraction of 30% to 35%. Two days later, a differential diagnosis was formed for the enlarged lymph nodes which included disseminated tuberculosis, infection (including the possibility of HIV), and neoplasm. A lymph node biopsy by way of mediastinoscopy was recommended.

The following day, the patient was seen by a cardiothoracic surgeon, who also recommended a mediastinoscopy and obtained consent from the patient for the procedure. That same day, an adenosine Cardiolite stress test was performed, with neither ischemia nor chest pain reported. The imaging portion of the study indicated several areas of prior infarction and an ejection fraction of 20%.

The following day, the man was seen by the defendant cardiologist, who added two cardiac agents to his medications. A plan was formulated to await results of a lymph node biopsy, scheduled for a few hours later, and to continue to follow the patient.

No complications occurred during the mediastinoscopy, but immediately after extubation, the man went into cardiopulmonary arrest. He was resuscitated but never regained consciousness. Two days later, he experience a second arrest and died.

Autopsy revealed triple-vessel coronary artery disease and a hemorrhagic septal infarction. The plaintiffs claimed that the decedent's presentation and coronary artery risk factors required that he not be cleared for surgery without undergoing coronary angiography. Angiography results, the plaintiff claimed, would have prompted bypass surgery and ensured the decedent's survival.

The defendant claimed that the treatment was proper, that a presurgery cardiac catheterization was not required, and that she had not been consulted to clear the decedent for surgery. The defendant further argued that the decedent's postsurgical cardiopulmonary arrest resulted from an adverse reaction to epinephrine and administration of 700 cc of IV fluid.

According to a published account, a defense verdict was returned.

Peritoneal Abscess, Colonic Rupture Missed
Sudden-onset abdominal pain brought a 69-year-old woman to the emergency department, where she was seen by a surgeon. He ordered abdominal CT, which was read by the defendant radiologist as showing free air. The next day a pelvic CT was read by the same radiologist, who concluded that the patient's colon appeared healthy. After undergoing a cholecystectomy the next day, the patient was soon released.

She returned to the hospital three days later with persistent pain, and a third CT scan showed free air. Exploratory laparotomy revealed a colonic rupture related to diverticulitis. In spite of aggressive intervention, the woman died several weeks later due to complications of sepsis.

The plaintiff alleged that the radiologist had misread the second CT, which had shown evidence of peritoneal abscess. The plaintiff claimed that a proper reading of this CT would have led to repair of the perforation before sepsis became fulminant.

The defense claimed that the reading of the pelvic CT was reasonable and that the woman's death was the result of comorbidities and complications from several previous surgeries.

A defense verdict was returned.

Infant Injured During (or After?) Cesarean Delivery
After a nonemergent cesarean delivery by a physician from a women's medical group in June 2001, the plaintiff infant was noted to be jittery and hypertonic, and stridor was developing, so she was admitted to a special care unit. Several hours later, the child's father noticed that her right hand was clenched in a fist except for the middle finger, which had a gash at the base.

He brought this to the attention of a nurse, who said it was probably just dried blood from the delivery. When she wiped the area, however, it began to bleed. The nurse then discovered a laceration, about 1.0 cm long and 0.5 cm deep, which extended into the bone of the finger. Two flexor tendons, the tendon pulleys, and a portion of the digital nerve had all been severed. Reconstructive surgery was performed two days later to reattach the tendons, rebuild the pulleys, and repair the nerve.

Because the infant could not participate actively in physical therapy, scar tissue developed. A second surgery was performed in March 2003 to release the tendons and nerve from the scar tissue.

By age 7, the girl had very limited use of her right middle finger and will need a third surgery to release additional scar tissue. This surgery has a success rate of only 65%, and function of the patient's finger will never be completely normal. The finger is also slightly shorter than the ring and index fingers. The plaintiff alleged res ipsa loquitur ("the thing speaks for itself").

Defense for the hospital argued that the laceration occurred during the cesarean delivery and was a known risk for this procedure. A resident obstetrician testified that she remembered the baby's hands being in the surgical field and "fighting" to come out as soon as the uterus was surgically entered. This, she claimed, was "the strangest thing she had ever seen."

Defense for the women's medical group argued that the laceration could not have occurred during the surgery based on the infant's face-down position at the time of delivery. It was alleged that the laceration must have occurred after the baby was handed off to a hospital staff member.

According to a published report, a $2,756,442 verdict was returned against the hospital. The women's medical group received a defense verdict.

Failure to Treat Ascending Cholangitis
In December 2002, a 45-year-old woman presented to the hospital with right upper quadrant abdominal pain, a urinary tract infection, and a pelvic infection. She also had a history of irritable bowel syndrome. The defendant family doctor, who had provided the patient's care for 10 years, admitted her and prescribed oral antibiotics to treat the urinary tract infection and the pelvic infection. Ultrasonography and magnetic resonance cholangiopancreatography showed a 3.0- to 4.0-cm mass at the head of the pancreas, a dilated common bile duct, and gallstones.

Lab test results included elevations in bilirubin, white blood cell count, and liver enzymes. The defendant gastroenterologist was called in for a consult.

Over the next few days, the woman's abdominal pain waxed and waned and shifted in location; her temperature dropped. After four days, her bilirubin level and white blood cell count spiked, so IV antibiotics were started. Two days later, the patient arrested and coded and remained in a coma until her death in May 2003.

The plaintiff claimed that the defendants failed to diagnose and treat ascending cholangitis from the time of the patient's admission until her cardiac arrest, resulting in sepsis and death.

The defendants claimed that the decedent did not have ascending cholangitis until two days before she went into arrest, at which time the condition was properly addressed. The defendants also claimed that there were no signs or symptoms of sepsis before that time and that the decedent had refused to consent to endoscopic retrograde cholangiopancreatography (ERCP) or surgical intervention. The defendants contended that a CT-guided biopsy was not performed because of the decedent's obesity.

The plaintiff denied that an ERCP or surgical intervention had been recommended and refused, since there was no record of this in the medical chart.

A defense verdict was returned.  

Reprinted with permission from Medical Malpractice Verdicts, Settlements and Experts, Lewis Laska, Editor, (800) 298-6288.

Did Patient Require Clearance for Surgery?
A 36-year-old man was admitted to the defendant hospital with congestive heart failure and shortness of breath. CT angiography revealed cardiomegaly and several enlarged mediastinal lymph nodes. His medical history included cigarette smoking and ongoing treatment for tuberculosis and diabetes.

Echocardiography performed soon after the man's admission revealed diffuse hypokinesis consistent with cardiomyopathy and an ejection fraction of 30% to 35%. Two days later, a differential diagnosis was formed for the enlarged lymph nodes which included disseminated tuberculosis, infection (including the possibility of HIV), and neoplasm. A lymph node biopsy by way of mediastinoscopy was recommended.

The following day, the patient was seen by a cardiothoracic surgeon, who also recommended a mediastinoscopy and obtained consent from the patient for the procedure. That same day, an adenosine Cardiolite stress test was performed, with neither ischemia nor chest pain reported. The imaging portion of the study indicated several areas of prior infarction and an ejection fraction of 20%.

The following day, the man was seen by the defendant cardiologist, who added two cardiac agents to his medications. A plan was formulated to await results of a lymph node biopsy, scheduled for a few hours later, and to continue to follow the patient.

No complications occurred during the mediastinoscopy, but immediately after extubation, the man went into cardiopulmonary arrest. He was resuscitated but never regained consciousness. Two days later, he experience a second arrest and died.

Autopsy revealed triple-vessel coronary artery disease and a hemorrhagic septal infarction. The plaintiffs claimed that the decedent's presentation and coronary artery risk factors required that he not be cleared for surgery without undergoing coronary angiography. Angiography results, the plaintiff claimed, would have prompted bypass surgery and ensured the decedent's survival.

The defendant claimed that the treatment was proper, that a presurgery cardiac catheterization was not required, and that she had not been consulted to clear the decedent for surgery. The defendant further argued that the decedent's postsurgical cardiopulmonary arrest resulted from an adverse reaction to epinephrine and administration of 700 cc of IV fluid.

According to a published account, a defense verdict was returned.

Peritoneal Abscess, Colonic Rupture Missed
Sudden-onset abdominal pain brought a 69-year-old woman to the emergency department, where she was seen by a surgeon. He ordered abdominal CT, which was read by the defendant radiologist as showing free air. The next day a pelvic CT was read by the same radiologist, who concluded that the patient's colon appeared healthy. After undergoing a cholecystectomy the next day, the patient was soon released.

She returned to the hospital three days later with persistent pain, and a third CT scan showed free air. Exploratory laparotomy revealed a colonic rupture related to diverticulitis. In spite of aggressive intervention, the woman died several weeks later due to complications of sepsis.

The plaintiff alleged that the radiologist had misread the second CT, which had shown evidence of peritoneal abscess. The plaintiff claimed that a proper reading of this CT would have led to repair of the perforation before sepsis became fulminant.

The defense claimed that the reading of the pelvic CT was reasonable and that the woman's death was the result of comorbidities and complications from several previous surgeries.

A defense verdict was returned.

Infant Injured During (or After?) Cesarean Delivery
After a nonemergent cesarean delivery by a physician from a women's medical group in June 2001, the plaintiff infant was noted to be jittery and hypertonic, and stridor was developing, so she was admitted to a special care unit. Several hours later, the child's father noticed that her right hand was clenched in a fist except for the middle finger, which had a gash at the base.

He brought this to the attention of a nurse, who said it was probably just dried blood from the delivery. When she wiped the area, however, it began to bleed. The nurse then discovered a laceration, about 1.0 cm long and 0.5 cm deep, which extended into the bone of the finger. Two flexor tendons, the tendon pulleys, and a portion of the digital nerve had all been severed. Reconstructive surgery was performed two days later to reattach the tendons, rebuild the pulleys, and repair the nerve.

Because the infant could not participate actively in physical therapy, scar tissue developed. A second surgery was performed in March 2003 to release the tendons and nerve from the scar tissue.

By age 7, the girl had very limited use of her right middle finger and will need a third surgery to release additional scar tissue. This surgery has a success rate of only 65%, and function of the patient's finger will never be completely normal. The finger is also slightly shorter than the ring and index fingers. The plaintiff alleged res ipsa loquitur ("the thing speaks for itself").

Defense for the hospital argued that the laceration occurred during the cesarean delivery and was a known risk for this procedure. A resident obstetrician testified that she remembered the baby's hands being in the surgical field and "fighting" to come out as soon as the uterus was surgically entered. This, she claimed, was "the strangest thing she had ever seen."

Defense for the women's medical group argued that the laceration could not have occurred during the surgery based on the infant's face-down position at the time of delivery. It was alleged that the laceration must have occurred after the baby was handed off to a hospital staff member.

According to a published report, a $2,756,442 verdict was returned against the hospital. The women's medical group received a defense verdict.

Failure to Treat Ascending Cholangitis
In December 2002, a 45-year-old woman presented to the hospital with right upper quadrant abdominal pain, a urinary tract infection, and a pelvic infection. She also had a history of irritable bowel syndrome. The defendant family doctor, who had provided the patient's care for 10 years, admitted her and prescribed oral antibiotics to treat the urinary tract infection and the pelvic infection. Ultrasonography and magnetic resonance cholangiopancreatography showed a 3.0- to 4.0-cm mass at the head of the pancreas, a dilated common bile duct, and gallstones.

Lab test results included elevations in bilirubin, white blood cell count, and liver enzymes. The defendant gastroenterologist was called in for a consult.

Over the next few days, the woman's abdominal pain waxed and waned and shifted in location; her temperature dropped. After four days, her bilirubin level and white blood cell count spiked, so IV antibiotics were started. Two days later, the patient arrested and coded and remained in a coma until her death in May 2003.

The plaintiff claimed that the defendants failed to diagnose and treat ascending cholangitis from the time of the patient's admission until her cardiac arrest, resulting in sepsis and death.

The defendants claimed that the decedent did not have ascending cholangitis until two days before she went into arrest, at which time the condition was properly addressed. The defendants also claimed that there were no signs or symptoms of sepsis before that time and that the decedent had refused to consent to endoscopic retrograde cholangiopancreatography (ERCP) or surgical intervention. The defendants contended that a CT-guided biopsy was not performed because of the decedent's obesity.

The plaintiff denied that an ERCP or surgical intervention had been recommended and refused, since there was no record of this in the medical chart.

A defense verdict was returned.  

Reprinted with permission from Medical Malpractice Verdicts, Settlements and Experts, Lewis Laska, Editor, (800) 298-6288.

Did Patient Require Clearance for Surgery?
A 36-year-old man was admitted to the defendant hospital with congestive heart failure and shortness of breath. CT angiography revealed cardiomegaly and several enlarged mediastinal lymph nodes. His medical history included cigarette smoking and ongoing treatment for tuberculosis and diabetes.

Echocardiography performed soon after the man's admission revealed diffuse hypokinesis consistent with cardiomyopathy and an ejection fraction of 30% to 35%. Two days later, a differential diagnosis was formed for the enlarged lymph nodes which included disseminated tuberculosis, infection (including the possibility of HIV), and neoplasm. A lymph node biopsy by way of mediastinoscopy was recommended.

The following day, the patient was seen by a cardiothoracic surgeon, who also recommended a mediastinoscopy and obtained consent from the patient for the procedure. That same day, an adenosine Cardiolite stress test was performed, with neither ischemia nor chest pain reported. The imaging portion of the study indicated several areas of prior infarction and an ejection fraction of 20%.

The following day, the man was seen by the defendant cardiologist, who added two cardiac agents to his medications. A plan was formulated to await results of a lymph node biopsy, scheduled for a few hours later, and to continue to follow the patient.

No complications occurred during the mediastinoscopy, but immediately after extubation, the man went into cardiopulmonary arrest. He was resuscitated but never regained consciousness. Two days later, he experience a second arrest and died.

Autopsy revealed triple-vessel coronary artery disease and a hemorrhagic septal infarction. The plaintiffs claimed that the decedent's presentation and coronary artery risk factors required that he not be cleared for surgery without undergoing coronary angiography. Angiography results, the plaintiff claimed, would have prompted bypass surgery and ensured the decedent's survival.

The defendant claimed that the treatment was proper, that a presurgery cardiac catheterization was not required, and that she had not been consulted to clear the decedent for surgery. The defendant further argued that the decedent's postsurgical cardiopulmonary arrest resulted from an adverse reaction to epinephrine and administration of 700 cc of IV fluid.

According to a published account, a defense verdict was returned.

Peritoneal Abscess, Colonic Rupture Missed
Sudden-onset abdominal pain brought a 69-year-old woman to the emergency department, where she was seen by a surgeon. He ordered abdominal CT, which was read by the defendant radiologist as showing free air. The next day a pelvic CT was read by the same radiologist, who concluded that the patient's colon appeared healthy. After undergoing a cholecystectomy the next day, the patient was soon released.

She returned to the hospital three days later with persistent pain, and a third CT scan showed free air. Exploratory laparotomy revealed a colonic rupture related to diverticulitis. In spite of aggressive intervention, the woman died several weeks later due to complications of sepsis.

The plaintiff alleged that the radiologist had misread the second CT, which had shown evidence of peritoneal abscess. The plaintiff claimed that a proper reading of this CT would have led to repair of the perforation before sepsis became fulminant.

The defense claimed that the reading of the pelvic CT was reasonable and that the woman's death was the result of comorbidities and complications from several previous surgeries.

A defense verdict was returned.

Infant Injured During (or After?) Cesarean Delivery
After a nonemergent cesarean delivery by a physician from a women's medical group in June 2001, the plaintiff infant was noted to be jittery and hypertonic, and stridor was developing, so she was admitted to a special care unit. Several hours later, the child's father noticed that her right hand was clenched in a fist except for the middle finger, which had a gash at the base.

He brought this to the attention of a nurse, who said it was probably just dried blood from the delivery. When she wiped the area, however, it began to bleed. The nurse then discovered a laceration, about 1.0 cm long and 0.5 cm deep, which extended into the bone of the finger. Two flexor tendons, the tendon pulleys, and a portion of the digital nerve had all been severed. Reconstructive surgery was performed two days later to reattach the tendons, rebuild the pulleys, and repair the nerve.

Because the infant could not participate actively in physical therapy, scar tissue developed. A second surgery was performed in March 2003 to release the tendons and nerve from the scar tissue.

By age 7, the girl had very limited use of her right middle finger and will need a third surgery to release additional scar tissue. This surgery has a success rate of only 65%, and function of the patient's finger will never be completely normal. The finger is also slightly shorter than the ring and index fingers. The plaintiff alleged res ipsa loquitur ("the thing speaks for itself").

Defense for the hospital argued that the laceration occurred during the cesarean delivery and was a known risk for this procedure. A resident obstetrician testified that she remembered the baby's hands being in the surgical field and "fighting" to come out as soon as the uterus was surgically entered. This, she claimed, was "the strangest thing she had ever seen."

Defense for the women's medical group argued that the laceration could not have occurred during the surgery based on the infant's face-down position at the time of delivery. It was alleged that the laceration must have occurred after the baby was handed off to a hospital staff member.

According to a published report, a $2,756,442 verdict was returned against the hospital. The women's medical group received a defense verdict.

Failure to Treat Ascending Cholangitis
In December 2002, a 45-year-old woman presented to the hospital with right upper quadrant abdominal pain, a urinary tract infection, and a pelvic infection. She also had a history of irritable bowel syndrome. The defendant family doctor, who had provided the patient's care for 10 years, admitted her and prescribed oral antibiotics to treat the urinary tract infection and the pelvic infection. Ultrasonography and magnetic resonance cholangiopancreatography showed a 3.0- to 4.0-cm mass at the head of the pancreas, a dilated common bile duct, and gallstones.

Lab test results included elevations in bilirubin, white blood cell count, and liver enzymes. The defendant gastroenterologist was called in for a consult.

Over the next few days, the woman's abdominal pain waxed and waned and shifted in location; her temperature dropped. After four days, her bilirubin level and white blood cell count spiked, so IV antibiotics were started. Two days later, the patient arrested and coded and remained in a coma until her death in May 2003.

The plaintiff claimed that the defendants failed to diagnose and treat ascending cholangitis from the time of the patient's admission until her cardiac arrest, resulting in sepsis and death.

The defendants claimed that the decedent did not have ascending cholangitis until two days before she went into arrest, at which time the condition was properly addressed. The defendants also claimed that there were no signs or symptoms of sepsis before that time and that the decedent had refused to consent to endoscopic retrograde cholangiopancreatography (ERCP) or surgical intervention. The defendants contended that a CT-guided biopsy was not performed because of the decedent's obesity.

The plaintiff denied that an ERCP or surgical intervention had been recommended and refused, since there was no record of this in the medical chart.

A defense verdict was returned.  

PHILADELPHIA — Sumatriptan and naratriptan do not appear to significantly raise the risk of major congenital malformations in fetuses that are exposed to the drugs in utero, according to the latest analysis of an international pregnancy registry.

Established in 1996, the GlaxoSmithKline registry has accumulated data on 849 pregnancies exposed to the drugs. Birth defects occurred in 4.5% of infants exposed in the first trimester or during all of their gestation, which was not significantly higher than that previously identified for women with migraines.

Major congenital malformations are known to occur in the offspring of women with migraines at a slightly higher rate than in the general population (3.4% vs. 2%-3%, respectively), Marianne C. Cunnington, Ph.D, of GlaxoSmithKline in Harlow, England, reported in a poster at the International Headache Congress.

The registry relies on a voluntary reporting strategy that encourages health care providers to submit information on exposed pregnancies as early as possible. Retrospective case reporting also is accepted. Pregnancy outcome is ascertained by medical records that the provider forwards after birth, or by medical records confirming other outcomes, including fetal demise or abortion.

At the outset, the registry collects data on the timing, dosage, duration, indication, and administration of the drugs; maternal demographics; expected date of delivery; and any prenatal testing. At follow-up, there is a review of the pregnancy outcome, drug exposure during pregnancy, and the women's headache history during pregnancy.

So far, the registry has amassed information on 761 pregnancies exposed to sumatriptan and 88 exposed to naratriptan. Outcomes are known for 570 of the sumatriptan-exposed pregnancies and 57 of the naratriptan-exposed pregnancies. Twenty-one sumatriptan-exposed pregnancies and 31 naratriptan-exposed pregnancies are pending delivery. The rest have been lost to follow-up, Dr. Cunnington noted in the poster at the congress, which was sponsored by the International Headache Society and the American Headache Society.

Among the sumatriptan-exposed pregnancies, there were 23 birth defects, 4 fetal deaths, 32 spontaneous fetal losses, and 11 induced abortions.

The malformations that occurred in infants who were exposed to sumatriptan in the first trimester included abnormal head circumference, single palmar crease and systolic murmur; moderate craniosynostosis; cerebral abnormality with developmental delay; partial cleft lip; ventricular septal defects; biliary atresia; diaphragmatic hernia; pyloric stenosis; anterior displacement of anus; hip dysplasia; polydactyly; malformation of left hand; and Down syndrome.

No data were available for the three birth defects that occurred in infants who were exposed to sumatriptan after the first trimester.

Among fetuses exposed to naratriptan, there were five spontaneous losses, one induced abortion, and one live infant with a 2.5-mm ventricular septal defect that was expected to close spontaneously.

Dr. Cunnington noted that five additional independent studies, including a Swedish study of more than 2,000 sumatriptan recipients, have failed to find an increase in birth defects associated with in utero exposure. “While its use in pregnancy cannot be encouraged,” she and her colleague Sara A. Ephross, Ph.D., wrote, “there is consistent evidence that sumatriptan is not associated with a substantial increase in the risk of major congenital malformations following exposure.”

To report pregnancies exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen combination, North American physicians can call 800–336-2176, and international physicians can call 910-256-0549.

The report was published online in Headache (doi: 10.1111/j.1526-4610.2009.01529.x).

PHILADELPHIA — Sumatriptan and naratriptan do not appear to significantly raise the risk of major congenital malformations in fetuses that are exposed to the drugs in utero, according to the latest analysis of an international pregnancy registry.

Established in 1996, the GlaxoSmithKline registry has accumulated data on 849 pregnancies exposed to the drugs. Birth defects occurred in 4.5% of infants exposed in the first trimester or during all of their gestation, which was not significantly higher than that previously identified for women with migraines.

Major congenital malformations are known to occur in the offspring of women with migraines at a slightly higher rate than in the general population (3.4% vs. 2%-3%, respectively), Marianne C. Cunnington, Ph.D, of GlaxoSmithKline in Harlow, England, reported in a poster at the International Headache Congress.

The registry relies on a voluntary reporting strategy that encourages health care providers to submit information on exposed pregnancies as early as possible. Retrospective case reporting also is accepted. Pregnancy outcome is ascertained by medical records that the provider forwards after birth, or by medical records confirming other outcomes, including fetal demise or abortion.

At the outset, the registry collects data on the timing, dosage, duration, indication, and administration of the drugs; maternal demographics; expected date of delivery; and any prenatal testing. At follow-up, there is a review of the pregnancy outcome, drug exposure during pregnancy, and the women's headache history during pregnancy.

So far, the registry has amassed information on 761 pregnancies exposed to sumatriptan and 88 exposed to naratriptan. Outcomes are known for 570 of the sumatriptan-exposed pregnancies and 57 of the naratriptan-exposed pregnancies. Twenty-one sumatriptan-exposed pregnancies and 31 naratriptan-exposed pregnancies are pending delivery. The rest have been lost to follow-up, Dr. Cunnington noted in the poster at the congress, which was sponsored by the International Headache Society and the American Headache Society.

Among the sumatriptan-exposed pregnancies, there were 23 birth defects, 4 fetal deaths, 32 spontaneous fetal losses, and 11 induced abortions.

The malformations that occurred in infants who were exposed to sumatriptan in the first trimester included abnormal head circumference, single palmar crease and systolic murmur; moderate craniosynostosis; cerebral abnormality with developmental delay; partial cleft lip; ventricular septal defects; biliary atresia; diaphragmatic hernia; pyloric stenosis; anterior displacement of anus; hip dysplasia; polydactyly; malformation of left hand; and Down syndrome.

No data were available for the three birth defects that occurred in infants who were exposed to sumatriptan after the first trimester.

Among fetuses exposed to naratriptan, there were five spontaneous losses, one induced abortion, and one live infant with a 2.5-mm ventricular septal defect that was expected to close spontaneously.

Dr. Cunnington noted that five additional independent studies, including a Swedish study of more than 2,000 sumatriptan recipients, have failed to find an increase in birth defects associated with in utero exposure. “While its use in pregnancy cannot be encouraged,” she and her colleague Sara A. Ephross, Ph.D., wrote, “there is consistent evidence that sumatriptan is not associated with a substantial increase in the risk of major congenital malformations following exposure.”

To report pregnancies exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen combination, North American physicians can call 800–336-2176, and international physicians can call 910-256-0549.

The report was published online in Headache (doi: 10.1111/j.1526-4610.2009.01529.x).

PHILADELPHIA — Sumatriptan and naratriptan do not appear to significantly raise the risk of major congenital malformations in fetuses that are exposed to the drugs in utero, according to the latest analysis of an international pregnancy registry.

Established in 1996, the GlaxoSmithKline registry has accumulated data on 849 pregnancies exposed to the drugs. Birth defects occurred in 4.5% of infants exposed in the first trimester or during all of their gestation, which was not significantly higher than that previously identified for women with migraines.

Major congenital malformations are known to occur in the offspring of women with migraines at a slightly higher rate than in the general population (3.4% vs. 2%-3%, respectively), Marianne C. Cunnington, Ph.D, of GlaxoSmithKline in Harlow, England, reported in a poster at the International Headache Congress.

The registry relies on a voluntary reporting strategy that encourages health care providers to submit information on exposed pregnancies as early as possible. Retrospective case reporting also is accepted. Pregnancy outcome is ascertained by medical records that the provider forwards after birth, or by medical records confirming other outcomes, including fetal demise or abortion.

At the outset, the registry collects data on the timing, dosage, duration, indication, and administration of the drugs; maternal demographics; expected date of delivery; and any prenatal testing. At follow-up, there is a review of the pregnancy outcome, drug exposure during pregnancy, and the women's headache history during pregnancy.

So far, the registry has amassed information on 761 pregnancies exposed to sumatriptan and 88 exposed to naratriptan. Outcomes are known for 570 of the sumatriptan-exposed pregnancies and 57 of the naratriptan-exposed pregnancies. Twenty-one sumatriptan-exposed pregnancies and 31 naratriptan-exposed pregnancies are pending delivery. The rest have been lost to follow-up, Dr. Cunnington noted in the poster at the congress, which was sponsored by the International Headache Society and the American Headache Society.

Among the sumatriptan-exposed pregnancies, there were 23 birth defects, 4 fetal deaths, 32 spontaneous fetal losses, and 11 induced abortions.

The malformations that occurred in infants who were exposed to sumatriptan in the first trimester included abnormal head circumference, single palmar crease and systolic murmur; moderate craniosynostosis; cerebral abnormality with developmental delay; partial cleft lip; ventricular septal defects; biliary atresia; diaphragmatic hernia; pyloric stenosis; anterior displacement of anus; hip dysplasia; polydactyly; malformation of left hand; and Down syndrome.

No data were available for the three birth defects that occurred in infants who were exposed to sumatriptan after the first trimester.

Among fetuses exposed to naratriptan, there were five spontaneous losses, one induced abortion, and one live infant with a 2.5-mm ventricular septal defect that was expected to close spontaneously.

Dr. Cunnington noted that five additional independent studies, including a Swedish study of more than 2,000 sumatriptan recipients, have failed to find an increase in birth defects associated with in utero exposure. “While its use in pregnancy cannot be encouraged,” she and her colleague Sara A. Ephross, Ph.D., wrote, “there is consistent evidence that sumatriptan is not associated with a substantial increase in the risk of major congenital malformations following exposure.”

To report pregnancies exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen combination, North American physicians can call 800–336-2176, and international physicians can call 910-256-0549.

The report was published online in Headache (doi: 10.1111/j.1526-4610.2009.01529.x).

ATLANTA — The yellow fever vaccine is contraindicated for individuals receiving immunosuppressive therapies and for those with immunosuppressant conditions, but it can be used with caution in pregnant and breastfeeding women and in HIV-infected individuals with mild immunosuppression and no symptoms.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) reached this conclusion at its fall meeting based on an evaluation of vaccine-associated serious adverse events in certain populations. ACIP recommended that the CDC update its current advisory for the use of yellow fever vaccine for U.S. citizens traveling to high-risk areas.

“Approximately 30,000 deaths are caused by yellow fever each year,” according to Dr. J. Erin Staples of the CDC.

A traveler's risk for yellow fever is based on several factors, including season of travel, immunization status, activities while traveling, and duration of exposure. Decisions regarding vaccination must balance the risk of contracting the disease against the risk of vaccine side effects, Dr. Staples said. The yellow fever vaccine is a live, attenuated vaccine, given as a single dose with a booster every 10 years. Some countries require proof of vaccination for travelers arriving from high-risk areas, she noted.

Safety studies have shown that approximately 10%-30% of vaccinees report mild systemic adverse events. Recent data suggest that the rate of serious events among vaccinees is 0.8/100,000 doses. Serious adverse events associated with the vaccine can include anaphylaxis, yellow fever–associated neurologic disease, and yellow fever vaccine–associated viscerotropic disease, she said.

The risk of transmission via breastfeeding is unknown. The working group recommended that yellow fever vaccine should be available to breastfeeding women if their travel to a high-risk area cannot be avoided or postponed, she said.

If a pregnant woman is planning to visit a region where the vaccine's potential risks outweigh the likelihood of contracting yellow fever, she should receive a medical waiver to fulfill international travel requirements, Dr. Staples said.

A section of the recommendations spells out additional circumstances for providing medical waivers, Dr. Staples said.

The yellow fever working group of ACIP determined that, based on the latest safety information, yellow fever vaccination is contraindicated for anyone with immunosuppression, including individuals with primary immunodeficiencies, malignant neoplasms, thymus disorder, transplants, and HIV infection with severe immunodeficiencies. The vaccine also is contraindicated in persons receiving radiation therapy, chemotherapy, high-dose systemic corticosteroids, and immunomodulatory drugs. Likewise, the vaccine is contraindicated for infants younger than 6 months of age and individuals with hypersensitivity to any of the vaccine's components.

ATLANTA — The yellow fever vaccine is contraindicated for individuals receiving immunosuppressive therapies and for those with immunosuppressant conditions, but it can be used with caution in pregnant and breastfeeding women and in HIV-infected individuals with mild immunosuppression and no symptoms.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) reached this conclusion at its fall meeting based on an evaluation of vaccine-associated serious adverse events in certain populations. ACIP recommended that the CDC update its current advisory for the use of yellow fever vaccine for U.S. citizens traveling to high-risk areas.

“Approximately 30,000 deaths are caused by yellow fever each year,” according to Dr. J. Erin Staples of the CDC.

A traveler's risk for yellow fever is based on several factors, including season of travel, immunization status, activities while traveling, and duration of exposure. Decisions regarding vaccination must balance the risk of contracting the disease against the risk of vaccine side effects, Dr. Staples said. The yellow fever vaccine is a live, attenuated vaccine, given as a single dose with a booster every 10 years. Some countries require proof of vaccination for travelers arriving from high-risk areas, she noted.

Safety studies have shown that approximately 10%-30% of vaccinees report mild systemic adverse events. Recent data suggest that the rate of serious events among vaccinees is 0.8/100,000 doses. Serious adverse events associated with the vaccine can include anaphylaxis, yellow fever–associated neurologic disease, and yellow fever vaccine–associated viscerotropic disease, she said.

The risk of transmission via breastfeeding is unknown. The working group recommended that yellow fever vaccine should be available to breastfeeding women if their travel to a high-risk area cannot be avoided or postponed, she said.

If a pregnant woman is planning to visit a region where the vaccine's potential risks outweigh the likelihood of contracting yellow fever, she should receive a medical waiver to fulfill international travel requirements, Dr. Staples said.

A section of the recommendations spells out additional circumstances for providing medical waivers, Dr. Staples said.

The yellow fever working group of ACIP determined that, based on the latest safety information, yellow fever vaccination is contraindicated for anyone with immunosuppression, including individuals with primary immunodeficiencies, malignant neoplasms, thymus disorder, transplants, and HIV infection with severe immunodeficiencies. The vaccine also is contraindicated in persons receiving radiation therapy, chemotherapy, high-dose systemic corticosteroids, and immunomodulatory drugs. Likewise, the vaccine is contraindicated for infants younger than 6 months of age and individuals with hypersensitivity to any of the vaccine's components.

ATLANTA — The yellow fever vaccine is contraindicated for individuals receiving immunosuppressive therapies and for those with immunosuppressant conditions, but it can be used with caution in pregnant and breastfeeding women and in HIV-infected individuals with mild immunosuppression and no symptoms.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) reached this conclusion at its fall meeting based on an evaluation of vaccine-associated serious adverse events in certain populations. ACIP recommended that the CDC update its current advisory for the use of yellow fever vaccine for U.S. citizens traveling to high-risk areas.

“Approximately 30,000 deaths are caused by yellow fever each year,” according to Dr. J. Erin Staples of the CDC.

A traveler's risk for yellow fever is based on several factors, including season of travel, immunization status, activities while traveling, and duration of exposure. Decisions regarding vaccination must balance the risk of contracting the disease against the risk of vaccine side effects, Dr. Staples said. The yellow fever vaccine is a live, attenuated vaccine, given as a single dose with a booster every 10 years. Some countries require proof of vaccination for travelers arriving from high-risk areas, she noted.

Safety studies have shown that approximately 10%-30% of vaccinees report mild systemic adverse events. Recent data suggest that the rate of serious events among vaccinees is 0.8/100,000 doses. Serious adverse events associated with the vaccine can include anaphylaxis, yellow fever–associated neurologic disease, and yellow fever vaccine–associated viscerotropic disease, she said.

The risk of transmission via breastfeeding is unknown. The working group recommended that yellow fever vaccine should be available to breastfeeding women if their travel to a high-risk area cannot be avoided or postponed, she said.

If a pregnant woman is planning to visit a region where the vaccine's potential risks outweigh the likelihood of contracting yellow fever, she should receive a medical waiver to fulfill international travel requirements, Dr. Staples said.

A section of the recommendations spells out additional circumstances for providing medical waivers, Dr. Staples said.

The yellow fever working group of ACIP determined that, based on the latest safety information, yellow fever vaccination is contraindicated for anyone with immunosuppression, including individuals with primary immunodeficiencies, malignant neoplasms, thymus disorder, transplants, and HIV infection with severe immunodeficiencies. The vaccine also is contraindicated in persons receiving radiation therapy, chemotherapy, high-dose systemic corticosteroids, and immunomodulatory drugs. Likewise, the vaccine is contraindicated for infants younger than 6 months of age and individuals with hypersensitivity to any of the vaccine's components.

GRAPEVINE, TEX. — Obese women who have bariatric surgery prior to pregnancy have less complicated gestations, and their children are markedly less obese than are siblings born prior to mom's surgery, according to a Canadian study.

“Less obesity is not even the most important finding—it's the improvement in their metabolic condition. Children born after their mother's surgery had 30% less insulin resistance compared to their brothers and sisters born before the surgery. Regarding other elements of the metabolic syndrome, they also had a 20% decrease in triglyceride levels, their HDL was increased by 12%, and their waist circumference to height ratio was 11% better,” Dr. Picard Marceau reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The implication of these findings is that the propensity to develop obesity and the metabolic syndrome is transmitted through the generations not only via genetic factors, but also epigenetically through the intrauterine environment, said Dr. Marceau of Laval University, Quebec City. “Morbid obesity is a congenital and treatable disease. To curb the vicious cycle of the obesity epidemic, the focus must be put on pregnancy,” he continued. “The emphasis should be shifted from preventing undernutrition in pregnancy to preventing overnutrition in our affluent society. Surgery before pregnancy is a good option.”

He and his coworkers studied 37 very obese mothers who collectively gave birth to 56 children prior to undergoing a biliopancreatic diversion with duodenal switch (BPD) for weight loss and another 54 children afterward. To beef up the study size, the investigators added another 10 morbidly obese women who had all 23 of their children prior to the BPD and 10 others who had all 19 of their children post surgery. Children born before the mother's bariatric surgery have been prospectively followed on average to age 19 years, while those born post surgery have been followed to age 10.

The mothers' preoperative body mass index averaged 48.5 kg/m

The birth weight of the children born after mom's surgery was 17% lower than that of their siblings born prior to surgery. The incidence of macrosomia was reduced by 86%.

Strikingly, the prevalence of severe obesity as defined by a BMI above the 90th percentile for age and sex was 75% less in the children born after the mother's surgery than in those born before. Abdominal fat accumulated in the postsurgical children at a rate five times slower than in the siblings born prior to surgery.

The impact of the salutary postsurgical intrauterine environment differed in boys and girls. In boys, it was manifest mainly as less weight gain; boys born after the mother's surgery had an 86% lower prevalence of obesity than did their older brothers. In contrast, the main effects noted in girls born after the mother's surgery were a 40% reduction in insulin resistance and a 35% decrease in percent body fat compared with their sisters born presurgically. The study was supported by the Canadian Institute of Health Research.

GRAPEVINE, TEX. — Obese women who have bariatric surgery prior to pregnancy have less complicated gestations, and their children are markedly less obese than are siblings born prior to mom's surgery, according to a Canadian study.

“Less obesity is not even the most important finding—it's the improvement in their metabolic condition. Children born after their mother's surgery had 30% less insulin resistance compared to their brothers and sisters born before the surgery. Regarding other elements of the metabolic syndrome, they also had a 20% decrease in triglyceride levels, their HDL was increased by 12%, and their waist circumference to height ratio was 11% better,” Dr. Picard Marceau reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The implication of these findings is that the propensity to develop obesity and the metabolic syndrome is transmitted through the generations not only via genetic factors, but also epigenetically through the intrauterine environment, said Dr. Marceau of Laval University, Quebec City. “Morbid obesity is a congenital and treatable disease. To curb the vicious cycle of the obesity epidemic, the focus must be put on pregnancy,” he continued. “The emphasis should be shifted from preventing undernutrition in pregnancy to preventing overnutrition in our affluent society. Surgery before pregnancy is a good option.”

He and his coworkers studied 37 very obese mothers who collectively gave birth to 56 children prior to undergoing a biliopancreatic diversion with duodenal switch (BPD) for weight loss and another 54 children afterward. To beef up the study size, the investigators added another 10 morbidly obese women who had all 23 of their children prior to the BPD and 10 others who had all 19 of their children post surgery. Children born before the mother's bariatric surgery have been prospectively followed on average to age 19 years, while those born post surgery have been followed to age 10.

The mothers' preoperative body mass index averaged 48.5 kg/m

The birth weight of the children born after mom's surgery was 17% lower than that of their siblings born prior to surgery. The incidence of macrosomia was reduced by 86%.

Strikingly, the prevalence of severe obesity as defined by a BMI above the 90th percentile for age and sex was 75% less in the children born after the mother's surgery than in those born before. Abdominal fat accumulated in the postsurgical children at a rate five times slower than in the siblings born prior to surgery.

The impact of the salutary postsurgical intrauterine environment differed in boys and girls. In boys, it was manifest mainly as less weight gain; boys born after the mother's surgery had an 86% lower prevalence of obesity than did their older brothers. In contrast, the main effects noted in girls born after the mother's surgery were a 40% reduction in insulin resistance and a 35% decrease in percent body fat compared with their sisters born presurgically. The study was supported by the Canadian Institute of Health Research.

GRAPEVINE, TEX. — Obese women who have bariatric surgery prior to pregnancy have less complicated gestations, and their children are markedly less obese than are siblings born prior to mom's surgery, according to a Canadian study.

“Less obesity is not even the most important finding—it's the improvement in their metabolic condition. Children born after their mother's surgery had 30% less insulin resistance compared to their brothers and sisters born before the surgery. Regarding other elements of the metabolic syndrome, they also had a 20% decrease in triglyceride levels, their HDL was increased by 12%, and their waist circumference to height ratio was 11% better,” Dr. Picard Marceau reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The implication of these findings is that the propensity to develop obesity and the metabolic syndrome is transmitted through the generations not only via genetic factors, but also epigenetically through the intrauterine environment, said Dr. Marceau of Laval University, Quebec City. “Morbid obesity is a congenital and treatable disease. To curb the vicious cycle of the obesity epidemic, the focus must be put on pregnancy,” he continued. “The emphasis should be shifted from preventing undernutrition in pregnancy to preventing overnutrition in our affluent society. Surgery before pregnancy is a good option.”

He and his coworkers studied 37 very obese mothers who collectively gave birth to 56 children prior to undergoing a biliopancreatic diversion with duodenal switch (BPD) for weight loss and another 54 children afterward. To beef up the study size, the investigators added another 10 morbidly obese women who had all 23 of their children prior to the BPD and 10 others who had all 19 of their children post surgery. Children born before the mother's bariatric surgery have been prospectively followed on average to age 19 years, while those born post surgery have been followed to age 10.

The mothers' preoperative body mass index averaged 48.5 kg/m

The birth weight of the children born after mom's surgery was 17% lower than that of their siblings born prior to surgery. The incidence of macrosomia was reduced by 86%.

Strikingly, the prevalence of severe obesity as defined by a BMI above the 90th percentile for age and sex was 75% less in the children born after the mother's surgery than in those born before. Abdominal fat accumulated in the postsurgical children at a rate five times slower than in the siblings born prior to surgery.

The impact of the salutary postsurgical intrauterine environment differed in boys and girls. In boys, it was manifest mainly as less weight gain; boys born after the mother's surgery had an 86% lower prevalence of obesity than did their older brothers. In contrast, the main effects noted in girls born after the mother's surgery were a 40% reduction in insulin resistance and a 35% decrease in percent body fat compared with their sisters born presurgically. The study was supported by the Canadian Institute of Health Research.

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances this summer.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications. And the reason for that is we believe that science has taken us up to a point where we are concerned,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press conference at the society's annual meeting.

Researchers at the meeting also presented new animal studies on the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestational development, as well as the possible continual exposure of the majority of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing the evidence of the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, who noted that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

The scientific statement is published in the June issue of Endocrine Reviews (2009;30:293–342).

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA, which is a synthetic monomer used in the production of polycarbonate plastics and epoxy resins, as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE.

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the development of the uterus. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri–Columbia, also reported a study at the press conference. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA. But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8–9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done … [and] we can't afford to wait until we have perfect data in humans. When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling.”

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Medicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

Bisphenol A, found in products such as plastic water bottles, was among the endocrine disruptors discussed at the meeting.

Source Courtesy University of Cincinnati

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances this summer.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications. And the reason for that is we believe that science has taken us up to a point where we are concerned,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press conference at the society's annual meeting.

Researchers at the meeting also presented new animal studies on the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestational development, as well as the possible continual exposure of the majority of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing the evidence of the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, who noted that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

The scientific statement is published in the June issue of Endocrine Reviews (2009;30:293–342).

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA, which is a synthetic monomer used in the production of polycarbonate plastics and epoxy resins, as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE.

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the development of the uterus. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri–Columbia, also reported a study at the press conference. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA. But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8–9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done … [and] we can't afford to wait until we have perfect data in humans. When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling.”

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Medicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

Bisphenol A, found in products such as plastic water bottles, was among the endocrine disruptors discussed at the meeting.

Source Courtesy University of Cincinnati

WASHINGTON — The potential health threat of environmental exposure to endocrine-disrupting chemicals such as bisphenol A has become a top concern of the Endocrine Society, which issued its first scientific statement on the substances this summer.

“There was no question about whether to prioritize endocrine-disrupting compounds as a No. 1 issue to explore above many other issues that were competing that have major public health implications. And the reason for that is we believe that science has taken us up to a point where we are concerned,” Dr. Robert M. Carey, president of the Endocrine Society, said at a press conference at the society's annual meeting.

Researchers at the meeting also presented new animal studies on the possible effects of bisphenol A (BPA) on cardiac arrhythmias and epigenetic imprinting during gestational development, as well as the possible continual exposure of the majority of the U.S. population to levels of the substance at 20 times the Environmental Protection Agency's accepted safe daily intake (50 mcg/kg).

The scientific statement is the “consensus of the best scientists in the world” in summarizing the evidence of the effects of endocrine-disrupting chemicals (EDCs) and in identifying basic and clinical research knowledge gaps. “Obviously we don't know all the answers—far from it—for EDCs, so this is extremely important,” said Dr. Carey, who noted that the EPA announced in April that it will require pesticide manufacturers to test 67 chemicals in their products to determine whether they disrupt the endocrine system.

The scientific statement is published in the June issue of Endocrine Reviews (2009;30:293–342).

“We present evidence that endocrine disruptors do have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid disease, metabolism and obesity, and … cardiovascular endocrinology,” Dr. Carey said.

EDCs noted in the review include environmental estrogens, or estrogen mimics, most notably BPA, which is a synthetic monomer used in the production of polycarbonate plastics and epoxy resins, as well as polychlorinated biphenyls, diethylstilbestrol, dioxins, and phthalates. Other EDCs identified in the report include antiandrogen substances such as the fungicide vinclozolin and the insecticide DDT and its metabolic derivative DDE.

In light of the findings highlighted in the review, the authors advised several courses of action to address in clinical practice. Clinicians should become educated about the sources and effects of environmental contaminant exposures in utero and across the life span, and should take a careful history of the onset of reproductive disorders along with an occupational and environmental exposure history, according to the statement. Clinicians also can advise patients about minimizing their risks of exposure.

Dr. Hugh Taylor said that he tells his patients to “avoid things that we know have a high level of bisphenol A,” such as hard plastic water bottles and canned goods. This will help to lower BPA levels “until we start to see it taken out of all the things that we are not even aware of that we are exposed to every day.”

Dr. Taylor reported a study in which he and his colleagues found that offspring of pregnant mice that had been injected with 5 mg/kg of BPA per day for a week had epigenetic changes in the methylation pattern of a gene involved in the development of the uterus. This altered methylation pattern, which was not seen in the offspring of control mice, resulted in a permanent increase in estrogen sensitivity, said Dr. Taylor, professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Other research, presented by Scott Belcher, Ph.D., of the University of Cincinnati, showed that BPA at nanomolar doses can act alone or in combination with estrogen to increase arrhythmic pulsing of ventricular cardiomyocytes from female rats and mice, as well as to increase the frequency of arrhythmias in whole hearts of female rats and mice.

A well-known researcher of BPA toxicology, Frederick vom Saal, Ph.D., of the University of Missouri–Columbia, also reported a study at the press conference. He and his colleagues found that an orally administered dose of 400 mg/kg BPA is continually excreted and does not accumulate in the body of female rhesus macaques, a good model for human metabolism of chemicals such as BPA. But the researchers found that the levels of biologically active BPA over a 24-hour period never dropped below average levels of the chemical that are found in people in the United States and other developed countries, suggesting that people are exposed to even higher levels. For people to have such high levels, they must be exposed to BPA from many unknown sources, Dr. vom Saal said, noting that 8–9 billion pounds of BPA are used in products worldwide each year.

Dr. Taylor argued that “we're not going to find unexposed human populations” to compare with exposed groups. “The human experiment will never be done … [and] we can't afford to wait until we have perfect data in humans. When we see associations in humans mimicking exactly what we've proven are cause and effect in animals, I think that's pretty compelling.”

The National Institutes of Health funded the BPA studies and the scientific statement. Additional funding for the statement came from the European Commission, the Belgian Study Group for Pediatric Endocrinology, and grants from the Belgian Fonds de la Recherche Scientific Medicale. One author reported that he has served on the EPA advisory board, has received honoraria for university lectures, and has served as an expert witness in federal court.

Bisphenol A, found in products such as plastic water bottles, was among the endocrine disruptors discussed at the meeting.

Source Courtesy University of Cincinnati

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, based on the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than controls to be large for gestational age.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have demonstrated that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy control women. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. Women with PCOS had less then six menses per year, whereas healthy control women had a history of regular menses. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did control women, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age (greater than 90th percentile), compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol than did the female offspring of controls.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxyprogesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

Female offspring of mothers with PCOS were more likely than controls to be large for gestational age.

Source MS. ANDERSON

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, based on the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than controls to be large for gestational age.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have demonstrated that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy control women. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. Women with PCOS had less then six menses per year, whereas healthy control women had a history of regular menses. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did control women, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age (greater than 90th percentile), compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol than did the female offspring of controls.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxyprogesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

Female offspring of mothers with PCOS were more likely than controls to be large for gestational age.

Source MS. ANDERSON

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, based on the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than controls to be large for gestational age.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have demonstrated that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy control women. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. Women with PCOS had less then six menses per year, whereas healthy control women had a history of regular menses. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did control women, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age (greater than 90th percentile), compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol than did the female offspring of controls.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxyprogesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

Female offspring of mothers with PCOS were more likely than controls to be large for gestational age.

Source MS. ANDERSON

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15%-25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy.

In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant woman has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said.

With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

In order to improve research in this area, it is imperative that health care providers and patient advocacy organizations encourage individuals with psoriasis to enroll in pregnancy registries, Dr. Kimball stressed. “Pregnancy registries are one of our most valuable tools for collecting information about how to best manage and counsel women prepartum, during pregnancy, and post partum, yet they are so [undersubscribed]. This is something that we can help change.”

Dr. Kimball said she has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and she has a fellowship program funded by Centocor.

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15%-25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy.

In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant woman has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said.

With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

In order to improve research in this area, it is imperative that health care providers and patient advocacy organizations encourage individuals with psoriasis to enroll in pregnancy registries, Dr. Kimball stressed. “Pregnancy registries are one of our most valuable tools for collecting information about how to best manage and counsel women prepartum, during pregnancy, and post partum, yet they are so [undersubscribed]. This is something that we can help change.”

Dr. Kimball said she has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and she has a fellowship program funded by Centocor.

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15%-25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy.

In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant woman has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said.

With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

In order to improve research in this area, it is imperative that health care providers and patient advocacy organizations encourage individuals with psoriasis to enroll in pregnancy registries, Dr. Kimball stressed. “Pregnancy registries are one of our most valuable tools for collecting information about how to best manage and counsel women prepartum, during pregnancy, and post partum, yet they are so [undersubscribed]. This is something that we can help change.”

Dr. Kimball said she has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and she has a fellowship program funded by Centocor.

SAN FRANCISCO — Survival rates for extremely preterm infants held steady from 2000 to 2002, compared with the 1990s, and neurologic outcomes may have improved in some places, preliminary data suggest.

These trends are illustrated in data on 1,478 infants with birth weights of 500–999 g born in the Case Western Reserve University system, Dr. Thomas K. Shimotake said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The likelihood of surviving to a corrected age of 20 months increased from 49% in 1982–1989 to 68% in 1990–1999, then stayed relatively flat with a nonsignificant increase in survival to 71% in 2000–2002 (Pediatrics 2005;115:997–1003).

Long-term follow-up of infants in the Case Western study suggest improved neurodevelopmental outcomes in the most recent years, added Dr. Shimotake, codirector of the neurointensive care nursery at the UCSF Children's Hospital.

The proportion of infants with “intact survival” (no impairments at 18- to 24-months of follow-up) increased from 12% in the 1980s to 21% in the 1990s, then dropped to 15% in 2000–2002. Rates for any neurosensory abnormality increased from 18% to 23% between the 1980s and 1990s, then decreased to 9% in 2000–2002. The proportion of infants with cerebral palsy increased from 8% in the 1980s to 13% in the 1990s, then fell to 5% in 2000–2002 (Pediatrics 2007;119:37–45).

“That's a pretty dramatic fall without any improvement in survival rates, which is good news for that population, but it may not be applicable to everybody. Other people have reported higher rates” of cerebral palsy, he said. The incidence of cerebral palsy in preterm infants still is much higher than the rate of 2–3/1,000 live births seen in the general population, and preterm infants are 20–30 times more likely than term infants to have cerebral palsy, he added.

Unpublished data released by the Vermont Oxford Network in 2006 showed severe disabilities in 29%-32% of extremely low-birth-weight infants at 18- to 24-month follow-up exams between 1999 and 2004, with severe disability seen in 25% of those whose follow-up exams occurred in 2005. “That's pretty close to the most recent information we have,” Dr. Shimotake said. “It will be interesting to see how this plays out over the next couple of years, to see if this is consistent with findings reported at Case Western and see if there are improvements in neurologic outcomes. Generally, people feel that there are.”

At UCSF, which sees a high-risk population, “our follow-up outcomes have not been as robust,” he noted. Although 60%-75% of infants born at 24–26 weeks' gestation survive, neurologic impairments affect 79% born at 24 weeks, 62% born at 25 weeks, and 60% born at 26 weeks.

Practice changes in the past 2 decades undoubtedly improved survival, Dr. Shimotake said. Prenatal steroid use increased from no use in the 1980s to 41% of extremely preterm infants in the 1990s to 78% in 2000–2002, and “it's probably higher than that now,” he said. Use of surfactants has increased to 80%-90% of these cases. The use of assisted ventilation increased initially between the 1980s and 1990s, then decreased because of awareness of the injurious effects of aggressive resuscitation and mechanical ventilation, he noted.

It's important to give the most up-to-date data on survival and outcomes when counseling parents of extremely preterm infants, Dr. Shimotake said. “It's nice that we can have babies survive at extremely low birth weights, but what's important is how these babies ultimately live,” he said.

Dr. Shimotake said he has no conflicts of interest related to these topics.

SAN FRANCISCO — Survival rates for extremely preterm infants held steady from 2000 to 2002, compared with the 1990s, and neurologic outcomes may have improved in some places, preliminary data suggest.

These trends are illustrated in data on 1,478 infants with birth weights of 500–999 g born in the Case Western Reserve University system, Dr. Thomas K. Shimotake said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The likelihood of surviving to a corrected age of 20 months increased from 49% in 1982–1989 to 68% in 1990–1999, then stayed relatively flat with a nonsignificant increase in survival to 71% in 2000–2002 (Pediatrics 2005;115:997–1003).

Long-term follow-up of infants in the Case Western study suggest improved neurodevelopmental outcomes in the most recent years, added Dr. Shimotake, codirector of the neurointensive care nursery at the UCSF Children's Hospital.

The proportion of infants with “intact survival” (no impairments at 18- to 24-months of follow-up) increased from 12% in the 1980s to 21% in the 1990s, then dropped to 15% in 2000–2002. Rates for any neurosensory abnormality increased from 18% to 23% between the 1980s and 1990s, then decreased to 9% in 2000–2002. The proportion of infants with cerebral palsy increased from 8% in the 1980s to 13% in the 1990s, then fell to 5% in 2000–2002 (Pediatrics 2007;119:37–45).

“That's a pretty dramatic fall without any improvement in survival rates, which is good news for that population, but it may not be applicable to everybody. Other people have reported higher rates” of cerebral palsy, he said. The incidence of cerebral palsy in preterm infants still is much higher than the rate of 2–3/1,000 live births seen in the general population, and preterm infants are 20–30 times more likely than term infants to have cerebral palsy, he added.

Unpublished data released by the Vermont Oxford Network in 2006 showed severe disabilities in 29%-32% of extremely low-birth-weight infants at 18- to 24-month follow-up exams between 1999 and 2004, with severe disability seen in 25% of those whose follow-up exams occurred in 2005. “That's pretty close to the most recent information we have,” Dr. Shimotake said. “It will be interesting to see how this plays out over the next couple of years, to see if this is consistent with findings reported at Case Western and see if there are improvements in neurologic outcomes. Generally, people feel that there are.”

At UCSF, which sees a high-risk population, “our follow-up outcomes have not been as robust,” he noted. Although 60%-75% of infants born at 24–26 weeks' gestation survive, neurologic impairments affect 79% born at 24 weeks, 62% born at 25 weeks, and 60% born at 26 weeks.

Practice changes in the past 2 decades undoubtedly improved survival, Dr. Shimotake said. Prenatal steroid use increased from no use in the 1980s to 41% of extremely preterm infants in the 1990s to 78% in 2000–2002, and “it's probably higher than that now,” he said. Use of surfactants has increased to 80%-90% of these cases. The use of assisted ventilation increased initially between the 1980s and 1990s, then decreased because of awareness of the injurious effects of aggressive resuscitation and mechanical ventilation, he noted.

It's important to give the most up-to-date data on survival and outcomes when counseling parents of extremely preterm infants, Dr. Shimotake said. “It's nice that we can have babies survive at extremely low birth weights, but what's important is how these babies ultimately live,” he said.

Dr. Shimotake said he has no conflicts of interest related to these topics.

SAN FRANCISCO — Survival rates for extremely preterm infants held steady from 2000 to 2002, compared with the 1990s, and neurologic outcomes may have improved in some places, preliminary data suggest.

These trends are illustrated in data on 1,478 infants with birth weights of 500–999 g born in the Case Western Reserve University system, Dr. Thomas K. Shimotake said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The likelihood of surviving to a corrected age of 20 months increased from 49% in 1982–1989 to 68% in 1990–1999, then stayed relatively flat with a nonsignificant increase in survival to 71% in 2000–2002 (Pediatrics 2005;115:997–1003).

Long-term follow-up of infants in the Case Western study suggest improved neurodevelopmental outcomes in the most recent years, added Dr. Shimotake, codirector of the neurointensive care nursery at the UCSF Children's Hospital.

The proportion of infants with “intact survival” (no impairments at 18- to 24-months of follow-up) increased from 12% in the 1980s to 21% in the 1990s, then dropped to 15% in 2000–2002. Rates for any neurosensory abnormality increased from 18% to 23% between the 1980s and 1990s, then decreased to 9% in 2000–2002. The proportion of infants with cerebral palsy increased from 8% in the 1980s to 13% in the 1990s, then fell to 5% in 2000–2002 (Pediatrics 2007;119:37–45).

“That's a pretty dramatic fall without any improvement in survival rates, which is good news for that population, but it may not be applicable to everybody. Other people have reported higher rates” of cerebral palsy, he said. The incidence of cerebral palsy in preterm infants still is much higher than the rate of 2–3/1,000 live births seen in the general population, and preterm infants are 20–30 times more likely than term infants to have cerebral palsy, he added.

Unpublished data released by the Vermont Oxford Network in 2006 showed severe disabilities in 29%-32% of extremely low-birth-weight infants at 18- to 24-month follow-up exams between 1999 and 2004, with severe disability seen in 25% of those whose follow-up exams occurred in 2005. “That's pretty close to the most recent information we have,” Dr. Shimotake said. “It will be interesting to see how this plays out over the next couple of years, to see if this is consistent with findings reported at Case Western and see if there are improvements in neurologic outcomes. Generally, people feel that there are.”

At UCSF, which sees a high-risk population, “our follow-up outcomes have not been as robust,” he noted. Although 60%-75% of infants born at 24–26 weeks' gestation survive, neurologic impairments affect 79% born at 24 weeks, 62% born at 25 weeks, and 60% born at 26 weeks.

Practice changes in the past 2 decades undoubtedly improved survival, Dr. Shimotake said. Prenatal steroid use increased from no use in the 1980s to 41% of extremely preterm infants in the 1990s to 78% in 2000–2002, and “it's probably higher than that now,” he said. Use of surfactants has increased to 80%-90% of these cases. The use of assisted ventilation increased initially between the 1980s and 1990s, then decreased because of awareness of the injurious effects of aggressive resuscitation and mechanical ventilation, he noted.

It's important to give the most up-to-date data on survival and outcomes when counseling parents of extremely preterm infants, Dr. Shimotake said. “It's nice that we can have babies survive at extremely low birth weights, but what's important is how these babies ultimately live,” he said.

Dr. Shimotake said he has no conflicts of interest related to these topics.